Hugo Théoret

Studies in Cognition: The Problems Solved and Created by Transcranial Magnetic Stimulation

The application of transcranial magnetic stimulation (TMS) to investigate important questions in cognitive neuroscience has increased considerably in the last few years. TMS can provide substantial insights into the nature and the chronometry of the computations performed by specific cortical areas during various aspects of cognition. However, the use of TMS in cognitive studies has many potential perils and pitfalls. Although TMS can help bridge the gap between psychological models and brain-based arguments of cognitive functions, hypothesis-driven carefully designed experiments that acknowledge the current limitations of TMS are critical.

Impaired motor facilitation during action observation in individuals with autism spectrum disorder

Abstract It has been suggested that social impairments observed in individuals with autism spectrum disorder (ASD) can be partly explained by an abnormal mirror neuron system (MNS) [1,2]. Studies on monkeys have shown that mirror neurons are cells in premotor area F5 that discharge when a monkey executes or sees a specific action or when it hears the corresponding action-related sound [3–5]. Evidence for the presence of a MNS in humans comes in part from studies using transcranial magnetic stimulation (TMS), where a change in the amplitude of the TMS-induced motor-evoked potentials (MEPs) during action observation has been demonstrated [6–9]. These data suggest that actions are understood when the representation of that action is mapped onto the observers own motor structures [10]. To determine if the neural mechanism matching action observation and execution is anomalous in individuals with ASD, TMS was applied over the primary motor cortex (M1) during observation of intransitive, meaningless finger movements. We show that overall modulation of M1 excitability during action observation is significantly lower in individuals with ASD compared with matched controls. In addition, we find that basic motor cortex abnormalities do not underlie this impairment.

Activation of Prefrontal Cortex by Transcranial Direct Current Stimulation Reduces Appetite for Risk during Ambiguous Decision Making

As adult humans, we are continuously faced with decisions in which proper weighing of the risk involved is critical. Excessively risky or overly cautious decision making can both have disastrous real-world consequences. Weighing of risks and benefits toward decision making involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC), but its role remains unclear. Repetitive transcranial magnetic stimulation studies have shown that disruption of the DLPFC increases risk-taking behavior. Transcranial direct current stimulation (tDCS) allows upregulation of activity in the DLPFC, and we predicted that it might promote more cautious decision making. Healthy participants received one of the following treatments while they performed the Balloon Analog Risk Task: (1) right anodal/left cathodal DLPFC tDCS, (2) left anodal/ right cathodal DLPFC tDCS, or (3) sham tDCS. This experiment revealed that participants receiving either one of the bilateral DLPFC tDCS strategies adopted a risk-averse response style. In a control experiment, we tested whether unilateral DLPFC stimulation (anodal tDCS over the right or left DLPFC with the cathodal electrode over the contralateral supraorbital area) was sufficient to decrease risk-taking behaviors. This experiment showed no difference in decision-making behaviors between the groups of unilateral DLPFC stimulation and sham stimulation. These findings extend the notion that DLPFC activity is critical for adaptive decision making, possibly by suppressing riskier responses. Anodal tDCS over DLPFC by itself did not significantly change risk-taking behaviors; however, when the contralateral DLPFC was modulated with cathodal tCDS, an important decrease in risk taking was observed. Also, the induced cautious decision-making behavior was observed only when activity of both DLPFCs was modulated. The ability to modify risk-taking behavior may be translated into therapeutic interventions for disorders such as drug abuse, overeating, or pathological gambling.

Repetitive TMS of the motor cortex improves ipsilateral sequential simple finger movements

Background: Disruption of cortical function can improve behavior. Motor cortex (M1) transcallosal interactions are mainly inhibitory; after unilateral damage to M1, there is increased excitability of the unaffected M1. Repetitive transcranial magnetic stimulation (rTMS) of M1 produces a temporary reduction in cortical excitability in the same M1 that outlasts the duration of the rTMS train. The authors hypothesize that reducing cortical excitability of M1 by rTMS may improve motor performance in the ipsilateral hand by releasing the contralateral M1 from transcallosal inhibition. Methods: Sixteen healthy volunteers participated. Using a sequential key-pressing task with the index finger, motor performance was monitored before and after rTMS (1 Hz for 10 minutes with the intensity below motor threshold) applied to the ipsilateral M1, contralateral M1, ipsilateral premotor area, or vertex (Cz). Results: rTMS of M1 shortened execution time of the motor task with the ipsilateral hand without affecting performance with the contralateral hand. This effect outlasted rTMS by at least 10 minutes, was specific for M1 stimulation, and was associated with increased intracortical excitability in the unstimulated M1. Conclusions: The authors’ results support the concept of an interhemispheric “rivalry.” They demonstrate the utility of repetitive transcranial magnetic stimulation to explore the functional facilitation of the unstimulated counterpart motor cortex, presumably via suppression of activity in the stimulated motor cortex and transcallosal inhibition.

Long-term and cumulative effects of sports concussion on motor cortex inhibition.

