Neurotransmitter levels in the basal ganglia are associated with intracortical circuit activity of the primary motor cortex in healthy humans.

BACKGROUND: The basal ganglia are strongly connected to the primary motor cortex (M1) and play a crucial role in movement control. Interestingly, several disorders showing abnormal neurotransmitter levels in basal ganglia also present concomitant anomalies in intracortical function within M1. OBJECTIVE/HYPOTHESIS: The main aim of this study was to clarify the relationship between neurotransmitter content in the basal ganglia and intracortical function at M1 in healthy individuals. We hypothesized that neurotransmitter content of the basal ganglia would be significant predictors of M1 intracortical function. METHODS: We combined magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation (TMS) to test this hypothesis in 20 healthy adults. An extensive TMS battery probing common measures of intracortical, and corticospinal excitability was administered, and GABA and glutamate-glutamine levels were assessed from voxels placed over the basal ganglia and the occipital cortex (control region). RESULTS: Regression models using metabolite concentration as predictor and TMS metrics as outcome measures showed that glutamate level in the basal ganglia significantly predicted short interval intracortical inhibition (SICI) and intracortical facilitation (ICF), while GABA content did not. No model using metabolite measures from the occipital control voxel was significant. CONCLUSIONS: Taken together, these results converge with those obtained in clinical populations and suggest that intracortical circuits in human M1 are associated with the neurotransmitter content of connected but distal subcortical structures crucial for motor function.

Exploratory analysis of cortical thickness in low- and high-fit young adults.

OBJECTIVE: Studies have shown changes in the human brain associated with physical activity and cardiorespiratory fitness (CRF). The effects of CRF on cortical thickness have been well-described in older adults, where a positive association between CRF and cortical thickness has been reported, but the impact of sustained aerobic activity in young adults remains poorly described. Here, exploratory analysis was performed on cortical thickness data that was collected in groups of fit and sedentary young adults. METHODS: Twenty healthy sedentary individuals (<2 h/week physical activity) were compared to 20 active individuals (>6 h/week physical activity) and cortical thickness was measured in 34 cortical areas. Cortical thickness values were compared between groups, and correlations between cortical thickness and VO2 max were tested. RESULTS: Cardiorespiratory fitness was significantly higher in active individuals compared to sedentary individuals. Cortical thickness was lower in regions of the left (lateral and medial orbitofrontal cortex, pars orbitalis, pars triangularis, rostral anterior cingulate cortex, superior temporal cortex and frontal pole) and right (lateral and medial orbitofrontal cortex and pars opercularis) hemispheres. Only the left frontal pole and right lateral orbitofrontal cortical thickness remained significant after false discovery rate correction. Negative correlations were observed between VO2 max and cortical thickness in the left (frontal pole) and right (caudal anterior cingulate and medial orbitofrontal cortex) hemispheres. CONCLUSION: The present exploratory analysis supports previous findings suggesting that neuroplastic effects of cardiorespiratory fitness may be attenuated in young compared with older individuals, underscoring a moderating effect of age on the relationship between fitness and cortical thickness.

The effects of transcranial direct current stimulation on corticospinal excitability: A systematic review of nonsignificant findings.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate brain activity through the application of low-intensity electrical currents. Based on its reported effects on corticospinal excitability (CSE), tDCS has been used to study cognition in healthy individuals and reduce symptoms in a variety of clinical conditions. Despite its increasing popularity as a research and clinical tool, high interindividual variability has been reported in the response to protocols using transcranial magnetic stimulation (TMS) to assess tDCS-induced changes in CSE leading to several nonsignificant findings. In this systematic review, studies that reported no significant modulation of CSE following tDCS were identified from PubMed and Embase (Ovid) databases. Forty-three articles were identified where demographic, TMS and tDCS parameters were extracted. Overall, stimulation parameters, CSE measurements and participant characteristics were similar to those described in studies reporting positive results and were likewise heterogeneous between studies. Small sample sizes and inadequate blinding were notable features of the reviewed studies. This systematic review suggests that studies reporting nonsignificant findings do not markedly differ from those reporting significant modulation of CSE.

