Altered motor system function in post-concussion syndrome as assessed via transcranial magnetic stimulation.

OBJECTIVE: It is unclear why specific individuals incur chronic symptoms following a concussion. This exploratory research aims to identify and characterize any neurophysiological differences that may exist in motor cortex function in post-concussion syndrome (PCS). METHODS: Fifteen adults with PCS and 13 healthy, non-injured adults were tested. All participants completed symptom questionnaires, and transcranial magnetic stimulation (TMS) was used to measure intracortical and transcallosal excitability and inhibition in the dominant motor cortex. RESULTS: Cortical silent period (p = 0.02, g = 0.96) and ipsilateral silent period (p = 0.04, g = 0.78) were shorter in the PCS group compared to the control group which may reflect reduced GABA-mediated inhibition in PCS. Furthermore, increased corticomotor excitability was observed in the left hemisphere but not the right hemisphere. CONCLUSIONS: These data suggest that persistent neurophysiological differences are present in those with PCS. The exact contributing factors to such changes remain to be investigated by future studies. SIGNIFICANCE: This study provides novel evidence of lasting neurophysiological changes in PCS.

A Single Bout of High-intensity Interval Exercise Increases Corticospinal Excitability, Brain-derived Neurotrophic Factor, and Uncarboxylated Osteolcalcin in Sedentary, Healthy Males.

Exercise induces neuroplasticity in descending motor pathways facilitating motor learning, and as such it could be utilized as an intervention in neurorehabilitation, for example when re-learning motor skills after stroke. To date, however, the neurophysiological and molecular mechanisms underlying exercise-induced neuroplasticity remain largely unknown impeding the potential utilization of exercise protocols as 'motor learning boosters' in clinical and non-clinical settings. Here, we assessed corticospinal excitability, intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI) using transcranial magnetic stimulation (TMS) and serum biochemical markers including brain-derived neurotrophic factor (BDNF), total and precursor cathepsin B (tCTSB, proCTSB), uncarboxylated and carboxylated osteocalcin (unOCN, cOCN) and irisin using ELISA. Measurements were carried out in sedentary, healthy males before and after a single session of high-intensity interval exercise (HIIE) or in individuals who rested and did not perform exercise (No Exercise). We found that HIIE increased corticospinal excitability, BDNF and unOCN, and decreased cOCN. We also determined that greater increases in BDNF were associated with increases in unOCN and irisin and decreases in cOCN only in participants who underwent HIIE, suggesting that unOCN and irisin may contribute to exercise-induced BDNF increases. Conversely, no changes other than a decrease in serum unOCN/tOCN were found in No Exercise participants. The present findings show that a single session of HIIE is sufficient to modulate corticospinal excitability and to increase BDNF and unOCN in sedentary, healthy males.

Fitness Level Influences White Matter Microstructure in Postmenopausal Women.

Aerobic exercise has both neuroprotective and neurorehabilitative benefits. However, the underlying mechanisms are not fully understood and need to be investigated, especially in postmenopausal women, who are at increased risk of age-related disorders such as Alzheimer's disease and stroke. To advance our understanding of the potential neurological benefits of aerobic exercise in aging women, we examined anatomical and functional responses that may differentiate women of varying cardiorespiratory fitness using neuroimaging and neurophysiology. A total of 35 healthy postmenopausal women were recruited (59 ± 3 years) and cardiorespiratory fitness estimated (22-70 mL/kg/min). Transcranial magnetic stimulation was used to assess -aminobutyric acid (GABA) and glutamate (Glu) receptor function in the primary motor cortex (M1), and magnetic resonance spectroscopy (MRS) was used to quantify GABA and Glu concentrations in M1. Magnetic resonance imaging was used to assess mean cortical thickness (MCT) of sensorimotor and frontal regions, while the microstructure of sensorimotor and other white matter tracts was evaluated through diffusion tensor imaging. Regression analysis revealed that higher fitness levels were associated with improved microstructure in pre-motor and sensory tracts, and the hippocampal cingulum. Fitness level was not associated with MCT, MRS, or neurophysiology measures. These data indicate that, in postmenopausal women, higher cardiorespiratory fitness is linked with preserved selective white matter microstructure, particularly in areas that influence sensorimotor control and memory.

