Changes in Choline Acetyltransferase Activity and High-Affinity Choline Uptake,but Not in Acetylcholinesterase Activity and Muscarinic Cholinergic Receptors,in Rat Somatosensory Cortex after Sciatic Nerve Injury

Selected cholinergic markers (choline acetyltransferase, acetylcholinesterase, muscarinic acetylcholine receptor, high-affinity choline uptake) were studied in the hindlimb representation areas of the rat somatosensory cortex and within the visual cortex 1 to 63 days after unilateral transection of the sciatic nerve. In the contralateral somatosensory cortex, peripheral deafferentation resulted in a significant reduction of choline acetyltransferase activity (by 15%) 3 days after sciatic nerve injury, and in a significant reduction of high-affinity choline uptake (by 30%) 1 day after nerve transection, in comparison to untreated control rats. Investigations in individual cortical layers revealed that the decrease of both choline acetyltransferase activity and high-affinity choline uptake sites was mainly due to reductions in cortical layer V. Acetylcholinesterase activity and [³H]quinuclidinyl benzilate binding to muscarinic acetylcholine receptors were not affected by unilateral transection of the sciatic nerve. In the ipsilateral somatosensory cortex, as well as in the visual cortex at both cortical hemispheres, no significant changes in the cholinergic parameters studied could be detected. The data indicate that peripheral deafferentation of the somatosensory cortex results in a transient change of presynaptic cholinergic parameters within the affected somatosensory area as early as 1 to 3 days after the lesion; thus, they emphasize the involvement of cholinergic mechanisms in cortical reorganizational events.     

Changes in choline acetyltransferase activity and high-affinity choline uptake, but not in acetylcholinesterase activity and muscarinic cholinergic receptors, in rat somatosensory cortex after sciatic nerve injury

Selected cholinergic markers (choline acetyltransferase, acetylcholinesterase, muscarinic acetylcholine receptor, high-affinity choline uptake) were studied in the hindlimb representation areas of the rat somatosensory cortex and within the visual cortex 1 to 63 days after unilateral transection of the sciatic nerve. In the contralateral somatosensory cortex, peripheral deafferentation resulted in a significant reduction of choline acetyltransferase activity (by 15%) 3 days after sciatic nerve injury, and in a significant reduction of high-affinity choline uptake (by 30%) 1 day after nerve transection, in comparison to untreated control rats. Investigations in individual cortical layers revealed that the decrease of both choline acetyltransferase activity and high-affinity choline uptake sites was mainly due to reductions in cortical layer V. Acetylcholinesterase activity and [3H]quinuclidinyl benzilate binding to muscarinic acetylcholine receptors were not affected by unilateral transection of the sciatic nerve. In the ipsilateral somatosensory cortex, as well as in the visual cortex at both cortical hemispheres, no significant changes in the cholinergic parameters studied could be detected. The data indicate that peripheral deafferentation of the somatosensory cortex results in a transient change of presynaptic cholinergic parameters within the affected somatosensory area as early as 1 to 3 days after the lesion; thus, they emphasize the involvement of cholinergic mechanisms in cortical reorganizational events.     

Effect of Seizures Induced by Intra-Amygdaloid Kainic Acid on Kainic Acid Binding Sites in Rat Hippocampus and Amygdala

[3H]Kainic acid binding sites with a slow dissociation rate in the rat limbic system were investigated in detail. Extensively washed membranes prepared from the hippocampal formation and from the region comprising the amygdala and the piriform cortex yielded non-linear Scatchard plots. Microdissection showed that the high-affinity component (affinity constant around 1 nM) was present in the hippocampal CA3 region (4.2 fmol/mg wet tissue) and the amygdaloid complex (4.6 fmol/mg wet tissue), whereas the remaining part of the hippocampal formation and the piriform lobe contained the low-affinity component (affinity constant 5-20 nM; 11.6 and 11.3 fmol/mg wet tissue, respectively). In the lateral + medial septum we detected only the low-affinity component. Severe limbic seizures, induced by unilateral injection of 0.7 or 0.8 microgram kainic acid in 0.3 microliter of phosphate-buffered saline into the amygdala, reduced kainic acid binding sites in the ipsilateral amygdala and CA3 region. The decline of kainic acid binding sites in the injected amygdala was followed by a similar effect in the contralateral amygdala ("mirror focus") and later by a moderate loss also in the contralateral CA3 region. Kainic acid receptor autoradiography demonstrated that binding sites were lost from the stratum lucidum in hippocampus. Septal lesion had no effect on kainic acid binding sites in the hippocampus. Comparison with previous results on the histopathological changes after this lesion shows that high-affinity kainic acid binding sites are preferentially located on neurons that undergo selective degenerations after severe kainic acid-induced seizures.     