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.

The neurobiological markers of acute alcohol's subjective effects in humans.

The ingestion of alcohol yields acute biphasic subjective effects: stimulation before sedation. Despite their predictive relevance to the development of alcohol use disorders (AUD), the neurobiological markers accounting for the biphasic effects of alcohol remain poorly understood in humans. Informed by converging lines of evidence, this study tested the hypothesis that alcohol ingestion acutely increases gamma-aminobutyric acid (GABA)-mediated inhibition, which would positively and negatively predict the feeling of stimulation and sedation, respectively. To do so, healthy participants (n = 20) ingested a single dose of 94% ABV alcohol (males: 1.0 ml/kg; females: 0.85 ml/kg) in a randomized placebo-controlled cross-over design. The alcohol's biphasic effects were assessed with the Brief-Biphasic Alcohol Effects Scale, and non-invasive neurobiological markers were measured with transcranial magnetic stimulation, before and every 30 min (up to 120 min) after the complete ingestion of the beverage. Results showed that acute alcohol ingestion selectively increased the duration of the cortical silent period (CSP) as compared to placebo, suggesting that alcohol increases non-specific GABAergic inhibition. Importantly, CSP duration positively and negatively predicted increases in the feeling of stimulation and sedation, respectively, suggesting that stimulation emerges as GABAergic inhibition increases and that sedation emerges as GABAergic inhibition returns to baseline values. Overall, these results suggest that modulations of GABAergic inhibition are central to the acute biphasic subjective effects of alcohol, providing a potential preventive target to curb the progression of at-risk individuals to AUD.

Dose-response of intermittent theta burst stimulation of the prefrontal cortex: A TMS-EEG study.

OBJECTIVE: Using concurrent transcranial magnetic stimulation (TMS) and electroencephalography (TMS-EEG), this study aims to compare the effect of three intermittent theta-burst stimulation (iTBS) doses on cortical activity in the left dorsolateral prefrontal (DLPFC) cortex. METHODS: Fourteen neurotypical participants took part in the following three experimental conditions: 600, 1200 and 1800 pulses. TMS-EEG recordings were conducted on the left DLPFC pre/post iTBS, including single-pulse TMS and short- and long-interval intracortical inhibition (SICI, LICI). TMS-evoked potentials (TEP) and event-related spectral perturbation (ERSP) were quantified. Linear mixed models were used to assess the effect of iTBS on brain activity. RESULTS: The effects of iTBS on DLPFC activity did not significantly differ between the three doses. Specifically, regardless of dose, iTBS modulated the amplitude of most TEP components (P30, N45, P60, P200), reduced SICI and LICI ratios of P30 and P200, and decreased ERSP power of theta oscillations. CONCLUSIONS: In neurotypical individuals, doubling or tripling the number of iTBS pulses does not result in stronger potentiation of prefrontal activity. However, all iTBS conditions induced significant modulations of DLPFC activity. SIGNIFICANCE: Replicating the study in clinical populations could help define optimal parameters for clinical applications.

No aftereffects of high current density 10 Hz and 20 Hz tACS on sensorimotor alpha and beta oscillations.

Application of transcranial alternating current stimulation (tACS) is thought to modulate ongoing brain oscillations in a frequency-dependent manner. However, recent studies report various and sometimes inconsistent results regarding its capacity to induce changes in cortical activity beyond the stimulation period. Here, thirty healthy volunteers participated in a randomized, cross-over, sham-controlled, double-blind study using EEG to measure the offline effects of tACS on alpha and beta power. Sham and high current density tACS (1 mA; 10 Hz and 20 Hz; 0.32 mA/cm2) were applied for 20 min over bilateral sensorimotor areas and EEG was recorded at rest before and after stimulation for 20 min. Bilateral tACS was not associated with significant changes in local alpha and beta power frequencies at stimulation sites (C3 and C4 electrodes). Overall, the present results fail to provide evidence that bilateral tACS with high current density applied over sensorimotor regions at 10 and 20 Hz reliably modulates offline brain oscillation power at the stimulation site. These results may have implications for the design and implementation of future protocols aiming to induce sustained changes in brain activity, including in clinical populations.

