Exposure to 2.45 GHz Radiation Triggers Changes in HSP-70, Glucocorticoid Receptors and GFAP Biomarkers in Rat Brain.

Brain tissue may be especially sensitive to electromagnetic phenomena provoking signs of neural stress in cerebral activity. Fifty-four adult female Sprague-Dawley rats underwent ELISA and immunohistochemistry testing of four relevant anatomical areas of the cerebrum to measure biomarkers indicating induction of heat shock protein 70 (HSP-70), glucocorticoid receptors (GCR) or glial fibrillary acidic protein (GFAP) after single or repeated exposure to 2.45 GHz radiation in the experimental set-up. Neither radiation regime caused tissue heating, so thermal effects can be ruled out. A progressive decrease in GCR and HSP-70 was observed after acute or repeated irradiation in the somatosensory cortex, hypothalamus and hippocampus. In the limbic cortex; however, values for both biomarkers were significantly higher after repeated exposure to irradiation when compared to control animals. GFAP values in brain tissue after irradiation were not significantly different or were even lower than those of nonirradiated animals in all brain regions studied. Our results suggest that repeated exposure to 2.45 GHz elicited GCR/HSP-70 dysregulation in the brain, triggering a state of stress that could decrease tissue anti-inflammatory action without favoring glial proliferation and make the nervous system more vulnerable.

Transcranial Focused Ultrasound Enhances Sensory Discrimination Capability through Somatosensory Cortical Excitation.

Low-intensity transcranial focused ultrasound (tFUS) has emerged as a non-invasive brain neuromodulation tool with high spatial specificity. Previous studies attributed tFUS-enhanced sensory performance to the ultrasound-induced inhibitory neural effects. However, to date there is no direct evidence validating the neural mechanism underlying ultrasound-mediated somatosensory enhancement. In this study, healthy human subjects (N = 9) were asked to perform tactile vibration frequency discrimination tasks while tFUS was directed onto the primary somatosensory cortex. During this task, we simultaneously recorded 64-channel electroencephalography (EEG) signals and investigated the brain responses at both EEG sensors and source domains by means of electrophysiological source imaging (ESI). The behavioral results indicated that the subjects' discrimination ability was improved by tFUS with an increased percentage of correct responses. EEG and ESI results revealed that tFUS neuromodulation was able to improve sensory discrimination capability through excitatory effects at the targeted sensory cortex.

The effect of Wi-Fi electromagnetic waves on neuronal response properties in rat barrel cortex.

There is a growing number of studies on the possible biological effects of Wi-Fi radiations on nervous system. In this study we investigated the effect of Wi-Fi exposure on single neuron responses to natural stimuli by using whisker to barrel pathway. This study was done on 29 male Wistar rats. Neuronal spontaneous activity and ON and OFF responses to displacement of principal whisker (PW), adjacent whisker (AW) and combination of PW-AW stimulation (as natural stimuli) were recorded in barrel cortex of anaesthetised rats. A D-link Wi-Fi device was used for 1 h exposure to 2.4 GHz microwaves in data mode (18.2 dBm and 44% for power and duty cycle). A condition test ratio (CTR) was calculated for assessing neuronal integrative properties. Wi-Fi radiations decreased CTR for ON responses. However, neuronal spontaneous activity and ON and OFF responses were not significantly changed following exposure to Wi-Fi signals. The results of this study demonstrated that exposure to Wi-Fi radiation could modulate integrative responses to natural stimuli in barrel cortex.

Spatiotemporal constraints on optogenetic inactivation in cortical circuits.

Optogenetics allows manipulations of genetically and spatially defined neuronal populations with excellent temporal control. However, neurons are coupled with other neurons over multiple length scales, and the effects of localized manipulations thus spread beyond the targeted neurons. We benchmarked several optogenetic methods to inactivate small regions of neocortex. Optogenetic excitation of GABAergic neurons produced more effective inactivation than light-gated ion pumps. Transgenic mice expressing the light-dependent chloride channel GtACR1 produced the most potent inactivation. Generally, inactivation spread substantially beyond the photostimulation light, caused by strong coupling between cortical neurons. Over some range of light intensity, optogenetic excitation of inhibitory neurons reduced activity in these neurons, together with pyramidal neurons, a signature of inhibition-stabilized neural networks ('paradoxical effect'). The offset of optogenetic inactivation was followed by rebound excitation in a light dose-dependent manner, limiting temporal resolution. Our data offer guidance for the design of in vivo optogenetics experiments.