Effect of ferric nitrilotriacetate on predominately cortical glial cell cultures

Cultured glial cells were exposed to ferric nitrilotriacetate (Fe-NTA) at varying concentrations. Studies of the exposed glial cells were performed at days 29 and 36 post-conceptional age (culture days 8 and 15). In addition to morphologic studies, biochemical assays including [³H]-flunitrazepam (FLU) specific binding, Ro5-4864-displaceable³H-FLU binding, and protein determinations were performed. At day 29 post-conceptional age, significant decreases in³H-FLU specific binding, Ro5-4864-displaceable³H-FLU binding, and protein determinations were discernible only in the presence of 100 M Fe-NTA. At day 36 post-conceptional age³H-FLU specific binding was significantly decreased at 20, 60, and 100 M Fe-NTA concentrations, while Ro5-4864-displaceable³H-FLU binding and protein determinations were significantly reduced at 60 and 100 M Fe-NTA concentrations. The effects of Fe-NTA exposure appear to be both concentration and duration-of-exposure related. When compared to previously reported neuronal cell culture, studies utilizing³H-FLU specific binding, Ro5-4864-displaceable³H-FLU binding, and protein determinations, glial cells appear to be significantly more resistant to chelated iron exposure.     

Down-Regulation of AMPA Glutamate Receptors Reduces Cerebrocortical Metabolic Response to Stimulation

We tested the hypothesis that chronic stimulation of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) glutamate receptors with an agonist causes down-regulation of the receptor protein and a decrement in basal and/or stimulated cerebral O2 consumption. Male Wistar rats were intradurally infused with 10 microM AMPA by an osmotic pump at a rate of 1 microl/h for 6 days. As a result, the specific binding of (S)-[3H]-5-fluorowillardiine to AMPA receptors in the cerebral cortex decreased 46% from 2.7 +/- 0.3 to 1.5 +/- 0.6 (density units). Under isoflurane anesthesia and after topical stimulation to the right cerebral cortex with 10(-3) M AMPA, cerebral blood flow (14C-iodoantipyrine method) and O2 consumption (cryomicrospectrophotometrically determined) were determined in control and down-regulated rats. Down-regulation of AMPA receptors did not alter basal O2 consumption. In control, after agonist stimulation, the O2 consumption in the ipsilateral cortex increased by 34%, (4.7 +/- 0.5 ml O2 x min(-1) x 100 g(-1) compared to 3.5 +/- 0.4 in the contralateral cortex). In the down-regulated rats, the O2 consumption did not significantly increase (4.0 +/- 1.5 ml O2 x min(-1) x 100 g(-1) compared to 3.3 +/- 1.7 in the contralateral cortex) after AMPA. In conclusion, following chronic simulation, AMPA receptors underwent down-regulation, but such down-regulation did not alter basal cerebrocortical blood flow or O2 consumption. AMPA down-regulation reduced the agonist stimulated increase in cortical O2 consumption.     

The ipsilateral human motor cortex can functionally compensate for acute contralateral motor cortex dysfunction

What promotes motor recovery from stroke? To date, studies of recovery from stroke have shown alterations in function in various cortical areas, including the contralesional (unaffected) motor cortex (M1). However, whether these changes contribute to recovery or are mere epiphenomena remains unclear. We therefore sought evidence that the ipsilateral M1 can compensate for dysfunction of the contralateral M1. We recorded the change in force production during a finger-tapping task in response to acute disruption of M1 function by repetitive transcranial magnetic stimulation (rTMS). Neither control (occipital) nor ipsilateral M1 rTMS lead to a change in tapping force. RTMS over contralateral M1 had a short-lived effect and induced changes in ipsilateral M1 excitability around the time that these behavioral effects abated, consistent with delayed compensation by the ipsilateral M1. Simultaneous bilateral M1 stimulation, designed to prevent compensation by the ipsilateral M1, had a large and prolonged effect on tapping force. This is the first demonstration that the ipsilateral primary motor cortex is capable of functionally significant compensation for focal contralateral cortical dysfunction in the adult human and provides a rational basis for interventional treatments aimed at promoting functional compensation in unaffected cortical areas after stroke.     

