M. Magnin

To improve anatomical definition and stereotactic precision of thalamic targets in neurosurgical treatments of chronic functional disorders, a new atlas of the human thalamus has been developed. This atlas is based on multiarchitectonic parcellation in sections parallel or perpendicular to the standard intercommissural reference plane. The calcium-binding proteins parvalbumin (PV), calbindin D-28K (CB), and calretinin (CR) were used as neurochemical markers to further characterize thalamic nuclei and delimit subterritories of functional significance for stereotactic explorations. Their overall distribution reveals a subcompartmentalization of thalamic nuclei into several groups. Predominant PV immunostaining characterizes primary somatosensory, visual and auditory nuclei, the ventral lateral posterior nucleus, reticular nucleus (R), and to a lesser degree also, lateral part of the centre median nucleus, and anterior, lateral, and inferior divisions of the pulvinar complex. In contrast, CB immunoreactivity is prevalent in medial thalamic nuclei (intralaminar and midline), the posterior complex, ventral posterior inferior nucleus, the ventral lateral anterior nucleus, ventral anterior, and ventral medial nuclei. The complementary distributions of PV and CB appear to correlate with distinct lemniscal and spinothalamic somatosensory pathways and to cerebellar and pallidal motor territories, respectively. Calretinin, while overlapping with CB in medial thalamic territories, is also expressed in R and limbic associated anterior group nuclei that contain little or no CB. Preliminary analysis indicates that interindividual nuclear variations cannot easily be taken into account by standardization procedures. Nevertheless, some corrections in antero-posterior coordinates in relation to different intercommissural distances are proposed.

We studied painful and non-painful somaesthetic sensations elicited by direct electrical stimulations of the insular cortex performed in 43 patients with drug refractory temporal lobe epilepsy, using stereotactically implanted depth electrodes. Painful sensations were evoked in the upper posterior part of the insular cortex in 14 patients, mostly in the right hemisphere. Non-painful sensations were elicited in the posterior part of the insular cortex in 16 patients, in both hemispheres. Thus, painful and non-painful somaesthetic representations in the human insula overlap. Both types of responses showed a trend toward a somatotopic organization. These results agree with previous anatomical and unit recording studies in monkeys indicating a participation of the posterior part of the insular cortex in processing both noxious and innocuous somaesthetic stimuli. In humans, both a posterior and an anterior pain-related cortical area have been described within the insular cortex using functional imaging. Our results help to define the respective functional roles of these two insular areas. Finally, lateralization in the right hemisphere of sites where painful sensations were evoked is coherent with the hypothesis of a preponderant role of this hemisphere in species survival.

Microelectrode-guided stereotactic operations performed in 29 parkinsonian patients allowed the recording of 86 cells located in the globus pallidus and 563 in thalamic nuclei. In the globus pallidus, the average firing rate was significantly higher in the internal (91+/-52 Hz) than in the external (60+/-21 Hz) subdivision. This difference was further accentuated when the average firing rate in the external subdivision was compared with that of the internal part of the internal subdivision (114+/-30 Hz). A rhythmic modulation in globus pallidus activities was observed in 19.7% of the cells, and this only during rest tremor episodes. In these cases, modulation frequency of unit activities was not statistically different from the rest tremor frequency (average: 4.6+/-0.5 vs 4. 4+/-0.4 Hz, respectively). In the medial thalamus, four types of unit activities could be defined. A sporadic type was mainly found in the parvocellular division of the mediodorsal nucleus (96.8% of the cells recorded) and in the centre median-parafascicular complex (74.2%). Two other types of activities characterized by random or rhythmic bursts fulfilling the extracellular criteria of low-threshold calcium spike bursts were concentrated in the central lateral nucleus (62.3%) and the paralamellar division of the mediodorsal nucleus (34.1%). These activities could be recorded independently of the presence of a rest tremor. When a tremor episode occurred, the rhythmic low-threshold calcium spike bursts had an interburst frequency similar to rest tremor frequency, although they were not synchronized with it. The fourth type, the so-called tremor locked, was also characterized by rhythmic bursts which, however, did not display low-threshold calcium spike burst properties. These bursts occurred only when a rest tremor was present and was in-phase with the electromyographic bursts. All tremor-locked cells were located in the centre median-parafascicular complex. In the lateral thalamus, cells exhibiting random or rhythmic low-threshold calcium spike bursts were found preponderantly in the ventral anterior nucleus (53.4%) and in the ventral lateral anterior nucleus (52.7%). Tremor-locked units were confined to the ventral division of the ventral lateral posterior nucleus (35.4%). None of the random or rhythmic low-threshold calcium spike bursting units responded to somatosensory stimuli or voluntary movements, either in the medial or in the lateral thalamus. The presence of low-threshold calcium spike bursts at the thalamic level, together with the paucity (8%) of responses to voluntary movements compared to what is found in normal non-human primates, demonstrate a pathological state of inhibition due to the overactivity of the internal subdivision of the globus pallidus units. Activities of the thalamic cells producing low-threshold calcium spike bursts are not synchronized with each other or with the tremor. However, this does not exclude a causal role of these activities in the generation of tremor. Indeed, it has been demonstrated that even random electrical stimulations of the rolandic cortex in parkinsonian patients induce tremor episodes, probably due to the triggering of rhythmic, low-threshold calcium spike-dependent, thalamocortical activities. Similarly, low-threshold calcium spike bursts could be at the origin of rigidity and dystonia through an activation of the supplementary motor area and of akinesia when reaching the pre-supplementary motor area. We conclude that the intrinsic oscillatory properties of individual neurons, combined with the dynamic properties of the thalamocortical circuitry, are responsible for the three cardinal parkinsonian symptoms.

Positive symptoms arise after lesions of the nervous system. They include neurogenic pain, tinnitus, abnormal movements, epilepsy and certain neuropsychiatric disorders. Stereotactic medial thalamotomies were performed on 104 patients with chronic therapy-resistant positive symptoms. Peroperative recordings of 2012 single units revealed an overwhelming unresponsiveness (99%) to sensory stimuli or motor activation. Among these unresponsive cells, 45.1% presented a rhythmic or random bursting activity. Rhythmic bursting activities had an average interburst interval of 263±46 ms corresponding to a frequency of 3.8±0.7 Hz. Frequency variations among the different symptoms were not statistically

Motor cortex stimulation (MCS) for neuropathic pain control induces focal cerebral blood flow changes involving regions with high density of opioid receptors. We studied the possible contribution of the endogenous opioid system to MCS-related pain relief.Changes in opioid receptor availability induced by MCS were studied with PET scan and [(11)C]diprenorphine in eight patients with refractory neuropathic pain. Each patient underwent two preoperative (test-retest) PET scans and one postoperative PET scan acquired after 7 months of chronic MCS.The two preoperative scans, performed at 2 weeks interval, did not show significant differences. Conversely, postoperative compared with preoperative PET scans revealed significant decreases of [(11)C]diprenorphine binding in the anterior middle cingulate cortex (aMCC), periaqueductal gray (PAG), prefrontal cortex, and cerebellum. Binding changes in aMCC and PAG were significantly correlated with pain relief.The decrease in binding of the exogenous ligand was most likely explained by receptor occupancy due to enhanced secretion of endogenous opioids. Motor cortex stimulation (MCS) may thus induce release of endogenous opioids in brain structures involved in the processing of acute and chronic pain. Correlation of this effect with pain relief in at least two of these structures supports the role of the endogenous opioid system in pain control induced by MCS.

We recorded laser‐evoked cortical potentials (LEPs) in 54 consecutive patients presenting with unilateral neuropathic central pain (n = 42) or with lateralized pain of non‐organic origin (n = 12). A number of cases in each group had superimposed hyperalgesia or allodynia. In patients with central pain, LEPs were significantly attenuated after stimulation over the painful territory, relative to stimulation of the homologous normal territory. LEP attenuation concerned not only patients with decreased pain/heat sensation, but also those with allodynia or hyperalgesia to laser pulses. In contrast, LEPs were never attenuated in patients with non‐organic forms of pain, in whom LEPs could even be enhanced to stimulation of the painful territory. Increased responses in non‐organic pain were a reminder of the cognitive modulation observed in normal subjects who direct attention to a laser stimulus. Enhanced LEPs never accompanied truly neuropathic hyperalgesia or allodynia. In central pain patients with exclusively spontaneous pain, LEP attenuation was more pronounced than that observed in those with allodynia and hyperalgesia. Patients with allodynia also presented occasionally ultra‐late responses (>700 ms) to stimulation of the painful side. The hypothesis that such responses may reflect activation of a slow conducting ‘medial’ pain system is discussed. We conclude that, as currently recorded, LEPs essentially reflect the activity of a ‘lateral’ pain system subserved at the periphery by rapidly conducting A‐δ fibres. They are useful to document the sensorial deficits (deafferentation) leading to neuropathic pain syndromes. Conversely, in the case of deafferentation, they fail to index adequately the affective aspects of pain sensation. On practical grounds, chronic pain coupled with reduced LEPs substantiates the diagnosis of neuropathic pain, whereas the finding of normal or enhanced LEPs to stimulation of a painful territory suggests the integrity of pain pathways, and does not support a neuropathic pathophysiology. In neuropathic cases, partial LEP preservation might increase the probability of developing provoked pain (allodynia/hyperalgesia). The possible predictive value of this phenomenon, when observed before the development of pain, remains to be demonstrated. In selected contexts (pain sine materia, non‐organic anaesthesia), normal or enhanced LEPs may support a psychogenic participation in the syndrome.

Thalamic and cortical activities are assumed to be time-locked throughout all vigilance states. Using simultaneous intracortical and intrathalamic recordings, we demonstrate here that the thalamic deactivation occurring at sleep onset most often precedes that of the cortex by several minutes, whereas reactivation of both structures during awakening is synchronized. Delays between thalamus and cortex deactivations can vary from one subject to another when a similar cortical region is considered. In addition, heterogeneity in activity levels throughout the cortical mantle is larger than previously thought during the descent into sleep. Thus, asynchronous thalamo-cortical deactivation while falling asleep probably explains the production of hypnagogic hallucinations by a still-activated cortex and the common self-overestimation of the time needed to fall asleep.

Afferent and efferent connections of the parabigeminal nucleus (PBG) of the cat have been demonstrated by means of horseradish peroxidase (HRP) tracing technique. Following HRP injection in the PBG, labelled cells were observed mainly in the deep layers of the ipsilateral superior colliculus (SC). The other labelled structures were the prepositus hypoglossi complex (PH), the ventral nucleus of the lateral geniculate body (LGV), the locus coeruleus, the cuneiform nucleus, the periaqueductal gray and the dorsomedial hypothalamic area. Efferent projections of the PBG were investigated by HRP injection in SC, LGV, PH, hypothalamus and in some acoustic relays, i.e. medial geniculate body and inferior colliculus. Only the PBG-SC projection appeared to be well systematized. The positive labelling of the PBG following injection of LGV and hypothalamus is discussed in terms of the specificity of the injection. The absence of afferent and efferent connections of the PGB with any acoustic relay tends to exclude this nucleus from the auditory system in contrast to previous suggestions. On the basis of the close reciprocal PBG-SC connections a possible role of the PBG within visuomotor tectal function is proposed.

The SII area and the posterior insular region are both activated by thermal stimuli in functional imaging studies. However, controversy remains as to a possible differential encoding of thermal intensity by each of these 2 contiguous areas. Using CO(2) laser stimulations, we analyzed the modifications induced by increasing thermal energy on evoked potentials recorded with electrodes implanted within SII and posterior insula in patients referred for presurgical evaluation of epilepsy. Although increasing stimulus intensities enhanced both SII and insular responses, the "dynamics" of their respective amplitude changes were different. SII responses were able to encode gradually the intensity of stimuli from sensory threshold up to a level next to pain threshold but tended to show a ceiling effect for higher painful intensities. In contrast, the posterior insular cortex failed to detect nonnoxious laser pulses but reliably encoded stimulus intensity variations at painful levels, without showing saturation effects for intensities above pain threshold. According to these results, one can assume that insular cortex could be more involved in the triggering of affective recognition of, and motor reaction to, noxious stimuli, whereas SII would be more dedicated to finer-grain discrimination of stimulus intensity, from nonpainful to painful levels.

This study used positron emission tomography (PET) and [11C]diprenorphine to compare the in vivo distribution abnormalities of brain opioid receptors (OR) in patients with peripheral (n = 7) and central post-stroke pain (CPSP, n = 8), matched for intensity and duration. Compared with age- and sex-matched controls, peripheral neuropathic pain (NP) patients showed bilateral and symmetrical OR binding decrease, while in CPSP binding decrease predominated in the hemisphere contralateral to pain. In CPSP patients, interhemispheric comparison demonstrated a significant decrease in opioid binding in posterior midbrain, medial thalamus and the insular, temporal and prefrontal cortices contralateral to the painful side. Peripheral NP patients did not show any lateralised decrease in opioid binding. Direct comparison between the central and peripheral groups confirmed a significant OR decrease in CPSP, contralateral to pain. While bilateral binding decrease in both NP groups may reflect endogenous opioid release secondary to chronic pain, the more important and lateralised decrease specific to CPSP suggests opioid receptor loss or inactivation in receptor-bearing neurons. Opioid binding decrease was much more extensive than brain anatomical lesions, and was not co-localised with them; metabolic depression (diaschisis) and/or degeneration of OR neurons-bearing secondary to central lesions appears therefore as a likely mechanism. Central and peripheral forms of NP may differ in distribution of brain opioid system changes and this in turn might underlie their different sensitivity to opiates.

