Les effets de la stimulation électrique transcrânienne à courant direct appliquée au cortex somatosensoriel primaire sur la perception vibrotactile

La stimulation électrique transcrânienne à courant direct (tDCS) est une technique non invasive de neuromodulation qui modifie l’excitabilité corticale via deux grosses électrodes de surface. Les effets dépendent de la polarité du courant, anodique = augmentation de l’excitabilité corticale et cathodique = diminution. Chez l’humain, il n’existe pas de consensus sur des effets de la tDCS appliquée au cortex somatosensoriel primaire (S1) sur la perception somesthésique. Nous avons étudié la perception vibrotactile (20 Hz, amplitudes variées) sur le majeur avant, pendant et après la tDCS appliquée au S1 controlatéral (anodale, a; cathodale, c; sham, s). Notre hypothèse « shift-gain » a prédit une diminution des seuils de détection et de discrimination pour la tDCS-a (déplacement vers la gauche de la courbe stimulus-réponse et une augmentation de sa pente). On attendait les effets opposés avec la tDCS-c, soit une augmentation des seuils (déplacement à droite et diminution de la pente). Chez la majorité des participants, des diminutions des seuils ont été observées pendant et immédiatement suivant la tDCS-a (1 mA, 20 min) en comparaison à la stimulation sham. Les effets n’étaient plus présents 30 min plus tard. Une diminution du seuil de discrimination a également été observée pendant, mais non après la tDCS-c (aucun effet pour détection). Nos résultats supportent notre hypothèse, uniquement pour la tDCS-a. Une suite logique serait d’étudier si des séances répétées de tDCS-a mènent à des améliorations durables sur la perception tactile. Ceci serait bénéfique pour la réadaptation sensorielle (ex. suite à un accident vasculaire cérébral).

The primary somatosensory cortex largely contributes to the early part of the cortical response elicited by nociceptive stimuli.

Research on the cortical sources of nociceptive laser-evoked brain potentials (LEPs) began almost two decades ago (Tarkka and Treede, 1993). Whereas there is a large consensus on the sources of the late part of the LEP waveform (N2 and P2 waves), the relative contribution of the primary somatosensory cortex (S1) to the early part of the LEP waveform (N1 wave) is still debated. To address this issue we recorded LEPs elicited by the stimulation of four limbs in a large population (n=35). Early LEP generators were estimated both at single-subject and group level, using three different approaches: distributed source analysis, dipolar source modeling, and probabilistic independent component analysis (ICA). We show that the scalp distribution of the earliest LEP response to hand stimulation was maximal over the central-parietal electrodes contralateral to the stimulated side, while that of the earliest LEP response to foot stimulation was maximal over the central-parietal midline electrodes. Crucially, all three approaches indicated hand and foot S1 areas as generators of the earliest LEP response. Altogether, these findings indicate that the earliest part of the scalp response elicited by a selective nociceptive stimulus is largely explained by activity in the contralateral S1, with negligible contribution from the secondary somatosensory cortex (S2).

Effects of unilateral decortication on β-adrenergic receptors in the remaining cortex and in the hypothalamus of female rats

Many experiments have been performed to evaluate the physiological role of catecholaminergic mechanisms of gonadotropin release. The purpose of the present study was to determine the concentration of β-adrenoreceptors in the remaining (right) cerebral cortex and in right and left hypothalamic halves of hemi-decorticated female rats which exhibited elevated plasma gonadotropin levels as observed previously. The density of β-receptors was measured using a high-affinity β-adrenergic ligand, iodocyanopindolol (ICYP). Scatchard estimates were obtained for maximum binding (B(max) fmol/mg of tissues) from pooled cerebral cortical and hypothalamic tissue of animals under several experimental conditions after hemi-decortication and sham operation. There was an increase in β-adrenoreceptor density in the remaining (right) cerebral cortex at all times examined in hemi-decorticate in comparison with the sham-operated animals (7 days, +10.9%; 21 days, +8.4%; 90 days, +22%; and 90 days plus ovariectomy, +34.8%). The number of β-adrenoreceptors in the right hypothalamic half in hemi-decorticates decreased at 21 days (-42.20%) and then increased at 90 days (+76.63%) and 90 days plus ovariectomy (+51.75%) when compared with the left hypothalamic half. At the same time there were no significant changes in the sham-operated animals when comparing the receptor density in the right and left hypothalamic halves, respectively. Thus, our results suggest a direct adrenergic pathway by which the left cortex can influence the right cortex and a crossed pathway to the contralateral hypothalamus changing adrenergic activity which can alter the β-adrenergic receptor binding capacity in the hypothalamus.

Analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex in neuropathic pain: Influence of theta burst stimulation priming

Background Conventional protocols of high-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to M1 can produce analgesia. Theta burst stimulation (TBS), a novel rTMS paradigm, is thought to produce greater changes in M1 excitability than conventional protocols. After a preliminary experiment showing no analgesic effect of continuous or intermittent TBS trains (cTBS or iTBS) delivered to M1 as single procedures, we used TBS to prime a subsequent session of conventional 10?Hz-rTMS. Methods In 14 patients with chronic refractory neuropathic pain, navigated rTMS was targeted over M1 hand region, contralateral to painful side. Analgesic effects were daily assessed on a visual analogue scale for the week after each 10?Hz-rTMS session, preceded or not by TBS priming. In an additional experiment, the effects on cortical excitability parameters provided by single- and paired-pulse TMS paradigms were studied. Results Pain level was reduced after any type of rTMS procedure compared to baseline, but iTBS priming produced greater analgesia than the other protocols. Regarding motor cortex excitability changes, the analgesic effects were associated with an increase in intracortical inhibition, whatever the type of stimulation, primed or non-primed. Conclusions The present results show that the analgesic effects of conventional 10?Hz-rTMS delivered to M1 can be enhanced by TBS priming, at least using iTBS. Interestingly, the application of cTBS and iTBS did not produce opposite modulations, unlike previously reported in other systems. It remains to be determined whether the interest of TBS priming is to generate a simple additive effect or a more specific process of cortical plasticity.

The role of the human posterior parietal cortex in memory-guided saccade execution: a double-pulse transcranial magnetic stimulation study

The present study investigated the role of the right posterior parietal cortex (PPC) in the triggering of memory-guided saccades by means of double-pulse transcranial magnetic stimulation (dTMS). Shortly before saccade onset, dTMS with different interstimulus intervals (ISI; 35, 50, 65 or 80 ms) was applied. For contralateral saccades, dTMS significantly decreased saccadic latency with an ISI of 80 ms and increased saccadic gain with an ISI of 65 and 80 ms. Together with the findings of a previous study during frontal eye field (FEF) stimulation the present results demonstrate similarities and differences between both regions in the execution of memory-guided saccades. Firstly, dTMS facilitates saccade triggering in both regions, but the timing is different. Secondly, dTMS over the PPC provokes a hypermetria of contralateral memory-guided saccades that was not observed during FEF stimulation. The results are discussed within the context of recent neurophysiological findings in monkeys.

Memory fields of neurons in the primate prefrontal cortex

Many prefrontal (PF) neurons convey information about both an object’s identity (what) and its location (where). To explore how they represent conjunctions of what and where, we explored the receptive fields of their mnemonic activity (i.e., their “memory fields”) by requiring monkeys to remember both an object and its location at many positions throughout a wide portion of central vision. Many PF neurons conveyed object information and had highly localized memory fields that emphasized the contralateral, but not necessarily foveal, visual field. These results indicate that PF neurons can simultaneously convey precise location and object information and thus may play a role in constructing a unified representation of a visual scene.

Functional activation in motor cortex reflects the direction and the degree of handedness

Handedness is the clearest example of behavioral lateralization in humans. It is not known whether the obvious asymmetry manifested by hand preference is associated with similar asymmetry in brain activation during movement. We examined the functional activation in cortical motor areas during movement of the dominant and nondominant hand in groups of right-handed and left-handed subjects and found that use of the dominant hand was associated with a greater volume of activation in the contralateral motor cortex. Furthermore, there was a separate relation between the degree of handedness and the extent of functional lateralization in the motor cortex. The patterns of functional activation associated with the direction and degree of handedness suggest that these aspects are independent and are coded separately in the brain.

