Effects of Recent Concussion on Brain Bioenergetics: A Phosphorus-31 Magnetic Resonance Spectroscopy Study.

BACKGROUND: Although clinical evaluations and neurocognitive assessments are commonly used to evaluate the extent of and recovery from concussion, brain bioenergetics could provide a more quantitative marker. The neurometabolic response to a concussion is thought to increase neuronal energy consumption and thus the demand for nucleoside triphosphate (NTP). OBJECTIVE: We investigated the possible disruption in high-energy metabolism within the prefrontal cortex of college athletes who had either had a concussion within the past 6 months (n=14) or had never had a concussion (n=13). We hypothesized that concussed athletes would have imbalanced brain bioenergetics resulting from increased NTP consumption, and these biochemical changes would correspond to impaired cognitive abilities. METHODS: We used phosphorus-31 magnetic resonance spectroscopy to quantify high-energy phosphates. We performed the neuroimaging in conjunction with neurocognitive assessments targeting prefrontal cortex-mediated tasks. RESULTS: Our results revealed significantly lower γ-NTP levels in the athletes after concussion. Although the concussed and non-concussed participants performed similarly in neurocognitive assessments, lower levels of γ-NTP were associated with worse scores on neurocognitive tasks. CONCLUSIONS: Our results support the concept of increased energy demand in the prefrontal cortex of a concussed brain, and we found that while neurocognitive assessments appear normal, brain energetics may be abnormal. A longitudinal study could help establish brain NTP levels as a biomarker to aid in diagnosis and to assess recovery in concussed patients.

Fluctuations in total antioxidant capacity, catalase activity and hydrogen peroxide levels of follicular fluid during bovine folliculogenesis.

Follicular fluid is an important environment for oocyte development, yet current knowledge regarding its in vivo oxidant and antioxidant levels remains limited. Examining follicular fluid oxidants and antioxidants will improve understanding of their changes in vivo and contribute to optimisation of in vitro maturation conditions. The aim of the present study was to consider selected markers, namely catalase (CAT) enzyme activity, total antioxidant capacity (TAC) and hydrogen peroxide (H(2)O(2)) in follicular fluid samples (n = 503) originating from bovine antral follicles. The dynamic changes in two relevant antioxidant measures and one reactive oxygen species (ROS) were measured through stages of bovine follicular development and the oestrous cycle. CAT activity and H(2)O(2) levels decreased significantly as follicle size increased, whereas TAC increased significantly as follicle size increased. Lower TAC and higher H(2)O(2) in small follicles suggest increased ROS in the initial stages of folliculogenesis. Because CAT levels are highest in the follicular fluid of small follicles in the setting of an overall low TAC, CAT may represent a dominant antioxidant defence in the initial stages of folliculogenesis. Future studies must focus on other reactive oxygen species and their various scavenger types during antral folliculogenesis.

A resting state functional magnetic resonance imaging study of concussion in collegiate athletes.

Sports-related concussions are currently diagnosed through multi-domain assessment by a medical professional and may utilize neurocognitive testing as an aid. However, these tests have only been able to detect differences in the days to week post-concussion. Here, we investigate a measure of brain function, namely resting state functional connectivity, which may detect residual brain differences in the weeks to months after concussion. Twenty-one student athletes (9 concussed within 6 months of enrollment; 12 non-concussed; between ages 18 and 22 years) were recruited for this study. All participants completed the Wisconsin Card Sorting Task and the Color-Word Interference Test. Neuroimaging data, specifically resting state functional Magnetic Resonance Imaging data, were acquired to examine resting state functional connectivity. Two sample t-tests were used to compare the neurocognitive scores and resting state functional connectivity patterns among concussed and non-concussed participants. Correlations between neurocognitive scores and resting state functional connectivity measures were also determined across all subjects. There were no significant differences in neurocognitive performance between concussed and non-concussed groups. Concussed subjects had significantly increased connections between areas of the brain that underlie executive function. Across all subjects, better neurocognitive performance corresponded to stronger brain connectivity. Even at rest, brains of concussed athletes may have to 'work harder' than their healthy peers to achieve similar neurocognitive results. Resting state brain connectivity may be able to detect prolonged brain differences in concussed athletes in a more quantitative manner than neurocognitive test scores.