Deep continuous theta burst stimulation of the operculo-insular cortex selectively affects Aδ-fibre heat pain.

KEY POINTS: Deep continuous theta burst stimulation (cTBS) of the right operculo-insular cortex delivered with a double cone coil selectively impairs the ability to perceive thermonociceptive input conveyed by Aδ-fibre thermonociceptors without concomitantly affecting the ability to perceive innocuous warm, cold or vibrotactile sensations. Unlike deep cTBS, superficial cTBS of the right operculum delivered with a figure-of-eight coil does not affect the ability to perceive thermonociceptive input conveyed by Aδ-fibre thermonociceptors. The effect of deep operculo-insular cTBS on the perception of Aδ-fibre input was present at both the contralateral and the ipsilateral hand. The magnitude of the increase in Aδ-heat detection threshold induced by the deep cTBS was significantly correlated with the intensity of the cTBS pulses. Deep cTBS delivered over the operculo-insular cortex is associated with a risk of transcranial magnetic stimulation-induced seizure. ABSTRACT: Previous studies have suggested a pivotal role of the insular cortex in nociception and pain perception. Using a double-cone coil designed for deep transcranial magnetic stimulation, our objective was to assess (1) whether continuous theta burst stimulation (cTBS) of the operculo-insular cortex affects differentially the perception of different types of thermal and mechanical somatosensory inputs, (2) whether the induced after-effects are lateralized relative to the stimulated hemisphere, and (3) whether the after-effects are due to neuromodulation of the insula or neuromodulation of the more superficial opercular cortex. Seventeen participants took part in two experiments. In Experiment 1, thresholds and perceived intensity of Aδ- and C-fibre heat pain elicited by laser stimulation, non-painful cool sensations elicited by contact cold stimulation and mechanical vibrotactile sensations were assessed at the left hand before, immediately after and 20 min after deep cTBS delivered over the right operculo-insular cortex. In Experiment 2, Aδ-fibre heat pain and vibrotactile sensations elicited by stimulating the contralateral and ipsilateral hands were evaluated before and after deep cTBS or superficial cTBS delivered using a flat figure-of-eight coil. Only the threshold to detect Aδ-fibre heat pain was significantly increased 20 min after deep cTBS. This effect was present at both hands. No effect was observed after superficial cTBS. Neuromodulation of the operculo-insular cortex using deep cTBS induces a bilateral reduction of the ability to perceive Aδ-fibre heat pain, without concomitantly affecting the ability to perceive innocuous warm, cold or vibrotactile sensations.

Impact of transcranial direct current stimulation on structural plasticity of the somatosensory system.

While there is a growing body of evidence regarding the behavioral and neurofunctional changes in response to the longitudinal delivery of transcranial direct current stimulation (tDCS), there is limited evidence regarding its structural effects. Therefore, the present study was intended to investigate the effect of repeatedly applied anodal tDCS over the primary somatosensory cortex on the gray matter (GM) and white matter (WM) compartment of the brain. Structural tDCS effects were, moreover, related to effects evidenced by functional imaging and behavioral assessment. tDCS was applied over the course of 5 days in 25 subjects with concomitant assessment of tactile acuity of the right and left index finger as well as imaging at baseline, after the last delivery of tDCS and at follow-up 4 weeks thereafter. Irrespective of the stimulation condition (anodal vs. sham), voxel-based morphometry revealed a behaviorally relevant decrease of GM in the precuneus co-localized with a functional change of its activity. Moreover, there was a decrease in GM of the bilateral lingual gyrus and the right cerebellum. Diffusion tensor imaging analysis showed an increase of fractional anisotropy exclusively in the tDCSanodal condition in the left frontal cortex affecting the final stretch of a somatosensory decision making network comprising the middle and superior frontal gyrus as well as regions adjacent to the genu of the corpus callosum. Thus, this is the first study in humans to identify structural plasticity in the GM compartment and tDCS-specific changes in the WM compartment in response to somatosensory learning.

Spatiotemporal changes of optical signals in the somatosensory cortex of neuropathic rats after electroacupuncture stimulation.

