Transcallosal Inhibition Research Articles

Lateralization of brain activity pattern during unilateral movement in Parkinson's disease.

We investigated the lateralization of brain activity pattern during performance of unilateral movement in drug-naïve Parkinson's disease (PD) patients with only right hemiparkinsonian symptoms. Functional MRI was obtained when the subjects performed strictly unilateral right hand movement. A laterality index was calculated to examine the lateralization. Patients had decreased activity in the left putamen and left supplementary motor area, but had increased activity in the right primary motor cortex, right premotor cortex, left postcentral gyrus, and bilateral cerebellum. The laterality index was significantly decreased in PD patients compared with controls (0.41 ± 0.14 vs. 0.84 ± 0.09). The connectivity from the left putamen to cortical motor regions and cerebellum was decreased, while the interactions between the cortical motor regions, cerebellum, and right putamen were increased. Our study demonstrates that in early PD, the lateralization of brain activity during unilateral movement is significantly reduced. The dysfunction of the striatum-cortical circuit, decreased transcallosal inhibition, and compensatory efforts from cortical motor regions, cerebellum, and the less affected striatum are likely reasons contributing to the reduced motor lateralization. The disruption of the lateralized brain activity pattern might be a reason underlying some motor deficits in PD, like mirror movements or impaired bilateral motor coordination.

A possible relationship between Takotsubo cardiomyopathy and female sex steroid-related modulation of functional cerebral asymmetry

Takotsubo cardiomyopathy (Tc) is a transient left ventricular apical ballooning syndrome, with symptoms and signs of acute myocardial infarction. Tc syndrome, which occurs predominantly in postmenopausal women, is characterized by increase of sympathetic activity.Studies on the gender-specific differences in sympatho-vagal regulation and functional cerebral asymmetry (FCA) imply that female pattern of dominance is characterized by the left hemisphere, which is believed to have parasympathetic predominance, whereas male pattern indicates dominance of the right hemisphere, which is believed to have sympathetic predominance. Fluctuating levels of female sex steroids are supposed to change FCA, modulating transcallosal inter-hemispheric inhibition across the menstrual cycle. The findings suggest that FCA is enhanced during the low steroid phase (menstrual phase), whereas, during high estrogen and/or progesterone phases (follicular and luteal phase) FCA is reduced. This theory is in line with concept of decreased magnitude of inter-hemispheric cortical lateralization in premenopausal women compared to men and postmenopausal women.Therefore, if postmenopausal women are more lateralized for a variety of cerebral functions, they have less balanced equilibrium between the right-sided sympathetic and left-sided parasympathetic predominance. Decrease of endogenous female sex steroid levels in postmenopausal women leads to reduced influence of estrogens to the left hemisphere, which is believed to have parasympathetic predominance. If both of these mechanisms result in sympatho-vagal imbalance, increasing sympathetic system activity in postmenopausal women, it seems reasonable why postmenopausal women became more susceptible to sympathetically-mediated syndromes such as Takotsubo cardiomyopathy.

Diffusion imaging and transcranial magnetic stimulation assessment of transcallosal pathways in chronic stroke

ObjectiveTo examine the relationship of transcallosal pathway microstructure and transcallosal inhibition (TCI) with motor function and impairment in chronic stroke. MethodsDiffusion-weighted magnetic resonance imaging and transcranial magnetic stimulation (TMS) data were collected from 24 participants with chronic stroke and 11 healthy older individuals. Post-stroke motor function (Wolf Motor Function Test) and level of motor impairment (Fugl-Meyer score) were evaluated. ResultsFractional anisotropy (FA) of transcallosal tracts between prefrontal cortices and the mean amplitude decrease in muscle activity during the ipsilateral silent period evoked by TMS over the non-lesioned hemisphere (termed NL-iSPmean) were significantly associated with level of motor impairment and motor function after stroke (p<0.05). A regression model including age, post-stroke duration, lesion volume, lesioned corticospinal tract FA, transcallosal prefrontal tract FA and NL-iSPmean accounted for 84% of variance in motor impairment (p<0.01). Both transcallosal prefrontal tract FA (ΔR2=0.12, p=0.04) and NL-iSPmean (ΔR2=0.09, p=0.04) accounted for unique variance in motor impairment level. ConclusionsPrefrontal transcallosal tract microstructure and TCI are each uniquely associated with motor impairment in chronic stroke. SignificanceUtilizing a multi-modal approach to assess transcallosal pathways may improve our capacity to identify important neural substrates of motor impairment in the chronic phase of stroke.

