Short-interval Interhemispheric Inhibition Research Articles

Contraction Phase and Force Differentially Change Motor Evoked Potential Recruitment Slope and Interhemispheric Inhibition in Young Versus Old.

Interhemispheric interactions are important for arm coordination and hemispheric specialization. Unilateral voluntary static contraction is known to increase bilateral corticospinal motor evoked potential (MEP) amplitude. It is unknown how increasing and decreasing contraction affect the opposite limb. Since dynamic muscle contraction is more ecologically relevant to daily activities, we studied MEP recruitment using a novel method and short interval interhemispheric inhibition (IHI) from active to resting hemisphere at 4 phases of contralateral ECR contraction: Rest, Ramp Up [increasing at 25% of maximum voluntary contraction (MVC)], Execution (tonic at 50% MVC), and Ramp Down (relaxation at 25% MVC) in 42 healthy adults. We analyzed the linear portion of resting extensor carpi radialis (ECR) MEP recruitment by stimulating at multiple intensities and comparing slopes, expressed as mV per TMS stimulation level, via linear mixed modeling. In younger participants (age ≤ 30), resting ECR MEP recruitment slopes were significantly and equally larger both at Ramp Up (slope increase = 0.047, p < 0.001) and Ramp Down (slope increase = 0.031, p < 0.001) compared to rest, despite opposite directions of force change. In contrast, Active ECR MEP recruitment slopes were larger in Ramp Down than all other phases (Rest:0.184, p < 0.001; Ramp Up:0.128, p = 0.001; Execution: p = 0.003). Older (age ≥ 60) participants’ resting MEP recruitment slope was higher than younger participants across all phases. IHI did not reduce MEP recruitment slope equally in old compared to young. In conclusion, our data indicate that MEP recruitment slope in the resting limb is affected by the homologous active limb contraction force, irrespective of the direction of force change. The active arm MEP recruitment slope, in contrast, remains relatively unaffected. Older participants had steeper MEP recruitment slopes and less interhemispheric inhibition compared to younger participants.

Phase Synchronicity of μ-Rhythm Determines Efficacy of Interhemispheric Communication Between Human Motor Cortices.

The theory of communication through coherence predicts that effective connectivity between nodes in a distributed oscillating neuronal network depends on their instantaneous excitability state and phase synchronicity (Fries, 2005). Here, we tested this prediction by using state-dependent millisecond-resolved real-time electroencephalography-triggered dual-coil transcranial magnetic stimulation (EEG-TMS) (Zrenner et al., 2018) to target the EEG-negative (high-excitability state) versus EEG-positive peak (low-excitability state) of the sensorimotor μ-rhythm in the left (conditioning) and right (test) motor cortex (M1) of 16 healthy human subjects (9 female, 7 male). Effective connectivity was tested by short-interval interhemispheric inhibition (SIHI); that is, the inhibitory effect of the conditioning TMS pulse given 10-12 ms before the test pulse on the test motor-evoked potential. We compared the four possible combinations of excitability states (negative peak, positive peak) and phase relations (in-phase, out-of-phase) of the μ-rhythm in the conditioning and test M1 and a random phase condition. Strongest SIHI was found when the two M1 were in phase for the high-excitability state (negative peak of the μ-rhythm), whereas the weakest SIHI occurred when they were out of phase and the conditioning M1 was in the low-excitability state (positive peak). Phase synchronicity contributed significantly to SIHI variation, with stronger SIHI in the in-phase than out-of-phase conditions. These findings are in exact accord with the predictions of the theory of communication through coherence. They open a translational route for highly effective modification of brain connections by repetitive stimulation at instants in time when nodes in the network are phase synchronized and excitable.SIGNIFICANCE STATEMENT The theory of communication through coherence predicts that effective connectivity between nodes in distributed oscillating brain networks depends on their instantaneous excitability and phase relation. We tested this hypothesis in healthy human subjects by real-time analysis of brain states by electroencephalography in combination with transcranial magnetic stimulation of left and right motor cortex. We found that short-interval interhemispheric inhibition, a marker of interhemispheric effective connectivity, was maximally expressed when the two motor cortices were in phase for a high-excitability state (the trough of the sensorimotor μ-rhythm). We conclude that findings are consistent with the theory of communication through coherence. They open a translational route to highly effectively modify brain connections by repetitive stimulation at instants in time of phase-synchronized high-excitability states.