BACKGROUND: Peripheral nerve injury causes physiological changes in primary afferent neurons. Neuropathic pain associated with peripheral nerve injuries may reflect changes in the excitability of the nervous system, including the spinothalamic tract. Current alternative medical research indicates that acupuncture stimulation has analgesic effects in various pain symptoms. However, activation changes in the somatosensory cortex of the brain by acupuncture stimulation remain poorly understood. The present study was conducted to monitor the changes in cortical excitability, using optical imaging with voltage-sensitive dye (VSD) in neuropathic rats after electroacupuncture (EA) stimulation. METHODS: Male Sprague-Dawley rats were divided into three groups: control (intact), sham injury, and neuropathic pain rats. Under pentobarbital anesthesia, rats were subjected to nerve injury with tight ligation and incision of the tibial and sural nerves in the left hind paw. For optical imaging, the rats were re-anesthetized with urethane, and followed by craniotomy. The exposed primary somatosensory cortex (S1) was stained with VSD for one hour. Optical signals were recorded from the S1 cortex, before and after EA stimulation on Zusanli (ST36) and Yinlingquan (SP9). RESULTS: After peripheral stimulation, control and sham injury rats did not show significant signal changes in the S1 cortex. However, inflamed and amplified neural activities were observed in the S1 cortex of nerve-injured rats. Furthermore, the optical signals and region of activation in the S1 cortex were reduced substantially after EA stimulation, and recovered in a time-dependent manner. The peak fluorescence intensity was significantly reduced until 90 min after EA stimulation (Pre-EA: 0.25 ± 0.04 and Post-EA 0 min: 0.01 ± 0.01), and maximum activated area was also significantly attenuated until 60 min after EA stimulation (Pre-EA: 37.2 ± 1.79 and Post-EA 0 min: 0.01 ± 0.10). CONCLUSION: Our results indicate that EA stimulation has inhibitory effects on excitatory neuronal signaling in the S1 cortex, caused by noxious stimulation in neuropathic pain. These findings suggest that EA stimulation warrants further study as a potential adjuvant modulation of neuropathic pain.

Synchrotron X-ray microtransections: a non invasive approach for epileptic seizures arising from eloquent cortical areas.

Synchrotron-generated X-ray (SRX) microbeams deposit high radiation doses to submillimetric targets whilst minimizing irradiation of neighboring healthy tissue. We developed a new radiosurgical method which demonstrably transects cortical brain tissue without affecting adjacent regions. We made such image-guided SRX microtransections in the left somatosensory cortex in a rat model of generalized epilepsy using high radiation doses (820 Gy) in thin (200 µm) parallel slices of tissue. This procedure, targeting the brain volume from which seizures arose, altered the abnormal neuronal activities for at least 9 weeks, as evidenced by a decrease of seizure power and coherence between tissue slices in comparison to the contralateral cortex. The brain tissue located between transections stayed histologically normal, while the irradiated micro-slices remained devoid of myelin and neurons two months after irradiation. This pre-clinical proof of concept highlights the translational potential of non-invasive SRX transections for treating epilepsies that are not eligible for resective surgery.

Transcranial magnetic stimulation (TMS) inhibits cortical dendrites.

One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca(2+) activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca(2+) activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively.

Manipulating neuronal activity in the mouse brain with ultrasound: A comparison with optogenetic activation of the cerebral cortex.

Low-intensity focused ultrasound induces neuronal activation via mechanisms that remain to be elucidated. We recorded local field potential fluctuations in the motor cortex in response to ultrasound stimulation of the somatosensory barrel cortex, comparing them to those recorded in response to optogenetic stimulation of interneurons and pyramidal neurons of the somatosensory cortex in the same animals. Comparison of the waveform produced by ultrasound stimulation to those produced by optogenetic stimulation revealed similarities between ultrasound-induced responses and optogenetically-induced responses to pyramidal cell stimulation, but not interneuron stimulation, which may indicate that ultrasound stimulation is mediated by excitation of cerebral cortical pyramidal neurons. Comparison of post mortem evoked responses to responses in living tissue confirmed the necessity for excitable tissue in the evoked response. Collectively, these experiments demonstrate an excitation-dependent response to low-frequency transdural ultrasound stimulation of cerebral cortical neuronal activity.

Optogenetic neuronal stimulation promotes functional recovery after stroke.