Evaluation of differences in brain neurophysiology and morphometry associated with hand function in individuals with chronic stroke.

Rehabilitation interventions need to be optimized to maximize therapeutic effects and minimize stroke-related disability. However, a comprehensive understanding of the neural substrates underlying recovery is lacking. The purpose of this study was to investigate relationships between brain anatomy, physiology and hand motor function in individuals with chronic stroke. Transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) approaches were used to evaluate cortical excitability and brain structural morphometry in individuals with chronic stroke. Hemispheric differences and relationships between these measures and hand dexterity were evaluated. Hemispheric differences were observed for TMS and MRI measures. Bilateral hand dexterity correlated with TMS resting motor threshold and precentral gyral thickness. Transcallosal inhibition across hemispheres was positively associated with midcallosal white matter volume. Regression modeling results demonstrated that combining TMS and MRI measures predicted unique amounts of variance in hand dexterity. RESULTS confirm and extend findings showing differences in brain structure and function after stroke. RESULTS suggested a structure-function relationship underlying interhemispheric connectivity in chronic stroke. The utility of combined TMS and MRI measures to predict motor function can be used in future investigations to aid identifying optimal biomarkers of stroke recovery to predict response to rehabilitation to maximize treatment outcomes.

Assessment of Inter-Hemispheric Imbalance Using Imaging and Noninvasive Brain Stimulation in Patients With Chronic Stroke

ObjectiveTo determine how interhemispheric balance in stroke, measured using transcranial magnetic stimulation (TMS), relates to balance defined using neuroimaging (functional magnetic resonance [fMRI], diffusion-tensor imaging [DTI]) and how these metrics of balance are associated with clinical measures of upper-limb function and disability. DesignCross sectional. SettingLaboratory. ParticipantsPatients with chronic stroke (N=10; age, 63±9y) in a population-based sample with unilateral upper-limb paresis. InterventionsNot applicable. Main Outcome MeasuresInterhemispheric balance was measured with TMS, fMRI, and DTI. TMS defined interhemispheric differences in the recruitment of corticospinal output, size of the corticomotor output maps, and degree of mutual transcallosal inhibition that they exerted on one another. fMRI studied whether cortical activation during the movement of the paretic hand was lateralized to the ipsilesional or to the contralesional primary motor cortex (M1), premotor cortex (PMC), and supplementary motor cortex (SMA). DTI was used to define interhemispheric differences in the integrity of the corticospinal tracts projecting from the M1. Clinical outcomes tested function (upper extremity Fugl-Meyer [UEFM]) and perceived disability in the use of the paretic hand (Motor Activity Log [MAL] amount score). ResultsInterhemispheric balance assessed with TMS relates differently to fMRI and DTI. Patients with high fMRI lateralization to the ipsilesional hemisphere possessed stronger ipsilesional corticomotor output maps (M1: r=.831, P=.006; PMC: r=.797, P=.01) and better balance of mutual transcallosal inhibition (r=.810, P=.015). Conversely, we found that patients with less integrity of the corticospinal tracts in the ipsilesional hemisphere show greater corticospinal output of homologous tracts in the contralesional hemisphere (r=.850, P=.004). However, an imbalance in integrity and output do not relate to transcallosal inhibition. Clinically, although patients with less integrity of corticospinal tracts from the ipsilesional hemisphere showed worse impairments (UEFM) (r=–.768, P=.016), those with low fMRI lateralization to the ipsilesional hemisphere had greater perception of disability (MAL amount score) (M1: r=.883, P=.006; PMC: r=.817, P=.007; SMA: r=.633, P=.062). ConclusionsIn patients with chronic motor deficits of the upper limb, fMRI may serve to mark perceived disability and transcallosal influence between hemispheres. DTI-based integrity of the corticospinal tracts, however, may be useful in categorizing the range of functional impairments of the upper limb. Further, in patients with extensive corticospinal damage, DTI may help infer the role of the contralesional hemisphere in recovery.

