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The Use of Magnetic Resonance Spectroscopy as a Tool for the Measurement of Bi-hemispheric Transcranial Electric Stimulation Effects on Primary Motor Cortex Metabolism

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of ...

University of Montréal

It is now well established that the human brain is endowed with a mechanism that pairs action perception with its execution. This system has been extensively studied using visual stimuli and recent evidence suggests that it is also responsive to the sound of motor actions. Here, we presented action (finger and tongue clicks) and acoustically matched sounds to investigate action-related sound processing in a 12-year-old child undergoing intracranial monitoring of epileptic seizures. Electroencephalography grids were located over a large portion of the right hemisphere, including motor cortex. Wavelet analysis carried out on electrodes overlying the functionally defined hand representation of the motor cortex revealed early (100 ms) and late (250-450 ms) decreases in mu rhythm power (12 and 20 Hz) selective for natural finger-clicks compared with control sounds. These data suggest the presence of a rapid, multimodal resonance mechanism modulating motor cortex activity.

Action related sounds induce early and late modulations of motor cortex activity.

Activity of the primary motor cortex (M1) during action observation is thought to reflect motor resonance. Here, we conducted three studies using transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEPs) of the first dorsal interosseus muscle (FDI) during action observation to determine: (i) the time course of M1 corticospinal excitability during the observation of a simple finger movement; (ii) the specificity of M1 modulation in terms of type of movement and muscle; and (iii) the relationship between M1 activity and measures of empathy and autistic traits. In a first study, we administered single-pulse TMS at 30-ms intervals during the observation of simple finger movements. Results showed enhanced corticospinal excitability occurring between 60 and 90 ms after movement onset. In a second experiment, TMS-induced MEPs were recorded from the FDI and abductor digiti minimi muscles while pulses were delivered 90 ms after movement onset during observation of simple finger movement and dot movement. Increased corticospinal excitability was restricted to finger movement and was present in both muscles. Finally, in an exploratory experiment, single-pulse TMS was administered at 30, 90 and 150 ms after movement onset, and participants were asked to complete the Empathy Quotient (EQ) and the Autism Spectrum Quotient (AQ). Correlational analysis revealed a significant link between motor facilitation at 90 ms and the EQ and AQ scores. These results suggest that corticospinal excitability modulation seen at M1 during action observation is the result of a rapid and crude automatic process, which may be related to social functioning.

Early non-specific modulation of corticospinal excitability during action observation.

Sports concussions affect thousands of individuals every year and are a major public health concern. Still, little is known about the long-term and cumulative effects of concussions on brain neurophysiology. The principal objective of this study was to investigate the long-lasting effects of multiple sports concussions on sensorimotor integration and somatosensory processing in a sample of 12 concussed athletes and 14 non-concussed athletes of similar age (mean, 23 years) and education (mean, 16 years). Right median nerve stimulation was paired with transcranial magnetic stimulation (TMS) of the left primary motor cortex to investigate sensorimotor integration with short latency afferent inhibition (SAI) and long latency afferent inhibition (LAI) at five interstimulus intervals (18, 20, 22, 100, 200 msec). Somatosensory evoked potentials (SEP) were recorded from the left centro-parietal region. We also investigated primary motor cortex inhibitory mechanisms with three TMS protocols: cortical silent period, long interval intracortical inhibition, and short interval intracortical inhibition. Motor evoked potentials were recorded from the right abductor pollicis brevis muscle. No differences were observed between groups for SAI, LAI, and SEP. However, cortical silent period duration was prolonged and long interval intracortical inhibition was enhanced in the concussed group. These findings suggest that multiple sports concussions lead to specific, long-term neurophysiological dysfunctions of intracortical inhibitory mechanisms in primary motor cortex while somatosensory processing and sensorimotor integration are spared. This study provides additional evidence for the presence of specific and stable alterations of GABA(B) receptor activity in primary motor cortex that may be of clinical value for prognosis and diagnosis.

Evidence for the specificity of intracortical inhibitory dysfunction in asymptomatic concussed athletes.