Clinical and research efforts have focused on promoting functional recovery after stroke. Brain stimulation strategies are particularly promising because they allow direct manipulation of the target area's excitability. However, elucidating the cell type and mechanisms mediating recovery has been difficult because existing stimulation techniques nonspecifically target all cell types near the stimulated site. To circumvent these barriers, we used optogenetics to selectively activate neurons that express channelrhodopsin 2 and demonstrated that selective neuronal stimulations in the ipsilesional primary motor cortex (iM1) can promote functional recovery. Stroke mice that received repeated neuronal stimulations exhibited significant improvement in cerebral blood flow and the neurovascular coupling response, as well as increased expression of activity-dependent neurotrophins in the contralesional cortex, including brain-derived neurotrophic factor, nerve growth factor, and neurotrophin 3. Western analysis also indicated that stimulated mice exhibited a significant increase in the expression of a plasticity marker growth-associated protein 43. Moreover, iM1 neuronal stimulations promoted functional recovery, as stimulated stroke mice showed faster weight gain and performed significantly better in sensory-motor behavior tests. Interestingly, stimulations in normal nonstroke mice did not alter motor behavior or neurotrophin expression, suggesting that the prorecovery effect of selective neuronal stimulations is dependent on the poststroke environment. These results demonstrate that stimulation of neurons in the stroke hemisphere is sufficient to promote recovery.

Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy.

Radiotherapy has shown some efficacy for epilepsies but the insufficient confinement of the radiation dose to the pathological target reduces its indications. Synchrotron-generated X-rays overcome this limitation and allow the delivery of focalized radiation doses to discrete brain volumes via interlaced arrays of microbeams (IntMRT). Here, we used IntMRT to target brain structures involved in seizure generation in a rat model of absence epilepsy (GAERS). We addressed the issue of whether and how synchrotron radiotherapeutic treatment suppresses epileptic activities in neuronal networks. IntMRT was used to target the somatosensory cortex (S1Cx), a region involved in seizure generation in the GAERS. The antiepileptic mechanisms were investigated by recording multisite local-field potentials and the intracellular activity of irradiated S1Cx pyramidal neurons in vivo. MRI and histopathological images displayed precise and sharp dose deposition and revealed no impairment of surrounding tissues. Local-field potentials from behaving animals demonstrated a quasi-total abolition of epileptiform activities within the target. The irradiated S1Cx was unable to initiate seizures, whereas neighboring non-irradiated cortical and thalamic regions could still produce pathological oscillations. In vivo intracellular recordings showed that irradiated pyramidal neurons were strongly hyperpolarized and displayed a decreased excitability and a reduction of spontaneous synaptic activities. These functional alterations explain the suppression of large-scale synchronization within irradiated cortical networks. Our work provides the first post-irradiation electrophysiological recordings of individual neurons. Altogether, our data are a critical step towards understanding how X-ray radiation impacts neuronal physiology and epileptogenic processes.

Focused ultrasound modulates region-specific brain activity.

We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animal's somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using image-guided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders.

Repetitive TMS of the somatosensory cortex improves writer's cramp and enhances cortical activity.

Since the somatosensory system is believed to be affected in focal dystonia, we focused on the modulation of the primary somatosensory cortex (SI) induced by repetitive transcranial magnetic stimulation (rTMS) in order to improve symptoms of writer's cramp. Patients with writer's cramp (N=9 in the pilot study and N=11 in the advanced study) were treated with 30-minute 1 Hz real- or sham-rTMS of the SI cortex every day for 5 days. Before and after rTMS, 1.5 T fMRI was examined during simple hand movements. While in the pilot study the rTMS coil was navigated over the SI cortex with a maximum of blood oxygenation-level dependent (BOLD) signal induced by passive movement, patients in the advanced study had the coil above the postcentral sulcus. After real-rTMS, 4 pilot study patients and 10 advanced study patients experienced subjective and objective improvement in writing, while only minimal changes were observed after sham-rTMS. Patients involved in the active movement task exhibited a rTMS-induced BOLD signal increase bilaterally in the SI cortex, posterior parietal cortex and in the supplementary motor area (P<0.001 corrected). After sham-rTMS, no BOLD signal changes were observed. In conclusion, 1 Hz rTMS of the SI cortex can improve writer's cramp while increasing the cortical activity in both hemispheres. Handwriting improved in most patients, as well as the subjective benefit, and lasted for 2-3 weeks. The beneficial effects of rTMS paralleled the functional reorganization in the SI cortex and connected areas, reflecting the impact of somatosensory system on active motion control.