Altered cortical excitability in anorexia nervosa

Recent EEG and positron emission tomography (PET) studies have reported hyperactivation of the right hemisphere in anorexia nervosa (AN). The aim of the present study was to test this notion by examining cortical excitability in subjects with AN using transcranial magnetic stimulation (TMS). We investigated thirteen patients meeting the DSM IV diagnostic criteria for AN and 14 controls age and sex matched. Each subject was assessed clinically using the Eating Disorder Inventory (EDI), the Eating Attitude Test (EAT) and Beck's Depression Inventory (BDI-II). TMS measures involved resting and active motor thresholds (RMT, AMT) as well as motor evoked potentials (MEP), cortical silent period duration (CSP), transcallosal inhibition (TCI), and short latency intracortical inhibition (SICI) of the first dorsal interosseous muscle (FDI) were assessed. Cortical esophageal MEP latencies (CL) were also recorded. The RMT and MEP onset latency of the FDI and the esophagus as well as duration of the TCI were significantly reduced in anorexic patients compared to the control group. There were no significant differences neither in AMT nor CSP between patients and controls. Moreover, we found significant negative correlations between the EAT scores and RMT, and TCI duration. Although anorexic patients had significantly higher BDI score, there was no correlation between it and cortical excitability. Anorexic individuals are characterized by pathologically increased motor and esophageal cortical excitability that significantly correlates with clinical symptoms of anorexia nervosa.

Age-related changes in motor cortical representation and interhemispheric interactions: a transcranial magnetic stimulation study.

To better understand the physiological mechanisms responsible for the differential motor cortex functioning in aging, we used transcranial magnetic stimulation to investigate interhemispheric interactions and cortical representation of hand muscles in the early phase of physiological aging, correlating these data with participants’ motor abilities. Right-handed healthy subjects were divided into a younger group (n = 15, mean age 25.4 ± 1.9 years old) and an older group (n = 16, mean age 61.1 ± 5.1 years old). Activity of the bilateral abductor pollicis brevis (APB) and abductor digiti minimi (ADM) was recorded. Ipsilateral silent period (ISP) was measured in both APBs. Cortical maps of APB and ADM were measured bilaterally. Mirror movements (MM) were recorded during thumb abductions. Motor abilities were tested using Nine Hole Peg Test, finger tapping, and grip strength. ISP was reduced in the older group on both sides, in terms of duration (p = 0.025), onset (p = 0.029), and area (p = 0.008). Resting motor threshold did not differ between groups. APB and ADM maps were symmetrical in the younger group, but were reduced on the right compared to the left hemisphere in the older group (p = 0.008). The APB map of the right hemisphere was reduced in the older group compared to the younger (p = 0.021). Older subjects showed higher frequency of MM and worse motor abilities (p < 0.001). The reduction of right ISP area correlated significantly with the worsening of motor performances. Our results showed decreased interhemispheric interactions in the early processes of physiological aging and decreased cortical muscles representation over the non-dominant hemisphere. The decreased ISP and increased frequency of MM suggest a reduction of transcallosal inhibition. These data demonstrate that early processes of normal aging are marked by a dissociation of motor cortices, characterized, at least, by a decline of the non-dominant hemisphere, reinforcing the hypothesis of the right hemi-aging model.

Congenital Mirror Movements in a New Italian Family.