Vertical eye movement-related responses of neurons in midbrain near intestinal nucleus of Cajal.W M King, A F Fuchs, and M MagninW M King, A F Fuchs, and M MagninPublished Online:01 Sep 1981https://doi.org/10.1152/jn.1981.46.3.549MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByBrain Stem Neural Circuits of Horizontal and Vertical Saccade Systems and their Frame of ReferenceNeuroscience, Vol. 392Computations underlying the visuomotor transformation for smooth pursuit eye movementsT. Scott Murdison, Guillaume Leclercq, Philippe Lefèvre, and Gunnar Blohm1 March 2015 | Journal of Neurophysiology, Vol. 113, No. 5Input-output organization of inhibitory neurons in the interstitial nucleus of Cajal projecting to the contralateral trochlear and oculomotor nucleusY. Sugiuchi, M. Takahashi, and Y. 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Central pain with dissociated thermoalgesic sensory loss is common in spinal and brainstem syndromes but not in cortical lesions. Out of a series of 270 patients investigated because of somatosensory abnormalities, we identified five subjects presenting with central pain and pure thermoalgesic sensory loss contralateral to cortical stroke. All of the patients had involvement of the posterior insula and inner parietal operculum. Lemniscal sensory modalities (position sense, graphaestesia, stereognosis) and somatosensory evoked potentials to non-noxious inputs were always preserved, while thermal and pain sensations were profoundly altered, and laser-evoked potentials to thermo-nocoiceptive stimuli were always abnormal. Central pain resulting from posterior parasylvian lesions appears to be a distinct entity that can be identified unambiguously on the basis of clinical, radiological and electrophysiological data. It presents with predominant or isolated deficits for pain and temperature sensations, and is paradoxically closer to pain syndromes from brainstem lesions affecting selectively the spinothalamic pathways than to those caused by focal lesions of the posterior thalamus. The term 'pseudo-thalamic' is therefore inappropriate to describe it, and we propose parasylvian or operculo-insular pain as appropriate labels. Parasylvian pain may be extremely difficult to treat; the magnitude of pain-temperature sensory disturbances may be prognostic for its development, hence the importance of early sensory assessment with quantitative methods.

The cingulate cortex (CC) as a part of the “medial” pain subsystem is generally assumed to be involved in the affective and/or cognitive dimensions of pain processing, which are viewed as relatively slow processes compared with the sensory-discriminative pain coding by the lateral second somatosensory area (SII)–insular cortex. The present study aimed at characterizing the location and timing of the CC evoked responses during the 1 s period after a painful laser stimulus, by exploring the whole rostrocaudal extent of this cortical area using intracortical recordings in humans. Only a restricted area in the median CC region responded to painful stimulation, namely the posterior midcingulate cortex (pMCC), the location of which is consistent with the so-called “motor CC” in monkeys. Cingulate pain responses showed two components, of which the earliest peaked at latencies similar to those obtained in SII. These data provide direct evidence that activations underlying the processing of nociceptive information can occur simultaneously in the “medial” and “lateral” subsystems. The existence of short-latency pMCC responses to pain further indicates that the “medial pain system” is not devoted exclusively to the processing of emotional information, but is also involved in fast attentional orienting and motor withdrawal responses to pain inputs. These functions are, not surprisingly, conducted in parallel with pain intensity coding and stimulus localization specifically subserved by the sensory-discriminative “lateral” pain system.

Emotions modulate pain perception, although the mechanisms underlying this phenomenon remain unclear. In this study, we show that intensity reports significantly increased when painful stimuli were concomitant to images showing human pain, whereas pictures with identical emotional values but without somatic content failed to modulate pain. Early somatosensory responses (<200 ms) remained unmodified by emotions. Conversely, late responses showed a significant enhancement associated with increased pain ratings, localized to the right prefrontal, right temporo-occipital junction, and right temporal pole. In contrast to selective attention, which enhances pain ratings by increasing sensory gain, emotions triggered by seeing other people's pain did not alter processing in SI-SII (primary and second somatosensory areas), but may have biased the transfer to, and the representation of pain in short-term memory buffers (prefrontal), as well as the affective assignment to this representation (temporal pole). Memory encoding and recall, rather than sensory processing, appear to be modulated by empathy with others' physical suffering.

Current knowledge on pain-related cerebral networks has relied so far on stimulus-induced brain responses, but not on the analysis of brain activity during spontaneous pain attacks. In this case report, correlation between intracerebral field potentials and online sensations during spontaneously painful epileptic seizures suggests a crucial role of the insula in the development of subjective pain. Attacks originated from a very limited dysplasia located in the posterior third of the right insula and propagated to other areas of the pain matrix, including the parietal operculum and the midcingulate gyrus. Concomitant painful symptoms started on the left hand or the left foot and extended in a few seconds to the whole left side of the body, sparing the head. Continuous during the first seconds of the attack, the painful feeling evolved to throbbing and remained so until it progressively vanished, together with the spike discharge. Stimulation of the insula, but not of other pain matrix regions, induced pain identical to that of seizures. After thermocoagulation of the insular epileptic focus, a short, transient exacerbation of seizures with same painful features but different location was observed before a long-lasting and complete remission of the attacks. Although these preliminary data need to be confirmed, they strongly suggest that if the full pain experience involves the pain matrix network, the posterior insula seems to play a leading role in the triggering of this network and the resulting emergence of subjective pain experience. Evidence from intracerebral EEG recordings of epileptic painful seizures reveals that the posterior insula seems to play a leading role in the triggering of the so called pain matrix cortical network and the resulting emergence of subjective pain experience.

Abstract Every night, the human brain produces thousands of downstates and spindles during non-REM sleep. Previous studies indicate that spindles originate thalamically and downstates cortically, loosely grouping spindle occurrence. However, the mechanisms whereby the thalamus and cortex interact in generating these sleep phenomena remain poorly understood. Using bipolar depth recordings, we report here a sequence wherein: (1) convergent cortical downstates lead thalamic downstates; (2) thalamic downstates hyperpolarize thalamic cells, thus triggering spindles; and (3) thalamic spindles are focally projected back to cortex, arriving during the down-to-upstate transition when the cortex replays memories. Thalamic intrinsic currents, therefore, may not be continuously available during non-REM sleep, permitting the cortex to control thalamic spindling by inducing downstates. This archetypical cortico-thalamo-cortical sequence could provide the global physiological context for memory consolidation during non-REM sleep.

The efficacy of repetitive transcranial magnetic stimulation (rTMS) of the motor cortex for neuropathic pain relief is founded on double-blind studies versus placebo. In these studies, however, the analgesic effect of active interventions remained modest compared with the placebo effect. This observation led us to re-evaluate the intrinsic placebo action on pain relief according to the relative timing of active and sham rTMS interventions. In a randomized controlled study including 45 patients, we compared the analgesic effect of sham rTMS that either preceded or followed an active rTMS, which could be itself either successful or unsuccessful. Placebo analgesia differed significantly when the sham rTMS session followed a successful or an unsuccessful active rTMS. Placebo sessions induced significant analgesia when they followed a successful rTMS (mean pain decrease of 11%), whereas they tended to worsen pain when following an unsuccessful rTMS (pain increase of 6%). Only when the sham intervention was applied before any active rTMS were placebo scores unchanged from the baseline. These results probably reflect an unconscious conditioned learning. The timing of placebo relative to active interventions should be taken into account in rTMS studies for pain relief, and possibly in other conditions too. The fact that placebo effects could be enhanced by a previous rTMS with an analgesic effect as low as 10% suggests that a 30% pain decrease threshold in therapeutic trials may be too severe because smaller analgesic effects may have a clinical significance too. Sham rTMS induces significant analgesia only when preceded by a successful active stimulation. Such a placebo modulation is probably related to an unconscious conditioned learning.

Conscious perception of painful stimuli needs the contribution of an extensive cortico-subcortical network, and is completed in less than one second. While initial activities in operculo-insular and mid-cingulate cortices have been extensively assessed, the activation timing of most areas supporting conscious pain has barely been studied. Here we used intracranial EEG to investigate the dynamics of 16 brain regions (insular, parietal, prefrontal, cingulate, hippocampal and limbic) during the first second following nociceptive-specific laser pulses. Three waves of activation could be defined according to their temporal relation with conscious perception, ascertained by voluntary motor responses. Pre-conscious activities were recorded in the posterior insula, operculum, mid-cingulate and amygdala. Antero-insular, prefrontal and posterior parietal activities started later and developed during time-frames consistent with conscious voluntary reactions. Responses from hippocampus, perigenual and perisplenial cingulate developed latest and persisted well after conscious perception occurred. Nociceptive inputs reach simultaneously sensory and limbic networks, probably through parallel spino-thalamic and spino-parabrachial pathways, and the initial limbic activation precedes conscious perception of pain. Access of sensory information to consciousness develops concomitant to fronto-parietal activity, while late-occurring responses in the hippocampal region, perigenual and posterior cingulate cortices likely underlie processes linked to memory encoding, self-awareness and pain modulation. Hum Brain Mapp 37:4301-4315, 2016. © 2016 Wiley Periodicals, Inc.

Thalamic pain is a severe and treatment-resistant type of central pain that may develop after thalamic stroke. Lesions within the ventrocaudal regions of the thalamus carry the highest risk to develop pain, but its emergence in individual patients remains impossible to predict. Because damage to the spino-thalamo-cortical system is a crucial factor in the development of central pain, in this study we combined detailed anatomical atlas-based mapping of thalamic lesions and assessment of spinothalamic integrity using quantitative sensory analysis and laser-evoked potentials in 42 thalamic stroke patients, of whom 31 had developed thalamic pain. More than 97% of lesions involved an area between 2 and 7 mm above the anterior–posterior commissural plane. Although most thalamic lesions affected several nuclei, patients with central pain showed maximal lesion convergence on the anterior pulvinar nucleus (a major spinothalamic target) while the convergence area lay within the ventral posterior lateral nucleus in pain-free patients. Both involvement of the anterior pulvinar nucleus and spinothalamic dysfunction (nociceptive thresholds, laser-evoked potentials) were significantly associated with the development of thalamic pain, whereas involvement of ventral posterior lateral nucleus and lemniscal dysfunction (position sense, graphaesthesia, pallaesthesia, stereognosis, standard somatosensory potentials) were similarly distributed in patients with or without pain. A logistic regression model combining spinothalamic dysfunction and anterior pulvinar nucleus involvement as regressors had 93% sensitivity and 87% positive predictive value for thalamic pain. Lesion of spinothalamic afferents to the posterior thalamus appears therefore determinant to the development of central pain after thalamic stroke. Sorting out of patients at different risks of developing thalamic pain may be achievable at the individual level by combining lesion localization and functional investigation of the spinothalamic system. As the methods proposed here do not need complex manipulations, they can be added to routine patients’ work up, and the results replicated by other investigators in the field. Thalamic pain can develop after thalamic stroke, and may be severe. Vartiainen et al. reveal that the patients at highest risk of developing thalamic pain have MRI lesions involving the anterior pulvinar region, together with altered spinothalamic transmission revealed by laser-evoked potentials. Identification of at-risk individuals will pave the way for early treatment.

Microelectrode recordings in the medial thalamus of 45 neurogenic pain patients undergoing medial thalamotomy revealed that most units (316/318) did not respond to somatosensory stimuli, and that half exhibited low-threshold calcium spike bursts. After medial thalamotomy, 67% of the patients reached a 50 to 100% pain relief, without somatosensory deficits. Colocalization of bursting activities and of the most efficient therapeutic lesions in the central lateral nucleus suggests a key role of this structure in neurogenic pain. We propose that neurogenic pain is due to an imbalance between central lateral and ventroposterior nuclei, resulting in an overinhibition of both by the thalamic reticular nucleus.

Resistance mechanisms of a strain (MSE) of Culex pipiens L., collected in southern France in 1979 and highly resistant to chlorpyrifos, were investigated by comparing the resistance characteristics to various organophosphates and carbamates in the absence or presence of synergists and determining the biochemical characteristics of four enzymes (esterases, glutathione-S-transferases, mixed function oxidases, and acetylcholinesterase) compared with a susceptible strain and a chlorpyrifos-resistant strain (S54) collected in the same area in 1960 and 1974, respectively. Chlorpyrifos resistance in S54 was due to a detoxifying esterase as previously described, whereas resistance in MSE was associated with an acetylcholinesterase insensitive to the inhibition by chlorpyrifoxon and some carbamates (propoxur, carbosulfan, and carbaryl), and with an increase of oxidative metabolism.

Summary: Purpose: Several animal studies suggest that the thalamus might be involved in the maintenance and propagation of epileptic seizures. However, electrophysiologic evidence for this implication in human partial epileptic seizures is still lacking. Considering the rich and reciprocal connectivity of the medial pulvinar (PuM) with the temporal lobe, we evaluated a potential participation of this thalamic nucleus in temporal lobe epilepsy (TLE). Methods: The electrophysiologic activity of PuM was recorded during stereoelectroencephalographic exploration of spontaneous temporal lobe seizures in 14 patients referred for presurgical assessment of refractory TLE. Results: We recorded PuM ictal activity in 80% of the 74 seizures that we analyzed. This activity was characterized by rhythmic slow‐waves or rhythmic spikes (RSW‐RS) or both or by low‐voltage fast activity (LVFA) in 64% and 36% of seizures, respectively. RSW‐RS occurred mostly in seizures arising from mesiotemporal structures, whereas LVFA was more frequently observed in seizures of neocortical origin. In the 15 seizures without PuM ictal activity, spreading of the seizure outside the onset zone never occurred, whereas it did in 78% of seizures with PuM ictal involvement. Discharge propagation was systematic when PuM involvement corresponded to LVFA, whatever the seizure onset zone was, whereas it represented only 66% of the seizures when PuM exhibited RSW‐RS. Conclusions: This study shows that ictal changes in PuM activity are frequently observed during temporal lobe seizures and suggests that this thalamic nucleus might participate in their propagation.

