Physiological, Anatomical and Metabolic Correlates of Aerobic Fitness in Human Primary Motor Cortex: A Multimodal Study.

Physical activity (PA) has been shown to benefit various cognitive functions and promote neuroplasticity. Whereas the effects of PA on brain anatomy and function have been well documented in older individuals, data are scarce in young adults. Whether high levels of cardiorespiratory fitness (CRF) achieved through regular PA are associated with significant structural and functional changes in this age group remains largely unknown. In the present study, twenty young adults that engaged in at least 8 hours per week of aerobic exercise during the last 5 years were compared to twenty sedentary controls on measures of cortical excitability, white matter microstructure, cortical thickness and metabolite concentration. All measures were taken in the left primary motor cortex and CRF was assessed with VO2max. Transcranial magnetic stimulation (TMS) revealed higher corticospinal excitability in high- compared to low-fit individuals reflected by greater input/output curve amplitude and slope. No group differences were found for other TMS (short-interval intracortical inhibition and intracortical facilitation), diffusion MRI (fractional anisotropy and apparent fiber density), structural MRI (cortical thickness) and magnetic resonance spectroscopy (NAA, GABA, Glx) measures. Taken together, the present data suggest that brain changes associated with increased CRF are relatively limited, at least in primary motor cortex, in contrast to what has been observed in older adults.

The neurophysiological aftereffects of brain stimulation in human primary motor cortex: a Sham-controlled comparison of three protocols.

Paired associative stimulation (PAS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) are non-invasive brain stimulation methods that are used to modulate cortical excitability. Whether one technique is superior to the others in achieving this outcome and whether individuals that respond to one intervention are more likely to respond to another remains largely unknown. In the present study, the neurophysiological aftereffects of three excitatory neurostimulation protocols were measured with transcranial magnetic stimulation (TMS). Twenty minutes of PAS at an ISI of 25 ms, anodal tDCS, 20-Hz tACS, and Sham stimulation were administered to 31 healthy adults in a repeated measures design. Compared with Sham, none of the stimulation protocols significantly modulated corticospinal excitability (input/ouput curve and slope, TMS stimulator intensity required to elicit MEPs of 1-mV amplitude) or intracortical excitability (short- and long-interval intracortical inhibition, intracortical facilitation, cortical silent period). Sham-corrected responder analysis estimates showed that an average of 41 (PAS), 39 (tDCS), and 39% (tACS) of participants responded to the interventions with an increase in corticospinal excitability. The present data show that three stimulation protocols believed to increase cortical excitability are associated with highly heterogenous and variable aftereffects that may explain a lack of significant group effects.

Stability and test-retest reliability of neuronavigated TMS measures of corticospinal and intracortical excitability.

The present study aimed at investigating the long-term stability and test-retest reliability of neuronavigated transcranial magnetic stimulation (nTMS) measures of cortical excitability, inhibition, and facilitation in the primary motor cortex. To fulfill these aims, thirty-one healthy adults underwent four nTMS sessions, over an average one-month period. Stability and test-retest reliability statistics were computed and analyzed to produce smallest real difference statistics, which indicate the absolute variation in a measurement that is likely to be the result of error (randomness). Excellent reliability was found for resting motor thresholds, which reflect baseline neuronal excitability. Good reliability statistics were found for input/output curve measurements, which reflect the excitability of a highly plastic neuronal population. Using the slope of mean amplitudes throughout the input/output curve or the stimulator intensity required to elicit motor evoked potentials of 1 mV presented good to excellent measurement reliability for global cortical excitability indexing, compared to mean MEP at a given intensity. Overall, this methodological study provides useful and novel information on transcranial magnetic stimulation interventions by providing smallest real difference statistics that inform on potential response thresholds across time, contributing to the validation of these measurements as clinical monitoring tools across time.

Transcranial Magnetic Stimulation and H1-Magnetic Resonance Spectroscopy Measures of Excitation and Inhibition Following Lorazepam Administration.

This study aimed at better understanding the neurochemistry underlying transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS) measurements as it pertains to GABAergic activity following administration of allosteric GABAA receptor agonist lorazepam. Seventeen healthy adults (8 females, 26.0 ±â€¯5.4 years old) participated in a double-blind, crossover, placebo-controlled study, where participants underwent TMS and MRS two hours after drug intake (placebo or lorazepam; 2.5 mg). Neuronavigated TMS measures reflecting cortical inhibition and excitation were obtained in the left primary motor cortex. Sensorimotor cortex and occipital cortex MRS data were acquired using a 3T scanner with a MEGA-PRESS sequence, allowing water-referenced [GABA] and [Glx] (glutamate + glutamine) quantification. Lorazepam administration decreased occipital [GABA], decreased motor cortex excitability and increased GABAA-receptor mediated motor cortex inhibition (short intracortical inhibition (SICI)). Lorazepam intake did not modulate sensorimotor [GABA] and TMS measures of intra-cortical facilitation, long-interval cortical inhibition, cortical silent period, and resting motor threshold. Furthermore, higher sensorimotor [GABA] was associated with higher cortical inhibition (SICI) following lorazepam administration, suggesting that baseline sensorimotor [GABA] may be valuable in predicting pharmacological or neuromodulatory treatment response. Finally, the differential effects of lorazepam on MRS and TMS measures, with respect to GABA, support the idea that TMS measures of cortical inhibition reflect synaptic GABAergic phasic inhibitory activity while MRS reflects extrasynaptic GABA.