Responsiveness of sensorimotor cortex during pharmacological intervention with bromazepam.

The aim of this study was to investigate the influence of bromazepam on EEG and the motor learning process when healthy subjects were submitted to a typewriting task. We investigated bromazepam due to its abuse by various populations and its prevalent clinical use among older individuals which are more sensitive to the negative effects of long half-life benzodiazepines. A randomized double-blind design was used with subjects divided into three groups: placebo (n=13), bromazepam 3mg (n=13) and bromazepam 6 mg (n=13). EEG data comprising theta, alpha and beta bands was recorded before, during and after the motor task. Our results showed a lower relative power value in the theta band in the Br 6 mg group when compared with PL. We also observed a reduction in relative power in the beta band in the Br 3mg and Br 6 mg when compared with PL group. These findings suggest that Br can contribute to a reduced working memory load in areas related to attention processes. On the other hand, it produces a higher cortical activation in areas associated with sensory integration. Such areas are responsible for accomplishing the motor learning task. The results are an example of the usefulness of integrating electrophysiological data, sensorimotor activity and a pharmacological approach to aid in our understanding of cerebral changes produced by external agents.

Changes in slow and fast alpha bands in subjects submitted to different amounts of functional electrostimulation.

OBJECTIVE: To examine the changes in slow (8-10Hz) and fast (10-12Hz) alpha bands of EEG in three groups of subjects submitted to different amounts of functional electrostimulation (FES). Our hypothesis is that different amounts of electrostimulation may cause different patterns of activation in the sensorimotor cortex. In particular, we expect to see an increase in alpha power due to habituation effects. We examine the two bands comprised by alpha rhythm (i.e., slow and fast alpha), since these two sub-rhythms are related to distinct aspects: general energy demands and specific motor aspects, respectively. METHODS: The sample was composed of 27 students, both sexes, aging between 25 and 40 years old. The subjects were randomly distributed in three groups: control (n=9), G24 (n=9) and G36 (n=9). A FES equipment (Neuro Compact-2462) was used to stimulate the right index finger extension. Simultaneously, the electroencephalographic signal was acquired. We investigated the absolute power in slow and fast alpha bands in the sensorimotor cortex. RESULTS: The G36 indicated a significant increasing in absolute power values in lower and higher alpha components, respectively, when compared with the control group. Particularly, in the following regions: pre-motor cortex and primary motor cortex. DISCUSSION: FES seems to promote cortical adaptations that are similar to those observed when someone learns a procedural task. FES application in the G36 was more effective in promoting such neural changes. The lower and higher components of alpha rhythms behave differently in their topographical distribution during FES application. These results suggest a somatotopic organization in primary motor cortex which can be represented by the fast alpha component.

Dissociated effects of quiet stance on standard and high-frequency (600 Hz) lower limb somatosensory evoked potentials.

OBJECTIVE: To verify whether standing can modulate somatosensory input from lower limb to the cortex. Somatosensory afferents have been evaluated not only by means of somatosensory evoked potentials recorded by means of classical wide-bandpass filtering (standard SEPs), but also by high-frequency somatosensory evoked potentials (HF-SEPs), which probably play a role in the processing of rapid adaptive changes. METHODS: Eight healthy subjects underwent right posterior tibial nerve (PTN) stimulation in two different conditions (standing and lying supine). Standard SEPs reflecting the activity of both subcortical and cortical generators further underwent digital filtering (300-800 Hz), in order to enhance HF-SEP components. RESULTS: Stance significantly reduces the P40 cortical component of standard SEPs. By contrast, HF-SEPs did not show any significant change between the two conditions. CONCLUSIONS: The lack of any gating effect on HF-SEPs lends further substance to the hypothesis that HF-SEPs play a pivotal role in the processing of somatosensory inputs related to rapid adaptive changes. SIGNIFICANCE: Our data confirm that standard and HF-SEPs reflect two distinct mechanisms with strongly different functional significance. Further studies are needed to definitively establish whether this dissociation is merely caused by the activation of anatomically different neuronal pools, or by the involvement of distinct functional mechanisms.

Differential columnar processing in local circuits of barrel and insular cortices.