The thalamic medial pulvinar nucleus (PuM) is fully developed only in primates and reaches its greatest extent in humans. To assess the reciprocal functional connectivity between PuM and cortex, we studied intracerebral-evoked responses obtained after PuM and cortical electrical stimulation in 7 epileptic patients undergoing depth electroencephalographic recordings. Cortical-evoked potentials (CEPs) to PuM stimulation were recorded from all explored cortical regions, except striate cortex, anterior cingulated, and postcentral gyrus. Percentages of cortical contacts pairs responding to PuM stimulation (CEPs response rate) ranged from 80% in temporal neocortex, temporoparietal (TP) junction, insula, and frontoparietal opercular cortex to 34% in mesial temporal regions. Reciprocally, PuM-evoked potentials (PEPs) response rates were 14% after cortical stimulation in insula and frontoparietal opercular cortex, 67% in the TP junction, 76% in temporal neocortex, and 80% in mesial temporal regions. Overall, our study of functional PuM connectivity in the human brain converges with most of the data from anatomical studies in monkeys, except for a strong amygdalohippocampal functional projection to PuM and an unexpected imbalance between some of the reciprocal pathways explored. This functional quantitative approach helps to clarify the functional role of PuM as well as its implication in temporal lobe epileptic seizures.

Antisera raised against the denatured polypeptide of two organophosphate-detoxifying esterases (B1 and A1) of Culex mosquitoes were used in an immunoblot method to quantify esterase production in resistant versus susceptible strains and to detect the presence of immunologically related proteins in other insects. It was demonstrated that esterase B1 of Culex quinquefasciatus and esterase A1 of Culex pipiens are overproduced in resistant strains by factors of at least 500-fold and 70-fold, respectively, as compared with the corresponding susceptible strains. These factors approximate the levels of resistance to the organophosphate chlorpyrifos determined by bioassay--i.e., about 800-fold and 100-fold, respectively. Antiesterase B1 antiserum was found to react with other type B esterases (B2 of C. quinquefasciatus and B3 of Culex tarsalis) but not with type A esterases (A1 of C. pipiens, A2 of C. quinquefasciatus, or A3 of C. tarsalis); similarly, antiesterase A1 antiserum was found to react with other type A esterases (A2 and A3) but not with type B esterases (B1, B2, and B3). Proteins immunologically related to esterase B1 were detected in Aedes aegypti L., Myzus persicae Sultzer, and Musca domestica L., although they were not overproduced in the organophosphate-resistant strains of these species. In none of these species were proteins immunologically related to esterase A1 found.

Intracortical evoked potentials to nonnoxious Aβ (electrical) and noxious Aδ (laser) stimuli within the human primary somatosensory (S1) and motor (M1) areas were recorded from 71 electrode sites in 9 epileptic patients. All cortical sites responding to specific noxious inputs also responded to nonnoxious stimuli, while the reverse was not always true. Evoked responses in S1 area 3b were systematic for nonnoxious inputs, but seen in only half of cases after nociceptive stimulation. Nociceptive responses were systematically recorded when electrode tracks reached the crown of the postcentral gyrus, consistent with an origin in somatosensory areas 1-2. Sites in the precentral cortex also exhibited noxious and nonnoxious responses with phase reversals indicating a local origin in area 4 (M1). We conclude that a representation of thermal nociceptive information does exist in human S1, although to a much lesser extent than the nonnociceptive one. Notably, area 3b, which responds massively to nonnoxious Aβ activation was less involved in the processing of noxious heat. S1 and M1 responses to noxious heat occurred at latencies comparable to those observed in the supra-sylvian opercular region of the same patients, suggesting a parallel, rather than hierarchical, processing of noxious inputs in S1, M1 and opercular cortex. This study provides the first direct evidence for a spinothalamic related input to the motor cortex in humans.

Summary Brain 11C-diprenorphine positron emission tomography scans help clinicians to select the best candidates for motor cortex stimulation among patients with severe refractory neuropathic pain. The clinical effects of motor cortex stimulation (MCS) for neuropathic pain (NP) is thought to be mediated primarily by the secretion of endogenous opioids in humans and in animal models. Because opioid receptor density is itself decreased in patients with NP, we investigated whether the magnitude and distribution of the remaining opioid receptors in patients with NP could be biological predictors of the pain-relieving effects of MCS. Using 11C-diprenorphine positron emission tomography scans, opioid receptor availability was assessed in 15 patients suffering refractory NP, who subsequently received chronically implanted MCS. All patients underwent 2 preoperative baseline scans at 2-wk intervals and were clinically assessed after 7 mo of chronic MCS. The levels of preoperative opioid-binding in the insula, thalamus, periaqueductal gray, anterior cingulate, and orbitofrontal cortex were significantly and positively correlated with postoperative pain relief at 7 mo. Patients with receptor density values below the lower limits in age-matched controls in the thalamus, periaqueductal gray and contralateral insula were the least likely to benefit from MCS. Opioid-receptor availability as shown in preoperative positron emission tomography scans appears to be related to the efficacy of MCS in NP and may help clinicians to select the candidates most likely to benefit from this procedure.

Summary We compare CE-SEPs, Aβ SEPs, and Aδ LEPs in healthy subjects and patients and conclude that there is a lack of nociceptive specificity of the concentric planar electrode. Laser-evoked potentials (LEPs) are acknowledged as the most reliable laboratory tool for assessing thermal and pain pathways. Electrical stimulation with a newly developed planar concentric electrode, delivering stimuli limited to the superficial skin layers, has been suggested to provide selective activation of Aδ fibres without the inconveniences linked to laser stimulation. The aim of our study was to compare the scalp and intracranial responses to planar concentric electrode stimulation (CE-SEPs) with those of LEPs and standard somatosensory-evoked potentials (SEPs). Sixteen healthy subjects, 6 patients with intracortical electrodes, and 2 patients with selective lesions of the spinothalamic pathway were submitted to Neodymium:Yttrium-Aluminium-Perovskite laser stimulations, and electrical stimulations using standard electrodes or planar concentric electrodes (CE). In both healthy controls and epileptic implanted patients, CE- and standard SEPs showed significantly shorter latencies than LEPs. This is consistent with Aβ-fibre activation, peripheral activation time being unable to account for longer LEP latencies. In the patients with spinothalamic lesions, LEPs were absent after stimulation of the affected territory, while CE-SEPs were still present. For these 2 reasons, we conclude that the planar CE does not selectively activate the Aδ and C fibers, but coexcites a significant proportion of large myelinated Aβ fibres that dominate the ensuing cortical response. The use of CE-SEPs for the detection of spinothalamic system lesions is therefore not warranted; the planar electrode can, however, represent a useful tool to study nociceptive reflexes, which can be reliably elicited even in the presence of Aβ coactivation.

Wakefulness, non-rapid eye movement (NREM), and rapid eye movement (REM) sleep are characterized by specific brain activities. However, recent experimental findings as well as various clinical conditions (parasomnia, sleep inertia) have revealed the presence of transitional states. Brief intrusions of wakefulness into sleep, namely, arousals, appear as relevant phenomena to characterize how brain commutes from sleep to wakefulness. Using intra-cerebral recordings in 8 drug-resistant epileptic patients, we analyzed electroencephalographic (EEG) activity during spontaneous or nociceptive-induced arousals in NREM and REM sleep. Wavelet spectral analyses were performed to compare EEG signals during arousals, sleep, and wakefulness, simultaneously in the thalamus, and primary, associative, or high-order cortical areas. We observed that 1) thalamic activity during arousals is stereotyped and its spectral composition corresponds to a state in-between wakefulness and sleep; 2) patterns of cortical activity during arousals are heterogeneous, their manifold spectral composition being related to several factors such as sleep stages, cortical areas, arousal modality ("spontaneous" vs nociceptive-induced), and homeostasis; 3) spectral compositions of EEG signals during arousal and wakefulness differ from each other. Thus, stereotyped arousals at the thalamic level seem to be associated with different patterns of cortical arousals due to various regulation factors. These results suggest that the human cortex does not shift from sleep to wake in an abrupt binary way. Arousals may be considered more as different states of the brain than as "short awakenings." This phenomenon may reflect the mechanisms involved in the negotiation between two main contradictory functional necessities, preserving the continuity of sleep, and maintaining the possibility to react.

The aim of this study was to evaluate the capacity of chickens to adapt to and compensate for early dietary restriction of non-phytate P (NPP) and/or Ca (10 to 21 d) in a later phase (22 to 35 d), and to determine whether compensatory processes depend on the P and Ca concentrations in the finisher diet. Four diets were formulated and fed to broilers from 10 to 21 d in order to generate birds with different mineral status: L1 (0.6% Ca, 0.30% NPP), L2 (0.6% Ca, 0.45% NPP), H1 (1.0% Ca, 0.30% NPP), and H2 (1.0% Ca, 0.45% NPP). On d 22, each group was divided into three groups which received a low (L, 0.48% Ca, 0.24% NPP), moderate (M, 0.70% Ca, 0.35% NPP), or high (H, 0.90% Ca, 0.35% NPP) finisher diet until 35 d, resulting in a total of 12 treatments. Lowering the Ca level enhanced apparent ileal digestibility of P (P AID) at 21 d especially with the high NPP level (Ca × NPP, P < 0.01). The lower bone mineralization observed at 21 d in broilers fed the L1 diet compared to those fed the H2 diet had disappeared by 35 d with long-term stimulation of the P AID with the low NPP level (P < 0.001). Although P AID and growth performance were improved in birds fed the L1 L compared to the L1 H and H2 H treatments, tibia characteristics tended to be lower in birds fed the L1 L compared to those fed the L1 H treatment. Birds fed the H1 M treatment had higher P AID, growth performance and tibia ash content than those fed the H1 H treatment. A significant increase in the mRNA levels of several genes encoding Ca and P transporters was observed at 35 d in birds fed the L1 followed by the L diet compared to birds fed the L1 followed by the M diet. In conclusion, chickens are able to adapt to early dietary changes in P and Ca through improvement of digestive efficiency in a later phase, and the extent of the compensation in terms of growth performance and bone mineralization depends on the P and Ca levels in the subsequent diet.

This study compares the amplitude, latency, morphology, scalp topography and intracranial generators of laser-evoked potentials (LEPs) to CO(2) and Nd:YAP laser stimuli.LEPs were assessed in 11 healthy subjects (6 men, mean age 39+/-10 years) using a 32-channel acquisition system. Laser stimuli were delivered on the dorsum of both hands (intensity slightly above pain threshold), and permitted to obtain lateralised (N1) and vertex components (N2-P2) with similar scalp distribution for both types of lasers.The N1-YAP had similar latencies but significantly higher amplitudes relative to N1-CO(2). The N2-P2 complex showed earlier latencies, higher amplitudes (N2) and more synchronised responses when using Nd:YAP stimulation. The distribution of intracranial generators assessed with source localization analyses (sLORETA) was similar for Nd:YAP and CO(2) lasers. The insular, opercular, and primary sensorimotor cortices were active during the N1 time-window, whereas the anterior midcingulate, supplementary motor areas and mid-anterior insulae were active concomitant to the N2-P2 complex.Earlier latencies and larger amplitudes recorded when using Nd:YAP pulses suggest a more synchronized nociceptive afferent volley with this type of laser.This, together with its handy utilization due to optic fibre transmission, may favour the use of Nd:YAP lasers in clinical settings.

Data concerning the possible role of a corollary discharge mechanism in the regulation of visual-oculomotor interactions are reviewed. Several modes of action for such a mechanism on the processing of visual information are discussed. Mere suppression of visual input during saccades is considered mostly as a peripheral mechanism. It is proposed that corollary discharge could either produce an active cancellation of the effects of eye movements on vision, or contribute to the evaluation that a given visual change is provoked by a saccade. Cancellation could occur at subcortical levels of visual processing although evaluation could occur at the cortical level.

Unilateral Vestibular Neurectomy (UVN) induces a postural syndrome whose compensation over time is underpinned by multimodal sensory substitution processes. However, at a chronic stage of compensation, UVN rats exhibit an enduring postural asymmetry expressed by an increase in the body weight on the ipsilesional paws. Given the anatomo-functional links between the vestibular nuclei and the primary somatosensory cortex (S1), we explored the interplay of vestibular and somatosensory cortical inputs following acute and chronic UVN. We determined whether the enduring imbalance in tactilo-plantar inputs impacts response properties of S1 cortical neurons and organizational features of somatotopic maps. We performed electrophysiological mapping of the hindpaw cutaneous representations in S1, immediately and one month after UVN. In parallel, we assessed the posturo-locomotor imbalance during the compensation process. UVN immediately induces an expansion of the cortical neuron cutaneous receptive fields (RFs) leading to a partial dedifferentiation of somatotopic maps. This effect was demonstrated for the ventral skin surface representations and was greater on the contralesional hindpaw for which the neuronal threshold to skin pressure strongly decreased. The RF enlargement was amplified for the representation of the ipsilesional hindpaw in relation to persistent postural asymmetries, but was transitory for the contralesional one. Our study shows, for the first time, that vestibular inputs exert a modulatory influence on S1 neuron’s cutaneous responses. The lesion-induced cortical malleability highlights the influence of vestibular inputs on tactile processing related to postural control.

To explore in human potential hippocampal projections within and outside the temporal lobe. We performed intra-cerebral electrical stimulations in seven patients investigated by depth electrodes for refractory epilepsy and analyzed the presence of evoked potentials (EPs) in all brain regions explored. Bipolar electrical stimulations, consisting of two series of 25 pulses of 1 ms duration, 0.2 Hz frequency, and 3 mA intensity, were delivered in a total of 36 hippocampal stimulations sites. Reproducible EPs were recorded in several brain regions with variable latencies, amplitudes and morphologies. Within the temporal lobe, EPs were present in the amygdala, entorhinal cortex, temporal pole and temporal neocortex. EPs were also observed in the frontal lobe, anterior cingulate gyrus and orbito-frontal cortex, midcingulate and posterior cingulate gyrus, insula and thalamic pulvinar nucleus. Our results demonstrate a large distribution of direct or indirect hippocampal projections. This widespread connectivity supports the previous definition of different networks involved mainly in memory and behavioral processes, implicating the temporal lobe, the cingulate gyrus or the prefrontal region. Our data provide some clues to further evaluate potential pathways of propagation of mesial temporal lobe seizure, via the insula or the pulvinar nucleus.

