Parieto-motor functional connectivity is impaired in Parkinson's disease

BackgroundBradykinesia in Parkinson's disease is associated with a difficulty in selecting and executing motor actions, likely due to alterations in the functional connectivity of cortico-cortical circuits.Objective/HypothesisOur aims were to analyse the functional interplay between the posterior parietal cortex and the ipsilateral primary motor area in Parkinson's disease using bifocal transcranial magnetic stimulation, to evaluate its modulation by dopaminergic treatment and its relationship to a simple choice reaction task.MethodsWe studied 12 Parkinson's disease patients with and without dopaminergic treatment and 12 healthy controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right posterior parietal cortex and the right primary motor area using different conditioning stimulus intensities and interstimulus intervals. Reaction and movement times were studied by a simple choice reaction task.ResultsIn controls, we observed a significant facilitation of motor evoked potential amplitudes at 4 ms interstimulus interval when conditioning stimulus intensity was set to 90% of resting motor threshold. This functional interaction was not observed in Parkinson's disease patients without dopaminergic treatment and was not restored with treatment. Moreover, correlation analyses revealed that Parkinson's disease patients with less impaired parieto-motor interaction were faster in executing reaching movements in a choice reaction time task, suggesting that the functional parieto-motor impairment described here could be related to bradykinesia observed in Parkinson's disease patients.ConclusionsParieto-motor functional connectivity is impaired in Parkinson's disease. The reduced efficacy of this connection could be related to presence of bradykinesia previously observed in Parkinson's disease.     

Changes in excitability of motor cortical circuitry in patients with parkinson's disease

Using the technique of transcranial magnetic stimulation over the motor areas of cortex and recording electromyographic (EMG) responses from the first dorsal interosseous muscle, we measured the excitability of corticocortical inhibitory circuits at rest using a double pulse paradigm, in 11 patients with Parkinson's disease (PD) studied both on (ON) and off (OFF) (after overnight withdrawal) their normal medication and in 10 age-matched control subjects. There was a significant decrease in the amount of corticocortical inhibition at short (1–5 msec) interstimulus intervals in patients relative to their controls, which improved after L -dopa intake. For comparison with previous reports using transcranial magnetic stimulation we also measured the duration of the EMG silent period when stimuli were given to voluntarily active muscle, and the threshold for evoking an EMG response in both the active and relaxed states. There was no change in the threshold for evoking EMG responses whether muscles were active or relaxed. However, the silent period was significantly prolonged when ON compared with OFF, although in neither state was the duration significantly different from that seen in normals. We suggest that there may be abnormalities of motor cortical inhibitory mechanisms in patients with Parkinson's disease that are not readily detected using threshold or silent period measurements alone.     

Homeostatic metaplasticity in the human somatosensory cortex

Long-term potentiation (LTP) and long-term depression (LTD) are regulated by homeostatic control mechanisms to maintain synaptic strength in a physiological range. Although homeostatic metaplasticity has been demonstrated in the human motor cortex, little is known to which extent it operates in other cortical areas and how it links to behavior. Here we tested homeostatic interactions between two stimulation protocols -- paired associative stimulation (PAS) followed by peripheral high-frequency stimulation (pHFS) -- on excitability in the human somatosensory cortex and tactile spatial discrimination threshold. PAS employed repeated pairs of electrical stimulation of the right median nerve followed by focal transcranial magnetic stimulation of the left somatosensory cortex at an interstimulus interval of the individual N20 latency minus 15 msec or N20 minus 2.5 msec to induce LTD- or LTP-like plasticity, respectively [Wolters, A., Schmidt, A., Schramm, A., Zeller, D., Naumann, M., Kunesch, E., et al. Timing-dependent plasticity in human primary somatosensory cortex. Journal of Physiology, 565, 1039-1052, 2005]. pHFS always consisted of 20-Hz trains of electrical stimulation of the right median nerve. Excitability in the somatosensory cortex was assessed by median nerve somatosensory evoked cortical potential amplitudes. Tactile spatial discrimination was tested by the grating orientation task. PAS had no significant effect on excitability in the somatosensory cortex or on tactile discrimination. However, the direction of effects induced by subsequent pHFS varied with the preconditioning PAS protocol: After PAS(N20-15), excitability tended to increase and tactile spatial discrimination threshold decreased. After PAS(N20-2.5), excitability decreased and discrimination threshold tended to increase. These interactions demonstrate that homeostatic metaplasticity operates in the human somatosensory cortex, controlling both cortical excitability and somatosensory skill.     

