Changes In Interhemispheric Inhibition Research Articles

Alteration of Interhemispheric Inhibition in Patients With Lateral Epicondylalgia

Patients with lateral epicondylalgia (LE) show alterations in the primary motor cortex (M1) contralateral to the affected side. Cortical alterations have been investigated by measuring intracortical facilitation/inhibition; however, their association with pain remains controversial. Furthermore, no studies have investigated changes in interhemispheric inhibition (IHI). IHI can be assessed using the ipsilateral silent period (iSP) known as the temporary inhibition of electromyographic activity evoked by transcranial magnetic stimulation in the ipsilateral M1 of the contracting muscle. To better understand the relationship between cortical alterations and pain in LE, this observational study investigated the relationship between iSP and pain in LE. Twenty-seven healthy volunteers and 21 patients with LE were recruited. The duration of iSP in the extensor carpi radialis brevis was measured. The IHI asymmetry ratio was calculated to determine the IHI balance. Pain and disability were scored using the Japanese version of the patient-rated elbow evaluation. We observed increased inhibitory input from the ipsilateral M1 on the affected side to the contralateral M1 in LE. Additionally, the IHI balance correlated with pain severity. Hence, regulating imbalanced IHI can potentially decrease lateral elbow pain in LE. PerspectivePatients with lateral epicondylalgia (LE) experience persistent pain and cortical alterations. However, there is no established relationship between cortical alterations and pain. This study demonstrated that the interhemispheric inhibition (IHI) balance is correlated with pain. Regulating imbalanced IHI can potentially decrease lateral elbow pain in patients with LE.

Relationship between the interlimb transfer of a visuomotor learning task and interhemispheric inhibition in healthy humans.

The "interlimb transfer" phenomenon consists of improved performance of the trained and untrained contralateral limbs after unilateral motor practice. We here assessed whether a visuomotor learning task can be transferred from one hemisphere to the other, whether this occurs symmetrically, and the cortical neurophysiological correlates of this phenomenon, focusing on interhemispheric connectivity measures. We enrolled 33 healthy subjects (age range: 24-73years). Participants underwent two randomized sessions, which investigated the transfer from the dominant to the nondominant hand and vice versa. Measures of cortical and intracortical excitability and interhemispheric inhibition were assessed through transcranial magnetic stimulation before and after a visuomotor task. The execution of the visuomotor task led to an improvement in motor performance with the dominant and nondominant hands and induced a decrease in intracortical inhibition in the trained hemisphere. Participants were also able to transfer the visuomotor learned skill. The interlimb transfer, however, only occurred from the dominant to the nondominant hand and positively correlated with individual learning-related changes in interhemispheric inhibition. We here demonstrated that the "interlimb transfer" of a visuomotor task occurs asymmetrically and relates to the modulation of specific inhibitory interhemispheric connections. The study results have pathophysiological, clinical, and neuro-rehabilitative implications.

Impact of interhemispheric inhibition on bimanual movement control in young and old

Interhemispheric interactions demonstrate a crucial role for directing bimanual movement control. In humans, a well-established paired-pulse transcranial magnetic stimulation paradigm enables to assess these interactions by means of interhemispheric inhibition (IHI). Previous studies have examined changes in IHI from the active to the resting primary motor cortex during unilateral muscle contractions; however, behavioral relevance of such changes is still inconclusive. In the present study, we evaluated two bimanual tasks, i.e., mirror activity and bimanual anti-phase tapping, to examine behavioral relevance of IHI for bimanual movement control within this behavioral framework. Two age groups (young and older) were evaluated as bimanual movement control demonstrates evident behavioral decline in older adults. Two types of IHI with differential underlying mechanisms were measured; IHI was tested at rest and during a motor task from the active to the resting primary motor cortex. Results demonstrate an association between behavior and short-latency IHI in the young group: larger short-latency IHI correlated with better bimanual movement control (i.e., less mirror activity and better bimanual anti-phase tapping). These results support the view that short-latency IHI represents a neurophysiological marker for the ability to suppress activity of the contralateral side, likely contributing to efficient bimanual movement control. This association was not observed in the older group, suggesting age-related functional changes of IHI. To determine underlying mechanisms of impaired bimanual movement control due to neurological disorders, it is crucial to have an in-depth understanding of age-related mechanisms to disentangle disorder-related mechanisms of impaired bimanual movement control from age-related ones.