Abstract Background The therapeutic influence of somatotopic matching between pain topography and motor cortex stimulation site for neuropathic pain ( NP ) remains controversial. Methods Thirty‐two patients suffering from NP involving the upper limb ( n = 20) or the face ( n = 12) received two high‐frequency rTMS neuronavigated sessions targeting hand and face motor cortical areas, versus placebo. The cortical target was defined by anatomical MRI and EMG responses in all patients, completed in 19 of them by functional MRI . Sessions were separated by at least 2 weeks and applied in random order. Pain relief was assessed using numerical rating scale ( NRS ). Results In terms of percentage of pain relief, rTMS over the hand motor area was significantly superior to both face rTMS and placebo. When comparing pre‐ and post‐ NRS scores, a significant decrease in pain was observed after hand area rTMS for the two pain localizations, while stimulation of the face area induced a slight but nonsignificant effect on upper limb pain after correction. Sham‐ rTMS did not exert any effect. The percentage of patients with clinically significant (&gt;30%) or mild (15–30%) pain relief did not differ, however, between rTMS addressed to the hand or face area. Conclusions The results do not support a somatotopic effect of motor rTMS for NP . Lack of clinically relevant somatotopic effects in upper limb or face pain suggests that much of the rTMS analgesic effect may depend on high‐order mechanisms involving cognitive and affective appraisal of pain, rather than on a sensory effect related to the specific motor area stimulated. Significance Strict somatotopic targeting of rTMS does not appear warranted for the treatment of upper limb or face NP . Since the hand motor area is easier to target and provides better results, it might be privileged for both types of pain.

Abstract Infection around metallic implants is a rare but severe complication of orthopaedic surgery. A novel animal model mimicking conditions of internal fixation devices was developed to evaluate the role of host proteins adsorbed on metallic devices in promoting adhesion and colonization of the material surfaces by Staphylococcus aureus . Small plates made of pure titanium were either fixed (three screws per plate) onto the iliac bones of guinea pigs or implanted into their subcutaneous space as controls. Five to 6 weeks after surgery, the plates and screws were removed from the previously killed animals, carefully rinsed in buffer, and tested in an in vitro assay of S. aureus adhesion to metallic surfaces. To evaluate the role of fibronectin in staphylococcal adhesion to explanted plates and screws, a mutant of S. aureus that is specifically defective in fibronectin adhesion due to decreased expression of the fibronectin adhesin was compared with its isogenic parental strain. A significant reduction in adhesion of the fibronectin adhesin‐defective mutant compared with the parental strain occurred on both the subcutaneously implanted and bone‐implanted metallic plates. The results of this specific biological assay suggest that fibronectin is present on bone‐implanted metallic devices and promotes attachment of S. aureus to their surfaces. This novel experimental model should help to characterize several parameters of bacterial adhesion to metallic orthopaedic devices and to develop novel anti‐adhesive strategies for preventing such infections.

The respective roles of the ventral posterior complex (VP) and of the more recently described VMpo (posterior part of the ventral medial nucleus) as thalamic relays for pain and temperature pathways have recently been the subject of controversy. Data we obtained in one patient after a limited left thalamic infarct bring some new insights into this debate. This patient presented sudden right-sided hypesthesia for both lemniscal (touch, vibration, joint position) and spinothalamic (pain and temperature) modalities. He subsequently developed right-sided central pain with allodynia. Projection of 3D magnetic resonance images onto a human thalamic atlas revealed a lesion involving the anterior two thirds of the ventral posterior lateral nucleus (VPL) and, to a lesser extent, the ventral posterior medial (VPM) and inferior (VPI) nuclei. Conversely, the lesion did not extend posterior and ventral enough to concern the putative location of the spinothalamic-afferented nucleus VMpo. Neurophysiological studies showed a marked reduction (67%) of cortical responses depending on dorsal column-lemniscal transmission, while spinothalamic-specific, CO2-laser induced cortical responses were only moderately attenuated (33%). Our results show that the VP is definitely involved in thermo-algesic transmission in man, and that its selective lesion can lead to central pain. However, results also suggest that much of the spino-thalamo-cortical volley elicited by painful heat stimuli does not transit through VP, supporting the hypothesis that a non-VP locus lying more posteriorly in the human thalamus is important for thermo-algesic transmission.

Two esterases, A1 and B1, displaying a high activity in organophosphate (OP) resistant Culex pipiens L. from southern France and in C. quinquefasciatus Say from California, respectively, have been analyzed. Both enzymes are shown to be soluble and to constitute a large proportion of the proteins (1–3% for esterase A1 and 6–12% for esterase B1). The size of native esterase A1 was estimated between 118 and 134 kDa, that of esterase B1 67 kDa. Upon SDS denaturation, esterase B1 leads a single polypeptide of 67 kDa which suggests that it is a monomeric protein; esterase A1 leads also a single polypeptide of 60 kDa suggesting a homodimeric structure of the protein. These observations are discussed with regards to esterase E4 of Myzus persicae Sultz.

Pollution relative to phosphorus excretion in poultry manure as well as the soaring prices of phosphate, a non-renewable resource, remain of major importance. Thus, a good understanding of bird response regarding dietary phosphorus (P) is a prerequisite to optimise the utilisation of this essential element in broiler diets. A database built from 15 experiments with 203 treatments was used to predict the response of 21-day-old broilers to dietary non-phytate P (NPP), taking into account the main factors of variation, calcium (Ca) and microbial phytase derived from Aspergillus niger, in terms of average daily feed intake (ADFI), average daily gain (ADG), gain to feed (G:F) and tibia ash concentration. All criteria evolve linearly (P < 0.001) and quadratically (P < 0.001) with dietary NPP concentration. Dietary Ca affected the intercept and linear component for ADG (P < 0.01), G:F (P < 0.05) and tibia ash concentration (P < 0.001), whereas for ADFI, it affected only the intercept (P < 0.01). Microbial phytase addition impacted on the intercept, the linear and the quadratic coefficient for ADFI (P < 0.01), ADG (P < 0.001) and G:F (P < 0.05), and on the intercept and the linear component (P < 0.001) for tibia ash concentration. An evaluation of these models was then performed on a database built from 28 experiments and 255 treatments that were not used to perform the models. Results showed that ADFI, ADG and Tibia ash concentration were predicted fairly well (slope and intercept did not deviate from 0 to 1, respectively), whereas this was not the case for G:F. The increase in dietary Ca concentration aggravated P deficiency for all criteria while phytase addition had a positive effect. The more P deficiency was marked, the more the bird response to ADFI, ADG, G:F and tibia ash concentration was exacerbated. It must also be considered that even if the decrease in dietary Ca may improve P utilisation, it could in turn become limiting for bone mineralisation. In conclusion, this meta-analysis provides ways to reduce dietary P in broiler diets without impairing performance, taking into account dietary Ca and microbial phytase.

Observing other people's pain increases our own reports to painful stimuli, a phenomenon that can be defined as 'compassional hyperalgesia' (CH). This functional magnetic resonance imaging study examined the neural correlates of CH, and whether CH could emerge when exposure to the driving stimulus was subliminal. Subjects received electric somatosensory stimuli while observing images of people undergoing painful or enjoyable somatic sensations, presented during a period allowing or not allowing conscious perception. The intensity attributed to painful stimuli increased significantly when these were delivered close to images showing human pain, but only when such images were consciously perceived. The basic core of the Pain Matrix (SI, SII, insula, mid-anterior cingulate) was activated by painful stimuli, but its activation magnitude did not increase during CH. Compassional hyperalgesia was associated with increased activity in polymodal areas involved in emotional tuning (anterior prefrontal, pregenual cingulated) and areas involved in multisensory integration and short-term memory (dorsolateral prefrontal, temporo-parieto-occipital junction). CH appears as a high-order phenomenon needing conscious appraisal of the eliciting visual stimulus, and supported by polymodal areas distinct from the basic Pain Matrix. This suggests that compassion to pain does not result from a mere 'sensory resonance' in pain networks, but rather from an interaction between the output of a first-line processing in the Pain Matrix, and the activity of a high-order network involving multisensory integration (temporo-parietal), encoding of internal states (mid-prefrontal) and short-time memory encoding (dorsolateral prefrontal). The Pain Matrix cannot be considered as an 'objective' correlate of the pain experience in all situations.

A decrease in dietary P, especially in finishing broilers (21 to 38 d old), is a crucial issue in poultry production from an environmental and economic point of view. Nevertheless, P must be considered together with other dietary components such as Ca and microbial phytase. Different corn and soybean meal-based diets varying in Ca [low (LCa) 0.37, medium (MCa) 0.57, and high (HCa) 0.77%], and nonphytate P [nPP; low (LnPP) 0.18 and high (HnPP) 0.32%] content were tested with and without microbial phytase [0 or 500 phytase units (FTU)/kg]. Feed intake, BW gain, bone mineralization, and mineral retention were examined in 144 Ross PM3 broilers (22 to 38 d old) reared in individual cages. Growth performance was not significantly affected by the treatments. Nevertheless, a numerical decrease of ADG and ADFI was observed in HCa-LnPP and LCa-HnPP associated with an increase of feed conversion ratio. Decreased dietary Ca reduced tibia ash content (Ca, linear: P < 0.001; quadratic: P = 0.034) and tibia ash weight for the highest level of nPP (Ca × nPP; P = 0.035). In parallel, increasing dietary Ca reduced the flow of retained P (P = 0.022) but also tibia ash weight in LnPP diets (Ca × nPP; P = 0.035). The responses of the animals in terms of tibia ash content and P retention were improved by the addition of microbial phytase especially for the lowest P diets (nPP × phytase, P = 0.021 and P = 0.009; respectively). Phytase increased dry tibia weight, bone breaking strength, and tibia diameter in broilers fed the highest Ca diets (Ca × phytase; P < 0.05). We conclude that is possible to decrease P levels in finishing broilers, if the Ca content is appropriate. Nevertheless, decreasing the dietary P and Ca cannot allow a maximization of bone mineralization, but the optimal threshold remains to be determined.

The ability of birds to modify dietary phosphorus utilisation when fed with low-phosphorus and calcium (Ca) diets was studied using different sequences of dietary phosphorus and Ca restriction (depletion) and recovery (repletion) during the grower and the finisher phases. A total of 3600 Ross 708 broilers were randomly divided into 10 replicate pens per treatment (60 per pen, six pens per block). Chicks were fed a common starter diet from days 0 to 10, then a grower control diet (C: 0.90% Ca, 0.39% non-phytate phosphorus, nPP), mid-level diet (M: 0.71% Ca, 0.35% nPP) or low Ca and nPP diet (L: 0.60% Ca, 0.30% nPP) from days 11 to 21, followed by a finisher diet C, M or L containing, respectively, 0.85%, 0.57% or 0.48% Ca and 0.35%, 0.29% or 0.24% nPP from days 22 to 37. Six treatment sequences were tested: CC, MM, LL, ML, LC and LM. Bone mineral content by dual-energy X-ray, tibia ash, toe ash weight and tibia breaking strength were measured on days 21 and 37. No significant effect was observed on growth performance throughout the experiment. Diet L reduced bone mineral content, breaking strength, tibia and toe ash by 9%, 13%, 11% and 10%, respectively, on day 21 (compared with diet C, for linear effect, P<0.05). On day 37, bone mineral content, breaking strength, tibia and toe ash remained lower compared with control values (CC v. MM v. LL, P<0.05 for linear and quadratic effects). Mineral depletion duration (ML v. LL) did not affect bone mineral status. Replenishing with the C diet during the finisher phase (LC) restored bone mineral content, tibia ash and toe ash weight better than the M diet did, but not to control levels (CC v. LC v. LM, for linear effect, P<0.05). These results confirm that dietary Ca and nPP may be reduced in the grower phase without affecting final growth performance or breaking strength as long as the finisher diet contains sufficient Ca and nPP. The practical applications of this strategy require further study in order to optimise the depletion and repletion steps.

Abstract The interruption of sleep by a nociceptive stimulus is favoured by an increase in the pre‐stimulus functional connectivity between sensory and higher level cortical areas. In addition, stimuli inducing arousal also trigger a widespread electroencephalographic (EEG) response reflecting the coordinated activation of a large cortical network. Because functional connectivity between distant cortical areas is thought to be underpinned by trans‐thalamic connections involving associative thalamic nuclei, we investigated the possible involvement of one principal associative thalamic nucleus, the medial pulvinar (PuM), in the sleeper's responsiveness to nociceptive stimuli. Intra‐cortical and intra‐thalamic signals were analysed in 440 intracranial electroencephalographic (iEEG) segments during nocturnal sleep in eight epileptic patients receiving laser nociceptive stimuli. The spectral coherence between the PuM and 10 cortical regions grouped in networks was computed during 5 s before and 1 s after the nociceptive stimulus and contrasted according to the presence or absence of an arousal EEG response. Pre‐ and post‐stimulus phase coherence between the PuM and all cortical networks was significantly increased in instances of arousal, both during N2 and paradoxical (rapid eye movement [REM]) sleep. Thalamo‐cortical enhancement in coherence involved both sensory and higher level cortical networks and predominated in the pre‐stimulus period. The association between pre‐stimulus widespread increase in thalamo‐cortical coherence and subsequent arousal suggests that the probability of sleep interruption by a noxious stimulus increases when it occurs during phases of enhanced trans‐thalamic transfer of information between cortical areas.