Reward processing abnormalities in Parkinson's disease

The primary motor cortex is important for motor learning and response selection, functions that require information on the expected and actual outcomes of behavior. Therefore, it should receive signals related to reward. Pathways from reward centers to motor cortex exist in primates. Previously, we showed that gamma aminobutyric acid–A–mediated inhibition in the motor cortex, measured by paired transcranial magnetic stimulation, changes with expectation and uncertainty of money rewards generated by a slot machine simulation. We examined the role of dopamine in this phenomenon by testing 13 mildly affected patients with Parkinson's disease, off and on dopaminergic medications, and 13 healthy, age‐matched controls. Consistent with a dopaminergic mechanism, reward expectation or predictability modulated the response to paired transcranial magnetic stimulation in controls, but not in unmedicated patients. A single dose of pramipexole restored this effect of reward, mainly by increasing the paired transcranial magnetic stimulation response amplitude during low expectation. Levodopa produced no such effect. Both pramipexole and levodopa increased risk‐taking behavior on the Iowa Gambling Task. However, pramipexole increased risk‐taking behavior more in patients showing lower paired transcranial magnetic stimulation response amplitude during low expectation. These results provide evidence that modulation of motor cortex inhibition by reward is mediated by dopamine signaling and that the physiological state of the motor cortex changes with risk‐taking tendency in patients on pramipexole. The cortical response to reward expectation may represent an endophenotype for risk‐taking behavior in patients on agonist treatment. © 2011 Movement Disorder Society     

Crossed inhibition of sensory cortex by 0.3 Hz transcranial magnetic stimulation of motor cortex.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of motor cortex causes persistent inhibitory effects in the targeted area. rTMS of motor cortex impairs sensory perception and results in a persistent change in cortical function at remote sites. The ability of rTMS to induce sustained changes in cortical function has led to studies testing its therapeutic efficacy in neurologic disorders, including epilepsy. Studies on the effect of low-frequency rTMS of motor cortex on the contralateral motor cortex have provided evidence for both inhibitory and excitatory changes. This study was designed to determine the effect of low-frequency rTMS of the right motor cortex on the contralateral sensory cortex. Before and after 0.3-Hz rTMS of right motor cortex, perception of ipsilateral threshold of cutaneous stimuli was assessed and somatosensory evoked potentials (SEPs) recorded after stimulation of the right thumb in eight normal subjects. In a control group of six subjects, sensory responses were assessed after rTMS anterior to the right motor cortex. After rTMS of motor cortex, detection of threshold sensory stimuli decreased by more than 50% compared with pre-rTMS (P < 0.05). The change in sensory perception lasted at least 30 minutes. No change was detected in the control group. Amplitude of the N20-P25 waveform of the SEP decreased from a mean of 0.84 muV before rTMS to 0.54 muV immediately after rTMS of motor cortex (P < 0.05). 0.3 Hz rTMS of motor cortex inhibits the contralateral sensory cortex.     