Vitamin D3 Supplemental Treatment for Mania in Youth with Bipolar Spectrum Disorders.

OBJECTIVE: We aimed to determine the effect of an open-label 8 week Vitamin D3 supplementation on manic symptoms, anterior cingulate cortex (ACC) glutamate, and γ-aminobutyric acid (GABA) in youth exhibiting symptoms of mania; that is, patients with bipolar spectrum disorders (BSD). We hypothesized that an 8 week Vitamin D3 supplementation would improve symptoms of mania, decrease ACC glutamate, and increase ACC GABA in BSD patients. Single time point metabolite levels were also evaluated in typically developing children (TD). METHODS: The BSD group included patients not only diagnosed with BD but also those exhibiting bipolar symptomology, including BD not otherwise specified (BD-NOS) and subthreshold mood ratings (Young Mania Rating Scale [YMRS] ≥8 and Clinical Global Impressions - Severity [CGI-S] ≥3). Inclusion criteria were: male or female participants, 6-17 years old. Sixteen youth with BSD exhibiting manic symptoms and 19 TD were included. BSD patients were asked to a take daily dose (2000 IU) of Vitamin D3 (for 8 weeks) as a supplement. Neuroimaging data were acquired in both groups at baseline, and also for the BSD group at the end of 8 week Vitamin D3 supplementation. RESULTS: Baseline ACC GABA/creatine (Cr) was lower in BSD than in TD (F[1,31]=8.91, p=0.007). Following an 8 week Vitamin D3 supplementation, in BSD patients, there was a significant decrease in YMRS scores (t=-3.66, p=0.002, df=15) and Children's Depression Rating Scale (CDRS) scores (t=-2.93, p=0.01, df=15); and a significant increase in ACC GABA (t=3.18, p=0.007, df=14). CONCLUSIONS: Following an 8 week open label trial with Vitamin D3, BSD patients exhibited improvement in their mood symptoms in conjunction with their brain neurochemistry.

Areas of the brain modulated by single-dose methylphenidate treatment in youth with ADHD during task-based fMRI: a systematic review.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder affecting 5% of children. Methylphenidate (MPH) is a common medication for ADHD. Studies examining MPH's effect on pediatric ADHD patients' brain function using functional magnetic resonance imaging (fMRI) have not been compiled. The goals of this systematic review were to determine (1) which areas of the brain in pediatric ADHD patients are modulated by a single dose of MPH, (2) whether areas modulated by MPH differ by task type performed during fMRI data acquisition, and (3) whether changes in brain activation due to MPH relate to clinical improvements in ADHD-related symptoms. METHODS: We searched the electronic databases PubMed and PsycINFO (1967-2011) using the following terms: ADHD AND (methylphenidate OR MPH OR ritalin) AND (neuroimaging OR MRI OR fMRI OR BOLD OR event related), and identified 200 abstracts, 9 of which were reviewed based on predefined criteria. RESULTS: In ADHD patients the middle and inferior frontal gyri, basal ganglia, and cerebellum were most often affected by MPH. The middle and inferior frontal gyri were frequently affected by MPH during inhibitory control tasks. Correlation between brain regions and clinical improvement was not possible due to the lack of symptom improvement measures within the included studies. CONCLUSIONS: Throughout nine task-based fMRI studies investigating MPH's effect on the brains of pediatric patients with ADHD, MPH resulted in increased activation within frontal lobes, basal ganglia, and cerebellum. In most cases, this increase "normalized" activation of at least some brain areas to that seen in typically developing children.