The distribution of the calcium-binding proteins calbindin-D28K (CB), parvalbumin (PV) and calretinin (CR), and of the nonphosphorylated neurofilament protein (with SMI-32) was investigated in the human basal ganglia to identify anatomofunctional territories. In the striatum, gradients of neuropil immunostaining define four major territories: The first (T1) includes all but the rostroventral half of the putamen and is characterized by enhanced matriceal PV and SMI-32 immunoreactivity (-ir). The second territory (T2) encompasses most part of the caudate nucleus (Cd) and rostral putamen (PuT), which show enhanced matriceal CB-ir. The third and fourth territories (T3 and T4) comprise rostroventral parts of Cd and PuT characterized by complementary patch/matrix distributions of CB- and CR-ir, and the accumbens nucleus (Acb), respectively. The latter is separated into lateral (prominently enhanced in CB-ir) and medial (prominently enhanced in CR-ir) subdivisions. In the pallidum, parallel gradients also delimit four territories, T1 in the caudal half of external (GPe) and internal (GPi) divisions, characterized by enhanced PV- and SMI-32-ir; T2 in their rostral half, characterized by enhanced CB-ir; and T3 and T4 in their rostroventral pole and in the subpallidal area, respectively, both expressing CB- and CR-ir but with different intensities. The subthalamic nucleus (STh) shows contrasting patterns of dense PV-ir (sparing only the most medial part) and low CB-ir. Expression of CR-ir is relatively low, except in the medial, low PV-ir, part of the nucleus, whereas SMI-32-ir is moderate across the whole nucleus. The substantia nigra is characterized by complementary patterns of high neuropil CB- and SMI-32-ir in pars reticulata (SNr) and high CR-ir in pars compacta (SNc) and in the ventral tegmental area (VTA). The compartmentalization of calcium-binding proteins and SMI-32 in the human basal ganglia, in particular in the striatum and pallidum, delimits anatomofunctional territories that are of significance for functional imaging studies and target selection in stereotactic neurosurgery.

Clearly, more clinical experience must be amassed to define in detail the possibilities of this surgical approach in disabling neuropsychiatric disorders. We propose, however, that the evidence for benign and efficient surgical intervention against the neuropsychiatric TCD syndrome is already compelling. The potential appearance of strong postoperative reactive manifestations requires a close association between surgery and psychotherapy, with the latter providing support for the integration of the new situation as well as the resolution of old unresolved issues.

Retinal projections to several telencephalic structures have been demonstrated in a wide range of mammalian species following intraocular injections of tritiated amino acids and cholera toxin subunit-B conjugated to horseradish peroxidase. Since these regions are also innervated by olfactory fibers, we investigated the distribution of convergent projections using simultaneous injections of different anterograde tracers in the eye and olfactory bulbs. Convergent projections from the retina and from the olfactory bulbs were observed in the piriform cortex, olfactory tubercle, the cortical region of the medial amygdala, lateral hypothalamus, and the bed nucleus of the stria terminalis. A few retinal fibers also invade the nucleus of the lateral olfactory tract, the bed nucleus of the accessory olfactory bulb and the diagonal band of Broca. Injections of retrograde tracers in the medial amygdala, the bed nucleus or the lateral hypothalamus shows that the visuo-olfactory convergence mainly involves projections originating from the accessory olfactory bulb, and to a lesser extent from the ventromedial region of the main olfactory bulb. Fewer than 20 retinotelencephalic ganglion cells were identified in the retina, mainly located contralateral to the injection site. Ganglion cells were medium sized and possessed two long slender opposing dendrites. These retinal and olfactory projections could provide an anatomical substrate for the modulation of gonadotropin hormone levels and the olfactory influence on light mediated rhythms related to reproductive physiology.

The identification of the pathways involved in seizure propagation remains poorly understood in humans. For instance, the respective role of the orbitofrontal cortex (OFC) and of the commissural pathways in the interhemispheric propagation of mesial temporal lobe seizures (mTLS) is a matter of debate. In order to address this issue, we have directly tested the functional connectivity between the hippocampus and the OFC in 3 epileptic patients undergoing an intra-cranial stereotactic EEG investigation. Bipolar electrical stimulations, consisting of two series of 25 pulses of 1 ms duration, 0.2 Hz frequency, and 3 mA intensity, were delivered in the hippocampus. Evoked potentials (EPs) were analysed for each series, separately. Grand average of reproducible EPs was then used to calculate latency of the first peak of each individual potential. Hippocampal stimulations evoked reproducible responses in the OFC in all 3 patients, with a mean latency of the first peak of 222 ms (range: 185–258 ms). Our data confirm a functionnal connectivity between the hippocampus and the OFC in human. This connectivity supports the potential role of the OFC in the propagation of mTLS.

Theories of binocular vision originally imagined by Newton provided the foundation for subsequent investigations of the visual system by early anatomists and physiologists. These studies led to the widely accepted concept that degree of optic fiber decussation in the chiasm is inversely related to frontal orientation of the optical axes of the eyes (law of Newton-Müller-Gudden). A survey of 23 species from 11 mammalian orders demonstrates that, in contrast to other visual pathways, the retinohypothalamic projection does not obey this general principle. In further contradiction, an unexpected finding in primates is the predominance of ipsilateral, rather than contralateral, retinal input to the suprachiasmatic nucleus. This unusual organization underlines the functional and evolutionary specificities of this ‘non-image forming’ visual pathway.

A method for computer analysis of nystagmic eye movements in vestibulo-ocular (VOR) and optokinetic (OKN) reflexes is developed. A fuzzy set theoretical approach is used to construct the slow cumulative eye position (SCEP) curve by eliminating fast components (saccades) from the eye movement signal. These procedures are able to perform automatically some pattern recognition tasks traditionally used in classical interactive programs when human operators distinguish between fast and slow phases of eye movements. The structure of the algorithm is as follows. A fuzzy clusters of slow and fast phases is made. An iterative method is used to refine the membership function of slow-phases, step by step, until a sufficiently discriminating membership function is obtained. Saccades are detected and removed from the eye position signal. SCEP is then built by interpolating between slow phases. A weighted least-squares curve fitting is made. Weighting coefficients are obtained from the last membership function resulting from the iterations. The curve fitting is referenced to the SCEP, and the parameters of VOR and OKN are calculated using this last curve.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

The authors report on the development, for studies in man, of a tungsten, glass-coated, light and simple microelectrode, that is implanted by hand in open operative conditions under the microscope and floats freely with the moving target tissue. This technique has provided limited but nevertheless satisfactory unit activity isolations. Intra-operative unit recordings were obtained from the dorsal horns of 2 spastic and 2 neurogenic pain patients. In the latter, dorsal horn deafferentation hyperactivities after a peripheral and a centro-peripheral lesion were recorded, characterized by a continuous, spontaneous and unalterable high frequency hyperactivity.

Abstract Decrease of thalamic blood flow contralateral to neuropathic pain has been described by several groups, but its relation with sensory deafferentation remains unclear. Here we report one instance where the thalamic effects of sensory deafferentation could be dissociated from those of neuropathic pain. A 50‐year‐old patient underwent a left medullary infarct leading to right‐sided thermal and pain hypaesthesia up to the third right trigeminal division, as well as in the left face. During the following months the patient developed neuropathic pain limited to the left side of the face. Although the territory with sensory loss was much wider in the right (non painful) than in the left (painful) side of the body, PET‐scan demonstrated significant reduction of blood flow in the right thalamus (contralateral to the small painful area) relative to its homologous region. After 3 months of right motor cortex stimulation the patient reported 60% relief of his left facial pain, and a new PET‐scan showed correction of the thalamic asymmetry. We conclude that thalamic PET‐scan hypoactivity contralateral to neuropathic pain does not merely reflect deafferentation, but appears related to the pain pathophysiology, and may be normalized in parallel with pain relief. The possible mechanisms linking thalamic hypoactivity and pain are discussed in relation with findings in epileptic patients, possible compensation phenomena and bursting thalamic discharges described in animals and humans. Restoration of thalamic activity in neuropathic pain might represent one important condition to obtain successful relief by analgesic procedures, including cortical neurostimulation.

The present study was conducted to assess the effect of 2 dietary Ca concentrations on P and Ca digestive and metabolic utilization in weanling pigs fed diets providing practical concentrations of P, with or without phytase. The responses of pigs fed diets adequate or moderately deficient in Ca and P postweaning were compared. A total of 60 pigs weaned at 28 d of age were used. Two groups of 30 pigs with differing mineral status resulted from a 10-d depletion period, during which the animals received depletion diets (DD) that consisted of corn-soybean meal with either 1.42% Ca and 0.80% P (DD+) or 0.67% Ca and 0.43% P (DD−), designed to achieve the same Ca:digestible P ratio. At the end of the depletion period, a plasma sample was taken from each pig and 12 pigs (6 from each group) were slaughtered for bone assessment to establish the baseline mineral status. The animals fed the DD− diet had signs of P deficiency with reduced plasma P (13%; P < 0.01) and femur ash concentration (8%; P < 0.05), and increased plasma Ca (9%; P < 0.05) and alkaline phosphatase activity (31%; P < 0.01). For the subsequent 25-d period, the remaining 24 pigs from each group were fed 1 of 4 repletion diets: 1) 0.56% P, 1.06% Ca; 2) 0.56% P, 0.67% Ca; 3) diet 1 + 1,000 phytase units (FTU) of Natuphos phytase/kg; and 4) diet 2 + 1,000 FTU of Natuphos phytase/kg. Total feces and urine were collected from d 5 to 11, and a blood sample was taken from each pig at d 11 and 25. The initial moderate P deficiency (DD−) stimulated Ca absorption (5%; P < 0.01), irrespective of the repletion diet, and stimulated P absorption (5%; DD × phytase, P < 0.05), only when the diets contained phytase. At the end of the repletion period, because of these compensatory phenomena, the depleted pigs achieved full recovery of femur DM and ash weight when they received phytase, whereas ash concentration tended to remain reduced by 3% (P = 0.08). Phosphorus digestibility was improved in the diets supplemented with phytase (73.0 vs. 56.0%; P < 0.001), whereas an increase in dietary Ca decreased P digestibility (65.6 vs. 63.4%; P < 0.05). Those 2 effects were independent, indicating that dietary Ca reduced equally P digestibility with and without phytase and did not influence the efficiency of phytase in releasing P in the digestive tract. In pigs fed diets with phytase, however, the reduction of Ca (Ca:P from 1.9 to 1.3) increased urinary P losses 5-fold. Those extra losses were due to a lack of Ca for skeleton ash deposition, resulting in a 4% reduction in femur ash concentration. In the end, reducing the dietary Ca:P from 1.9 to 1.3 in a practical diet containing 0.56% P did not improve the efficiency of phytase in releasing P. Moreover, the reduction in dietary Ca (Ca:P) caused an imbalance between Ca and P that impaired bone mineralization.

Environmental effects of excess P from manure and the soaring price of phosphates are major issues in pig production. To optimize P utilization, it is crucial to improve our capacity to predict the amount of P absorbed, while taking into account the main factors of variation. Mathematical modeling can represent the complexity of the processes and interactions in determining the digestive utilization of P in growing pigs. This paper describes and evaluates a model developed to simulate the fate of the dietary forms of P in the digestive tract of growing pigs, with particular emphasis on the effect of dietary Ca and exogenous phytase on P digestive utilization. The model consists of 3 compartments associated with specific anatomical sections: stomach, proximal small intestine, and distal small intestine. The main metabolic processes occurring in these sections are, respectively, P solubilization/insolubilization and phytate P hydrolysis, and P absorption and P insolubilization. Model parameters governing these flows were derived from in vitro and in vivo literature data. The sensitivity analysis revealed that the model was stable within a large range of model parameter values (±1.5 SD). The model was able to predict the efficacy of Aspergillus niger microbial phytase in accordance with literature values, as well as the decreased efficacy of plant phytase compared with microbial phytase. The prediction capabilities of the model were assessed by comparing actual and simulated P and Ca apparent total-tract digestibility (ATTD) based on published pig data not used for model development. Prediction of P digestibility across 66 experiments and 281 observations was adequate [P ATTD observed = 0.24 (SE, 0.943) + 0.98 (SE, 0.0196) × P ATTD predicted; R2, 0.90; disturbance error (ED), 96.5%], whereas prediction of Ca digestibility across 47 experiments and 193 observations was less accurate (Ca ATTD observed = 11.1 + 0.75 × Ca ATTD predicted; R2, 0.78; ED, 20.4%). A lack of agreement between experimental and simulated Ca digestibility was found. This model is, therefore, useful in evaluating P digestibility for different feedstuffs and feeding strategies. It can also be used to provide insight for improving dietary P utilization, especially from plant sources, by quantifying the effect of the mean sources of variation affecting P utilization.

Both repeated practice and sleep improve long-term retention of information. The assumed common mechanism underlying these effects is memory reactivation, either on-line and effortful or off-line and effortless. In the study reported here, we investigated whether sleep-dependent memory consolidation could help to save practice time during relearning. During two sessions occurring 12 hr apart, 40 participants practiced foreign vocabulary until they reached a perfect level of performance. Half of them learned in the morning and relearned in the evening of a single day. The other half learned in the evening of one day, slept, and then relearned in the morning of the next day. Their retention was assessed 1 week later and 6 months later. We found that interleaving sleep between learning sessions not only reduced the amount of practice needed by half but also ensured much better long-term retention. Sleeping after learning is definitely a good strategy, but sleeping between two learning sessions is a better strategy.

Key points Sleep spindles have recently been shown to occur not only across multiple neocortical regions but also locally in restricted cortical areas. Here we show that local spindles are indeed present in the human posterior thalamus. Thalamic local spindles had lower spectral power than non‐local ones. While non‐local thalamic spindles had equal local and non‐local cortical counterparts, local thalamic spindles had significantly more local cortical counterparts (i.e. occurring in a single cortical site). The preferential association of local thalamic and cortical spindles supports the notion of thalamocortical loops functioning in a modular way. Abstract Sleep spindles are believed to subserve many sleep‐related functions, from memory consolidation to cortical development. Recent data using intracerebral recordings in humans have shown that they occur across multiple neocortical regions but may also be spatially restricted to specific brain areas (local spindles). The aim of this study was to characterize spindles at the level of the human posterior thalamus, with the hypothesis that, besides the global thalamic spindling activity usually observed, local spindles could also be present in the thalamus. Using intracranial, time‐frequency EEG recordings in 17 epileptic patients, we assessed the distribution of thalamic spindles during natural sleep stages N2 and N3 in six thalamic nuclei. Local spindles (i.e. spindles present in a single pair of recording contacts) were observed in all the thalamic regions explored, and compared with non‐local spindles in terms of intrinsic properties and cortical counterparts. Thalamic local and non‐local spindles did not differ in density, frequency or duration, but local spindles had lower spectral power than non‐local ones. Each thalamic spindle had a cortical counterpart. While non‐local thalamic spindles had equal cortical local and non‐local counterparts, local thalamic spindles had significantly more local cortical counterparts (i.e. occurring in a single cortical site). The preferential association of local thalamic and cortical spindles supports the notion of thalamocortical loops functioning in a modular way.