It is known that transcranial direct current stimulation (tDCS) can induce polarity-specific shifts in brain excitability of the primary motor cortex (M1) with anodal tDCS enhancing and cathodal tDCS reducing cortical excitability. However, less is known about its impact on specific intracortical inhibitory mechanisms, such as γ-aminobutyric acid B (GABAB)-mediated inhibition. Consequently, the aim of the present study was to assess the impact of anodal and cathodal tDCS on M1 intracortical inhibition in healthy individuals. Long-interval intracortical inhibition (LICI) and cortical silent period (CSP) duration, both presumably mediated by GABAB receptors, were assessed using transcranial magnetic stimulation immediately before and after a 20 min session of tDCS over the left M1. Anodal tDCS significantly enhanced motor evoked potential size and reduced CSP duration, whereas it had no effect on LICI. Cathodal stimulation did not significantly modulate motor evoked potential size, CSP duration or LICI. This study provides evidence that anodal tDCS, presumably by synaptic plasticity mechanisms, has a direct effect on GABAB-meditated inhibition assessed by the CSP, but not by LICI. Our results further suggest that CSP and LICI probe distinct intracortical inhibitory mechanisms as they are differentially modulated by anodal tDCS. Finally, these data may have clinical value in patients in whom a pathological increase in CSP duration is present, such as schizophrenia.

Anodal transcranial direct current stimulation modulates GABAB-related intracortical inhibition in the M1 of healthy individuals.

Transcranial magnetic stimulation (TMS) can provide an index of intracortical excitability/inhibition balance. However, the neurochemical substrate of these measures remains unclear. Pharmacological studies suggest the involvement of GABAA and GABAB receptors in TMS protocols aimed at measuring intracortical inhibition, but this link remains inferential. Proton magnetic resonance spectroscopy ((1)H-MRS) permits measurement of GABA and glutamate + glutamine (Glx) concentrations in the human brain and might help in the direct empirical assessment of the relationship between TMS inhibitory measures and neurotransmitter concentrations. In the present study, MRS-derived relative concentrations of GABA and Glx measured in the left M1 of healthy participants were correlated with TMS measures of intracortical inhibition. Glx levels were found to correlate positively with TMS-induced silent period duration, whereas no correlation was found between GABA concentration and TMS measures. The present data demonstrate that specific TMS measures of intracortical inhibition are linked to shifts in cortical Glx, rather than GABA neurotransmitter levels. Glutamate might specifically interact with GABAB receptors, where higher MRS-derived Glx concentrations seem to be linked to higher levels of receptor activity.

Relationship between transcranial magnetic stimulation measures of intracortical inhibition and spectroscopy measures of GABA and glutamate+glutamine.

To perform strictly unilateral movements, the brain relies on a large cortical and subcortical network. This network enables healthy adults to perform complex unimanual motor tasks without the activation of contralateral muscles. However, mirror movements (involuntary movements in ipsilateral muscles that can accompany intended movement) can be seen in healthy individuals if a task is complex or fatiguing, in childhood, and with increasing age. Lateralization of movement depends on complex interhemispheric communication between cortical (i.e., dorsal premotor cortex, supplementary motor area) and subcortical (i.e., basal ganglia) areas, probably coursing through the corpus callosum (CC). Here, we will focus on transcallosal interhemispheric inhibition (IHI), which facilitates complex unilateral movements and appears to play an important role in handedness, pathological conditions such as Parkinson's disease, and stroke recovery.

Interhemispheric control of unilateral movement.

Recent studies have shown, in asymptomatic concussed athletes, metabolic disruption in the primary motor cortex (M1) and abnormal intracortical inhibition lasting for more than six months. The present study aims to assess if these neurochemical and neurophysiological alterations are persistent and linked to M1 cortical thickness.

Article	Year
Action related sounds induce early and late modulations of motor cortex activity. Neuroreport\| PubMed ID: 20087234	2010
Early non-specific modulation of corticospinal excitability during action observation. The European journal of neuroscience\| PubMed ID: 20374291	2010
Evidence for the specificity of intracortical inhibitory dysfunction in asymptomatic concussed athletes. Journal of neurotrauma\| PubMed ID: 21219259	2011
Anodal transcranial direct current stimulation modulates GABAB-related intracortical inhibition in the M1 of healthy individuals. Neuroreport\| PubMed ID: 23196416	2013
Relationship between transcranial magnetic stimulation measures of intracortical inhibition and spectroscopy measures of GABA and glutamate+glutamine. Journal of neurophysiology\| PubMed ID: 23221412	2013
Interhemispheric control of unilateral movement. Neural plasticity\| PubMed ID: 23304559	2012
Multimodal assessment of primary motor cortex integrity following sport concussion in asymptomatic athletes. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology\| PubMed ID: 24462505	2014

Sara Tremblay

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