Mirror movements (MMs) occur on the contralateral side of a limb being used intentionally. Because few families with congenital MMs and no other neurological signs have been reported, the underlying mechanisms of MMs are still not entirely clear. We report on the clinical, genetic, neurophysiological and neuroimaging findings of 10 of 26 living members of a novel four-generation family with congenital MMs. DCC and RAD51 were sequenced in affected members of the family. Five of the ten subjects with MMs underwent neurophysiological and neuroimaging evaluations. The neurophysiological evaluation consisted of electromyographic (EMG) mirror recordings, investigations of corticospinal excitability, and analysis of interhemispheric inhibition using transcranial magnetic stimulation techniques. The neuroimaging evaluation included functional MRI during finger movements. Eight (all females) of the ten members examined presented MMs of varying degrees at the clinical assessment. Transmission of MMs appears to have occurred according to an autosomal-dominant fashion with variable expression. No mutation in DCC or RAD51 was identified. EMG mirror activity was higher in MM subjects than in healthy controls. Short-latency interhemispheric inhibition was reduced in MM subjects. Ipsilateral motor-evoked potentials were detectable in the most severe case. The neuroimaging evaluation did not disclose any significant abnormalities in MM subjects. The variability of the clinical features of this family, and the lack of known genetic abnormalities, suggests that MMs are heterogeneous disorders. The pathophysiological mechanisms of MMs include abnormalities of transcallosal inhibition and corticospinal decussation.

Task-induced brain activity in aphasic stroke patients: what is driving recovery?

The estimated prevalence of aphasia in the UK and the USA is 250 000 and 1 000 000, respectively. The commonest aetiology is stroke. The impairment may improve with behavioural therapy, and trials using cortical stimulation or pharmacotherapy are undergoing proof-of-principle investigation, but with mixed results. Aphasia is a heterogeneous syndrome, and the simple classifications according to the Broca-Wernicke-Lichtheim model inadequately describe the diverse communication difficulties with which patients may present. Greater knowledge of how intact neural networks promote recovery after aphasic stroke, either spontaneously or in response to interventions, will result in clearer hypotheses about how to improve the treatment of aphasia. Twenty-five years ago, a pioneering study on healthy participants heralded the introduction of functional neuroimaging to the study of mechanisms of recovery from aphasia. Over the ensuing decades, such studies have been interpreted as supporting one of three hypotheses, which are not mutually exclusive. The first two predate the introduction of functional neuroimaging: that recovery is the consequence of the reconstitution of domain-specific language systems in tissue around the lesion (the 'perilesional' hypothesis), or by homotopic cortex in the contralateral hemisphere (the 'laterality-shift' hypothesis). The third is that loss of transcallosal inhibition to contralateral homotopic cortex hinders recovery (the 'disinhibition' hypothesis). These different hypotheses at times give conflicting views about rehabilitative intervention; for example, should one attempt to activate or inhibit a contralateral homotopic region with cortical stimulation techniques to promote recovery? This review proposes that although the functional imaging data are statistically valid in most cases, their interpretation has often favoured one explanation while ignoring plausible alternatives. In our view, this is particularly evident when recovery is attributed to activity in 'language networks' occupying sites not observed in healthy participants. In this review we will argue that much of the distribution of what has often been interpreted as language-specific activity, particularly in midline and contralateral cortical regions, is an upregulation of activity in intact domain-general systems for cognitive control and attention, responding in a task-dependent manner to the increased 'effort' when damaged downstream domain-specific language networks are impaired. We further propose that it is an inability fully to activate these systems that may result in sub optimal recovery in some patients. Interpretation of the data in terms of activity in domain-general networks affords insights into novel approaches to rehabilitation.