A controlled clinical crossover trial of exercise training to improve cognition and neural communication in pediatric brain tumor survivors.

OBJECTIVE: To assess the efficacy of aerobic exercise training to improve controlled attention, information processing speed and neural communication during increasing task load and rest in pediatric brain tumor survivors (PBTS) treated with cranial radiation. METHODS: Participants completed visual-motor Go and Go/No-Go tasks during magnetoencephalography recording prior to and following the completion of 12-weeks of exercise training. Exercise-related changes in response accuracy and visual-motor latency were evaluated with Linear Mixed models. The Phase Lag Index (PLI) was used to estimate functional connectivity during task performance and rest. Changes in PLI values after exercise training were assessed using Partial Least Squares analysis. RESULTS: Exercise training predicted sustained (12-weeks) improvement in response accuracy (p<0.05) during No-Go trials. Altered functional connectivity was detected in theta (4-7Hz) alpha (8-12Hz) and high gamma (60-100Hz) frequency bands (p<0.001) during Go and Go/No-Go trials. Significant changes in response latency and resting state connectivity were not detected. CONCLUSION: These findings support the efficacy of aerobic exercise to improve controlled attention and enhance functional mechanisms under increasing task load in participants. SIGNIFICANCE: It may be possible to harness the beneficial effects of exercise as therapy to promote cognitive recovery and enhance brain function in PBTS.

No changes in corticospinal excitability, biochemical markers, and working memory after six weeks of high-intensity interval training in sedentary males.

A single bout of aerobic exercise modulates corticospinal excitability, intracortical circuits, and serum biochemical markers such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1). These effects have important implications for the use of exercise in neurorehabilitation. Here, we aimed to determine whether increases in cardiorespiratory fitness (CRF) induced by 18 sessions of high-intensity interval training (HIIT) over 6 weeks were accompanied by changes in corticospinal excitability, intracortical excitatory and inhibitory circuits, serum biochemical markers and working memory (WM) capacity in sedentary, healthy, young males. We assessed motor evoked potential (MEP) recruitment curves for the first dorsal interosseous (FDI) both at rest and during tonic contraction, intracortical facilitation (ICF), and short-interval intracortical inhibition (SICI) using transcranial magnetic stimulation (TMS). We also examined serum levels of BDNF, IGF-1, total and precursor (pro) cathepsin B (CTSB), as well as WM capacity. Compared to pretraining, CRF was increased and ICF reduced after the HIIT intervention, but there were no changes in corticospinal excitability, SICI, BDNF, IGF-1, total and pro-CTSB, and WM capacity. Further, greater CRF gains were associated with larger decreases in total and pro-CTSB and, only in Val/Val carriers, with larger increases in SICI. Our findings confirm that HIIT is efficacious in promoting CRF and show that corticospinal excitability, biochemical markers, and WM are unchanged after 18 HIIT bouts in sedentary males. Understanding how aerobic exercise modulates M1 excitability is important in order to be able to use exercise protocols as an intervention, especially in rehabilitation following brain injuries.

Human motor cortical organization is influenced by handedness.

Although there is some evidence that handedness is associated with structural and functional differences in the motor cortex, findings remain inconclusive. Here, we evaluated whether handedness influences the location, size and overlap of the cortical representations of upper limb muscles across hemispheres in right- versus left-handed individuals. Using transcranial magnetic stimulation, the cortical representations of abductor pollicis brevis, flexor carpi radialis and biceps brachii muscles were mapped bilaterally with a 6 by 5 grid space. Results indicate that right-handers had more lateral and posterior representations in the non-dominant hemisphere as well as greater overall cortical territory compared to left-handers. Right- and left-handers did not differ in the extent of overlap between muscle representations. Our findings suggest that human motor cortical organization of upper limb muscles is indeed influenced by handedness, specifically with regard to the location of non-dominant cortical muscle representations and the size of cortical territory dedicated to upper limb muscle representations.