Increased Amyloid Precursor Protein and Tau Expression Manifests as Key Secondary Cell Death in Chronic Traumatic Brain Injury

In testing the hypothesis of Alzheimer's disease (AD)‐like pathology in late stage traumatic brain injury (TBI), we evaluated AD pathological markers in late stage TBI model. Sprague–Dawley male rats were subjected to moderate controlled cortical impact (CCI) injury, and 6 months later euthanized and brain tissues harvested. Results from H&E staining revealed significant 33% and 10% reduction in the ipsilateral and contralateral hippocampal CA3 interneurons, increased MHCII‐activated inflammatory cells in many gray matter (8–20‐fold increase) and white matter (6–30‐fold increased) regions of both the ipsilateral and contralateral hemispheres, decreased cell cycle regulating protein marker by 1.6‐ and 1‐fold in the SVZ and a 2.3‐ and 1.5‐fold reductions in the ipsilateral and contralateral dentate gyrus, diminution of immature neuronal marker by two‐ and onefold in both the ipsilateral and contralateral SVZ and dentate gyrus, and amplified amyloid precursor protein (APP) distribution volumes in white matter including corpus callosum, fornix, and internal capsule (4–38‐fold increase), as well as in the cortical gray matter, such as the striatum hilus, SVZ, and dentate gyrus (6–40‐fold increase) in TBI animals compared to controls (P's < 0.001). Surrogate AD‐like phenotypic markers revealed a significant accumulation of phosphorylated tau (AT8) and oligomeric tau (T22) within the neuronal cell bodies in ipsilateral and contralateral cortex, and dentate gyrus relative to sham control, further supporting the rampant neurodegenerative pathology in TBI secondary cell death. These findings indicate that AD‐like pathological features may prove to be valuable markers and therapeutic targets for late stage TBI. J. Cell. Physiol. 232: 665–677, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.     

Effects of MK-801 on nitrite and cGMP levels during focal cerebral ischemia in rats.

Glutamate is a major excitatory neurotransmitter in the mammalian central nervous system and initiates the events leading to ischemic brain damage. Glutamate receptor antagonists are being used to reduce neuronal damage observed after hypoxia and ischemia. The glutamate receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo-(a,d)-cyclohepten-5,10-imine maleate (MK-801) crosses the blood-brain barrier readily and produces a non-competitive use-dependent blockade of the N-methyl-D-aspartate subtype of glutamate receptor. The aim of this study was to investigate effects of MK-801 administered before and just after the onset of ischemia in rats on nitrite and cyclic guanosine monophosphate (cGMP) levels. Focal cerebral ischemia in rats was produced by permanent occlusion of right middle cerebral artery (MCAO). Nitrite and cGMP levels were measured in both cortex and cerebellum at 0, 10, and 60 min following MCAO. The same parameters were measured in rats treated with MK-801 (0.5 mg/kg, i.p.) 30 min before or just after MCAO. Ipsilateral cortical nitrite levels were increased relative to contralateral cortex after MCAO. No significant changes were observed in cerebellum. The cGMP concentrations in both sides of the cortex and cerebellum were increased at 10 and 60 min compared with 0 min values. cGMP level in the ipsilateral cortex was higher than contralateral cortex, whereas the opposite was found for the cerebellum. MK-801 treatment before or just after MCAO decreased significantly nitrite and cGMP production. Our data indicate that MK-801 treatment before or just after focal ischemia prevents the increase in NO and cGMP production.     

Transient focal cerebral ischemia down-regulates glutamate transporters GLT-1 and EAAC1 expression in rat brain

Transient focal cerebral ischemia leads to extensive excitotoxic neuronal damage in rat cerebral cortex. Efficient reuptake of the released glutamate is essential for preventing glutamate receptor over-stimulation and neuronal death. Present study evaluated the expression of the glial (GLT-1 and GLAST) and neuronal (EAAC1) subtypes of glutamate transporters after transient middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia in rats. Between 24h to 72h of reperfusion after transient MCAO, GLT-1 and EAAC1 protein levels decreased significantly (by 36% to 56%, p < 0.05) in the ipsilateral cortex compared with the contralateral cortex or sham control. GLT-1 and EAAC1 mRNA expression also decreased in the ipsilateral cortex of ischemic rats at both 24h and 72h of reperfusion, compared with the contralateral cortex or sham control. Glutamate transporter down-regulation may disrupt the normal clearance of the synaptically-released glutamate and may contribute to the ischemic neuronal death.     