Changes in motor cortical excitability in patients with Sydenham's chorea

The neurophysiological characteristics of motor cortex have been well characterized in patients with Huntington's disease. We present the first data on cortical excitability in patients with Sydenham's chorea. Motor cortex excitability was examined using transcranial magnetic stimulation in 16 patients in the early clinical stages of Sydenham's chorea and in 17 age- and sex-matched control subjects. Investigations included resting and active motor threshold, motor evoked potential, input-output curves, contralateral silent period, and transcallosal inhibition. Resting and active motor threshold were significantly higher and motor evoked potentials were significantly smaller in patients in comparison with controls. The input-output curves were shallower in both hemispheres of patients with chorea compared with controls. No significant differences were seen in silent period or transcallosal inhibition duration. Sydenham's chorea is characterized by reduced excitability of corticospinal output similar to that observed in Huntington's disease.

Expansion of sensorimotor cortical activation for unilateral hand motion during contralateral hand deafferentation

Acute deprivation of unilateral sensory input rapidly enhances contralateral hand motor function, but the underlying mechanisms remain poorly understood. We herein used functional MRI to evaluate, in 14 healthy individuals, motor cortical activation for right finger motion before, during, and after sensory deprivation of left forearm induced by reversible, noninvasive ischemic nerve block (INB). Before INB, the motor task activated the left primary sensorimotor cortex (SM1) as expected. During INB, the volume of the left SM1 activation significantly increased, and, after INB, it returned to the pre-INB, baseline level. The effectiveness of the INB of the left forearm was ensured by confirming disappearance of the activation in right primary sensory cortex that is normally caused by tactile stimulation of the left index finger. These findings demonstrate that acute deafferentation of unilateral forearm causes rapid and reversible changes in the neural substrates for contralateral finger motion, mediated possibly by attenuation of transcallosal interhemispheric inhibition.

Improvement of language functions in a chronic non-fluent post-stroke aphasic patient following bilateral sequential theta burst magnetic stimulation

In chronic non-fluent aphasia patients, inhibition of the intact right hemisphere (RH), by transcranial magnetic stimulation (TMS) or similar methods, can induce improvement in language functions. The supposed mechanism behind this improvement is a release of preserved left hemisphere (LH) language networks from RH transcallosal inhibition. Direct stimulation of the damaged LH can sometimes bring similar results too. Therefore, we developed a novel treatment approach that combined direct LH (Broca’s area (BA)) stimulation, by intermittent theta burst stimulation (TBS), with homologue RH area’s inhibition, by continuous TBS. We present the results of application of 15 daily sessions of the described treatment approach in a right-handed patient with chronic post-stroke non-fluent aphasia. The intervention appeared to improve several language functions, but most notably propositional speech, semantic fluency, short-term verbal memory, and verbal learning. Bilateral TBS modulation of activation of the language-related areas of both hemispheres seems to be a feasible and promising way to induce recovery in chronic aphasic patients. Due to potentially cumulative physiological effects of bilateral stimulation, the improvements may be even greater than following unilateral interventions.

Longitudinal changes of motor cortical excitability and transcallosal inhibition after subcortical stroke

ObjectiveA general lack of longitudinal studies on interhemispheric interactions following stroke led us to use transcranial magnetic stimulation (TMS) to examine changes in corticospinal/intracortical excitability and transcallosal inhibition over a 1-year period following subcortical stroke. MethodsWe measured TMS parameters such as motor threshold (MT), short-interval intracortical inhibition (SICI), and ipsilateral silent period (iSP) and evaluated clinical scores at three time-points (T1, T2, and T3) in 24 patients and 25 age-matched healthy subjects. ResultsAt T1, we observed reduced MTs and SICIs with prolonged iSPs in the unaffected hemisphere (UH). In contrast, increased MTs and reduced SICIs were observed in the affected hemisphere (AH). These abnormalities gradually reduced and no MEP response to TMS at T1 predicted a worse prognosis. The prolonged iSP at T1 was associated with more severe impairments, but it did not necessarily predict a worse prognosis after 1year. ConclusionsUH excitability was increased at the post-acute time-period, which may have resulted in enhanced transcallosal inhibition to the AH. However, it is unclear whether there was a causal relationship between the enhanced transcallosal inhibition and the extent of clinical recovery. SignificanceThis is the first study to demonstrate changes in transcallosal inhibition over a longitudinal period following stroke.

