Magnetoencephalography-based identification of functional connectivity network disruption following mild traumatic brain injury.

Mild traumatic brain injury (mTBI) leads to long-term cognitive sequelae in a significant portion of patients. Disruption of normal neural communication across functional brain networks may explain the deficits in memory and attention observed after mTBI. In this study, we used magnetoencephalography (MEG) to examine functional connectivity during a resting state in a group of mTBI subjects (n = 9) compared with age-matched control subjects (n = 15). We adopted a data-driven, exploratory analysis in source space using phase locking value across different frequency bands. We observed a significant reduction in functional connectivity in band-specific networks in mTBI compared with control subjects. These networks spanned multiple cortical regions involved in the default mode network (DMN). The DMN is thought to subserve memory and attention during periods when an individual is not engaged in a specific task, and its disruption may lead to cognitive deficits after mTBI. We further applied graph theoretical analysis on the functional connectivity matrices. Our data suggest reduced local efficiency in different brain regions in mTBI patients. In conclusion, MEG can be a potential tool to investigate and detect network alterations in patients with mTBI. The value of MEG to reveal potential neurophysiological biomarkers for mTBI patients warrants further exploration.

Ethanol-induced loss-of-righting response during ethanol withdrawal in male and female rats: associations with alterations in Arc labeling.

BACKGROUND: There is increasing evidence for relevant sex differences in responses to ethanol. Several investigations have found differences in expression and recovery from ethanol withdrawal (EW) in people and across various animal models. We have found that female rats recover more quickly than male rats and show differential responses to various behavioral assessments and pharmacological challenges during withdrawal. The purpose of this study was to determine whether sex differences in EW behaviors extend to the hypnotic effects of acute ethanol administration. METHODS: We used a repeated measures design to assess duration and latency for loss-of-righting reflex following an acute injection of ethanol (4.2 g/kg; 20% w/v) to pair-fed control or ethanol-withdrawn animals at 1 and 3 days EW in male, female, and ovariectomized female (OVX) rats. We determined protein levels of the activity-regulated cytoskeletal protein (Arc), used as a marker for synaptic activity in glutamatergic synapses, in the motor cortex and prefrontal cortex across these same treatment conditions. RESULTS: Ethanol-withdrawn animals had a reduced ethanol-induced sleep time compared to controls at 1 day EW. Sleep time remained shortened at 3 days EW for males and OVX, but not females. Arc protein levels in motor cortex and preoptic nuclei significantly increased at 1 day EW across all sex conditions, suggestive of an association with the reduced ethanol-induced sleep times during EW. Arc levels increased further for males and OVX, but not females, at the 3 days EW time point. CONCLUSIONS: These findings add further support to sex differences in effects of and responses to ethanol. They suggest that the more rapid recovery from EW for females than males also includes expression of tolerance to the hypnotic effects of ethanol. These sex differences may involve some differential neuroadaptations in glutamatergic signaling.

Dynamic encoding of face information in the human fusiform gyrus.

Humans' ability to rapidly and accurately detect, identify and classify faces under variable conditions derives from a network of brain regions highly tuned to face information. The fusiform face area (FFA) is thought to be a computational hub for face processing; however, temporal dynamics of face information processing in FFA remains unclear. Here we use multivariate pattern classification to decode the temporal dynamics of expression-invariant face information processing using electrodes placed directly on FFA in humans. Early FFA activity (50-75 ms) contained information regarding whether participants were viewing a face. Activity between 200 and 500 ms contained expression-invariant information about which of 70 faces participants were viewing along with the individual differences in facial features and their configurations. Long-lasting (500+ms) broadband gamma frequency activity predicted task performance. These results elucidate the dynamic computational role FFA plays in multiple face processing stages and indicate what information is used in performing these visual analyses.

Sex and regional differences in effects of chronic intermittent ethanol exposure on subsequent excitotoxic challenges in hippocampal slice cultures.

The organotypic hippocampal slice culture technique was used to study how the effects of repeated ethanol withdrawal might differ between males and females at the cellular level, including potential modulation of subsequent insults. A chronic intermittent ethanol (CIE) exposure paradigm was employed, with 3 days of exposure followed by 24 h withdrawal for 3 cycles. Slices were next exposed to corticosterone (CORT) or pentylenetetrazol (PTZ) for 24 h then imaged for propidium iodide (PI) signal intensities. There were sex-selective responses in the CA1 region and dentate gyrus of the hippocampal slice cultures to treatment with CIE and/or CORT or PTZ. The 50 mM CIE alone generally did not increase the PI signal, but enhanced sensitivity to the toxic effects of CORT (particularly for females) and PTZ (particularly for males). In contrast, 100 mM CIE elicited a toxic response that was greater in females than males, and was exacerbated by exposure to PTZ. These data showed that hippocampal sexual dimorphism influences sensitivity to ethanol and other toxic chemicals even in an immature state. Low-dose CIE may attenuate harm from additional challenges in a hippocampal sex- and region-selective manner. These findings add to the growing evidence of important neurobiological sex differences in responses to chronic ethanol exposure and withdrawal.