Motor cortex plasticity can indicate vulnerability to motor fluctuation and high L-DOPA need in drug-naïve Parkinson's disease

IntroductionMotor cortex plasticity is reported to be decreased in Parkinson's disease in studies which pooled patients in various stages of the disease. Whether the early decrease in plasticity is related to the motor signs or is linked to the future development of motor complications of treatment is unclear. The aim of the study was to test if motor cortex plasticity and its cerebellar modulation are impaired in treatment-naïve Parkinson's disease, are related to the motor signs of the disease and predict occurrence of motor complications of treatment.MethodsTwenty-nine denovo patients with Parkinson's disease were longitudinally assessed for motor complications for four years. Using transcranial magnetic stimulation, the plasticity of the motor cortex and its cerebellar modulation were measured (response to paired-associative stimulation alone or preceded by 2 active cerebellar stimulation protocols), both in the untreated state and after a single dose of L-DOPA. Twenty-six matched, healthy volunteers were tested, only without L-DOPA.ResultsPatients and healthy controls had similar proportions of responders and non-responders to plasticity induction. In the untreated state, the more efficient was the cerebellar modulation of motor cortex plasticity, the lower were the bradykinesia and rigidity scores. The extent of the individual plastic response to paired associative stimulation could indicate a vulnerability to develop early motor fluctuation but not dyskinesia.ConclusionsMeasuring motor cortex plasticity in denovo Parkinson's disease could be a neurophysiological parameter that may help identify patients with greater propensity for early motor fluctuations.     

High-frequency repetitive transcranial magnetic stimulation over the primary motor cortex relieves musculoskeletal pain in patients with Parkinson's disease: A randomized controlled trial

BackgroundPain is common in Parkinson's disease, and there is no effective treatment. We conducted a clinical trial to determine whether high-frequency repetitive transcranial magnetic stimulation over the primary motor cortex alleviates musculoskeletal pain in patients with Parkinson's disease.MethodsIn this single-center and double-blind trial, 52 patients with Parkinson's disease and musculoskeletal pain were randomly allocated to 26-member groups receiving 5 sessions of either 20-Hz repetitive transcranial magnetic stimulation or sham stimulation over the primary motor cortex. The participants underwent assessments in the “ON” medication state at baseline, after the fifth session, and at 2- and 4-week follow-up timepoints. The primary outcomes were pain scores on a numeric rating scale. The secondary outcomes were scores on clinical scales assessing motor symptoms, depression, anxiety, autonomic symptoms, sleep quality, and the overall severity of Parkinson's disease.ResultsAnalyses revealed significant group × time interactions for numeric rating scale pain scores (p < 0.001), motor symptom scores (p < 0.001), depression scores (p = 0.009), anxiety scores (p = 0.013), and overall disease severity scores (p < 0.001). Post hoc analyses confirmed that the repetitive transcranial magnetic stimulation group, but not the sham stimulation group, exhibited significant improvements in numeric rating scale pain scores, motor symptom scores, depression scores, anxiety scores, and overall disease severity scores.ConclusionHigh-frequency repetitive transcranial magnetic stimulation over the primary motor cortex may be an effective adjunct therapy for alleviating musculoskeletal pain in patients with Parkinson's disease.     

Suppression of cutaneous perception by magnetic pulse stimulation of the human brain.

We have demonstrated that magnetic pulse stimulation of the sensorimotor cortex suppresses perception of threshold electrical stimuli to the fingers of the contralateral hand. Maximum suppression of perception occurs when the fingers are stimulated 30-90 msec after the magnetic pulse. Thereafter, errors in perception of the cutaneous stimulus decrease to control levels by 300-400 msec after the magnetic pulse. The period of maximum suppression of perception coincides with the period during which cortically generated somatosensory evoked potentials (SEPs) are enhanced following magnetic pulse stimulation of the brain. The duration of suppression of perception, however, outlasts the duration of SEP enhancement. When the magnetic pulse is delivered after finger stimulation there is also suppression of perception. The suppression of perception is maximal when the magnetic pulse occurs 20-30 msec after finger stimulation. This interval coincides with the arrival of the afferent volley at the primary sensory cortex.     