Low Rate Repetitive Transcranial Magnetic Stimulation (rTMS) and Gait Rehabilitation after Stroke

Background: After stroke the unaffected hemisphere is dis-inhibited, due to reduction in trans-callosal inhibition from the damaged hemisphere this in turn may increase inhibition of the affected hemisphere and could impair functional recovery. Objective: Low rate rTMS assumed to help gait rehabilitation as well as EEG synchronization after stroke. Are these two variables correlated? Methods: Thirty stroke patients were treated by conventional physical therapy program as well as rTMS at 1 Hz three sessions per week. The following parameters including quantitative electroencephalogram (QEEG), timed up and go test (TUG), Fugl- Meyer scale (FMS), Cadence and gait Speed were measured before and after six weeks of the treatment program. Compared to 15 stroke patients received physiotherapy program only. Results: All gait evaluation tests were improved after treatment in both groups, however the study group showed significant improvement than the control one. In the study group; there was significant improvement of the relative alpha band power spectrum over the treated as well as the untreated hemisphere. The relative theta/beta ratio over the central regions shows significant improvement as well. There were no significant correlations between the EEG power spectrum and the improvement of the gait evaluation tests. Conclusion: Although rTMS for the unaffected hemisphere after stroke improves the gait ability of the patient as well as the fast frequency band of the EEG yet they are not correlated to each other.

Visual callosal connections: role in visual processing in health and disease

Visual cortical areas in the two sides of the brain are interconnected by interhemispheric fibers passing through the splenium of the corpus callosum. In this review, we summarize data concerning the anatomical features of visual callosal connections, their roles in basic visual processing, and how their alterations contribute to visual deficits in different human neuropathologies. Splenial fibers represent a population of excitatory axons with varying diameters, which interconnect cortical columns with similar functional properties (i.e., same orientation selectivity) in the two hemispheres. Their branches activate simultaneously distinct iso-oriented columns in the contralateral hemisphere, thus mediating forms of stimulus-dependent interhemispheric synchronization. Callosal branches also make synapses onto GABAergic cells, resulting in an inhibitory modulation of visual processing that involves both iso-oriented and cross-oriented cortical networks. Interhemispheric inhibition appears to predominate at short latencies following callosal activation, whereas excitation becomes more robust with increasing delays. These callosal effects are dynamically adapted to the incoming visual activity, so that stimuli providing only weak afferent input are facilitated by callosal pathways, whereas strong visual input via the retinogeniculate pathway tends to be offset by transcallosal inhibition. We also review data highlighting the contribution of callosal input activity to maturation of visual function during early 'critical periods' in brain development and describe how interhemispheric transfer of visual information is rerouted in cases of callosal agenesis or following splenial damage. Finally, we provide an overview of alterations in splenium anatomy or function that may be at the basis of visual defects in several pathologic conditions.

Recent advances in the treatment of post-stroke aphasia.