The representation of the ipsilateral visual field in human cerebral cortex

Previous studies of cortical retinotopy focused on influences from the contralateral visual field, because ascending inputs to cortex are known to be crossed. Here, functional magnetic resonance imaging was used to demonstrate and analyze an ipsilateral representation in human visual cortex. Moving stimuli, in a range of ipsilateral visual field locations, revealed activity: (i) along the vertical meridian in retinotopic (presumably lower-tier) areas; and (ii) in two large branches anterior to that, in presumptive higher-tier areas. One branch shares the anterior vertical meridian representation in human V3A, extending superiorly toward parietal cortex. The second branch runs antero-posteriorly along lateral visual cortex, overlying motion-selective area MT. Ipsilateral stimuli sparing the region around the vertical meridian representation also produced signal reductions (perhaps reflecting neural inhibition) in areas showing contralaterally driven retinotopy. Systematic sampling across a range of ipsilateral visual field extents revealed significant increases in ipsilateral activation in V3A and V4v, compared with immediately posterior areas V3 and VP. Finally, comparisons between ipsilateral stimuli of different types but equal retinotopic extent showed clear stimulus specificity, consistent with earlier suggestions of a functional segregation of motion vs. form processing in parietal vs. temporal cortex, respectively.

The acquisition of skilled motor performance: Fast and slow experience-driven changes in primary motor cortex

Behavioral and neurophysiological studies suggest that skill learning can be mediated by discrete, experience-driven changes within specific neural representations subserving the performance of the trained task. We have shown that a few minutes of daily practice on a sequential finger opposition task induced large, incremental performance gains over a few weeks of training. These gains did not generalize to the contralateral hand nor to a matched sequence of identical component movements, suggesting that a lateralized representation of the learned sequence of movements evolved through practice. This interpretation was supported by functional MRI data showing that a more extensive representation of the trained sequence emerged in primary motor cortex after 3 weeks of training. The imaging data, however, also indicated important changes occurring in primary motor cortex during the initial scanning sessions, which we proposed may reflect the setting up of a task-specific motor processing routine. Here we provide behavioral and functional MRI data on experience-dependent changes induced by a limited amount of repetitions within the first imaging session. We show that this limited training experience can be sufficient to trigger performance gains that require time to become evident. We propose that skilled motor performance is acquired in several stages: “fast” learning, an initial, within-session improvement phase, followed by a period of consolidation of several hours duration, and then “slow” learning, consisting of delayed, incremental gains in performance emerging after continued practice. This time course may reflect basic mechanisms of neuronal plasticity in the adult brain that subserve the acquisition and retention of many different skills.

Localization of visual stimuli after striate cortex damage in monkeys: parallels with human blindsight.

Blindsight is a phenomenon in which human patients with damage to striate cortex deny any visual sensation in the resultant visual field defect but can nonetheless detect and localize stimuli when persuaded to guess. Although monkeys with striate lesions have also been shown to exhibit some residual vision, it is not yet clear to what extent the residual capacities in monkeys parallel the phenomenon of human blindsight. To clarify this issue, we trained two monkeys with unilateral lesions of striate cortex to make saccadic eye movements to visual targets in both hemifields under two conditions. In the condition analogous to clinical perimetry, they failed to initiate saccades to targets presented in the contralateral hemifield and thus appeared "blind." Only in the condition where the fixation point was turned off simultaneously with the onset of the target--signaling the animal to respond at the appropriate time--were monkeys able to localize targets contralateral to the striate lesion. These results indicate that the conditions under which residual vision is demonstrable are similar for monkeys with striate cortex damage and humans with blindsight.

Parameters affecting conscious versus unconscious visual discrimination with damage to the visual cortex (V1).

When the visual (striate) cortex (V1) is damaged in human subjects, cortical blindness results in the contralateral visual half field. Nevertheless, under some experimental conditions, subjects demonstrate a capacity to make visual discriminations in the blind hemifield (blindsight), even though they have no phenomenal experience of seeing. This capacity must, therefore, be mediated by parallel projections to other brain areas. It is also the case that some subjects have conscious residual vision in response to fast moving stimuli or sudden changes in light flux level presented to the blind hemifield, characterized by a contentless kind of awareness, a feeling of something happening, albeit not normal seeing. The relationship between these two modes of discrimination has never been studied systematically. We examine, in the same experiment, both the unconscious discrimination and the conscious visual awareness of moving stimuli in a subject with unilateral damage to V1. The results demonstrate an excellent capacity to discriminate motion direction and orientation in the absence of acknowledged perceptual awareness. Discrimination of the stimulus parameters for acknowledged awareness apparently follows a different functional relationship with respect to stimulus speed, displacement, and stimulus contrast. As performance in the two modes can be quantitatively matched, the findings suggest that it should be possible to image brain activity and to identify the active areas involved in the same subject performing the same discrimination task, both with and without conscious awareness, and hence to determine whether any structures contribute uniquely to conscious perception.