Diffusion Tensor Imaging in Contact and Non-Contact University-Level Sport Athletes.

Subconcussive hits to the head and physical fitness both have been associated with alterations in white matter (WM) microstructure in partly overlapping areas of the brain. The aim of the present study was to determine whether WM damage associated with repeated exposure to subconcussive hits to the head in university level contact sports athletes is modulated by high levels of fitness. To this end, 72 students were recruited: 24 athletes practicing a varsity contact sport (A-CS), 24 athletes practicing a varsity non-contact sport (A-NCS), and 24 healthy non-athletes (NA). Participants underwent a magnetic resonance imaging session that included diffusion-weighted imaging. Between-groups, statistical analyses were performed with diffusion tensor imaging measures extracted by tractometry of sections of the corpus callosum and the corticospinal tract. Most significant effects were found in A-NCS who exhibited higher fractional anisotropy (FA) values than A-CS in almost all segments of the corpus callosum and in the corticospinal tract. The A-NCS also showed higher FA compared with NA in the anterior regions of the corpus callosum and the corticospinal tracts. No group difference was found between the A-CS and the NA groups. These data suggest that repeated subconcussive hits to the head lead to anisotropic changes in the WM that may counteract the beneficial effects associated with high levels of fitness.

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.

Neurophysiological aftereffects of 10 Hz and 20 Hz transcranial alternating current stimulation over bilateral sensorimotor cortex.

Alpha (8-12 Hz) and beta (13-30 Hz) oscillations are believed to be involved in motor control. Their modulation with transcranial alternating current stimulation (tACS) has been shown to alter motor behavior and cortical excitability. The aim of the present study was to determine whether tACS applied bilaterally over sensorimotor cortex at 10 Hz and 20 Hz modulates interhemispheric interactions and corticospinal excitability. Thirty healthy volunteers participated in a randomized, cross-over, sham-controlled, double-blind protocol. Sham and active tACS (10 Hz, 20 Hz, 1 mA) were applied for 20 min over bilateral sensorimotor areas. The physiological effects of tACS on corticospinal excitability and interhemispheric inhibition were assessed with transcranial magnetic stimulation. Physiological mirror movements were assessed to measure the overflow of motor activity to the contralateral M1 during voluntary muscle contraction. Bilateral 10 Hz tACS reduced corticospinal excitability. There was no significant effect of tACS on physiological mirror movements and interhemispheric inhibition. Ten Hz tACS was associated with response patterns consistent with corticospinal inhibition in 57% of participants. The present results indicate that application of tACS at the alpha frequency can induce aftereffects in sensorimotor cortex of healthy individuals.

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.

Neural function in DCC mutation carriers with and without mirror movements.

OBJECTIVE: Recently identified mutations of the axon guidance molecule receptor gene, DCC, present an opportunity to investigate, in living human brain, mechanisms affecting neural connectivity and the basis of mirror movements, involuntary contralateral responses that mirror voluntary unilateral actions. We hypothesized that haploinsufficient DCC+/- mutation carriers with mirror movements would exhibit decreased DCC mRNA expression, a functional ipsilateral corticospinal tract, greater "mirroring" motor representations, and reduced interhemispheric inhibition. DCC+/- mutation carriers without mirror movements might exhibit some of these features. METHODS: The participants (n = 52) included 13 DCC+/- mutation carriers with mirror movements, 7 DCC+/- mutation carriers without mirror movements, 13 relatives without the mutation or mirror movements, and 19 unrelated healthy volunteers. The multimodal approach comprised quantitative real time polymerase chain reaction, transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI) under resting and task conditions, and measures of white matter integrity. RESULTS: Mirror movements were associated with reduced DCC mRNA expression, increased ipsilateral TMS-induced motor evoked potentials, increased fMRI responses in the mirroring M1 and cerebellum, and markedly reduced interhemispheric inhibition. The DCC+/- mutation, irrespective of mirror movements, was associated with reduced functional connectivity and white matter integrity. INTERPRETATION: Diverse connectivity abnormalities were identified in mutation carriers with and without mirror movements, but corticospinal effects and decreased peripheral DCC mRNA appeared driven by the mirror movement phenotype. ANN NEUROL 2019;85:433-442.