Bilateral motor priming for post stroke upper extremity hemiparesis: A randomized pilot study.

Bilateral priming, device assisted bilateral symmetrical wrist flexion/extension, is a noninvasive neuromodulation technique that can be used in the clinic. We examined the additive effect of bilateral motor priming and task specific training in individuals with severe upper limb hemiparesis. This is a parallel assignment, single-masked, randomized exploratory pilot study with three timepoints (pre-/post-intervention and follow up). Participants received either bilateral motor priming or health care education followed by task specific training. Sixteen participants who were at least 6 months post-stroke and had a Fugl Meyer Upper Extremity (FMUE) score between 23 and 38 were randomized. Our primary and secondary measures were Chedoke Arm & Hand Activity Index 9 (CAHAI-9) and the FMUE respectively. We determined changes in interhemispheric inhibition using transcranial magnetic stimulation. We hypothesized that improvement in the priming group would persist at follow up. There was no between-group difference in the CAHAI. The improvement in the FMUE was significantly greater in the experimental group at follow up (t = 2.241, p = 0.045). Both groups improved in the CAHAI. There was a significant between-group difference in the secondary outcome measure (FMUE) where the bilateral priming group had an average increase of 10 points from pre-intervention to follow up.

Cortical contributions to sensory gating in the ipsilateral somatosensory cortex during voluntary activity.

It has long been known that the somatosensory cortex gates sensory inputs from the contralateral side of the body. Here, we examined the contribution of the ipsilateral somatosensory cortex (iS1) to sensory gating during index finger voluntary activity. The amplitude of the P25/N33, but not other somatosensory evoked potential (SSEP) components, was reduced during voluntary activity compared with rest. Interhemispheric inhibition between S1s and intracortical inhibition in the S1 modulated the amplitude of the P25/N33. Note that changes in interhemispheric inhibition between S1s correlated with changes in cortical circuits in the ipsilateral motor cortex. Our findings suggest that cortical circuits, probably from somatosensory and motor cortex, contribute to sensory gating in the iS1 during voluntary activity in humans. An important principle in the organization of the somatosensory cortex is that it processes afferent information from the contralateral side of the body. The role of the ipsilateral somatosensory cortex (iS1) in sensory gating in humans remains largely unknown. Using electroencephalographic (EEG) recordings over the iS1 and electrical stimulation of the ulnar nerve at the wrist, we examined somatosensory evoked potentials (SSEPs; P14/N20, N20/P25 and P25/N33 components) and paired-pulse SSEPs between S1s (interhemispheric inhibition) and within (intracortical inhibition) the iS1 at rest and during tonic index finger voluntary activity. We found that the amplitude of the P25/N33, but not other SSEP components, was reduced during voluntary activity compared with rest. Interhemispheric inhibition increased the amplitude of the P25/N33 and intracortical inhibition reduced the amplitude of the P25/N33, suggesting a cortical origin for this effect. The P25/N33 receives inputs from the motor cortex, so we also examined the contribution of distinct sets of cortical interneurons by testing the effect of ulnar nerve stimulation on motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the ipsilateral motor cortex with the coil in the posterior-anterior (PA) and anterior-posterior (AP) orientation. Afferent input attenuated PA, but not AP, MEPs during voluntary activity compared with rest. Notably, changes in interhemispheric inhibition correlated with changes in PA MEPs. Our novel findings suggest that interhemispheric projections between S1s and intracortical circuits, probably from somatosensory and motor cortex, contribute to sensory gating in the iS1 during voluntary activity in humans.

Corticomotor plasticity following unilateral strength training

We used transcranial magnetic stimulation (TMS) to investigate 3 weeks of unilateral leg strength training on ipsilateral motor cortex (iM1) excitability, and short-latency intracortical inhibition (SICI). Right leg dominant participants (n = 14) were randomly divided into either a strength training (ST) or control group. The ST group completed 9 training sessions (4 sets of 6 to 8 repetitions of single right leg squats). We observed a 41% increase in right leg strength, and a 35% increase in strength of the untrained left leg (P < 0.01). There was a significant increase in motor evoked potential (MEP) amplitude recruitment curve for the untrained left leg (P < 0.01). SICI of the iM1 decreased by 21% for the untrained left leg (P < 0.01). The findings provide evidence for corticomotor adaptation for unilateral leg strength training within the iM1 that is modulated by changes in interhemispheric inhibition.

