The insula of Reil revisited: multiarchitectonic organization in macaque monkeys.

The insula of Reil represents a large cortical territory buried in the depth of the lateral sulcus and subdivided into 3 major cytoarchitectonic domains: agranular, dysgranular, and granular. The present study aimed at reinvestigating the architectonic organization of the monkey's insula using multiple immunohistochemical stainings (parvalbumin, PV; nonphosphorylated neurofilament protein, with SMI-32; acetylcholinesterase, AChE) in addition to Nissl and myelin. According to changes in density and laminar distributions of the neurochemical markers, several zones were defined and related to 8 cytoarchitectonic subdivisions (Ia1-Ia2/Id1-Id3/Ig1-Ig2/G). Comparison of the different patterns of staining on unfolded maps of the insula revealed: 1) parallel ventral to dorsal gradients of increasing myelin, PV- and AChE-containing fibers in middle layers, and of SMI-32 pyramidal neurons in supragranular layers, with merging of dorsal and ventral high-density bands in posterior insula, 2) definition of an insula "proper" restricted to two-thirds of the "morphological" insula (as bounded by the limiting sulcus) and characterized most notably by lower PV, and 3) the insula proper is bordered along its dorsal, posterodorsal, and posteroventral margin by a strip of cortex extending beyond the limits of the morphological insula and continuous architectonically with frontoparietal and temporal opercular areas related to gustatory, somatosensory, and auditory modalities.

Does greater low frequency EEG activity in normal immaturity and in children with epilepsy arise in the same neuronal network?

Greater low frequency power (<8 Hz) in the electroencephalogram (EEG) at rest is normal in the immature developing brain of children when compared to adults. Children with epilepsy also have greater low frequency interictal resting EEG activity. Whether these power elevations reflect brain immaturity due to a developmental lag or the underlying epileptic pathophysiology is unclear. The present study addresses this question by analyzing spectral EEG topographies and sources for normally developing children and children with epilepsy. We first compared the resting EEG of healthy children to that of healthy adults to isolate effects related to normal brain immaturity. Next, we compared the EEG from 10 children with generalized cryptogenic epilepsy to the EEG of 24 healthy children to isolate effects related to epilepsy. Spectral analysis revealed that global low (delta: 1-3 Hz, theta: 4-7 Hz), medium (alpha: 8-12 Hz) and high (beta: 13-25 Hz) frequency EEG activity was greater in children without epilepsy compared to adults, and even further elevated for children with epilepsy. Topographical and tomographic EEG analyses showed that normal immaturity corresponded to greater delta and theta activity at fronto-central scalp and brain regions, respectively. In contrast, the epilepsy-related activity elevations were predominantly in the alpha band at parieto-occipital electrodes and brain regions, respectively. We conclude that lower frequency activity can be a sign of normal brain immaturity or brain pathology depending on the specific topography and frequency of the oscillating neuronal network.

Thalamocortical theta coherence in neurological patients at rest and during a working memory task.

We simultaneously recorded the local field potential (LFP) in the thalamus and the electroencephalogram (EEG) on the scalp of 5 patients suffering from neurogenic pain, epilepsy and movement disorders. In an earlier study [], we have investigated the slowing of EEG and the high thalamocortical coherence in the framework of thalamocortical dysrhythmia, the common underlying pathophysiology. The current study focuses on the effects of different cognitive conditions. When patients rested with eyes closed, a theta peak dominated the EEG spectra. The peak height was reduced upon opening the eyes, reminiscent of the classical alpha blocking. This peak reduction also appeared in the thalamic LFP recording. When patients activated their working memory by counting backwards, the theta peak increased in scalp EEG or in the LFP recorded in thalamic nuclei VA/VL. The coherence estimates between EEG and LFP ranged between 21% and 76% for different patients and cognitive conditions (mean: 50%). The involvement of both cortex and thalamus in working memory and the high thalamocortical coherence underline, in addition to cortico-cortical interactions, the importance of thalamocortical modules in the generation of higher cognitive functions.

[Toward a unified theory of positive symptoms]. / Vers une théorie unifiée des symptômes positifs.