High-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce neuropathic pain, but intermittent “theta-burst” stimulation (iTBS) could be a better alternative because of shorter duration and greater ability to induce cortical plasticity. Here we compared head-to-head the pain-relieving efficacy of the two modalities when applied daily for 5 days to patients with neuropathic pain. Forty-six patients received 20 Hz-rTMS and/or iTBS protocols and 39 of them underwent the full two procedures in a random cross-over design. They rated pain intensity, sleep quality, fatigue and general health status daily during 5 consecutive weeks. Pain relief during the month following stimulation was superior after 20 Hz-rTMS relative to iTBS (F(1,38) = 4.645; p = 0.037). Correlation between respective levels of maximal relief showed a significant deviation toward the 20 Hz-rTMS effect. A greater proportion of individuals responded to 20 Hz-rTMS (52% vs 32%, 95 %CI[0.095–3.27]; p = 0.06), and reports of fatigue significantly improved after 20 Hz-rTMS relative to iTBS (p = 0.01). General health and sleep quality scores did not differentiate both techniques. High-frequency rTMS appeared superior to iTBS for neuropathic pain relief. Adequate matching between the oscillatory activity of motor cortex and that of rTMS may increase synaptic efficacy, thus enhancing functional connectivity of motor cortex with distant structures involved in pain regulation.

Orexins/hypocretins are two neuropeptides that influence many behaviours, such as feeding, sleep or arousal. Orexin A/hypocretin-1 (OXA) and orexin B/hypocretin-2 (OXB) bind to two metabotropic receptors, named the OX1 and OX2 receptors. The lateral geniculate complex of the thalamus is one of the many targets of orexinergic fibres derived from the lateral hypothalamus, although the impact of orexins on the ventrolateral geniculate nucleus (VLG) is poorly understood. The VLG, an important relay station of the subcortical visual system, is implicated in visuomotor and/or circadian processes. Therefore, in this study we evaluated the effects of orexins on single VLG neurons using a patch-clamp technique in vitro. Surprisingly, orexins depolarised the majority of the recorded neurons regardless of their localisation in the borders of the VLG. In addition, data presented in this article show that neurons synthesising NO were also affected by OXA. Moreover, immunohistochemical staining of OXB revealed the moderate density of orexinergic fibbers in the VLG. Our study using specific orexin receptor antagonists suggests that the OX2 receptor has a dominant role in the observed effects of OXA. To our knowledge, this article is the first to show orexinergic modulation of the VLG. These findings strengthen the postulated link between orexins and the circadian system, and propose a new role of these neuropeptides in the modulation of visuomotor functions.

While nociceptive cortical activation is now well characterized in humans, understanding of the nociceptive thalamus remains largely fragmentary. We used laser stimuli and intracerebral electrodes in 17 human subjects to record nociceptive-specific field responses in 4 human thalamic nuclei and a number of cortical areas. Three nuclei known to receive spinothalamic (STT) projections in primates (ventro-postero-lateral [VPL], anterior pulvinar [PuA], and central lateral [CL]) exhibited responses with similar latency, indicating their parallel activation by nociceptive afferents. Phase coherence analysis, however, revealed major differences in their functional connectivity: while VPL and PuA drove a limited set of cortical targets, CL activities were synchronized with a large network including temporal, parietal, and frontal areas. Our data suggest that STT afferents reach simultaneously a set of lateral and medial thalamic regions unconstrained by traditional nuclear borders. The broad pattern of associated cortical networks suggests that a single nociceptive volley is able to trigger the sensory, cognitive, and emotional activities that underlie the complex pain experience. The medial pulvinar, an associative nucleus devoid of STT input, exhibited delayed responses suggesting its dependence on descending cortico-thalamic projections. Its widespread cortical connectivity suggests a role in synchronizing parietal, temporal, and frontal activities, hence contributing to the access of noxious input to conscious awareness.

Thalamic and cortical neurons are richly and reciprocally interconnected and support recurrent functional loops in the intact brain, but the role of this circuitry is still poorly understood. Here, we present evidence—from cellular and from functional neuroimaging in control and clinical domains—that thalamocortical resonance is not only a prerequisite for normal cognition, but that its perturbation, in a dynamic sense (e.g. a dysrhythmia) can underlie a variety of neurological and psychiatric disorders.

The retinal projection to the basal telencephalon was studied in eight species of primates from the suborders Strepsirhini and Haplorhini, including one anthropoid primate, the gibbon. Animals received an intraocular injection of tritiated amino acids and the distribution of retinal fibers and terminals was demonstrated by autoradiographic techniques in horizontal and coronal sections. In all species a discrete group of labeled retinal fibers is observed to branch off from the dorsolateral aspect of the optic tract at the level of the suprachiasmatic nucleus. These fibers, destined to the basal telencephalon, are topographically distinct from the retinal fibers which innervate the suprachiasmatic nucleus and medial hypothalamic regions. The fibers of the retinotelencephalic tract course dorsally above the supraoptic nucleus through the lateral hypothalamic area and then proceed further rostrally and laterally below the diagonal band of Broca towards the olfactory tubercle. Within the olfactory tubercle, terminal distribution of label is observed in the mediocaudal region along the granular cell layer II. In the macaque this cellular layer shows a characteristic thickening in the region of retinal terminals which is evident in both coronal and horizontal section. In some species this labeled region is seen within the superficial bulge of the tubercle on the ventral aspect of basal telencephalon. In all primates the retinal projection to olfactory tubercle is bilateral. In prosimians label is predominantly contralateral to the injected eye, in New World monkeys label is equally distributed on both sides of the brain and in Old World monkeys label is mainly found ipsilaterally. Retinal fibers were also seen in the periamygdaloid region but never extended as far as piriform cortex. These results, in addition to previous studies in other mammalian orders, confirm that the basal telencephalon, and in particular the olfactory tubercle, constitutes a region of visual and olfactory convergence. This sensory integration may be related to photic and chemosensory modulation of reproductive physiology and behavior.

Wakefulness and paradoxical sleep (PS) share a similar electrophysiological trait, namely, a more elevated level of high-frequency activities at both thalamic and cortical levels relative to slow wave sleep (SWS). The spatio-temporal binding of these high-frequency activities within thalamo-cortical networks is presumed to generate cognitive experiences during wakefulness. Similarly during PS, this phenomenon could be at the origin of the perceptual experiences forming dreams. However, contents of dreams often present some bizarre features which depart from our cognitive experiences in waking. This suggests some differences in processing and/or integration of brain activities during waking and PS. Using intracranial recordings in epileptic patients we observed, specifically during PS, the presence of unexpected delta frequency oscillations, as well as a surprisingly low amount of high-frequency activities, in a posterior region of the thalamus, the medial pulvinar nucleus (PuM). This discrepancy between activities in a thalamic nucleus and its related cortical areas may compromise the spatio-temporal binding of the high-frequency activities, resulting in altered perceptual experiences during dream periods.

Retinal projections were studied in species from 8 orders of mammals using anterograde tracing techniques. The olfactory tubercle of basal telencephalon receives a projection from the retina in all animals. In all species the course of labelled fibers is similar and the terminal distribution of label along the internal border of the granular cell layer is restricted to the mediocaudal region of the tubercle. These shared characteristics suggest that this pathway is a typical mammalian feature, possibly providing for convergence of visual and chemosensory information in telencephalon.

A strain of Culex quinquefasciatus collected in February 1986 in Bouaké, Ivory Coast (West Africa), was tested for resistance to various insecticides. Low but consistent resistance ratios (RR = 3–4) were observed for five organophosphates and two carbamates. Use of the synergist S,S,S-tributylphosphorotrithioate (DEF) showed that esterases or glutathione-S-transferases played a major role in organophosphate resistance. Two highly active esterases, A2 and B2, were detected in Bouaké mosquitoes. Selection with chlorpyrifos increased significantly the frequency of these enzymes, confirming that they are involved in organophosphate resistance. High resistance ratios to deltamethrin (RR = 62.5) and DDT (RR = 380) also were recorded. Only part of the deltamethrin resistance could be suppressed by piperonyl butoxide, and no part of the DDT resistance could be suppressed by this synergist or by chlorfenethol (DMC). These results suggest that oxidases are responsible for a part of the resistance to deltamethrin and that some other mechanism, most likely knock-down resistance, is involved in resistance to this insecticide and to DDT.

1. The impact of modified mineral status and dietary Ca:P ratio on Ca and P utilisation was measured in chicks with or without phytase supplementation. 2. In a preliminary study, 4 diets were given to chicks from 3 to 15 d of age: D1 (6.5 g P/kg and Ca:P = 1.5) and D2, D3 and D4 (6.0, 5.4 and 5.0 g P/kg, respectively, and Ca:P = 1.2). Growth performance was similar across diets. Tibia ash was similar in chicks given D1 and D2, but was gradually depressed from D2 to D4 (-22%). 3. In the depletion period, two groups of chicks, with similar performance, but with different mineral status were achieved by feeding them, from 5 to 15 d of age, diets with a similar Ca:P ratio of 1.2, but containing 6.3 or 5.2 g P/kg. 4. During the subsequent 11 d of the repletion period, chicks from each of the two previous groups were given one of the 4 diets containing 5.7 g P/kg, but differing in their Ca (8.3 and 5.3 g Ca/kg) and microbial phytase (0 or 1000 FTU, Natuphos levels in a 2 x 2 x 2 factorial arrangement. 5. At the end of the repletion period, the initially depleted chicks could not be differentiated from the non-depleted chicks, indicating the capacity of chicks to compensate for their initial depleted mineral status. 6. Interaction between dietary Ca and phytase levels was not significant. Phytase improved growth performance and bone characteristics. Reduced dietary Ca enhanced feed intake and growth rate, but depressed bone dry matter and ash weight. 7. At the end, diets supplemented with phytase maximised bone ash weight when chicks were fed with a Ca:P ratio of 1.5 but elicited the highest growth rate when chicks were fed with a Ca:P ratio of 0.9.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has shown efficacy in relieving neuropathic pain. Whether its analgesic effect also applies to acute physiological nociception remains unclear due to previous contradictory findings.To provide an in-depth investigation of the effects of motor cortex HF-rTMS on acute laser-evoked pain and excitability of nociceptive networks in healthy subjects.Randomized, placebo-controlled, double-blind, cross-over study in 20 healthy participants. Laser heat stimuli at nociceptive threshold were delivered to the right hand, allowing assessment of: (a) subjective pain intensity and unpleasantness; (b) laser-evoked potentials (LEPs, 128 electrodes) and their source model; (c) sympathetic skin responses, and (d) spino-thalamic pathway excitability. Data were collected before and 20 minutes after a session of neuro-navigated 20 Hz rTMS to the contralateral motor cortex.Subjective pain reports to thermal laser pulses, amplitude of late cortical potentials and sympathetic skin responses were decreased after cortical stimulation, to a similar extent whether it was active or placebo. Early cortical potentials and nociceptive network excitability remained identical before and after rTMS, as did anatomical sources of LEPs.Our results do not provide evidence for a genuine anti-nociceptive effect of rTMS on acute physiological pain. We suggest that motor cortex rTMS may act upon high-order networks linked to the emotional and cognitive appraisal of chronic pain, and/or modulate pathologically sensitized networks, rather than change the physiological transmission within an intact nervous system. Such dichotomy is reminiscent of that observed with most drugs used for neuropathic pain.

Neuropathic pain can be conceptualized as the result of an "aberrant learning" process, associated with maladaptive plasticity of the nervous system. A number of modifications of the peripheral nervous system have been described in animal models of neuropathic pain, but their relation with different symptoms in humans is far from fully understood. We note in particular ectopic discharges in damaged myelinated fibers, abnormal activity in undamaged fibers, overexpression of calcium channels increasing the release of excitatory neurotransmitters, and sympathetic sprouting towards the spinal ganglia. Spinal mechanisms involve central sensitization, kindling and potentiation phenomena. Underlying these phenomena may be connectivity changes--still controversial--of non-nociceptive terminals and variations in the sensitivity of postsynaptic receptors. Also contributing to these pathophysiologic modifications are attenuation of spinal inhibition by selective neuronal loss and the development of inflammatory phenomena, including cytokine secretion by macrophages and glial cells. Changes in the dorsal horn modify the activity of projections towards the brainstem and increase spinal hyperactivity still further by feedback loops. These effects are delayed, suggesting that maintenance of spinal sensitization requires the involvement of mechanisms of descending facilitation involving the brainstem. These phenomena induce changes in the activity of thalamocortical networks, which develop autonomous processes that maintain the pain. The cortical representation of body areas change after nervous lesions, and these changes may correlate with the emergence of pain. Neuropathic allodynia and hyperalgesia are supported by cortical modifications that experimental models reproduce very incompletely. Experimental allodynia and neuropathic allodynia share the activation of the cortical pain matrix as well as the bilateralization of insular activity. However, although experimental allodynia tends to increase the activity of limbic and affective networks of the perigenual and orbitofrontal cortex, in neuropathic allodynia, analgesic procedures lead to increased activity in these structures. This suggests that their role in experimental allodynia would likely be reactive and protective, and that inability to generate their activation may contribute to the clinical expression of neuropathic pain.