Oscillatory beta activity mediates neuroplastic effects of motor cortex stimulation in humans

Continuous theta burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation protocol that can inhibithumanmotor cortex (M1) excitability and impair movement for ≤1 h. While offering valuable insights into brain function and potential therapeutic benefits, these neuroplastic effects are highly variable between individuals. The source of this variability, and the electrophysiological mechanisms underlying the inhibitory after-effects, are largely unknown. In this regard, oscillatory activity at beta frequency (15-35 Hz) is of particular interest as it is elevated in motor disorders such as Parkinson's disease and modulated during the generation of movements. Here, we used a source-level magnetoencephalography approach to investigate the hypothesis that the presence of neuroplastic effects following cTBS is associated with concurrent changes in oscillatory M1 beta activity. M1 cortices were localized with a synthetic aperture magnetometry beamforming analysis of visually cued index finger movements. Virtual electrode analysis was used to reconstruct the spontaneous and movement-related oscillatory activity in bilateral M1 cortices, before and from 10 to 45 min after cTBS. We demonstrate that 40 s of cTBS applied over left M1 reduced corticospinal excitability in the right index finger of 8/16 participants. In these responder participants only, cTBS increased the power of the spontaneous beta oscillations in stimulated M1 and delayed reaction times in the contralateral index finger. No further changes were observed in the latency or power of movement-related beta oscillations. These data provide insights into the electrophysiological mechanisms underlying cTBS-mediated impairment of motor function and demonstrate the association between spontaneous oscillatory beta activity in M1 and the inhibition of motor function. © 2013 the authors.

The influence of interhemispheric connections on ongoing and evoked orientation preference maps and spiking activity in the cat primary visual cortex

In the primary visual cortex, neurons with similar physiological features are clustered together in columns extending through all six cortical layers. These columns form modular orientation preference maps. Long-range lateral fibers are associated to the structure of orientation maps since they do not connect columns randomly; they rather cluster in regular intervals and interconnect predominantly columns of neurons responding to similar stimulus features. Single orientation preference maps – the joint activation of domains preferring the same orientation - were observed to emerge spontaneously and it was speculated whether this structured ongoing activation could be caused by the underlying patchy lateral connectivity. Since long-range lateral connections share many features, i.e. clustering, orientation selectivity, with visual inter-hemispheric connections (VIC) through the corpus callosum we used the latter as a model for long-range lateral connectivity. In order to address the question of how the lateral connectivity contributes to spontaneously generated maps of one hemisphere we investigated how these maps react to the deactivation of VICs originating from the contralateral hemisphere. To this end, we performed experiments in eight adult cats. We recorded voltage-sensitive dye (VSD) imaging and electrophysiological spiking activity in one brain hemisphere while reversible deactivating the other hemisphere with a cooling technique. In order to compare ongoing activity with evoked activity patterns we first presented oriented gratings as visual stimuli. Gratings had 8 different orientations distributed equally between 0º and 180º. VSD imaged frames obtained during ongoing activity conditions were then compared to the averaged evoked single orientation maps in three different states: baseline, cooling and recovery. Kohonen self-organizing maps were also used as a means of analysis without prior assumption (like the averaged single condition maps) on ongoing activity. We also evaluated if cooling had a differential effect on evoked and ongoing spiking activity of single units. We found that deactivating VICs caused no spatial disruption on the structure of either evoked or ongoing activity maps. The frequency with which a cardinally preferring (0º or 90º) map would emerge, however, decreased significantly for ongoing but not for evoked activity. The same result was found by training self-organizing maps with recorded data as input. Spiking activity of cardinally preferring units also decreased significantly for ongoing when compared to evoked activity. Based on our results we came to the following conclusions: 1) VICs are not a determinant factor of ongoing map structure. Maps continued to be spontaneously generated with the same quality, probably by a combination of ongoing activity from local recurrent connections, thalamocortical loop and feedback connections. 2) VICs account for a cardinal bias in the temporal sequence of ongoing activity patterns, i.e. deactivating VIC decreases the probability of cardinal maps to emerge spontaneously. 3) Inter- and intrahemispheric long-range connections might serve as a grid preparing primary visual cortex for likely junctions in a larger visual environment encompassing the two hemifields.