Longitudinal assessment of 1H-MRS (GABA and Glx) and TMS measures of cortical inhibition and facilitation in the sensorimotor cortex.

The purpose of the present study was to investigate the long-term stability of water-referenced GABA and Glx neurometabolite concentrations in the sensorimotor cortex using MRS and to assess the long-term stability of GABA- and glutamate-related intracortical excitability using transcranial magnetic stimulation (TMS). Healthy individuals underwent two sessions of MRS and TMS at a 3-month interval. A MEGA-PRESS sequence was used at 3 T to acquire MRS signals in the sensorimotor cortex. Metabolites were quantified by basis spectra fitting and metabolite concentrations were derived using unsuppressed water reference scans accounting for relaxation and partial volume effects. TMS was performed using published standards. After performing stability and reliability analyses for MRS and TMS, reliable change indexes were computed for all measures with a statistically significant test-retest correlation. No significant effect of time was found for GABA, Glx and TMS measures. There was an excellent ICC and a strong correlation across time for GABA and Glx. Analysis of TMS measure stability revealed an excellent ICC for rMT CSP and %MSO and a fair ICC for 2 ms SICI. There was no significant correlation between MRS and TMS measures at any time point. This study shows that MRS-GABA and MRS-Glx of the sensorimotor cortex have good stability over a 3-month period, with variability across time comparable to that reported in other brain areas. While resting motor threshold, %MSO and CSP were found to be stable and reliable, other TMS measures had greater variability and lesser reliability.

BDNF Val66Met polymorphism is associated with altered activity-dependent modulation of short-interval intracortical inhibition in bilateral M1.

The BDNF Val66Met polymorphism is associated with impaired short-term plasticity in the motor cortex, short-term motor learning, and intermanual transfer of a procedural motor skill. Here, we investigated the impact of the Val66Met polymorphism on the modulation of cortical excitability and interhemispheric inhibition through sensorimotor practice of simple dynamic skills with the right and left first dorsal interosseous (FDI) muscles. To that end, we compared motor evoked potentials (MEP) amplitudes and short-interval intracortical inhibition (SICI) in the bilateral representations of the FDI muscle in the primary motor cortex (M1), and interhemispheric inhibition (IHI) from the left to right M1, before and after right and left FDI muscle training in an alternated sequence. Val66Met participants did not differ from their Val66Val counterparts on motor performance at baseline and following motor training, or on measures of MEP amplitude and IHI. However, while the Val66Val group displayed significant SICI reduction in the bilateral M1 in response to motor training, SICI remained unchanged in the Val66Met group. Further, Val66Val group's SICI decrease in the left M1, which was also observed following unimanual training with the right hand in the Control Right group, was correlated with motor improvement with the left hand. The potential interaction between left and right M1 activity during bimanual training and the implications of altered activity-dependent cortical excitability on short-term motor learning in Val66Met carriers are discussed.

Action Video Game Playing Is Reflected In Enhanced Visuomotor Performance and Increased Corticospinal Excitability.

Action video game playing is associated with improved visuomotor performance; however, the underlying neural mechanisms associated with this increased performance are not well understood. Using the Serial Reaction Time Task in conjunction with Transcranial Magnetic Stimulation, we investigated if improved visuomotor performance displayed in action video game players (actionVGPs) was associated with increased corticospinal plasticity in primary motor cortex (M1) compared to non-video game players (nonVGPs). Further, we assessed if actionVGPs and nonVGPs displayed differences in procedural motor learning as measured by the SRTT. We found that at the behavioral level, both the actionVGPs and nonVGPs showed evidence of procedural learning with no significant difference between groups. However, the actionVGPs displayed higher visuomotor performance as evidenced by faster reaction times in the SRTT. This observed enhancement in visuomotor performance amongst actionVGPs was associated with increased corticospinal plasticity in M1, as measured by corticospinal excitability changes pre- and post- SRTT and corticospinal excitability at rest before motor practice. Our results show that aVGPs, who are known to have better performance on visual and motor tasks, also display increased corticospinal excitability after completing a novel visuomotor task.