It is acknowledged that the emotional state created by visual inputs can modulate the way we feel pain; however, little is known about how acute pain influences the emotional assessment of what we see. In this study healthy subjects scored affective images while receiving painful or innocuous electrical shocks. Painful stimuli did not make unpleasant images more unpleasant, but rendered pleasant pictures significantly less pleasant. Brain responses to visual inputs (64-channels electroencephalogram) mirrored behavioural results, showing pain-induced effects in the orbitofrontal cortex, the subgenual portion of the cingulate gyrus, the anterior prefrontal and the temporal cortices, exclusively during presentation of pleasant images. In addition to this specific effect on pleasant pictures, pain also produced non-specific effects upon all categories of images, engaging cerebral areas associated with attention, alertness and motor preparation (middle-cingulate, supplemental motor, prefrontal cortex). Thus, pain appears to have a dual influence on visual processing: a non-specific effect related to orienting phenomena; and a more specific action exerted on supra-modal limbic areas involved in the production of affective states. The latter correlated with changes in the subjective appraisal of visual stimuli, and may underlie not only the change in their subjective assessment but also reactive processes aimed at coping with unpleasant contexts.

Behavioral reactions to sensory stimuli during sleep are scarce despite preservation of sizeable cortical responses. To further understand such dissociation, we recorded intracortical field potentials to painful laser pulses in humans during waking and all-night sleep. Recordings were obtained from the three cortical structures receiving 95% of the spinothalamic cortical input in primates, namely the parietal operculum, posterior insula, and mid-anterior cingulate cortex. The dynamics of responses during sleep differed among cortical sites. In sleep Stage 2, evoked potential amplitudes were similarly attenuated relative to waking in all three cortical regions. During paradoxical, or rapid eye movements (REM), sleep, opercular and insular potentials remained stable in comparison with Stage 2, whereas the responses from mid-anterior cingulate abated drastically, and decreasing below background noise in half of the subjects. Thus, while the lateral operculo-insular system subserving sensory analysis of somatic stimuli remained active during paradoxical-REM sleep, mid-anterior cingulate processes related to orienting and avoidance behavior were suppressed. Dissociation between sensory and orienting-motor networks might explain why nociceptive stimuli can be either neglected or incorporated into dreams without awakening the subject.

Sleep disruption by painful stimuli is frequently observed both in clinical and experimental conditions. Nociceptive stimuli produce significantly more arousals (30% of stimuli) than non-nociceptive ones. However, even if they do not interrupt sleep, they can trigger a variety of other reactions. Reflex behaviours in response to nociceptive stimuli can be observed during all sleep stages, and are more likely to occur in association with an arousal than alone. Cardiac activation represents a robust sympathetically driven effect preserved whatever the state of vigilance, even if its magnitude can be modulated by a concomitant cortical arousal. Not withstanding these reactions, incorporation of nociceptive stimuli into dream content remains limited. At cortical level, laser-evoked potential studies demonstrate that the processing of nociceptive stimulations is partly conserved during all sleep stages. Furthermore, when nociceptive stimulations interrupt sleep, the cortical response presents a late component suggesting that the stimulation has to be cognitively processed in order to produce a subsequent arousal. More complex reactions to nociceptive stimulations were occasionally reported. In this context, an epileptic patient with intracerebral electrodes implanted for therapeutic purposes allowed us extending these observations. This patient exhibited finger lifts in response to stimulations delivered during paradoxical (REM) sleep. This motor reaction was previously used during wakefulness to indicate that the stimulation had been perceived. When these finger lifts occurred a systematic re-activation of the anterior cingulate preceded each movement. This observation suggests that during PS, not only the processing of sensory inputs but also the capacity for the sleeper to intentionally indicate his perception could be preserved under particular circumstances. L’interruption du sommeil par la douleur est fréquemment observée en conditions clinique et expérimentale. Des stimuli nociceptifs provoquent significativement plus de réveils que des stimuli non douloureux, et même s’ils n’interrompent pas le sommeil, ils peuvent induire d’autres types de réactions. Ainsi, des réflexes comportementaux, pouvant être observés dans tous les stades de sommeil, sont le plus souvent associés à des éveils. La réactivation cardiaque sympathique est présente, quel que soit le stade de vigilance, mais son amplitude est modulée par la concomitance d’un éveil cortical. En revanche, l’incorporation des stimuli nociceptifs dans le contenu onirique reste peu fréquente. Les études par potentiels évoqués au laser montrent que le traitement cortical de l’information nociceptive est partiellement maintenu au cours de tous les stades de sommeil. De plus, lorsque les stimulations interrompent le sommeil, la réponse corticale comporte une composante tardive suggérant qu’un traitement cognitif est nécessaire pour que cette stimulation induise par la suite un éveil. Des réactions plus complexes ont été occasionnellement rapportées. Dans ce contexte, nous présentons le cas d’une patiente épileptique, enregistrée en bilan préchirurgical à l’aide d’électrodes intracérébrales, qui au cours du sommeil paradoxal a spontanément effectué une consigne apprise à l’éveil, à savoir lever son index en réponse aux stimulations nociceptives. Ce mouvement du doigt était précédé d’une activation systématique du cortex cingulaire antérieur. Cela suggère qu’au cours du sommeil paradoxal, le traitement de l’information sensorielle est préservé mais également que le dormeur peut garder la possibilité d’indiquer intentionnellement sa perception.

Shrinking of deafferented somatosensory regions after neural damage is thought to participate to the emergence of neuropathic pain, and pain-relieving procedures have been reported to induce the normalization of altered cortical maps. While repetitive magnetic stimulation (rTMS) of the motor cortex can lessen neuropathic pain, no evidence has been provided that this is concomitant to changes in sensory maps. Here, we assessed in healthy volunteers the ability of 2 modes of motor cortex rTMS commonly used in pain patients to induce changes in pain thresholds and plastic phenomena in the S1 cortex. Twenty minutes of high-frequency (20 Hz) rTMS significantly increased pain thresholds in the contralateral hand, and this was associated with the expansion of the cortical representation of the hand on high-density electroencephalogram source analysis. Neither of these effects were observed after sham rTMS, nor following intermittent theta-burst stimulation (iTBS). The superiority of 20-Hz rTMS over iTBS to induce sensory plasticity may reflect its better match with intrinsic cortical motor frequencies, which oscillate at around 20 Hz. rTMS-induced changes might partly counterbalance the plasticity induced by a nerve lesion, and thus substantiate the use of rTMS to treat human pain. However, a mechanistic relation between S1 plasticity and pain-relieving effects is far from being established.

The optimization of dietary phosphorus (P) and calcium (Ca) supply requires a better understanding of the effect of dietary fiber content of co-products on the digestive utilization of minerals. This study was designed to evaluate the effects of dietary fiber content from 00-rapeseed meal (RSM) on P and Ca digestibility throughout the gastrointestinal tract in growing pigs fed diets without or with microbial phytase. In total, 48 castrated male pigs (initial BW=36.1±0.4 kg) were housed in metabolic crates for 29 days. After an 8-day adaptation period, pigs were allocated to one of the eight treatments. The impact of dietary fiber was modulated by adding whole RSM (wRSM), dehulled RSM (dRSM) or dRSM supplemented with 4.5% or 9.0% rapeseed hulls (dRSMh1 and dRSMh2). Diets contained 0 or 500 phytase unit of microbial phytase per kg. From day 14 to day 23, feces and urine were collected separately to determine apparent total tract digestibility (ATTD) and apparent retention (AR) of P and Ca. At the end of the experiment, femurs and digestive contents were sampled. No effect of variables of interest was observed on growth performance. Microbial phytase increased ATTD and AR of P (P<0.001) but the P equivalency with the wRSM diet was lower than expected. Moreover, stomach inorganic P (iP) solubility was improved by microbial phytase (P<0.001). The ATTD of Ca was not affected by microbial phytase which increased AR of Ca and femur characteristics (P<0.05). Ileal recovery of P was not affected by microbial phytase but cecal recovery was considerably reduced by microbial phytase (P<0.001). The decrease in digesta pH between the distal ileum and cecum (7.6 v. 5.9) enhanced the solubility of iP and may have improved its absorption, as supported by the negative relationship between soluble iP and pH (R2=0.40, P<0.001 without microbial phytase and R2=0.24, P=0.026 with microbial phytase). The inclusion of hulls improved the solubility of iP (P<0.05). In conclusion, dehulling does not largely increase nutrient digestibility although dRSM seems to improve the efficacy of microbial phytase in releasing phosphate in the stomach. Moreover, dietary fiber may affect solubilization process in the cecum which potentiates the effect of microbial phytase on P digestibility.

Abstract Connections of the accessory optic system (AOS) with the pretectum are described in the macaque monkey. Injections of tritiated amino acids in the pretectum demonstrate a major contralateral projection to the dorsal (DTN), lateral (LTN), and medial (MTN) terminal nuclei of the AOS and a sparser projection to the ipsilateral LTN. Injections of retrograde tracers, Fast Blue (FB), or wheat germ agglutinin horseradish peroxidase (WGA‐HRP) plus nonconjugated horseradish peroxidase (HRP) in the LTN show that the pretectal‐LTN projection originates from two nuclei. The main source of pretectal efferents to the LTN is from the pretectal olivary nucleus (OPN) and is entirely contralateral. This projection, which appears unique to primates, originates from the large multipolar cells of the OPN. In addition to this projection, the nucleus of the optic tract (NOT) projects to the ipsilateral LTN, as in nonprimates. Injection of WGA‐HRP in the pretectum shows a reciprocal predominantely ipsilateral projection from the LTN to the pretectum. Retinas were observed after injection of FB in the LTN. The retinal ganglion cells projecting to the AOS are mainly distributed near the fovea and in the nasal region of the contralateral eye, suggesting a nasotemporal pattern of decussation. The demonstration of a direct connection between LTN and OPN forces to a reconsideration of the functional role of the AOS. Previous descriptions of luminance responsive cells in the LTN support a possible participation of this nucleus in the control of the pupillary light reflex.

Abstract Electrophysiological recording of single neurons was used to describe the representation of visual space in area 17, and the technique of retrograde transport of horseradish peroxidase (HRP) was applied to relate these results to projections from the thalamus in the prosimian primate Microcebus murinus . The visuotopic organization of area 17 was found to resemble that of other primates. On the dorsal surface, the border of area 17 corresponds to the representation of the vertical meridian. Proceeding medially across the surface the location of receptive fields descends along the vertical meridian, while moving caudally receptive fields progress temporally. Most of the dorsolateral surface is devoted to central vision and corresponds to a well developed area centralis. Following HRP injections in striate cortex, columns of labeled cells were found in the dorsal lateral geniculate (dLGN) extending orthogonally across all six layers. These columns run in a general ventrodorsal and caudorostral direction, parallel to a line connecting the cellular discontinuities corresponding to the optic disc. These discontinuities are present in magnocellular layer 1 and parvocellualr layers 5 and 6, thus receiving from the nasal retina of the contralateral eye. The representation of the vertical meridian is situated in the ventromedial portion of the dLGN, and the monocular field is represented in the dorsal extremity. Anterior dLGN projects to the calcarine fissure (lower field). and posterior dLGN projects to the ventral surface of the cortex (upper field). Exptrgeniculate input to area 17 was found to originate from the pulvinar. HRP labeled cells were located in two distinct divisions of this nucleus, the cytoarchitecture of which is described. In addition, projections to occipital cortex were found to arise form the intralaminar nuclei.

Abstract BACKGROUND Stereotactic lesion in the Forel's field H (campotomy) was proposed in 1963 to treat Parkinson disease (PD) symptoms. Despite its rationale, very few data on this approach have emerged. Additionally, no study has assessed its effects on nonmotor symptoms, neuropsychological functions and quality of life. OBJECTIVE To provide a prospective 2-yr assessment of motor, nonmotor, neuropsychological and quality of life variables after unilateral campotomy. METHODS Twelve PD patients were prospectively evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS), the Dyskinesia Rating Scale and the Parkinson's disease quality of life questionnaire (PDQ39) before campotomy, and after 6 and 24 mo. Nonmotor, neuropsychiatric, neuropsychological and quality of life variables were assessed. The impact of PD on global health was also rated. RESULTS A significant reduction in contralateral rest tremor (65.7%, P &lt; .001), rigidity (87.8%, P &lt; .001), bradykinesia (68%, P &lt; .001) and axial symptoms (24.2%, P &lt; .05) in offmedication condition led to a 43.9% reduction in UPSDRS III scores 2 yr after campotomy ( P &lt; .001). Gait improved by 31.9% ( P &lt; .05) and walking time to cover 7 m was reduced by 43.2% ( P &lt; .05). Pain decreased by 33.4% ( P &lt; .01), while neuropsychiatric and neuropsychological functions did not change. Quality of life improved by 37.8% ( P &lt; .05), in line with a 46.7% reduction of disease impact on global health ( P &lt; .001). CONCLUSION A significant 2-yr improvement of motor symptoms, gait performance and pain was obtained after unilateral campotomy without significant changes to cognition. Quality of life markedly improved in parallel with a significant reduction of PD burden on global health.

Nociceptive stimuli disrupt sleep, but may, or may not, entail an arousal. While arousal reactions go along with the activation of a widespread cortical network, the factors enabling such activation remain unknown. Here we used intracranial EEG in humans to test the relation between the cortical activity immediately preceding a noxious stimulus and the capacity of such a stimulus to trigger arousal. Intracranial EEG signals were analyzed during all-night sleep in 14 epileptic patients (4 women), who received laser stimuli slightly above their individual pain threshold. During 5 s preceding each stimulus, the functional correlation (spectral phase-coherence) between the main spinothalamic sensory area (posterior insula) and 12 other brain regions, grouped in four networks, as well as their spectral contents, were contrasted according to the presence of a stimulus-induced arousal, and then fed into a logistic regression model to assess their predictive value. Enhanced prestimulus phase-coherence between the sensory posterior insula and neocortical and limbic areas increased significantly the probability of arousal to nociceptive stimuli, in both slow-wave (N2) and rapid eye movements/paradoxical sleep. Furthermore, during N2 sleep, arousal was facilitated by stimulus delivery in periods of attenuated slow-wave activity. Together, these data indicate that sleep micro-states with enhanced interareal communication facilitate information transfer from sensory to higher-order cortical areas, and hence physiological arousal.SIGNIFICANCE STATEMENT Sleep is commonly subdivided into stages based on specific electrophysiological characteristics; however, within each single sleep stage, the functional state of the brain is continuously changing. Here we show that the probability for a phasic noxious stimulus to entail an arousal is modulated by the prestimulus interareal phase-coherence between sensory and higher-level cortical areas. Fluctuations in interareal communication immediately before the noxious stimulus may determine the responsiveness to incoming input by facilitating or preventing the transfer of noxious information from sensory to multiple higher-level cortical networks.