Quantitative in vivo receptor binding IV: Detection of muscarinic receptor down-regulation by equilibrium and by tracer kinetic methods

Newly-developed methods for estimation of in vivo binding to neurotransmitter receptors should enable the detection and quantification of physiologic or pathologic changes in receptor numbers. In the present study, both equilibrium and kinetic experimental strategies for in vivo muscarinic receptor determination were applied to the detection of receptor changes induced by chronic inhibition of acetylcholinesterase in the rat. Following one week of treatment, in vitro receptor autoradiography utilizing [³H]scopolamine revealed significant losses of muscarinic binding in the cerebral cortex, hippocampus, striatum and in cranial nerve motor nuclei. The in vivo distribution of [³H]scopolamine, following infusion to approach equilibrium binding in the brain, revealed reductions in binding which paralleled the pattern and magnitude of changes detected in vitro. A simplified tracer kinetic estimation following bolus injection of the ligand also detected substantial reductions in forebrain muscarinic receptor binding. These results indicate the feasibility of detecting receptor changes underlying neuropathologic conditions in vivo, and suggest that either equilibrium or kinetic experimental approaches may be extended to clinical research applications with the use of positron or single-photon emission tomography.Special issue dedicated to Dr. Louis Sokoloff.     

Static, transient and permanent organization of GABA receptor expression in calbindin-positive interneurons in response to amygdala kindled seizures

We tested the hypothesis that experimentally produced epilepsy (by kindling) may induce changes in GABAA receptor expression in some but not all interneuron populations. Using laser capture microdissection and quantitative polymerase chain reaction (QPCR) analysis, GABAA receptor alpha subunit expression in calbindin- (CBir) and parvalbumin- (Parvir) immunoreactive interneurons was compared between normal brains and brains in which amygdala kindled seizure responses were permanently established. Two weeks after the last seizure response, Cbir neurons in the hilus and/or perirhinal cortex up-regulated the expression of alpha2, alpha3 and alpha5 subunit mRNAs up to 900%. In contrast, no changes were found in Parvir neurons. In Cbir neurons contralateral to the amygdala kindling site alpha1 subunit mRNA expression was increased. In both Cbir and Parvir neurons, the coordinated subunit expression patterns ipsilateral (fully kindled) and contralateral (partially kindled) to the kindling site suggested that permanent and transient co-expressional relationships occur respectively. In the perirhinal cortex alpha2 protein was up-regulated in the processes but not in the cell somas of calbindin-positive neurons, whereas alpha3 subunit protein expression was up-regulated on the cell bodies of Cbir neurons in the hilus. These data indicate that different interneuron populations may selectively reorganize their GABAA subunit expression in response to seizures.     

Frontal distribution of early cortical somatosensory evoked potentials to median nerve stimulation

The topography of early frontal SEPs (P20 and N26) to left median nerve stimulation was studied in 30 normal subjects and 3 patients with the left frontal bone defect. The amplitudes of P20 and N26 were maximum at the frontal electrode (F4) contralateral to the stimulation and markedly decreased at frontal electrodes ipsilateral to the site of stimulation. There was, however, no latency difference of P20 and N26 between ipsilateral and contralateral frontal electrodes. These results suggest that the origin of the ipsilateral and contralateral P20 and N26 is the same. The wide distribution of P20 and N26 over both frontal areas could be explained by assuming a smearing effect from generators actually located in the rolandic fissure and motor cortex.     

Autoradiographic Localization of Angiotensin II Receptor Binding Sites on Noradrenergic Neurons of the Locus Coeruleus of the Rat

The locus coeruleus (LC) of the rat was lesioned by microinjection of selective neurotoxins into the brainstem. 6-Hydroxydopamine (6-OHDA), 3 micrograms/microliter, given unilaterally at two sites 0.6 mm apart on the rostro-caudal axis of the LC, was used to lesion catecholamine-containing neuronal elements. Ibotenic acid, 2.5 micrograms/0.5 microliters, administered similarly was used to lesion nerve cell bodies. Two weeks after administration of the neurotoxin, lesion efficacy was determined based on the norepinephrine content of the cerebral cortex ipsi- and contralateral to the lesion. 6-OHDA lesions of the LC caused a 46% reduction in ipsilateral cortical norepinephrine and a 60% reduction in specific 125I-[Sar1, Ile8]-angiotensin II (125I-SIAII) binding in the LC. Ibotenic acid lesions of the LC caused a 73% reduction in ipsilateral cortical norepinephrine and a 81% reduction in specific 125I-SIAII binding in the LC. These results indicate that AII receptor binding sites in the LC are localized on noradrenergic nerve cell bodies or their dendritic and axonal ramifications within the LC.     