Dynamic 31 P spectroscopic imaging of skeletal muscles combining flyback echo-planar spectroscopic imaging and compressed sensing.

PURPOSE: Dynamic phosphorus MR spectroscopic imaging (31 P-MRSI) experiments require temporal resolution on the order of seconds to concurrently assess different muscle groups. A highly accelerated pulse sequence combining flyback echo-planar spectroscopic imaging (EPSI) and compressed sensing was developed and tested in a phantom and healthy humans during an exercise-recovery challenge of the lower leg muscles, using a clinical 3T MRI. METHODS: A flyback EPSI readout designed to achieve 2.25 × 2.25 cm2 resolution over a 18 × 18 cm2 field of view (i.e., 8 × 8 matrix) was combined with compressed sensing through the inclusion of pseudorandom gradient blips to sub-sample the ky-kt dimensions by a factor of 2.7×, achieving a temporal resolution of 9 s. The sequence was first tested in a phantom to assess performance compared to fully sampled EPSI (fidEPSI) and phase encoded chemical shift imaging (fidCSI). Then, tests were performed in 11 healthy volunteers during an exercise-recovery challenge of the lower leg muscles. Voxels containing tissue from different muscle groups were evaluated measuring percentage phosphocreatine (%PCr) depletion, time constant of PCr recovery (τPCr) and intracellular pH at rest and following exercise. RESULTS: The sequence was capable to track the dynamic PCr response of multiple muscles simultaneously. No statistical differences were found in the metabolite ratio, pH or linewidth when compared with fidEPSI and fidCSI in the phantom study. Dynamic experiments showed differences in PCr depletion when comparing soleus with gastrocnemius muscles. Intracellular pH, τPCr and %PCr decrease were consistent with reported values. CONCLUSION: Highly accelerated 31 P-MRSI combining flyback EPSI and compressed sensing is capable of assessing concurrent energy metabolism in multiple muscle groups using a clinical 3T MR system.

Exercise-Induced Neuroplasticity: A Mechanistic Model and Prospects for Promoting Plasticity.

Aerobic exercise improves cognitive and motor function by inducing neural changes detected using molecular, cellular, and systems level neuroscience techniques. This review unifies the knowledge gained across various neuroscience techniques to provide a comprehensive profile of the neural mechanisms that mediate exercise-induced neuroplasticity. Using a model of exercise-induced neuroplasticity, this review emphasizes the sequence of neural events that accompany exercise, and ultimately promote changes in human performance. This is achieved by differentiating between neuroplasticity induced by acute versus chronic aerobic exercise. Furthermore, this review emphasizes experimental considerations that influence the opportunity to observe exercise-induced neuroplasticity in humans. These include modifiable factors associated with the exercise intervention and nonmodifiable factors such as biological sex, ovarian hormones, genetic variations, and fitness level. To maximize the beneficial effects of exercise in health, disease, and following injury, future research should continue to explore the mechanisms that mediate exercise-induced neuroplasticity. This review identifies some fundamental gaps in knowledge that may serve to guide future research in this area.

Sources of Variability and Improvements in the Measure of GABA using MEGA-PRESS at 3T.

With the emergence of research investigating the role of gamma-aminobutyric acid (GABA) in neurological and neuropsychiatric diseases, it is important to understand the variability in GABA as measured through magnetic resonance spectroscopy (MRS) and how this variability may affect the interpretation of results. This review addresses methodological sources of variation documented in the current literature on the measurement of GABA. GABA differences related to hardware, acquisition, post-processing and quantification are discussed, and methods to account for or remove this variability are highlighted. Additionally, factors such as time, age, biological sex, hormones, and brain region, which may affect GABA MRS, are reviewed to aid in study design. This review is meant to assist in measuring GABA comparably between studies and improve GABA methodology to allow the use of GABA MRS in a clinical setting in the future.