OBJECTIVE Using transcranial magnetic stimulation paradigms, this study investigated motor cortex integrity as a function of an athletes prior history of concussions. PATIENTS AND METHODS Motor cortex excitatory and inhibitory mechanisms were studied in athletes using four different transcranial magnetic stimulation protocols, namely 1) resting motor threshold, 2) intracortical inhibition and intracortical facilitation in a paired-pulse paradigm, 3) excitability of the corticospinal system using an input-output curve, and 4) intracortical inhibition in a cortical silent-period paradigm. Motor-evoked potentials were recorded from the first dorsal interosseous muscle of the right hand. RESULTS Cortical silent-period duration in athletes who have experienced multiple concussions was prolonged when compared to that of normal control participants. Linear regression suggested that concussion severity was the main factor explaining motor cortex dysfunction. Moreover, when we retested the athletes, the cortical silent period was more prolonged in those who sustained another concussion after baseline testing had occurred. CONCLUSION Findings from this study indicate that sports-related concussions result in long-term motor system dysfunctions that seem to be attributable to subclinical intracortical inhibitory system abnormalities. This study also shows that sustaining subsequent concussions exacerbates this deficit, and thus provides additional support for the contention that the adverse effects of sports-related concussions on intracortical inhibitory systems are cumulative.

Acute and Chronic Changes in Diffusivity Measures after Sports Concussion

Despite negative neuroimaging findings in concussed athletes, studies indicate that the acceleration and deceleration of the brain after concussive impacts result in metabolic and electrophysiological alterations that may be attributable to changes in white matter resulting from biomechanical strain. In the present study we investigated the effects of sports concussion on white matter using three different diffusion tensor imaging (DTI) measures: fractional anisotropy (FA), mean diffusivity (MD), and axial diffusivity (AD). We compared a group of 10 non-concussed athletes with a group of 18 concussed athletes of the same age (mean age 22.5 years) and education (mean 16 years) using a voxel-based approach (VBA) in both the acute and chronic post-injury phases. All concussed athletes were scanned 1-6 days post-concussion and again 6 months later in a 3T Siemens Trio(™) MRI. Three 2×2 repeated-measures analyses of variance (ANOVAs) were conducted, one for each measure of DTI used in the current study. There was a main group effect of FA, which was increased in dorsal regions of both corticospinal tracts (CST) and in the corpus callosum in concussed athletes at both time points. There was a main group effect of AD in the right CST, where concussed athletes showed elevated values relative to controls at both time points. MD values were decreased in concussed athletes, in whom analyses revealed significant group differences in the CST and corpus callosum at both time points. Although the use of VBA does limit the analyses to large tracts, and it has clinical limitations with regard to individual analyses, our results nevertheless indicate that sports concussions do result in changes in diffusivity in the corpus callosum and CST that are not detected using conventional neuroimaging techniques.

Improved naming after TMS treatments in a chronic, global aphasia patient – case report

We report improved ability to name pictures at 2 and 8 months after repetitive transcranial magnetic stimulation (rTMS) treatments to the pars triangularis portion of right Broca’s homologue in a 57 year-old woman with severe nonfluent/global aphasia (6.5 years post left basal ganglia bleed, subcortical lesion). TMS was applied at 1 Hz, 20 minutes a day, 10 days, over a two-week period. She received no speech therapy during the study. One year after her TMS treatments, she entered speech therapy with continued improvement. TMS may have modulated activity in the remaining left and right hemisphere neural network for naming.

EEG evidence for the presence of an action observation–execution matching system in children

In the adult human brain, passive observation of actions performed by others activates some of the same cortical areas that are involved in the execution of actions, thereby contributing to action recognition. This mechanism appears to occur through activation of a population of action‐coding cells known as mirror neurons (MN). In the adult motor cortex, performing actions and observing human movement reduces the magnitude of the mu (8–13 Hz) rhythm, possibly reflecting MN system activity. Despite the wealth of information available regarding the adult MN system, little is known about its existence in children. Here, we used EEG to probe mu rhythm modulation in 15 children during observation and execution of hand actions. Our data show that mu rhythm attenuation occurs in children under 11 years old during observation of hand movements. Similarly to what has been reported in adults, observation of goal/object‐orientated movement produces greater modulation of the mu rhythm than intransitive movement. These data confirm the existence of an observation–execution matching system in the immature human brain and may be of clinical value in the understanding of neurodevelopmental disorders associated with a faulty MN system, such as autism spectrum disorder.

Mutations in DCC cause congenital mirror movements.

Humans who display involuntary symmetrical limb movements carry mutations in a gene required for nerve growth across the midline. Mirror movements are involuntary contralateral movements that mirror voluntary ones and are often associated with defects in midline crossing of the developing central nervous system. We studied two large families, one French Canadian and one Iranian, in which isolated congenital mirror movements were inherited as an autosomal dominant trait. We found that affected individuals carried protein-truncating mutations in DCC (deleted in colorectal carcinoma), a gene on chromosome 18q21.2 that encodes a receptor for netrin-1, a diffusible protein that helps guide axon growth across the midline. Functional analysis of the mutant DCC protein from the French Canadian family revealed a defect in netrin-1 binding. Thus, DCC has an important role in lateralization of the human nervous system.

Braille character discrimination in blindfolded human subjects.

&NA; Visual deprivation may lead to enhanced performance in other sensory modalities. Whether this is the case in the tactile modality is controversial and may depend upon specific training and experience. We compared the performance of sighted subjects on a Braille character discrimination task to that of normal individuals blindfolded for a period of five days. Some participants in each group (blindfolded and sighted) received intensive Braille training to offset the effects of experience. Blindfolded subjects performed better than sighted subjects in the Braille discrimination task, irrespective of tactile training. For the left index finger, which had not been used in the formal Braille classes, blindfolding had no effect on performance while subjects who underwent tactile training outperformed non‐stimulated participants. These results suggest that visual deprivation speeds up Braille learning and may be associated with behaviorally relevant neuroplastic changes.