Randomized, crossover, sham-controlled, double-blind study of transcranial direct current stimulation of left DLPFC on executive functions .

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique commonly used to modulate cognitive functions; so-called "anodal" stimulation is considered to increase cortical excitability while "cathodal" stimulation is presumed to have the opposite result. Yet, a growing number of recent studies question the robustness of this polarity-dependent effect, namely because of the important inter-individual variability with regards to tDCS modulatory effects. A plausible reason for this heterogenous response may lay in task impurity issues in the evaluation of cognitive functions. OBJECTIVE: To address the question of task impurity the NIH-Examiner, a neuropsychological test battery that uses latent variables, which assess the common variance across multiple measures of a given concept, was administered to 24 healthy individuals following tDCS. This battery contains 11 tasks and provides latent variables for general executive functioning, fluency, cognitive control and working memory. METHODS: Anodal, cathodal, and sham stimulation (20 minutes, 1.5 mA) was administered over left dorsolateral prefrontal cortex and right supra-orbital area in a randomized, crossover, sham-controlled, double blind protocol. RESULTS: Factorial scores and task performance indices of executive function were not modulated by tDCS. CONCLUSIONS: Offline tDCS has limited impact on executive functions at both the task and factorial levels. This suggests that reducing task impurity does not increase the effectiveness of tDCS in modulating cognitive functions.

Non-invasive brain stimulation in information systems research: A proof-of-concept study.

One of the founding experiments in the field of Neuro-Information-Systems (NeuroIS), which aims at exploring the neural correlates of the technology acceptance model, suggests that perceived ease of use (PEoU) is associated with activity in the dorsolateral prefrontal cortex (DLPFC) while perceived usefulness is associated with activity in the insula, caudate nucleus and anterior cingulate cortex. To further assess the link between DLPFC and PEoU, transcranial direct current stimulation (tDCS) was applied over bilateral DLPFC (F3 and F4) immediately before an online shopping task. Forty-two participants were divided in three stimulation groups: left anodal/right cathodal, left cathodal/right anodal and sham. No change in PEoU was observed post stimulation but participants in the left anodal/right cathodal stimulation group took longer to make a purchase compared to sham stimulation and had different visual fixation patterns over the buy buttons. This is, to our knowledge, the first use of non-invasive brain stimulation in the field of NeuroIS. Although the involvement of DLPFC in PEoU could not be confirmed, the present study suggests that non-invasive brain stimulation may be a useful research tool in NeuroIS.

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.

Mesocorticolimbic Connectivity and Volumetric Alterations in DCC Mutation Carriers.