Motor cortical plasticity is impaired in Unverricht–Lundborg disease

Patients with Unverricht–Lundborg disease, also referred to as progressive myoclonus epilepsy type 1, exhibit widespread motor symptoms and signs in addition to epileptic seizures, which suggest abnormal excitability of the primary motor pathways. To explore the plasticity of the sensory–motor cortex, we employed a modern neurophysiological method, the paired associative stimulation protocol, which resembles the concept of long‐term potentiation of experimental studies. Seven patients with genetically verified Unverricht–Lundborg disease and 13 healthy control subjects were enrolled in the study to characterize cortical sensory–motor plasticity. In the study protocol, peripheral electric median nerve stimulation preceded navigated transcranial magnetic stimulation targeted to the representation area of thenar musculature on the contralateral primary motor cortex. The protocol consisted of 132 transcranial magnetic stimulation trials at 0.2 Hz, preceded by peripheral sensory stimulation at 25 ms. Motor‐evoked potential amplitudes were analyzed at baseline and after the paired associative stimulation protocol at an intensity of 130% of the individual motor threshold. The patients with Unverricht–Lundborg disease exhibited an average decrease of 15% in motor‐evoked potential amplitudes 30 minutes after paired associative stimulation, whereas in the control subjects, a significant increase (101%) was observed (P < .05), as expected. The results indicate a lack of normal cortical plasticity in Unverricht–Lundborg disease, which stresses the role of abnormal motor cortical functions or sensorimotor integration as possible pathophysiological contributors to the motor symptoms. The impaired cortical plasticity may be associated with the previously reported structural and physiological abnormalities of the primary motor cortex. © 2011 Movement Disorder Society     

Effects of low frequency and low intensity repetitive paired pulse stimulation of the primary motor cortex.

OBJECTIVE: Following a previous report [Bestmann et al. Clin Neurophysiol 2004;115:755-64] that pairs of subthreshold pulses of transcranial magnetic stimulation (TMS) can show temporal summation, we explored whether repeated application of pairs of stimulation could produce long-lasting after effects on the excitability of the human motor cortex. METHODS: Twelve healthy subjects received 25 min repetitive paired pulse magnetic stimulation (paired rTMS) given at a frequency of about 0.6 Hz over the left primary motor cortex (500 paired stimuli in total). The interval between the paired stimuli was 3 ms and the intensity of both stimuli was 80% of active motor threshold. The resting and active motor threshold, MEP recruitment curve, short interval intracortical inhibition (SICI) and facilitation, and the duration of the cortical silent period (SP) were tested for the right first interosseous muscle (FDI) before and two times after the end of 25 min paired rTMS. RESULTS: Prolonged subthreshold paired rTMS produced a significant decrease in excitability in the corticospinal projection to FDI: resting motor threshold was significantly increased and MEP recruitment was significantly decreased, SICI was significantly increased at 2 and 4 ms and the SP was significantly increased in duration. CONCLUSIONS: Prolonged low frequency paired rTMS at subthreshold intensity can modulate cortical excitability by producing inhibitory effects that outlast the period of stimulation.     

Somatosensory evoked potential recovery in kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (kii AlS/PDC).

OBJECTIVE: To evaluate the recovery function of the sensory cortex in patients with Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (Kii ALS/PDC) using somatosensory evoked potentials (SEPs) elicited by paired stimuli of the median nerve at the wrist. METHODS: Five patients with Kii ALS/PDC were compared with 5 patients with classical ALS, 5 with Parkinson's disease (PD), and 7 healthy normal volunteers. SEPs were recorded from the hand sensory area contralateral to the side of stimulation. Recovery functions of N20-P25 and P25-N33 components were evaluated by comparing the second SEPs elicited by paired pulse stimuli at various interstimulus intervals (ISIs, 20-300 ms) with the SEPs elicited by single stimuli. RESULTS: Conventional SEPs to a single stimulus had a normal latency and size in all patients. The recovery function of the N20-P25 and P25-N33 components showed significantly less suppression at short ISIs without any facilitation at long ISIs in Kii ALS/PDC patients than in normal subjects, classical ALS or PD patients. CONCLUSIONS: In Kii ALS/PDC, the sensory cortex is disinhibited or hyperexcitable. These abnormalities may reflect cortical pathology in the sensory cortex and may be partly due to a secondary effect on the sensory cortex from the primary parkinsonian pathological changes.     