Enhanced Phosphodiestric Breakdown of Phosphatidylinositol Bisphosphate After Experimental Brain Injury

Abstract: Regional levels of lactate and inositol 1,4,5-trisphosphate (IP₃), a cellular second messenger of the excitatory neurotransmitter system, were measured after lateral fluid percussion (FP) brain injury in rats. At 5 min postinjury, tissue lactate concentrations were significantly elevated in the cortices and hippocampi of both the ipsilateral and contralateral hemispheres. By 20 min postinjury, lactate concentrations were elevated only in the cortices and hippocampus of the ipsilateral hemisphere. Whereas the IP₃ concentrations were elevated in the hippocampi of the ipsilateral and contralateral hemisphere and in the cortex of ipsilateral hemisphere at 5 min postinjury, no elevation in these sites was found at 20 min postinjury. Histologic analysis revealed neuronal damage in the cortex and CA3 regions of hippocampus ipsilateral to the injury at 24 h postinjury. The present results suggest activation of the phosphoinositide signal transduction pathway at the onset of injury and of a possible requirement of early persistent metabolic dysfunction (>20 min) such as the lactate accumulation in the delayed neuronal damage.     

Bilateral changes in glutamate uptake,muscarinic receptor binding and acetylcholinesterase level in the rat hippocampus after unilateral entorhinal cortex lesions

This report examines the effects of unilateral electrolytic and knife-cut lesions of entorhinal cortex on glutamate uptake, the muscarinic receptor [³H]QNB binding and acetylcholinesterase (AChE) activity in the dorsal and ventral parts of the ipsi- and contralateral hippocampus of the rat.We found that (1) in unoperated, control rats there are no pre-existing differences in the level of the investigated markers between the right and left hippocampus, (2) both electrolytic and knife-cut lesions of the entorhinal cortex evoke bilateral changes in the investigated markers and (3) the character of the response is dependent on the survival time and on the hippocampal part involved. Four days after operation a substantial reduction in glutamate uptake was found in both the dorsal and ventral parts of the ipsi- and contralateral hippocampus. At the same time there was a drop in muscarinic receptor binding, while AChE activity was not affected. The decrease in glutamate uptake persisted on the 21st postoperative day, whereas muscarinic receptor binding was enhanced, in comparison with the control level, in the ventral part of both the ipsi- and contralateral hippocampus. This overshoot was not so evident on the 30th postoperative day; glutamate uptake at that time reached or even surpassed the control level. Enhancement of AChE activity on the ipsi- and contralateral sides was noted on both the 21st and 30th day after operation.We suggest the following interpretation of these results: (1) glutamatergic projections from the entorhinal cortex to the hippocampus are bilateral, (2) some transneuronal changes probably contribute to the decline in glutamate uptake, particularly on the contralateral side, (3) neuronal depolarization does not seem to be the only mechanism responsible for the decrease in muscarinic receptor binding and (4) some compensatory mechanisms occur in the hippocampus at a later time after the lesion.Moreover, we believe that the use of the contralateral side as a control should be considered with caution in studies with unilaterally lesioned animals.     

Changes in the Solubility of Glial Fibrillary Acidic Protein After Ischemic Brain Damage in the Mouse

Abstract: In the present study, changes in the content of glial fibrillary acidic protein (GFAP) in mouse cortex were investigated at different time intervals after unilateral middle cerebral artery occlusion. The GFAP content was assessed semiquantitatively by ELISA and immunoblotting. GFAP immunoreactivity was determined for each animal separately in protein fractions obtained from the ipsilateral, lesioned cortex and the contralateral, unlesioned cortex. Changes in the GFAP content of the lesioned cortex with respect to that of the unlesioned cortex were calculated for each fraction individually. GFAP was detectable in all protein fractions with a significant amount recovered from the aqueous extracts. A pronounced increase in the GFAP content of the lesioned cortex was observed. As measured by ELISA, this increase was maximal 5 days after injury and significantly more pronounced for the soluble and the Triton X-100-soluble protein fractions (mean increase 7 days after lesion, 281.4 and 240.2%, respectively) than for the crude cytoskeletal fraction (mean increase, 153.3%). A small and transient increase in GFAP immunoreactivity was also found in all protein fractions prepared from the contralateral, unlesioned cortex. These results were confirmed by immunoblotting.     

Somatostatin receptors in the senescent rat brain: a quantitative autoradiographic study.