The axon guidance cue receptor DCC (deleted in colorectal cancer) plays a critical role in the organization of mesocorticolimbic pathways in rodents. To investigate whether this occurs in humans, we measured (1) anatomical connectivity between the substantia nigra/ventral tegmental area (SN/VTA) and forebrain targets, (2) striatal and cortical volumes, and (3) putatively associated traits and behaviors. To assess translatability, morphometric data were also collected in Dcc-haploinsufficient mice. The human volunteers were 20 DCC+/- mutation carriers, 16 DCC+/+ relatives, and 20 DCC+/+ unrelated healthy volunteers (UHVs; 28 females). The mice were 11 Dcc+/- and 16 wild-type C57BL/6J animals assessed during adolescence and adulthood. Compared with both control groups, the human DCC+/- carriers exhibited the following: (1) reduced anatomical connectivity from the SN/VTA to the ventral striatum [DCC+/+: p = 0.0005, r(effect size) = 0.60; UHV: p = 0.0029, r = 0.48] and ventral medial prefrontal cortex (DCC+/+: p = 0.0031, r = 0.53; UHV: p = 0.034, r = 0.35); (2) lower novelty-seeking scores (DCC+/+: p = 0.034, d = 0.82; UHV: p = 0.019, d = 0.84); and (3) reduced striatal volume (DCC+/+: p = 0.0009, d = 1.37; UHV: p = 0.0054, d = 0.93). Striatal volumetric reductions were also present in Dcc+/- mice, and these were seen during adolescence (p = 0.0058, d = 1.09) and adulthood (p = 0.003, d = 1.26). Together these findings provide the first evidence in humans that an axon guidance gene is involved in the formation of mesocorticolimbic circuitry and related behavioral traits, providing mechanisms through which DCC mutations might affect susceptibility to diverse neuropsychiatric disorders.SIGNIFICANCE STATEMENT Opportunities to study the effects of axon guidance molecules on human brain development have been rare. Here, the identification of a large four-generational family that carries a mutation to the axon guidance molecule receptor gene, DCC, enabled us to demonstrate effects on mesocorticolimbic anatomical connectivity, striatal volumes, and personality traits. Reductions in striatal volumes were replicated in DCC-haploinsufficient mice. Together, these processes might influence mesocorticolimbic function and susceptibility to diverse neuropsychiatric disorders.

A review of the effects of physical activity and sports concussion on brain function and anatomy.

Physical activity has been associated with widespread anatomical and functional brain changes that occur following acute exercise or, in the case of athletes, throughout life. High levels of physical activity through the practice of sports also lead to better general health and increased cognitive function. Athletes are at risk, however, of suffering a concussion, the effects of which have been extensively described for brain function and anatomy. The level to which these effects are modulated by increased levels of fitness is not known. Here, we review literature describing the effects of physical activity and sports concussions on white matter, grey matter, neurochemistry and cortical excitability. We suggest that the effects of sports concussion can be coufounded by the effects of exercise. Indeed, available data show that the brain of athletes is different from that of healthy individuals with a non-active lifestyle. As a result, sports concussions take place in a context where structural/functional plasticity has occurred prior to the concussive event. The sports concussion literature does not permit, at present, to separate the effects of intense and repeated physical activity, and the abrupt removal from such activities, from those of concussion on brain structure and function.

Increased Myo-Inositol in Primary Motor Cortex of Contact Sports Athletes without a History of Concussion.

The objective of the study was to determine whether repetitive hits to the head at a subclinical level are associated with structural and functional brain abnormalities and whether these effects are influenced by high levels of fitness associated with intense physical activity. Seventy-two college students were recruited: 24 nonathletic, 24 athletes practicing a varsity contact sport, and 24 athletes practicing a varsity noncontact sport. They were recruited for a neuropsychological evaluation and a magnetic resonance imaging session that included magnetic resonance spectroscopy of primary motor cortex (M1) and prefrontal cortex and susceptibility-weighted imaging. There was no evidence for reduced cognitive performance or presence of micro bleeds in contact sports athletes. Abnormalities in contact sports athletes were found for myo-inositol concentration (mIns) in M1, where levels were significantly higher compared with noncontact sports athletes (p = 0.016) and nonathletes (p = 0.029). In prefrontal cortex, glutamate + glutamine (Glx) was significantly reduced in contact sports athletes compared with noncontact sports athletes (p = 0.016), and a similar reduction was observed for gamma-aminobutyric acid (GABA) levels (p = 0.005). Varsity contact sports are associated with area-specific alterations in mIns concentration in the primary motor cortex. In the prefrontal cortex, high levels of fitness could modulate the effects of head impact exposure on prefrontal metabolite concentration. Indeed, although athletes in contact and noncontact sports show different neurometabolic profiles, they do not differ from sedentary controls.