Defined more than one century ago, the concept of positive symptoms has become obsolete, except in the psychiatric domain. However, its relevance remains intact today when considering such pathophysiologies as neuropathic (phantom) pain, movement disorders, tinnitus, epilepsy, and psychiatric disorders. Beside their very different clinical characteristics, all these symptoms arise from a lesion in the nervous system. Furthermore, they are paradoxical in the sense that they correspond to a spontaneous hyperactivity of the injured functional system, concomitant to the usual deficits resulting from the lesion. Could these similarities reflect the existence of some common pathophysiological process? A peculiar electrophysiological property of thalamic cells is likely to be compatible with this hypothesis. A thalamic cell produces action potentials when depolarised by excitatory inputs. Conversely, its ability to produce action potentials is decreased or even completely suppressed when the same cell is hyperpolarized by inhibitory influences. However, depending on its level of hyperpolarization, this cell can also produce rhythmic paradoxical bursts of activity at low frequency (3-4 Hz). In this context, a lesion involving, for example, the somatosensory excitatory fibres gives rise to hyperpolarization of the corresponding thalamic cells, which may produce such rhythmic bursting activity. This causes an increase of low frequency thalamo-cortical activity, which, through reduction of collateral cortico-cortical inhibition, induces high frequency activity in neighbouring thalamo-cortical loops ("edge effect"). This leads to the appearance of the clinical symptoms, in this case, pain. Electrophysiological recordings performed in patients suffering from sensory or motor positive symptoms have shown the presence of such deleterious sequence of events. Furthermore, the efficiency of neurosurgical treatments that are used against some positive symptoms can be explained on the basis of such a dynamic process. Both considerations support the validity of the proposed hypothesis and open avenues for the control of other positive symptoms.

Multiarchitectonic and stereotactic atlas of the human thalamus.

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.

Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients.

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.

Thalamus and neurogenic pain: physiological, anatomical and clinical data.

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.

A silver and gold technique for axons and axon-bundles in formalin-fixed central and peripheral nervous tissue.

We have modified the reduced silver procedure of Liesegang and added a gold treatment. The technique has been successfully and routinely used to impregnate both peripheral and central nervous tissues of mice of different ages, and central nervous tissue of man. It was applied on conventionally (formalin) fixed and cryostat-cut material. In the periphery, nerves, individual axons, and sensory and motor endings stained a dark purple. In the brain, both bundles of axons and individual fine axonal branches were stained. When counterstained by a Nissl method, an excellent overall image of CNS structure is obtained.

Effects of medial thalamotomy and pallido-thalamic tractotomy on sleep and waking EEG in pain and Parkinsonian patients.

OBJECTIVES: Investigation of sleep and sleep EEG before and after stereotactic neurosurgery. METHODS: All-night polysomnographic recordings were obtained in 3 neurogenic pain patients and 3 parkinsonian patients. One subject of each group was recorded in addition 3 months after surgery. Stereotactic operations were performed in the medial thalamus and on the pallido-thalamic tract to relieve neurogenic pain and parkinsonian symptoms, respectively. RESULTS: Sleep efficiency was little affected by the surgical intervention in neurogenic pain patients and a dramatic reduction in REM sleep occurred, which had recovered in the subject recorded after 3 months. After the surgery parkinsonian patients showed an increase in total sleep time and in sleep efficiency, and a decrease in REM sleep latency. Sleep efficiency remained elevated in the 3 months follow-up. Medial thalamotomy abolished spindle frequency activity (SFA) in the power and coherence spectra in non-REM sleep stage 2 systematically. Pallido-thalamic tractotomy attenuated SFA only to varying degrees. After 3 months SFA had reemerged. The alpha peak of the waking EEG was shifted to lower frequencies after surgery in 5 of 6 patients and had reverted to the original frequency 3 months later. CONCLUSIONS: Medial thalamotomy or pallido-thalamic tractotomy had acute and reversible effects on the EEG and long-term deleterious side effects of stereotactic surgery on sleep and sleep EEG are improbable. The results provide further evidence for the involvement of the human thalamus in the generation of sleep spindles.