The columnar organization is most apparent in the whisker barrel cortex but seems less apparent in the gustatory insular cortex. We addressed here whether there are any differences between the two cortices in columnar information processing by comparing the spatiotemporal patterns of excitation spread in the two cortices using voltage-sensitive dye imaging. In contrast to the well known excitation spread in the horizontal direction in layer II/III induced in the barrel cortex by layer IV stimulation, the excitation caused in the insular cortex by stimulation of layer IV spread bidirectionally in the vertical direction into layers II/III and V/VI, displaying a columnar image pattern. Bicuculline or picrotoxin markedly extended the horizontal excitation spread in layer II/III in the barrel cortex, leading to a generation of excitation in the underlying layer V/VI, whereas those markedly increased the amplitude of optical responses throughout the whole column in the insular cortex, subsequently widening the columnar image pattern. Such synchronous activities as revealed by the horizontal and vertical excitation spreads were consistently induced in the barrel and insular cortices, respectively, even by stimulation of different layers with varying intensities. Thus, a unique functional column existed in the insular cortex, in which intracolumnar communication between the superficial and deep layers was prominent, and GABA(A) action is involved in the inhibition of the intracolumnar communication in contrast to its involvement in intercolumnar lateral inhibition in the barrel cortex. These results suggest that the columnar information processing may not be universal across the different cortical areas.

Modulation of high-frequency (600 Hz) somatosensory-evoked potentials after rTMS of the primary sensory cortex.

Somatosensory inputs to the primary sensory cortex (S1) after median nerve stimulation include temporally overlapping parallel processing, as reflected by standard low-frequency somatosensory-evoked potentials (LF-SEPs) and high-frequency SEPs (HF-SEPs), the latter being more sensitive to arousal and to other rapid adaptive changes. Experimental data suggest that cortical HF-SEPs are formed by two successive pre- and postsynaptic components, respectively, generated in the terminal part of thalamo-cortical radiation (early burst) and in specialized neuronal pools within S1 (later burst). In eight healthy subjects, slow (1 Hz) or rapid (10 Hz) repetitive transcranial magnetic stimulations (rTMS), which are known to induce opposite changes on cortical excitability, applied on S1 did not modify LF-SEPs, while HF-SEPs showed a series of dissociate changes in the early and later high-frequency burst, moreover occurring with a different time-course. Slow rTMS caused an immediate and lasting decrease of the later burst activity, coupled with an immediate increase of the earlier part of the burst, suggesting that inhibition of cortical excitability triggered opposite, compensatory effects at subcortical levels; rapid rTMS induced a delayed increase of later HF-SEPs, leaving unaltered the earlier subcortical burst. Findings causally demonstrate that LF- and HF-SEPs reflect two distinct functional pathways for somatosensory input processing, and that early and late high-frequency burst do actually reflect the activity of different generators, as suggested by experimental data. Possible underlying neurophysiological phenomena are discussed.

Corticofugal modulation of the tactile response coherence of projecting neurons in the gracilis nucleus.

Precise and reproducible spike timing is one of the alternatives of the sensory stimulus encoding. We test coherence (repeatability) of the response patterns elicited in projecting gracile neurons by tactile stimulation and its modulation provoked by electrical stimulation of the corticofugal feedback from the somatosensory (SI) cortex. To gain the temporal structure we adopt the wavelet-based approach for quantification of the functional stimulus-neural response coupling. We show that the spontaneous firing patterns (when they exist) are essentially random. Tactile stimulation of the neuron receptive field strongly increases the spectral power in the stimulus and 5- to 15-Hz frequency bands. However, the functional coupling (coherence) between the sensory stimulus and the neural response exhibits ultraslow oscillation (0.07 Hz). During this oscillation the stimulus coherence can temporarily fall below the statistically significant level, i.e., the functional stimulus-response coupling may be temporarily lost for a single neuron. We further demonstrate that electrical stimulation of the SI cortex increases the stimulus coherence for about 60% of cells. We find no significant correlation between the increment of the firing rate and the stimulus coherence, but we show that there is a positive correlation with the amplitude of the peristimulus time histogram. The latter argues that the observed facilitation of the neural response by the corticofugal pathway, at least in part, may be mediated through an appropriate ordering of the stimulus-evoked firing pattern, and the coherence enhancement is more relevant in gracilis nucleus than an increase of the number of spikes elicited by the tactile stimulus.