Bodies adapt orientation-independent face representations.

Faces and bodies share a great number of semantic attributes, such as gender, emotional expressiveness, and identity. Recent studies demonstrate that bodies can activate and modulate face perception. However, the nature of the face representation that is activated by bodies remains unknown. In particular, face and body representations have previously been shown to have a degree of orientation specificity. Here we use body-face adaptation aftereffects to test whether bodies activate face representations in an orientation-dependent manner. Specifically, we used a two-by-two design to examine the magnitude of the body-face aftereffect using upright and inverted body adaptors and upright and inverted face targets. All four conditions showed significant body-face adaptation. We found neither a main effect of body orientation nor an interaction between body and face orientation. There was a main effect of target face orientation, with inverted target faces showing larger aftereffects than upright target faces, consistent with traditional face-face adaptation. Taken together, these results suggest that bodies adapt and activate a relatively orientation-independent representation of faces.

Voluntary wheel running attenuates ethanol withdrawal-induced increases in seizure susceptibility in male and female rats.

We recently found that voluntary wheel running attenuated ethanol withdrawal-induced increased susceptibility to chemoconvulsant-induced seizures in male rats. Since female rats recover from ethanol withdrawal (EW) more quickly than male rats across several behavioral measures, this study was designed to determine whether the effects of exercise on EW seizures also exhibited sex differences. Animals were maintained under no-wheel, locked-wheel or free-wheel conditions and ethanol was administered by liquid diet for 14 days with control animals pair-fed an isocaloric diet, after which seizure thresholds were determined at 1 day or 3 days of EW. Consistent with previous reports, females ran significantly more than males, regardless of diet condition. Introduction of the ethanol-containing liquid diet dramatically increased running for females during the day (rest) phase, with little impact on night phase activity. Consistent with previous reports, EW increased seizure susceptibility at 1 day in non-exercising males and females and at 3 days in males. These effects were attenuated by access to running wheels in both sexes. We also assessed the effects of sex, ethanol diet and exercise on ethanol clearance following an acute ethanol administration at 1 day EW in a separate set of animals. Blood ethanol concentrations at 30 min post-injection were lower in males, ethanol-exposed animals, and runners, but no interactions among these factors were detected. Interestingly, females displayed more rapid ethanol clearance than males and there were no effects of either diet or wheel access on clearance rates. Taken together, these data suggest that voluntary wheel running during ethanol administration provides protective effects against EW seizures in both males and females. This effect may be mediated, in part, in male, but not in female rat, by effects of exercise on early pharmacokinetic contributions. This supports the idea that encouraging alcoholics to exercise may benefit their recovery.

Running wheel activity protects against increased seizure susceptibility in ethanol withdrawn male rats.

Ethanol withdrawal is a dysphoric condition that arises from termination of ethanol intake by dependent individuals. Common withdrawal symptoms include anxiety, increased reactivity to stimuli and increased seizure susceptibility as well as the risk of increased seizure severity. We use an animal model of dependence and withdrawal to study withdrawal behaviors and potential underlying neurobiological mechanisms. For a number of years, we have quantified pentylenetetrazol seizure thresholds as an assessment of ethanol withdrawal at both one day and three days of withdrawal. Typically, we see a significant decrease in seizure threshold (increased sensitivity to seizure induction) that persists through three days of withdrawal for male rats. Increasing evidence indicates that voluntary exercise affords protection against various challenges to physical and psychological health, including ethanol-related challenges. Therefore, the current study investigated the effect of voluntary wheel running on seizure susceptibility following chronic ethanol administration and withdrawal. We found that voluntary wheel running attenuated the increased sensitivity to pentylenetetrazol-induced seizures observed with ethanol withdrawal, at both the one-day and three-day time points. This result was especially interesting as animals with access to the running wheels consumed more of the ethanol-containing diet. These findings showed that chronic voluntary wheel running reduces the severity of ethanol withdrawal in our animal model and suggest that exercise-based interventions may have some utility in the clinical management of heavy drinking and alcohol withdrawal.