Changes in interhemispheric inhibition from active to resting primary motor cortex during a fine-motor manipulation task

The effect of performance of a sensorimotor task on the interhemispheric inhibition (IHI) induced from the active primary motor cortex (M1) to the resting M1 was examined in 10 right-handed subjects. Transcranial magnetic stimulation (TMS) was performed to produce motor evoked potentials (MEP) in the resting right (Rt)-first dorsal interosseous (FDI). For the paired-TMS paradigm, a conditioning stimulus (CS) was delivered to the Rt-M1, and its intensity was adjusted from 0.6 to 1.4 times the resting motor threshold of the MEP in the left (Lt)-FDI in 0.2 steps. The test stimulus was delivered to the Lt-M1, and its intensity was adjusted to evoke similar MEP amplitudes in the Rt-FDI among the task conditions. The interstimulus interval was fixed at 10 ms. As a sensorimotor task, a fine-motor manipulation (FM) task (using chopsticks to pick up, transport, and release glass balls) was adopted. In addition, an isometric abduction (IA) task was also performed as a control task. These tasks were carried out with the left hand. The IHI from the active to the resting M1 observed during the FM task was markedly increased compared with that induced during the IA task, and this effect was not dependent on the MEP amplitude evoked in the active Lt-FDI by the CS. The present findings suggest that the increased IHI from the active to the resting M1 observed during the FM task was linked to reductions in the activity of the ipsilateral intracortical inhibitory circuit, as we reported previously.

Changes in interhemispheric inhibition following successful epilepsy surgery: a TMS study

Epileptic foci can influence cortical excitability, brain perfusion and metabolism not only directly in the focus or perifocally, but also in remote areas. Effects of successful epilepsy surgery on cortical networks and changes in excitability have rarely been addressed. We report a study on changes in interhemispheric inhibition following successful surgical removal of an epileptic focus. Eighteen patients (11 females, 7 males, mean age 34.2 years) were enrolled in this transcranial magnetic stimulation (TMS) study. All patients were seizure free after surgery and had identical antiepileptic medication pre- and postsurgically. Investigations were performed before and at least 3 months after surgery. Motor thresholds (MT) and motor evoked potentials (MEPs) of interhemispheric paired pulse paradigms were investigated on both hemispheres. Resection of the epileptic focus resulted in a significant change in interhemispheric inhibition (IHI). The ability of the non-focal hemisphere to inhibit the motor cortex (M1) of the focal hemisphere significantly increased (p=0.02) and normalized to the level of the other hemisphere. In summary, this TMS study suggests that an epileptic focus can modulate interhemispheric inhibitory interactions between the motor cortices. A decreased susceptibility of M1 of the focal hemisphere or alterations in the non-focal hemispheric inhibitory output may be underlying mechanisms. These findings may contribute to a better understanding of widespread functional impairments in focal epilepsy.

Neural correlates of age-related changes in cortical neurophysiology

Functional imaging studies of cortical motor systems in humans have demonstrated age-related reorganisation often attributed to anatomical and physiological changes. In this study we investigated whether aspects of brain activity during a motor task were influenced not only by age, but also by neurophysiological parameters of the motor cortex contralateral to the moving hand. Twenty seven right-handed volunteers underwent functional magnetic resonance imaging whilst performing repetitive isometric right hand grips in which the target force was parametrically varied between 15 and 55% of each subject’s own maximum grip force. For each subject we characterised two orthogonal parameters, BG (average task-related activity for all hand grips) and BF (the degree to which task-related activity co-varied with peak grip force). We used transcranial magnetic stimulation (TMS) to assess task-related changes in interhemispheric inhibition from left to right motor cortex (IHIc) and to perform measures relating to left motor cortex excitability during activation of the right hand. Firstly, we found that BG in right (ipsilateral) motor cortex was greater with increasing values of age2 and IHIc. Secondly, BF in left ventral premotor cortex was greater in older subjects and in those in whom contralateral M1 was less responsive to TMS stimulation. In both cases, neurophysiological parameters accounted for variability in brain responses over and above that explained by ageing. These results indicate that neurophysiological markers may be better indicators of biological ageing than chronological age and point towards the mechanisms by which reconfiguration of distributed brain networks occurs in the face of degenerative changes.