The influence of interhemispheric connections on ongoing and evoked orientation preference maps and spiking activity in the cat primary visual cortex

In the primary visual cortex, neurons with similar physiological features are clustered together in columns extending through all six cortical layers. These columns form modular orientation preference maps. Long-range lateral fibers are associated to the structure of orientation maps since they do not connect columns randomly; they rather cluster in regular intervals and interconnect predominantly columns of neurons responding to similar stimulus features. Single orientation preference maps – the joint activation of domains preferring the same orientation - were observed to emerge spontaneously and it was speculated whether this structured ongoing activation could be caused by the underlying patchy lateral connectivity. Since long-range lateral connections share many features, i.e. clustering, orientation selectivity, with visual inter-hemispheric connections (VIC) through the corpus callosum we used the latter as a model for long-range lateral connectivity. In order to address the question of how the lateral connectivity contributes to spontaneously generated maps of one hemisphere we investigated how these maps react to the deactivation of VICs originating from the contralateral hemisphere. To this end, we performed experiments in eight adult cats. We recorded voltage-sensitive dye (VSD) imaging and electrophysiological spiking activity in one brain hemisphere while reversible deactivating the other hemisphere with a cooling technique. In order to compare ongoing activity with evoked activity patterns we first presented oriented gratings as visual stimuli. Gratings had 8 different orientations distributed equally between 0º and 180º. VSD imaged frames obtained during ongoing activity conditions were then compared to the averaged evoked single orientation maps in three different states: baseline, cooling and recovery. Kohonen self-organizing maps were also used as a means of analysis without prior assumption (like the averaged single condition maps) on ongoing activity. We also evaluated if cooling had a differential effect on evoked and ongoing spiking activity of single units. We found that deactivating VICs caused no spatial disruption on the structure of either evoked or ongoing activity maps. The frequency with which a cardinally preferring (0º or 90º) map would emerge, however, decreased significantly for ongoing but not for evoked activity. The same result was found by training self-organizing maps with recorded data as input. Spiking activity of cardinally preferring units also decreased significantly for ongoing when compared to evoked activity. Based on our results we came to the following conclusions: 1) VICs are not a determinant factor of ongoing map structure. Maps continued to be spontaneously generated with the same quality, probably by a combination of ongoing activity from local recurrent connections, thalamocortical loop and feedback connections. 2) VICs account for a cardinal bias in the temporal sequence of ongoing activity patterns, i.e. deactivating VIC decreases the probability of cardinal maps to emerge spontaneously. 3) Inter- and intrahemispheric long-range connections might serve as a grid preparing primary visual cortex for likely junctions in a larger visual environment encompassing the two hemifields.

Long-term Postoperative Atrophy Of Contralateral Hippocampus And Cognitive Function In Unilateral Refractory Mtle With Unilateral Hippocampal Sclerosis.

This study aimed to evaluate long-term atrophy in contralateral hippocampal volume after surgery for unilateral MTLE, as well as the cognitive outcome for patients submitted to either selective transsylvian amygdalohippocampectomy (SelAH) or anterior temporal lobe resection (ATL). We performed a longitudinal study of 47 patients with MRI signs of unilateral hippocampal sclerosis (23 patients with right-sided hippocampal sclerosis) who underwent surgical treatment for MTLE. They underwent preoperative/postoperative high-resolution MRI as well as neuropsychological assessment for memory and estimated IQ. To investigate possible changes in the contralateral hippocampus of patients, we included 28 controls who underwent two MRIs at long-term intervals. The volumetry using preoperative MRI showed significant hippocampal atrophy ipsilateral to the side of surgery when compared with controls (p<0.0001) but no differences in contralateral hippocampal volumes. The mean postoperative follow-up was 8.7 years (± 2.5 SD; median=8.0). Our patients were classified as Engel I (80%), Engel II (18.2%), and Engel III (1.8%). We observed a small but significant reduction in the contralateral hippocampus of patients but no volume changes in controls. Most of the patients presented small declines in both estimated IQ and memory, which were more pronounced in patients with left TLE and in those with persistent seizures. Different surgical approaches did not impose differences in seizure control or in cognitive outcome. We observed small declines in cognitive scores with most of these patients, which were worse in patients with left-sided resection and in those who continued to suffer from postoperative seizures. We also demonstrated that manual volumetry can reveal a reduction in volume in the contralateral hippocampus, although this change was mild and could not be detected by visual analysis. These new findings suggest that dynamic processes continue to act after the removal of the hippocampus, and further studies with larger groups may help in understanding the underlying mechanisms.