Aphasia is an impairment of language use following brain damage. There is no consensual definition of aphasia beyond this general description (Code and Petheram, 2011). In a more restricted definition, however, aphasia is an impairment of linguistic processing at the phonological, morphological, lexical semantic or syntactic level which is usually caused by lesions of the left cerebral hemisphere. This impairment can affect language reception and expression depending on the various aphasic syndromes (McNeil and Pratt, 2001). Aphasia results in restrictions in those activities of daily living which rely on communication. In terms of the International Classification of Functioning, Disability and Health (WHO, 2001), limitations in functional communication pose significant challenges to social participation (Davidson et al., 2008) and reduce the patients’ quality of life (Kauhanen et al., 1999; Shadden, 2005). Recent data on the incidence of aphasia following stroke range between 0.02 and 0.06 % with a prevalence between 0.1 and 0.4 % in the developed world (Code and Petheram, 2011). Spontaneous behavioral recovery usually occurs to some degree in the weeks to months after stroke and depends on many factors such as the infarct size and location and the severity of initial stroke deficits (Cramer, 2008). Traditionally, proposed mechanisms of the neurological intrinsic recovery are the resolution of edema surrounding the infarcted area (Katzman et al., 1977; Lo, 1986) and reperfusion of incompletely damaged, but highly vulnerable perilesional tissue (see Donnan et al., 2013). These local mechanisms are supposed to support early recovery (in days to weeks after stroke) and do not depend on behavioral experience but have been targeted by pharmacological treatments: of more than a thousand drugs tested in animal models, 114 have been studied in clinical trials (Perez de la Ossa and Davalos, 2007) and to date none of these potentially neuroprotective agents was found to be effective in humans. Only rapid reperfusion with recombinant tissue plasminogen activator (rTPA) does improve functional outcome after ischemic stroke, but its use is limited by a short therapeutic window (4.5 hours following stroke), the risk of hemorrhage and potential ischemia/reperfusion injury (Lakhan et al., 2009). In contrast, neuronal network reorganization, which also occurs spontaneously, has been related to later recovery and can be influenced by environmental and behavioral factors (Cramer, 2008; Nudo, 2011, 2013). On the molecular level, regulation of gene expression in the unaffected peri-infarct tissue seems to favour the synthesis of growth promoting and to suppress the synthesis of growth inhibiting proteins thus creating a permissive environment for axonal/dendritic sprouting and may thus offer a window of opportunity for behavioural interventions to be effective (Carmichael, 2006). Even after standard treatments provided by the health care systems, the majority of people with aphasia have a chronic communication disability. Speech and language therapy (SLT) is the current standard of care for aphasia treatment but supplemental therapeutic strategies are emerging. The aim of this short review is to give an overview of current advances in research on behavioural, pharmacological and electrophysiological treatments for post-stroke aphasia.

Intracranial Hemorrhage in the Corpus Callosum Presenting as Callosal Disconnection Syndrome: FDG-PET and Tractography: A Case Report.

We report the findings of 18F-fluorodeoxyglocese positron emission tomography (FDG-PET) and diffusion tensor tractography (DTT) in a right-handed patient presenting with callosal disconnection syndrome, including alien hand syndrome, after an anterior communicating artery aneurysmal rupture. The 49-year-old patient had right hemiparesis and unintended movement of the right hand during action of the left hand. A brain magnetic resonance imaging revealed lesions in the upper part of the genu and body in the corpus callosum as well as hemorrhage in the inter-hemispheric fissure. We observed extensive disruption of corpus callosum fibers in the upper genu and trunk by DTT for the evaluation of inter-hemispheric connection. FDG-PET revealed severe hypometabolism in the left cerebral hemisphere, including basal ganglia and thalamus, and hypermetabolism in the right cerebral hemisphere. Based on findings of FDG-PET and DTT, the callosal disconnection syndrome presented in the patient could be the result of loss of transcallosal inhibition in the contralateral hemisphere.

Invasive neurostimulation in stroke rehabilitation.

The last decade has seen a growing interest in adjuvant treatments that synergistically influence mechanisms underlying rehabilitation of paretic upper limb in stroke. One such approach is invasive neurostimulation of spared cortices at the periphery of a lesion. Studies in animals have shown that during training of paretic limb, adjuvant stimulation targeting the peri-infarct circuitry enhances mechanisms of its reorganization, generating functional advantage. Success of early animal studies and clinical reports, however, failed to translate to a phase III clinical trial. As lesions in humans are diffuse, unlike many animal models, peri-infarct circuitry may not be a feasible, or consistent target across most. Instead, alternate mechanisms, such as changing transcallosal inhibition between hemispheres, or reorganization of other viable regions in motor control, may hold greater potential. Here, we review comprehensive mechanisms of clinical recovery and factors that govern which mechanism(s) become operative when. We suggest novel approaches that take into account a patient's initial clinical-functional state, and findings from neuroimaging and neurophysiology to guide to their most suitable mechanism for ideal targeting. Further, we suggest new localization schemes, and bypass strategies that indirectly target peri-lesional circuitry, and methods that serve to counter technical and theoretical challenge in identifying and stimulating such targets at the periphery of infarcts in humans. Last, we describe how stimulation may modulate mechanisms differentially across varying phases of recovery- a temporal effect that may explain missed advantage in clinical trials and help plan for the next stage. With information presented here, future trials would effectively be able to target patient's specific mechanism(s) with invasive (or noninvasive) neurostimulation for the greatest, most consistent benefit.