The companion paper (Llinás et al., 2001) presents evidence, at both cellular and network levels, for the role of resonant oscillatory thalamocortical properties in normal and pathological brain function. Here we present confirmatory single cell electrophysiology from the thalami of thalamocortical dysrhythmia (TCD) patients and review our surgical approach towards the relief of this chronic disabling condition, in its many forms. The goal of surgery is a rebalancing of the abnormal thalamocortical oscillation responsible for TCD. Our approach uses small strategically placed pre-thalamic and medial thalamic lesions that serve to make subcritical the low frequency thalamocortical reentry network attractor via desinhibition and desamplification. The lesions address classical and new stereotactic targets that provide therapeutic efficiency coupled with the sparing of the specific thalamocortical loops.

Stereotactic neurosurgery aims at placing therapeutic lesions or chronic stimulating electrodes at very precise locations within the brain. Microelectrode recording and macrostimulation are used in addition to anatomoradiological techniques to optimize targeting. Recently, the usefulness of electrophysiological procedures has been questioned. Based on more than 500 therapeutic stereotactic lesions in the last 10 years at the thalamic and subthalamic levels, we evaluate here retrospectively the utility of the two electrophysiological procedures. In two of the three stereotactic targets considered in this study, intraoperative electrophysiological confirmation is mandatory because of the target size with respect to interindividual anatomical variations and of the more or less close vicinity of eloquent structures.

Abstract The organization of the accessory optic system (AOS) has been studied in the macaque monkey following intravitreal injections of tritiated amino acids in one eye. Retinal projections to the dorsal (DTN) and the lateral (LTN) terminal nuclei are identical to those previously described in other primate species. We observed an additional group of retinorecipient cells of the AOS, located between the cerebral peduncle and the substantia nigra, which we define as the interstitial nucleus of the superior fasciculus, medial fibers. In this report, we focus our attention on the medial terminal nucleus (MTN). Although a ventral division of this nucleus (MTNv) was not observed in the macaque, the retina projects to a group of cells in the midbrain reticular formation (MRF), which we argue to be homologous to the dorsal division of the MTN (MTNd). To provide evidence in support of this homology, the retinal projection to the MTNv and MTNd was also examined in 21 additional species from 11 orders of mammals including carnivores, marsupials, lagomorphs, rodents, bats, insectivores, tree shrews, hyraxes, pholidotess, edentates, and five additional species of primates. Whereas the retina projects to both ventral and dorsal divisions in all species studied, in haplorhine primates only the projection to the MTNd is conserved. The relative topological position of the MTNd in the MRF, dorsomedial to the substantia nigra and ventrolateral to the red nucleus, remains constant throughout the mammals. The trajectory of fiber paths innervating the MTNd is also similar in all species. In addition, the MTNd has comparable afferent and efferent connections with retina, pretectum, and vestibular nuclei in all species thus far studied. These results support the unequivocal conclusion that the MTNd is an unvarying feature of the mammalian AOS.

The projections of the nucleus of the optic tract were studied in the cat by simultaneous use of two distinct retrograde tracers (Fast Blue and Diamidino Yellow) injected in the inferior olive and the prepositus hypoglossi nucleus. Following injections of diamidino yellow in one structure and fast blue in the other, a significant number of retrogradely labeled neurons projecting to either target were observed dispersed in the nucleus of the optic tract. Three populations of labeled cells were found: one which projected to the inferior olive, a second to the nucleus prepositus hypoglossi, and a third which projected by means of a bifurcating axon to both of these structures. Quantification of these results reveals that 72% of the total number of labeled neurons are labeled by the IO injection, the remaining cells being labeled by the NPH injection. Double-labeled neurons represent more than 7% of the total number of the labeled cells. Tentative inferences as to the electrophysiological properties of the nucleus of the optic tract are discussed in the context of the optokinetic system.

This study aimed to create a stereotactic two-dimensional description of the human insula based on accurate radiological morphometric studies.Seventy-five normal cerebral MRIs were selected and drawings of the insula then obtained from serial sagittal slices. These drawings were digitalized before superimposing the anterior (AC) and posterior (PC) commissures as references. This allowed us to quantify interindividual anatomical variations in a large cohort of subjects.The morphometric analysis of the insula revealed a more complex shape than previously described. This structure is delimited by four peri-insular sulci (anterior, superior, posterior and inferior) instead of the three sulci classically mentioned. Males have a statistically larger surface area than females, according to a correlated index. Precise measurements of the different insular components allowed us to quantify their potential interindividual anatomical variations and to define their average shapes and stereotactic locations.These data create a two-dimensional template of the human insula, with regard to the classical AC-PC stereotactic reference system. They furthermore allow us to quantify the probability that a given element of this structure is located at a predefined position. This should be useful in functional neuroimaging studies and in insular surgery for diagnostic and therapeutic goals.

Despite sleep-induced drastic decrease of self-awareness, human sleep allows some cognitive processing of external stimuli. Here we report the fortuitous observation in a patient who, while being recorded with intra-cerebral electrodes, was able, during paradoxical sleep, to reproduce a motor behaviour previously performed at wake to consciously indicate her perception of nociceptive stimulation. Noxious stimuli induced behavioural responses only if they reached the cortex during periods when mid-frontal networks (pre-SMA, pre-motor cortex) were pre-activated. Sensory responses in the opercular cortex and insula were identical whether the noxious stimulus was to evoke or not a motor behaviour; conversely, the responses in mid-anterior cingulate were specifically enhanced for stimuli yielding motor responses. Neuronal networks implicated in the voluntary preparation of movements may be reactivated during paradoxical sleep, but only if behavioural-relevant stimuli reach the cortex during specific periods of “motor awareness”. These local activation appeared without any global sleep stage change. This observation opens the way to further studies on the currently unknown capacity of the sleeping brain to interact meaningfully with its environment.

Using spectral edge frequency (SEF95) and dimension of activation (DA), a new tool derived from the dimension of correlation, we assessed the activation of thalamus and cortex in the different vigilance states.Results were gathered from intracerebral recordings performed in 12 drug-resistant epileptic patients during video-stereoelectroencephalographic (SEEG) monitoring.In the cortex, we observed a progressive decrease of DA from wake to sleep, with minimal DA values characterizing the deep slow wave sleep (dSWS) stage. During paradoxical sleep (PS), cortical level of activity returned to DA values similar to those obtained during wakefulness. In the thalamus, DA values during wakefulness were higher than the values observed during light SWS (ISWS), deep SWS (dSWS) and PS; there were no significant differences between the 3 sleep stages. Similar variations were observed with SEF95.DA analysis proved reliable for quantification of cortical activity, in agreement with data issued from classical vigilance states scoring and spectral analysis. At the thalamic level, only 2 levels of activity within a sleep wake cycle were observed, pointing to dissociated levels of activation between the thalamus and the neocortex during ISWS and PS.

Abstract Although motor cortex stimulation (MCS) is being increasingly used to treat chronic refractory neuropathic pain in humans, its mechanisms of action remain elusive. Studies in animals have suggested the involvement of subcortical structures, in particular, the thalamus. Most of these studies have been performed in rats, a species presenting significant differences in thalamic anatomy and function relative to primates, in particular, a very limited number of thalamic GABA interneurons. The aim of this study was to investigate the effects of MCS on single-unit activities of the thalamic ventral posterior lateral (VPL) nucleus in cats, which contains substantial numbers of GABA interneurons. Spontaneous and evoked activities of VPL units were studied before and after MCS. Motor cortex stimulation induced significant depression of the wide-dynamic-range (WDR) cells' firing rate, concomitant with activity enhancement of nonnociceptive (NN) units. More than half of WDR cells showed a significant decrease in the firing rate, while a similar proportion of NN units exhibited the opposite after-effect. Maximal firing attenuation of WDR cells occurred when the MCS location matched somatotopically their receptive field. Repetition of MCS runs led to an accentuation of WDR depression. After peripheral stimulation, evoked activity in each cell showed MCS effects similar to those observed in spontaneous activity. These data demonstrate a selective top–down inhibition by MCS of nonspecific nociceptive (WDR) cells, enhanced by somatotopic concordance and stimulation repetition, in parallel to facilitation of NN cells. These 2 outcomes may play a role in the complex analgesic effect of MCS observed in neuropathic pain conditions.

The posterior insula (PI) has been proposed as a potential neurostimulation target for neuropathic pain relief as it represents a key-structure in pain processing. However, currently available data remain inconclusive as to efficient stimulation parameters.As frequency was shown to be the most correlated parameter to pain relief, this study aims to evaluate the potential modulatory effects of low frequency (LF-IS, 50 Hz) and high-frequency (HF-IS, 150 Hz) posterior insular stimulation on the activity of somatosensory thalamic nuclei.Epidural bipolar electrodes were placed over the PI of healthy adult cats, and extracellular single-unit activities of nociceptive (NS), nonnociceptive (NN), and wide dynamic range (WDR) thalamic cells were recorded within the ventral posterolateral nucleus and the medial division of the thalamic posterior complex. Mean discharge frequency and burst firing mode were analyzed before and after either LF-IS or HF-IS.LF-IS showed a significant thalamic modulatory effects increasing the firing rate of NN cells (p ≤ 0.03) and decreasing the burst firing of NS cells (p ≤ 0.03), independently of the thalamic nucleus. Conversely, HF-IS did not induce any change in firing properties of the three recorded cell types.These data indicate that 50 Hz IS could be a better candidate to control neuropathic pain.

Fungi of the genus Aspergillus are widespread in the environment where they produce large quantities of airborne conidia. Inhalation of Aspergillus spp. conidia in immunocompromised individuals can cause a wide spectrum of diseases, ranging from hypersensitivity responses to lethal invasive infections. Upon deposition in the lung epithelial surface, conidia encounter and interact with complex microbial communities that constitute the lung microbiota. The lung microbiota has been suggested to influence the establishment and growth of Aspergillus spp. in the human airways. However, the mechanisms underlying this interaction have not yet been sufficiently investigated. In this study, we aimed to evaluate the presence of commensal bacteria antagonistic to Aspergillus in the lung. To this end, we enriched and isolated bacterial strains able to inhibit the germination of conidia from bronchoalveolar lavage fluid (BALF) samples of lung transplant recipients. We used a novel enrichment method based on a soft agar overlay plate assay in which bacteria are directly in contact with conidia and for which inhibition can be readily observed during enrichment. We isolated a total of five bacterial strains, identified as Pseudomonas aeruginosa, and able to inhibit the germination and growth of Aspergillus fumigatus in a soft agar confrontation assay, as well as in a high-throughput multiplate assay. Moreover, we also showed a strong inhibition of A. fumigatus growth on Calu-3 cell culture monolayers. However, the isolated P. aeruginosa strains were shown to cause significant damage to the cell monolayers. Overall, we validated this novel one-step enrichment approach for the isolation of bacterial strains antagonistic to A. fumigatus from BALF samples. This opens up a new venue for targeted enrichment of antagonistic bacterial strains against specific fungal pathogens.

69 patients suffering from chronic therapy-resistant neurogenic pain of peripheral and/or central origin underwent a stereotactic medial thalamotomy. Medial thalamic unit recordings were performed peroperatively, allowing the physiological confirmation of the electrode location and the recognition of a specific physiopathology. Thanks to these recordings, a concept was developed, based on the presence of an imbalance between medial (nucleus centralis lateralis mainly) and lateral (nucleus ventroposterior) thalamic nuclei, resulting in an over-inhibition of both by the reticular thalamic nucleus, and then in a paradoxical activation of pain-related cortical areas. The medial thalamotomy, re-actualized by new technical, anatomical and physiological data, offers a 50-100% relief to 67% of all patients with peripheral as well as central neurogenic pain, on all body localizations, without producing neurological deficits and without risk for the development of iatrogenic pain.

Abstract The accessory optic system (AOS) was studied in an anthropoid primate by using anterograde transport of tritiated amino acids and autoradiographic techniques. The course of the accessory optic tract (AOT) and the retinal projection to the terminal nuclei are described in the gibbon and compared to that of other mammals. The AOT consists of a superior fasciculus, which includes both an anterior and a posterior fiber branch. An inferior fasciculus of the AOT is absent. In contrast to previous reports in haplorhine primates, which describe the AOS as consisting of only the dorsal (DTN) and the lateral (LTN) terminal nuclei, we find that in the gibbon, three cellular groups receive a bilateral projection, predominantly from the contralateral retina. According to cytoarchitecture and topographic location, two of these nuclei correspond to the DTN and the LTN. The third cellular group, situated dorsomedial to the substantia nigra, receives a distinct retinal projection and extends rostrocaudally for 2.0 mm in the mesencephalon. This nucleus is homologous to the dorsal division of the medial terminal nucleus (MTN) in other mammals. There was no evidence for a ventral division of the MTN, which in nonprimates is typically situated at the ventromedial base of the cerebral peduncle. Examination of brain morphology in primates suggests that the ventral division of the MTN has been displaced from its phylogenetically stable location in the medial part of the ventral midbrain to a more dorsal position. This shift appears to be a consequence of the overall morphological influences resulting from the relative enlargement of the pons in this region. The demonstration of a direct retinal projection to the MTN in the gibbon, as well as recent reports in other primates, indicates that a complete AOS consisting of three terminal nuclei is a feature common to all mammals.