To examine the effects of aging on the density and distribution of somatostatin receptors (SS-R) in the rat brain, receptor autoradiography for SS-R was carried out in rats aged 3 and 24 months using 125I-labeled Tyr11-SS-14. Autoradiograms were quantitatively assessed by an image analyzer to evaluate changes in the expression of SS-R due to senescence. Statistically significant decreases in SS-R binding were found in specific regions of the brains of senescent rats as compared to young adult rats. The regions affected included the periaqueductal gray matter (73% loss versus young adult rats), the interpeduncular nucleus (73% loss), the pontine nucleus (63% loss), the superior colliculus (46% loss), the ventral tegmental area (46% loss), the temporal cortex (39% loss), the frontal cortex (34% loss), the hippocampus (33% loss), the amygdala (27% loss) and the claustrum (26% loss). There was no significant change in SS-R expression in the spinal cord with aging. Significant reductions in SS-R binding in these brain regions may be involved in the impairment of sensory and cognitive function that can occur with aging.     

Effect of Unilateral Perinatal Hypoxic-Ischemic Brain Injury in the Rat on Dopamine D1 and D2 Receptors and Uptake Sites: A Quantitative Autoradiographic Study

The effect of a unilateral perinatal hypoxic-ischemic brain injury on dopamine D1 and D2 receptors and uptake sites was investigated in rats by using in vitro quantitative binding autoradiography, 2-3 weeks after the insult. We observed significant decreases in the Bmax and KD for [3H]SCH 23390-labeled D1 and in the Bmax for [3H]spiperone-labeled D2 receptors in the lesioned caudate-putamen in rats with moderate brain injury (visible loss in hemispheric volume ipsilateral to the injury) compared with the nonlesioned contralateral caudate-putamen or with control rats. Changes in [3H]SCH 23390 and [3H]spiperone binding predominated in the dorsolateral part of the lesioned caudate-putamen. Pronounced reduction in [3H]SCH 23390 binding was also observed in the substantia nigra pars reticulata on the side of the lesion. In contrast, we did not observe any significant change in Bmax or KD for [3H]mazindol-labeled dopamine uptake sites. Similarly, no significant changes in the levels of dopamine or its metabolites were found on the side of the lesion. The observed reductions in striatal dopamine D1 and D2 receptors are a reflection of striatal cell loss induced by the hypoxic-ischemic injury. The absence of changes in [3H]mazindol binding or dopamine levels in the lesioned caudate-putamen indicates that the dopaminergic presynaptic structures are preserved.     

MEP Latencies Predict the Neuromodulatory Effect of cTBS Delivered to the Ipsilateral and Contralateral Sensorimotor Cortex

Background

Recently, it was shown that the highly variable after-effect of continuous theta-burst stimulation (cTBS) of the primary motor cortex (M1) can be predicted by the latency of motor-evoked potentials (MEPs) recorded before cTBS. This suggests that at least part of this inter-individual variability is driven by differences in the neuronal populations preferentially activated by transcranial magnetic stimulation (TMS).

Methods

Here, we recorded MEPs, TMS-evoked brain potentials (TEPs) and somatosensory-evoked potentials (SEPs) to investigate the effects of cTBS delivered over the primary sensorimotor cortex on both the ipsilateral and contralateral M1, and the ipsilateral and contralateral primary somatosensory cortex (S1).

Results

We confirm that the after-effects of cTBS can be predicted by the latency of MEPs recorded before cTBS. Over the hemisphere onto which cTBS was delivered, short-latency MEPs at baseline were associated with an increase of MEP magnitude (i.e. an excitatory effect of cTBS) whereas late-latency MEPs were associated with reduced MEPs (i.e. an inhibitory effect of cTBS). This relationship was reversed over the contralateral hemisphere, indicating opposite effects of cTBS on the responsiveness of the ipsilateral and contralateral M1. Baseline MEP latencies also predicted changes in the magnitude of the N100 wave of TEPs elicited by stimulation of the ipsilateral and contralateral hemisphere, indicating that this TEP component is specifically dependent on the state of M1. Finally, there was a reverse relationship between MEP latency and the effects of cTBS on the SEP waveforms (50–130 ms), indicating that after-effects of cTBS on S1 are opposite to those on M1.

Conclusion

Taken together, our results confirm that the variable after-effects of cTBS can be explained by differences in the neuronal populations activated by TMS. Furthermore, our results show that this variability also determines remote effects of cTBS in S1 and the contralateral hemisphere, compatible with inter-hemispheric and sensorimotor interactions.