Obesity is a risk factor for stroke and neurodegenerative disease. Excess body fat has been linked to impaired glucose metabolism, insulin resistance, and impulsivity and may be a precursor to decline in attention and executive cognitive function. Here, we investigated the effects of high BMI on regional cerebral blood flow (rCBF) using single photon emission computed tomography (SPECT) imaging in healthy subjects. A total of 16 adult men and 20 adult women were recruited from the community between January 2003 and July 2009 as part of a healthy brain study (HBS) conducted at the Amen Clinics, a private medical facility. Participants in the study were screened to exclude medical, neurological, and psychiatric conditions, including substance abuse. Subjects were categorized as normal or overweight according to BMI. Using a two sample t-test, we determined the effects of BMI on rCBF in normal vs. overweight subjects. Subjects were matched for age and gender. Statistical parametric mapping (SPM) revealed a higher BMI in healthy individuals that is associated with decreased rCBF in Broadmann areas 8, 9, 10, 11, 32, and 44, brain regions involved in attention, reasoning, and executive function (P < 0.05, corrected for multiple comparisons). We found that an elevated BMI is associated with decreased rCBF in the prefrontal cortex of a healthy cohort. These results indicate that elevated BMI may be a risk factor for decreased prefrontal cortex function and potentially impaired executive function.

The ubiquitin proteasome system, generally known for its function in protein degradation, also appears to play an important role in regulating membrane trafficking. A role for the proteasome in regulating presynaptic release and vesicle trafficking has been proposed for invertebrates, but it remains to be tested in mammalian presynaptic terminals. We used the fluorescent styrylpyridinium dye FM4-64 to visualize changes in the recycling pool of vesicles in hippocampal culture under pharmacological inhibition of the proteasome. We found that a 2 h inhibition increases the recycling pool of vesicles by 76%, with no change in the rate or total amount of dye release. Interestingly, enhancement did not depend on protein synthesis but did depend on synaptic activity; blocking action potentials during proteasome inhibition abolished the effect whereas increasing neuronal activity accelerated the effect with an increased recycling pool evident after 15 min. We propose that the proteasome acts as a negative-feedback regulator of synaptic transmission, possibly serving a homeostatic role.

The authors recruited 100 active and former National Football League players, representing 27 teams and all positions. Players underwent a clinical history, brain SPECT imaging, qEEG, and multiple neuropsychological measures, including MicroCog. Relative to a healthy-comparison group, players showed global decreased perfusion, especially in the prefrontal, temporal, parietal, and occipital lobes, and cerebellar regions. Quantitative EEG findings were consistent, showing elevated slow waves in the frontal and temporal regions. Significant decreases from normal values were found in most neuropsychological tests. This is the first large-scale brain-imaging study to demonstrate significant differences consistent with a chronic brain trauma pattern in professional football players.

Suicide has a high comorbidity with impulsivity and depression, and finding imaging biomarkers indicative of patients at high risk for suicidal behavior is invaluable to the clinician. Using single-photon emission computed tomography (SPECT) imaging, we have previously reported regional cerebral blood flow (rCBF) decreases in the medial prefrontal cortex, ventral tegmental area and subgenual cingulate cortex (Brodmann area 25 (BA 25)), a region found to be hypoperfused with treatment-resistant depression. From 2007 to 2010, we have extended our analysis to include nine additional completed suicides. In all, 27 healthy, age- and gender-matched subjects from a previously acquired healthy brain study served as controls to our 21 completed suicides. All 21 suicides had been previously diagnosed with depression according to Diagnostic and Statistical Manual of Mental Disorder-IV criterion. Voxel-by-voxel analyses were performed using statistical parametric mapping to compare the differences in technetium-99m hexamethylpropylene amine oxime brain uptake between the groups. Factor analysis of the data identified the top 10 regions of hypoperfusion in the suicidal group, including the bilateral superior frontal lobes, the right precuneus, the rolandic operculum, postcentral gyrus, left caudate and insular cortex. We also demonstrate more focal decreases in rCBF in the subgenual cingulate cortex (BA 25) in 18 subjects, supporting our previous hypothesis that hypoperfusion of BA 25 may be a risk factor for suicide in depressed patients. This work suggests that SPECT might be useful in predicting risk for suicide completion in subjects with depression or treatment-resistant depression. Further investigation of this work is necessary to better understand the predictive value of this finding.

Background: National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public.Objective: To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls.Method: A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models.Results: NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification.Conclusion: Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This study carries implications for the neurological safety of NFL players.