Somatotopy and temporal dynamics of sensorimotor interactions: evidence from double afferent inhibition

Moving and interacting with the world requires that the sensory and motor systems share information, but while some information about tactile events is preserved during sensorimotor transfer the spatial specificity of this information is unknown. Afferent inhibition (AI) studies, in which corticospinal excitability (CSE) is inhibited when a single tactile stimulus is presented before a transcranial magnetic stimulation pulse over the motor cortex, offer contradictory results regarding the sensory‐to‐motor transfer of spatial information. Here, we combined the techniques of AI and tactile repetition suppression (the decreased neurophysiological response following double stimulation of the same vs. different fingers) to investigate whether topographic information is preserved in the sensory‐to‐motor transfer in humans. We developed a double AI paradigm to examine both spatial (same vs. different finger) and temporal (short vs. long delay) aspects of sensorimotor interactions. Two consecutive electrocutaneous stimuli (separated by either 30 or 125 ms) were delivered to either the same or different fingers on the left hand (i.e. index finger stimulated twice or middle finger stimulated before index finger). Information about which fingers were stimulated was reflected in the size of the motor responses in a time‐constrained manner: CSE was modulated differently by same and different finger stimulation only when the two stimuli were separated by the short delay (P = 0.004). We demonstrate that the well‐known response of the somatosensory cortices following repetitive stimulation is mirrored in the motor cortex and that CSE is modulated as a function of the temporal and spatial relationship between afferent stimuli.     

Specific forms of neural activity associated with tactile space awareness

Left tactile extinction, in which a left tactile stimulus fails to access consciousness only when a right stimulus is presented simultaneously, offers a model for studying tactile awareness from its transitory absence. Pairs of transcranial magnetic stimuli (TMS) on the parietal cortex inhibit contralateral tactile perception when separated by an interval of 1 ms. We have applied this technique on the left parietal cortex of right brain damaged (RBD) patients and normal subjects and have shown a selective lack of paired TMS inhibitory effects on right tactile perception of patients during bimanual stimulation. TMS effects were normal during unimanual right stimulation. These results suggest the presence of a specific pattern of inhibitory/excitatory interactions in parietal brain areas as critical for tactile awareness.     

Direct current stimulation over the human sensorimotor cortex modulates the brain's hemodynamic response to tactile stimulation

Tactile stimuli produce afferent signals that activate specific regions of the cerebral cortex. Noninvasive transcranial direct current stimulation (tDCS) effectively modulates cortical excitability. We therefore hypothesised that a single session of tDCS targeting the sensory cortices would alter the cortical response to tactile stimuli. This hypothesis was tested with a block‐design functional magnetic resonance imaging protocol designed to quantify the blood oxygen level‐dependent response to controlled sinusoidal pressure stimulation applied to the right foot sole, as compared with rest, in 16 healthy young adults. Following sham tDCS, right foot sole stimulation was associated with activation bilaterally within the precentral cortex, postcentral cortex, middle and superior frontal gyri, temporal lobe (subgyral) and cingulate gyrus. Activation was also observed in the left insula, middle temporal lobe, superior parietal lobule, supramarginal gyrus and thalamus, as well as the right inferior parietal lobule and claustrum (false discovery rate corrected, P < 0.05). To explore the regional effects of tDCS, brain regions related to somatosensory processing, and cortical areas underneath each tDCS electrode, were chosen as regions of interest. Real tDCS, as compared with sham tDCS, increased the percent signal change associated with foot stimulation relative to rest in the left posterior paracentral lobule. These results indicate that tDCS acutely modulated the cortical responsiveness to controlled foot pressure stimuli in healthy adults. Further study is warranted, in both healthy individuals and patients with sensory impairments, to link tDCS‐induced modulation of the cortical response to tactile stimuli with changes in somatosensory perception.     