Motor cortex-induced plasticity by noninvasive brain stimulation

The aim of this study was to test and compare the effects of a within-subject design of repetitive transcranial magnetic stimulation (rTMS) [coupled with sham transcranial direct current stimulation (tDCS)] and tDCS (coupled with sham rTMS) on the motor cortex excitability and also compare the results against sham tDCS/sham rTMS. We conducted a double-blinded, randomized, sham-controlled, cross-over trial. Eleven right-handed, healthy individuals (five women, mean age: 39.8 years, SD 13.4) received the three interventions (cross-over design) in a randomized order: (a) high-frequency (HF) rTMS (+sham tDCS), (b) anodal tDCS (+sham rTMS), and (c) sham stimulation (sham rTMS+sham tDCS). Cortical excitability measurements [motor threshold, motor evoked potential (MEP), intracortical facilitation and inhibition, and transcallosal inhibition] and motor behavioral assessments were used as outcome measures. Between-group analysis of variance showed that MEP amplitude after HF rTMS was significantly higher than MEP amplitude after anodal tDCS (P=0.001). Post-hoc analysis showed a significant increase in MEP amplitude after HF rTMS (25.3%, P=0.036) and a significant decrease in MEP amplitude after anodal tDCS (-32.7%, P=0.001). There was a similar increase in motor function as indexed by Jebsen-Taylor Hand Function Test in the two active groups compared with sham stimulation. In conclusion, here, we showed that although both techniques induced similar motor gains, they induce opposing results in cortical excitability. HF rTMS is associated with an increase in corticospinal excitability, whereas 20 min of tDCS induces the opposite effect. We discuss potential implications of these results to future clinical experiments using rTMS or tDCS for motor function enhancement.

Modulation of transcallosal inhibition by bilateral activation of agonist and antagonist proximal arm muscles

Transcallosal inhibitory interactions between proximal representations in the primary motor cortex remain poorly understood. In this study, we used transcranial magnetic stimulation to examine the ipsilateral silent period (iSP; a measure of transcallosal inhibition) in the biceps and triceps brachii during unilateral and bilateral isometric voluntary contractions. Healthy volunteers performed 10% of maximal isometric voluntary elbow flexion or extension with one arm while the contralateral arm remained at rest or performed 30% of maximal isometric voluntary elbow flexion or extension. The iSP was measured in the arm performing 10% contractions, and electromyographic (EMG) recordings were comparable across conditions. The iSP onset and duration in the biceps and triceps brachii were comparable. In both muscles, the iSP depth and area were increased during bilateral contractions of homologous agonist muscles (extension-extension and flexion-flexion) compared with a unilateral contraction, whereas during bilateral contractions of nonhomologous antagonist muscles (extension-flexion and flexion-extension), the iSP depth and area were decreased compared with a unilateral contraction, and sometimes facilitation of EMG was seen. This effect was never observed during bilateral activation of homologous muscles. The size of responses evoked by cervicomedullary electrical stimulation in the arm that made 10% contractions remained unchanged across conditions. Thus transcallosal inhibition targeting triceps and biceps brachii is upregulated by voluntary contraction of the contralateral agonist muscle and downregulated by voluntary contraction of the contralateral antagonist muscle. We speculate that these reciprocal task-dependent interactions between bilateral flexor and extensor arm regions of the motor cortex may contribute to coupling between the arms during motor behavior.