Microsurgical DREZ-otomy for the treatment of spasticity and pain in the lower limbs.

The authors report on a series of 53 bedridden patients suffering from harmful spasticity in one (6) or both (47) lower limbs, who were treated with microsurgical DREZ-otomy. Surgery was performed to treat fixed abnormal postures in flexion in 49 patients and hyperextension in 3, and, additionally, to treat pain in 37 patients. Microsurgical DREZ-otomy was introduced in 1972, on the basis of anatomical studies of the human dorsal root entry zone (DREZ) showing a topographical segregation of the afferent fibers according to their size and functional destinations. It consists of a 2 mm deep microsurgical lesion directed at a 45 degrees angle in the posterolateral sulcus and penetrating the dorsal root entry zone in its ventrolateral aspect, at the level of all the rootlets considered involved in spasticity (and pain). It destroys mainly the lateral (nociceptive) and central (myotatic) afferent fibers as well as the facilitatory medial part of the Lissauer tract, while sparing most of the medial (lemniscal) fibers, the suppressor lateral part of the Lissauer tract, and more or less of the dorsal horn (DH). The postoperative results were evaluated after a mean follow-up period of 3 years and 4 months. Both spasticity and spasms were significantly decreased or suppressed in 75% and 88.2% of the patients, respectively. When present, pain was relieved without abolition of sensation in 91.6%. These benefits--combined with complementary orthopedic surgery in 23 patients--resulted in either disappearance or marked reduction of the abnormal postures in 85.3% of the patients and of articular limitations in 96.8%. Mild-to-severe complications occurred in 25 patients and precipitated or were responsible for death in 5. This is explained by the fact that the general and neurological conditions of most of the patients--especially those affected by multiple sclerosis--were precarious. MDT has, however, enabled a majority of these severely disabled patients to sit and lie comfortably, and has allowed them to reach a significantly improved quality of life.

Microanatomic and vascular aspects of the temporomesial region.

OBJECTIVE: The aim of this work was to provide a detailed description of the arterial vascularization of the temporomesial region (TMR), correlated with the definitions of the macroscopic and cytoarchitectonic subdivisions of this area. METHODS: Selective colored arterial injections were performed in 16 hemispheres to study their blood supply. Four hemispheres were used to illustrate the macroscopic aspect of the TMR and were then cut into thin sections and stained with Nissl's stain to study the cytoarchitectonic areas. RESULTS: The surface of the TMR is subdivided into several areas: anteriorly, the lateral olfactory gyrus is covered by prepiriform cortex; dorsomedially, the semilunar gyrus and uncus hippocampi consist, respectively, of cortical amygdaloid nucleus and hippocampal cytoarchitectonic fields; and ventrolaterally, the anterior part of the parahippocampal gyrus is covered by periamygdaloid cortex, entorhinal, and transentorhinal areas and its posterior part is covered by Fields TH and TF per Von Economo and subicular complex. Six cortical arterial groups were defined: Group I, anterosuperior parahippocampal arteries (mean, 3.9 arteries) vascularize the ambiens, semilunar, and lateral olfactory gyri (origins: middle cerebral artery, anterior choroidal artery [AChA], posterior cerebral artery [PCA], and internal carotid artery); Group II, anteroinferior parahippocampal arteries (mean, 2.8 arteries) irrigate the anterior ventrolateral region of the parahippocampal gyrus (origins: middle cerebral artery, PCA, and AChA); Group III, medial uncal arteries (mean, 1.9 arteries) supply the medial part of uncus hippocampi (origins: AChA and PCA); Group IV, lateral uncal arteries (mean, 2.9 arteries) vascularize the lateral part of the uncus hippocampi (origins: AChA and PCA); Group V, several small posterior parahippocampal arteries irrigate Fields TF and TH per Von Economo (origins: PCA and AChA); and Group VI, posterior hippocampal arteries (mean, 3.2 arteries) irrigate the posterior part of hippocampal formation (origin: PCA). Many anastomoses are found among these arteries, particularly in the ventrolateral part of the TMR. Three groups of amygdaloid arteries were defined: Group I, the anterolateral group (mean, 5.7 arteries) (origin: middle cerebral artery); Group II, the medial group (mean, 6.4 arteries) (origins: AChA, internal carotid artery, and PCA); and Group III, the posterolateral group (mean, 5 arteries) (origins: AChA and internal carotid artery). CONCLUSION: We hope that this work will be useful for any microneurosurgical procedures on the TMR. We have clarified the macroscopic and histological definitions of the cortical and nuclear areas of the TMR and the arterial groups closely related to them. The systematic analysis of the variability of the arterial vascularization of this area was our second goal; such a goal, however, requires more observations to be exhaustive. The numerous interterritorial anastomoses found inside the TMR imply that a selective presurgical injection of short-acting barbiturates to evaluate its functions (Wada test) may well result in its diffusion to other areas of the TMR.