Study of Cerebello-Thalamocortical Pathway by Transcranial Magnetic Stimulation in Parkinson's Disease

BackgroundAlthough functional changes in the activation of the cerebellum in Parkinson's disease (PD) patients have been consistently described, it is still debated whether such altered cerebellar activation is a natural consequence of PD pathophysiology or rather it involves compensatory mechanisms.Objective/HypothesisWe used different forms of cerebellar transcranial magnetic stimulation to evaluate the hypothesis that altered cerebello-cortical interactions can be observed in PD patients and to evaluate the role of dopaminergic treatment.MethodsWe studied the effects of a single cerebellar magnetic pulse over the excitability of the contralateral primary motor cortex tested with motor-evoked potentials (MEPs) (cerebellar-brain inhibition—CBI) in a group of 16 PD patients with (ON) and without dopaminergic treatment (OFF), and in 16 age-matched healthy controls. Moreover, we also tested the effects of cerebellar continuous theta-burst stimulation (cTBS) on MEP amplitude, short intracortical inhibition (SICI) and short intracortical facilitation (SICF) tested in the contralateral M1 in 13 PD patients in ON and OFF and in 16 age-matched healthy controls.ResultsCBI was evident in controls but not in PD patients, even when tested in both ON and OFF conditions. Similarly, cerebellar cTBS reduced MEP amplitude and SICI in controls but not in PD patients under any condition.Conclusion(s)These results demonstrate that PD patients have deficient short-latency and long-lasting cerebellar-thalamocortical inhibitory interactions that cannot be promptly restored by standard dopaminergic medication.     

A transcranial magnetic stimulation study of inhibitory deficits in the motor cortex in patients with schizophrenia

It has been proposed that inhibitory deficits play a crucial role in the pathophysiological process of schizophrenia as suggested by post-mortem, neuropsychological and neurophysiological evidence. We hypothesised that patients with schizophrenia would demonstrate abnormalities of cortical inhibition in the motor cortex with single and paired pulse transcranial magnetic stimulation (TMS). Patients with DSM-IV schizophrenia (n=22) and normal volunteers (n=21) participated in the study. Electromyographic recordings from the abductor pollicis brevis (APB) muscle were made during focal TMS stimulation to the contra-lateral motor cortex. The threshold intensity to produce a motor response, the size of the motor evoked potential, the duration of the silent period, and the cortical inhibition and facilitation to paired pulse TMS were measured. The patient group demonstrated a reduction in length of the silent period and a reduction in cortical inhibition with paired stimuli. No changes were found in motor threshold, motor evoked potential size, or cortical facilitation. The study demonstrated deficits of cortical inhibition in the motor cortex of patients with schizophrenia. These deficits appear to be of cortical origin. Their relationship to dysfunction in other cortical networks requires further elucidation.     

A motor cortex excitability and gait analysis on Parkinsonian patients

Transcranial magnetic stimulation (TMS) parameters were recorded in a lower limb muscle and correlated with the gait parameters of 25 patients with Parkinson's disease (PD) with and without dopamine substitution treatment (DST) and 10 control subjects. Single and paired‐pulse TMS were recorded in the tibialis anterior muscle (TA). Gait analysis was performed using a 3D motion analysis system. Parkinsonian patients (PP) did not differ from the control subjects (CS) in terms of relaxed motor threshold, active motor threshold (AMT), cortical silent period (CSP), motor‐evoked potential (MEP) amplitude and area, or paired‐pulse TMS with short interstimulus intervals (ISI). At longer ISIs, paired‐pulse TMS showed that the amplitudes of the conditioned MEPs were lower in untreated PP than in CS. DST partially compensated for this difference. Gait analysis showed that the gait of PP undergoing no treatment was slower and the stride length shorter than normal. Both of these parameters improved under DST, however. Analysis of data obtained on all the subjects combined showed that both of the latter parameters were correlated with the paired‐pulse MEP amplitude and area at longer ISIs. In PP, the cortical areas responsible for the lower limb movements seem to undergo intracortical facilitation (ICF) impairments, whereas the intracortical inhibition process is normal. The ICF level was found to be associated to the stride length and the velocity. The fact that only these two gait parameters were found to be dopa responsive indicates that dopaminergic treatment may improve gait disorders by restoring the ICF. © 2010 Movement Disorder Society     