The effect of age on task-related modulation of interhemispheric balance

Normal aging is associated with less lateralised task-related activation of the primary motor cortices. It has been hypothesized, but not tested, that this phenomenon is mediated transcallosaly. We have used Transcranial Magnetic Stimulation to look for age-related changes in interhemispheric inhibition (IHI). Thirty healthy individuals (aged 19–78 years) were studied using a paired-pulse protocol at rest and during a low-strength isometric contraction with the right hand. The IHI targeting the right motor cortex was assessed at two intervals, 10 ms (IHI10) and 40 ms (IHI40). The corticospinal excitability of the left hemisphere was assessed by means of input–output curves constructed during voluntary construction. Age was not correlated with IHI10 or IHI40 at rest. During muscle contraction IHI tended to increase at both intervals. However, this increase in IHI during the active condition (changeIHI) was less evident with advancing age for the 40 ms interval (r = 0.444, P = 0.02); in fact a degree of disinhibition was often present. There was no correlation between age and changeIHI10. Age was negatively correlated with the area under the recruitment curve (r = −0.585, P = 0.001) and the size of the maximum MEP collected (r = −0.485, P = 0.007). ChangeIHI and measures of corticospinal excitability were not intercorrelated. In conclusion, task-related increases in interhemispheric inhibition seem to diminish with advancing age. This phenomenon is specific for long-latency IHI and may underlie the age-related bihemispheric activation seen in functional imaging studies. The mechanism underlying changes in IHI with advancing age and the association with changes in corticospinal excitability need further investigation.

Side of lesion influences interhemispheric inhibition in subjects with post-stroke hemiparesis

Objective To examine changes in interhemispheric inhibition (IHI) during homologous muscle activation in healthy subjects and in people with hemiparesis. Methods IHI in the abductor pollicus brevis (APB) muscle was examined using paired transcranial magnetic stimulation. Stimuli were delivered while the target APB was at rest or activated, and while the non-target contralateral APB was at rest or activated. Results In control subjects, IHI in the resting target APB was enhanced during activation of the contralateral APB, and was greater from the dominant hemisphere to the non-dominant. In stroke subjects, IHI in the non-affected APB was not modulated during voluntary activation of the affected APB, but was influenced by the prior dominance of affected hemisphere. Bilateral muscle activation did not elicit any changes in IHI in either group. Conclusions IHI is asymmetrical between hemispheres but only when the target muscle is at rest. Subjects with stroke have an impaired ability to modulate IHI during unilateral muscle activation. Significance In people with stroke, the extent and modulation of interhemispheric transfer is influenced by the prior dominance of the affected hemisphere. This may impact on the efficacy of treatment interventions incorporating bilateral activation.

Plastic changes in interhemispheric inhibition with practice of a two-hand force production task: a transcranial magnetic stimulation study

We studied the effects of practice of an unusual two-hand finger force production task on electromyographic and force responses to transcranial magnetic stimulation (TMS). Prior to practice, force production by a hand resulted in decreased TMS-induced responses in the other hand. After practice, fingers that were explicitly required to produce force during practice showed a significant drop in these inhibitory effects, while other fingers did not. We conclude that interhemispheric inhibitory projections can show plastic changes that favor the execution of a practiced task.

Functional imaging in stroke recovery.

Assessing neurobiology of brain systems can provide information not available from anatomic or behavioral assessment. Such information may be of value in understanding, defining, and prescribing potential therapeutic interventions that target restorative brain events after stroke. A number of methods have been used to study stroke recovery, each with its relative merits and limitations. Several studies suggest that greater injury is associated with reduced laterality of brain activity. This might be in relation to changes in interhemispheric inhibition and is a phenomenon that is likely useful for functional gains in some patients. Many other features of brain activity change in the months after a stroke, including the site and size of activation in relevant brain network nodes. While there is incomplete agreement regarding which features of altered brain activity predict and parallel better behavioral outcome, studies converge on the conclusion that best outcome is achieved by activating the brain in a pattern that most resembles the normal state.