Somatosensory function following dorsal root entry zone lesions in patients with neurogenic pain or spasticity.

The goal of this study was to assess the effects of the dorsal root entry zone (DREZ) lesioning procedure, microsurgical DREZ-otomy (MDT), on spinal cord somatosensory function based on peri- and intraoperative clinical and electrophysiological data. The study was performed prospectively on a series of 20 patients suffering from either chronic neurogenic pain or spasticity. Physiological observations were made of the intraoperative evoked electrospinographic recordings as collected from the surface of the spinal cord. The MDT procedure produced analgesia or severe hypalgesia, moderate hypesthesia, and only slight deficits in proprioception and cutaneous spatial discrimination on the body segments operated on. These clinical data correlated well with evoked electrospinographic recordings, which showed a moderate effect of MDT on presynaptic compound action potentials recorded from the spinal cord (N11 and N21), a partial or even reversible effect on the cortical postcentral N20 wave, a more marked effect on the postsynaptic dorsal horn waves N13 and N24 related to large primary afferent fibers, and a disappearance of dorsal horn waves related to finer afferents (N2 and possibly N3). These data provide evidence for an acceptably selective action of MDT on spinal cord nociceptive mechanisms, and for a partial, often slight, involvement of the other somatosensory domains. The presence of abnormal evoked electrospinographic waves is discussed in relation to the mechanisms of neurogenic pain and spasticity. The hypothesis of a "retuning" of the dorsal horn as the mode of action of MDT is presented.

Brain sources of EEG gamma frequency during volitionally meditation-induced, altered states of consciousness, and experience of the self.

Multichannel EEG of an advanced meditator was recorded during four different, repeated meditations. Locations of intracerebral source gravity centers as well as Low Resolution Electromagnetic Tomography (LORETA) functional images of the EEG 'gamma' (35-44 Hz) frequency band activity differed significantly between meditations. Thus, during volitionally self-initiated, altered states of consciousness that were associated with different subjective meditation states, different brain neuronal populations were active. The brain areas predominantly involved during the self-induced meditation states aiming at visualization (right posterior) and verbalization (left central) agreed with known brain functional neuroanatomy. The brain areas involved in the self-induced, meditational dissolution and reconstitution of the experience of the self (right fronto-temporal) are discussed in the context of neural substrates implicated in normal self-representation and reality testing, as well as in depersonalization disorders and detachment from self after brain lesions.

Ablative neurosurgical procedures for the treatment of chronic pain.

This article is devoted to ablative neurosurgical procedures used for the treatment of chronic pain. The authors detail only those procedures that are currently performed. The procedures are classified as those directed to the peripheral nerves, spinal roots and cranial nerves; the dorsal root entry zone; the ascending extra-lemniscal pathways. The authors have analyzed the results of their own series and those published in the literature. They concentrate on the rationale and neurophysiological effects of the operations.

Microelectrode recording and macrostimulation in thalamic and subthalamic MRI guided stereotactic surgery.

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.

Neuropsychiatric thalamocortical dysrhythmia: surgical implications.

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.

Chronic neurogenic pain and the medial thalamotomy.

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.