High‐frequency rTMS over the supplementary motor area for treatment of Parkinson's disease

Dysfunction of the basal ganglia‐thalamocortical motor circuit is a fundamental model to account for motor symptoms in Parkinson's disease (PD). Using high‐frequency repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA), we investigated whether modulation of SMA excitability engenders therapeutic effects on motor symptoms in PD. In this double‐blind placebo‐controlled study, 99 patients were enrolled and assigned randomly to SMA‐stimulation and sham‐stimulation groups. For SMA stimulation, 20 trains of 50 transcranial magnetic stimuli at 5 Hz were delivered at an intensity of 110% active motor threshold for leg muscles in one session. The sham stimulation was 20 trains of electric stimuli given through electrodes fixed on the head to mimic the cutaneous sensation during rTMS. Each session of intervention was carried out once a week for the first 8 weeks. The SMA stimulation, in contrast to the sham stimulation, engendered significant improvements in total scores and motor scores of the Unified Parkinson's Disease Rating Scale. Mean improvements in motor scores were 4.5 points in the SMA‐stimulation group and ?0.1 points in the sham‐stimulation group. Results indicate that 5 Hz rTMS over SMA modestly improves motor symptoms in PD patients; SMA is a potential stimulation site for PD treatment. © 2008 Movement Disorder Society     

Targeted-Plasticity in the Corticospinal Tract After Human Spinal Cord Injury

Spinal cord injury (SCI) often results in impaired or absent sensorimotor function below the level of the lesion. Recent electrophysiological studies in humans with chronic incomplete SCI demonstrate that voluntary motor output can be to some extent potentiated by noninvasive stimulation that targets the corticospinal tract. We discuss emerging approaches that use transcranial magnetic stimulation (TMS) over the primary motor cortex and electrical stimulation over a peripheral nerve as tools to induce plasticity in residual corticospinal projections. A single TMS pulse over the primary motor cortex has been paired with peripheral nerve electrical stimulation at precise interstimulus intervals to reinforce corticospinal synaptic transmission using principles of spike-timing dependent plasticity. Pairs of TMS pulses have also been used at interstimulus intervals that mimic the periodicity of descending indirect (I) waves volleys in the corticospinal tract. This data, along with information about the extent of the injury, provides a new framework for exploring the contribution of the corticospinal tract to recovery of function following SCI.     

Cooperative processing in primary somatosensory cortex and posterior parietal cortex during tactile working memory

In the present study, causal roles of both the primary somatosensory cortex (SI) and the posterior parietal cortex (PPC) were investigated in a tactile unimodal working memory (WM) task. Individual magnetic resonance imaging‐based single‐pulse transcranial magnetic stimulation (spTMS) was applied, respectively, to the left SI (ipsilateral to tactile stimuli), right SI (contralateral to tactile stimuli) and right PPC (contralateral to tactile stimuli), while human participants were performing a tactile‐tactile unimodal delayed matching‐to‐sample task. The time points of spTMS were 300, 600 and 900 ms after the onset of the tactile sample stimulus (duration: 200 ms). Compared with ipsilateral SI, application of spTMS over either contralateral SI or contralateral PPC at those time points significantly impaired the accuracy of task performance. Meanwhile, the deterioration in accuracy did not vary with the stimulating time points. Together, these results indicate that the tactile information is processed cooperatively by SI and PPC in the same hemisphere, starting from the early delay of the tactile unimodal WM task. This pattern of processing of tactile information is different from the pattern in tactile‐visual cross‐modal WM. In a tactile‐visual cross‐modal WM task, SI and PPC contribute to the processing sequentially, suggesting a process of sensory information transfer during the early delay between modalities.