Sara Tremblay

Interhemispheric Control of Unilateral Movement

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 Parkinsons disease, and stroke recovery.

Early non-specific modulation of corticospinal excitability during action observation

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.

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

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.

Evidence for the Specificity of Intracortical Inhibitory Dysfunction in Asymptomatic Concussed Athletes

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.

Multimodal assessment of primary motor cortex integrity following sport concussion in asymptomatic athletes

OBJECTIVE 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. METHODS Sixteen active football players who sustained their last concussion, on average, three years prior to testing and 14 active football players who never sustained a concussion were recruited for a single session of proton magnetic resonance spectroscopy ((1)H-MRS) and transcranial magnetic stimulation (TMS). Measures of M1 and whole brain cortical thickness were acquired, and (1)H-MRS data were acquired from left M1 using a MEGA-PRESS sequence. Cortical silent period (CSP) and long-interval intracortical inhibition (LICI) were measured with TMS applied over left M1. RESULTS No significant group differences were observed for metabolic concentrations, TMS measures, and cortical thickness. However, whereas GABA and glutamate levels were positively correlated in control athletes, this relationship was absent in concussed athletes. CONCLUSION These data suggest the general absence of neurophysiologic, neurometabolic and neuroanatomical disruptions in M1 three years following the last concussive event. However, correlational analyses suggest the presence of a slight metabolic imbalance between GABA and glutamate concentrations in the primary motor cortex of concussed athletes. SIGNIFICANCE The present study highlights the importance of multimodal assesments of the impacts of sport concussions.

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

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 &ggr;-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.

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

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.

Probing the effects of mild traumatic brain injury with transcranial magnetic stimulation of the primary motor cortex.

Abstract Primary objective: The present paper systematically reviews studies using transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) to assess cortical excitability, intra-cortical inhibition/facilitation and synaptic plasticity following mild traumatic brain injury (mTBI). Methods: Articles using TMS over M1 in patients with mTBI or sport-related concussion indexed in PubMed and published between 1998 and September 2014 were included in the present review. Main outcomes and results: From the 17 articles that matched search criteria, results from various TMS paradigms were summarized and divided in three main areas of interest: motor cortical excitability/facilitation, motor cortical inhibition and cortical plasticity. Although studies suggest a trend of abnormal intra-cortical inhibition following mTBI, no clear and specific pattern emerges from the surveyed data. Conclusions: At this time and with the possible exception of intra-cortical inhibitory measures, TMS cannot reliably detect changes in M1 excitability in individuals with mTBI or a concussion at both the acute and chronic stages of injury. This may be explained by the small number of studies and large variety of stimulation parameters. Additional longitudinal and multimodal studies are needed to better understand the nature of the excitability changes that may occur within M1 following mTBI.

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 neurological and psychiatric disorders such as stroke and depression. Yet, the mechanisms underlying its ability to modulate brain excitability to improve clinical symptoms remains poorly understood. To help improve this understanding, proton magnetic resonance spectroscopy ((1)H-MRS) can be used as it allows the in vivo quantification of brain metabolites such as γ-aminobutyric acid (GABA) and glutamate in a region-specific manner. In fact, a recent study demonstrated that (1)H-MRS is indeed a powerful means to better understand the effects of tDCS on neurotransmitter concentration. This article aims to describe the complete protocol for combining tDCS (NeuroConn MR compatible stimulator) with (1)H-MRS at 3 T using a MEGA-PRESS sequence. We will describe the impact of a protocol that has shown great promise for the treatment of motor dysfunctions after stroke, which consists of bilateral stimulation of primary motor cortices. Methodological factors to consider and possible modifications to the protocol are also discussed.

Theta burst stimulation to characterize changes in brain plasticity following mild traumatic brain injury: a proof-of-principle study

PURPOSE Recent studies investigating the effects of mild traumatic brain injury (mTBI) suggest the presence of unbalanced excitatory and inhibitory mechanisms within primary motor cortex (M1). Whether these abnormalities are associated with impaired synaptic plasticity remains unknown. METHODS The effects of continuous theta burst stimulation (cTBS) on transcranial magnetic stimulation-induced motor evoked potentials (MEPs) were assessed on average two weeks and six weeks following mTBI in five individuals. RESULTS The procedure was well-tolerated by all participants. Continuous TBS failed to induce a significant reduction of MEP amplitudes two weeks after the injury, but response to cTBS normalized six weeks following injury, as a majority of patients became asymptomatic. CONCLUSIONS These preliminary results suggest that cTBS can be used to assess M1 synaptic plasticity in subacute phase following mTBI and may provide insights into neurobiological substrates of symptoms and consequences of mTBI.