Adaptive threshold hunting reveals differences in interhemispheric inhibition between young and older adults.

Interhemispheric inhibition between bilateral motor cortices is important for the performance of unimanual activities and may be compromised with advancing age. Conventionally, interhemispheric inhibition is assessed using paired-pulse transcranial magnetic stimulation (TMS) with constant conditioning and test stimulation parameters. Adaptive threshold hunting TMS, whereby a target motor-evoked potential amplitude is maintained in the presence of the conditioning, may provide an alternative means of assessment. Furthermore, interhemispheric inhibition may suppress late indirect-waves more so than early indirect-waves which can be preferentially elicited using anterior-posterior (AP) and posterior-anterior (PA) induced currents, respectively. The aim of this study was to assess age-related effects on interhemispheric inhibition using both conventional and threshold hunting techniques with PA- and AP-induced current. In 15 young and 15 older adults, short (10ms) and long (40ms) interval interhemispheric inhibition was examined in the nondominant extensor carpi radialis muscle at rest and during voluntary extension of the contralateral wrist. With the conventional technique, there were no age-related differences in short-interval interhemispheric inhibition. With threshold hunting and AP-induced current, young adults exhibited greater short-interval interhemispheric inhibition during contralateral activation compared with rest and compared with older adults. Furthermore, long-interval interhemispheric inhibition was greater in older adults compared with young for both conventional and threshold hunting techniques. Age-related differences in interhemispheric inhibition are evident with threshold hunting using PA- and AP-induced current.

Callosal anatomical and effective connectivity between primary motor cortices predicts visually cued bimanual temporal coordination performance

Default in-phase coupling of hand movements needs to be suppressed when temporal coordination is required for out-of-phase bimanual movements. There is lack of knowledge on how the brain overrides these default in-phase movements to enable a required interval of activity between hands. We used a visually cued bimanual temporal coordination (vc-BTC) paradigm with a constant rhythmical time base of 1s, to test the accuracy of in-phase and out-of-phase (0.1, 0.2,…,0.9) finger tapping. We hypothesized that (1) stronger anatomical and effective interhemispheric connectivity between the hand areas of the primary motor cortex (M1HAND) predict higher temporal offsets between hands in the out-of-phase conditions of the vc-BTC; (2) patients with relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) have reduced interhemispheric connectivity and altered between-hand coupling. Anatomical connectivity was determined by fractional anisotropy of callosal hand motor fibers (FA-hCMF). Effective connectivity was probed by short interval interhemispheric inhibition (S-IHI) using paired-coil transcranial magnetic stimulation (TMS). In healthy subjects, higher FA-hCMF and S-IHI correlated with higher temporal offsets between hands in the out-of-phase conditions of the tapping test. FA-hCMF was reduced in patients with RRMS but not in CIS, while S-IHI was reduced in both patient groups. These abnormalities were associated with smaller temporal offsets between hands leading to less deviation from the required phasing in the out-of-phase tapping conditions. Findings provide multiple levels of evidence that callosal anatomical and effective connectivity between the hand areas of the motor cortices play important roles in visually cued bimanual temporal coordination performance.

Carbamazepine reduces short-interval interhemispheric inhibition in healthy humans

Objective We sought to elucidate the influence of centrally active drugs on interhemispheric inhibition (IHI) between primary motor cortices in healthy humans. Methods We therefore studied IHI before and 2 h after intake of a single oral dose of carbamazepine, dextrometorphane, lorazepam, or placebo and compared it with the well known results for short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Drugs were tested in separate sessions and in random order. Results While SICI and ICF were not altered by carbamazepine, IHI was reduced at the interstimulus interval of 8 ms. Dextrometorphane tended to enhance SICI and to reduce ICF and had no effect on IHI. Lorazepam reduced ICF as expected and enhanced IHI at the long intervals of 50 and 80 ms. A moderate trend for interhemispheric facilitation was inconsistently observed at the interval 2 ms and blocked by carbamazepine. In addition, carbamazepine increased the motor threshold. Conclusions We conclude that circuits mediating short interstimulus intervals of IHI are susceptible to sodium channel blockade. Significance The results increase our knowledge of interhemispheric transmission.

Motor callosal disconnection in early relapsing‐remitting multiple sclerosis

In relapsing-remitting multiple sclerosis (RRMS) the corpus callosum (CC) is often and early affected by macroscopic lesions when investigated by conventional MRI. We sought to determine to which extent microstructural and effective disconnection of the CC are already present in RRMS patients at the earliest stages of the disease prior to evidence of macroscopic CC lesion. We compared 16 very early RRMS patients (median expanded disability status scale (EDSS), 1.5; range, 0-2.0) to an age-matched group of healthy controls and focused analysis to the motor CC, i.e. that part of the CC relaying interhemispheric motor information. A combined functional magnetic resonance imaging/diffusion tensor imaging fiber-tracking procedure was applied to identify the callosal motor fibers (CMFs) connecting the hand areas of the primary motor cortices of the two hemispheres. Fractional anisotropy (FA) within the motor CC (FA-CC) assessed the CMF microstructural integrity. Bifocal paired transcranial magnetic stimulation (TMS) tested short-interval interhemispheric inhibition (S-IHI), an established measure of CMF effective connectivity. FA-CC and S-IHI were significantly reduced in early RRMS compared to healthy controls. Furthermore, a significant linear correlation between microstructure (FA-CC) and function (S-IHI) in the controls was broken down in the patients. These abnormalities were obtained in the absence of macroscopic CMF lesion in conventional MRI, and whilst motor hand/arm function in the nine-hole-peg test and corticospinal conduction time were normal. Findings suggest that reductions in FA and S-IHI may serve as surrogate markers of motor callosal disconnection at the earliest stages of RRMS prior to development of macroscopic lesion.

Inhibitory circuits and the nature of their interactions in the human motor cortex – a pharmacological TMS study

Inhibitory circuits are crucial in modulating corticospinal output in the primary motor cortex (M1). Relatively little is known about how these inhibitory circuits interact. Here we measured three forms of inhibition in M1 by paired-pulse transcranial magnetic stimulation: short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and short-interval interhemispheric inhibition (SIHI). We specifically tested their interactions under pharmacological challenge with a single oral dose of diazepam, a positive allosteric modulator of the gamma-aminobutyric acid type A receptor (GABA A R), or baclofen, a specific agonist at the GABA type B receptor (GABA B R). Motor evoked potentials were recorded bilaterally from the first dorsal interosseous muscle in eight right-handed healthy volunteers. Diazepam enhanced SICI, and baclofen produced a trend towards enhanced LICI, corroborating the view that SICI reflects inhibition mediated by the GABA A R, and LICI very likely reflects inhibition mediated by the GABA B R. The pharmacology of SIHI was inconclusive and warrants further investigation. Findings strongly suggest that SICI, LICI and SIHI recruit three distinct inhibitory circuits in the human M1. The interactions between SIHI and SICI, LICI and SIHI, and LICI and SICI were all negative, that is SIHI suppressed SICI, and LICI suppressed both SIHI and SICI. Diazepam partially restored SICI in the presence of LICI, while all other interactions remained unaffected by diazepam or baclofen. It will be argued that the negative interactions between SIHI and SICI, LICI and SIHI, and LICI and SICI are most likely due to presynaptic GABA B R-mediated autoinhibition.