Epigenetic mechanisms regulate cue memory underlying discriminative behavior.

The burgeoning field of neuroepigenetics has introduced chromatin modification as an important interface between experience and brain function. For example, epigenetic mechanisms like histone acetylation and DNA methylation operate throughout a lifetime to powerfully regulate gene expression in the brain that is required for experiences to be transformed into long-term memories. This review highlights emerging evidence from sensory models of memory that converge on the premise that epigenetic regulation of activity-dependent transcription in the sensory brain facilitates highly precise memory recall. Chromatin modifications may be key for neurophysiological responses to transient sensory cue features experienced in the "here and now" to be recapitulated over the long term. We conclude that the function of epigenetic control of sensory system neuroplasticity is to regulate the amount and type of sensory information retained in long-term memories by regulating neural representations of behaviorally relevant cues that guide behavior. This is of broad importance in the neuroscience field because there are few circumstances in which behavioral acts are devoid of an initiating sensory experience.

Inhibition of histone deacetylase 3 via RGFP966 facilitates cortical plasticity underlying unusually accurate auditory associative cue memory for excitatory and inhibitory cue-reward associations.

Epigenetic mechanisms are key for regulating long-term memory (LTM) and are known to exert control on memory formation in multiple systems of the adult brain, including the sensory cortex. One epigenetic mechanism is chromatin modification by histone acetylation. Blocking the action of histone de-acetylases (HDACs) that normally negatively regulate LTM by repressing transcription has been shown to enable memory formation. Indeed, HDAC inhibition appears to facilitate memory by altering the dynamics of gene expression events important for memory consolidation. However, less understood are the ways in which molecular-level consolidation processes alter subsequent memory to enhance storage or facilitate retrieval. Here we used a sensory perspective to investigate whether the characteristics of memory formed with HDAC inhibitors are different from naturally-formed memory. One possibility is that HDAC inhibition enables memory to form with greater sensory detail than normal. Because the auditory system undergoes learning-induced remodeling that provides substrates for sound-specific LTM, we aimed to identify behavioral effects of HDAC inhibition on memory for specific sound features using a standard model of auditory associative cue-reward learning, memory, and cortical plasticity. We found that three systemic post-training treatments of an HDAC3-inhibitor (RGPF966, Abcam Inc.) in rats in the early phase of training facilitated auditory discriminative learning, changed auditory cortical tuning, and increased the specificity for acoustic frequency formed in memory of both excitatory (S+) and inhibitory (S-) associations for at least 2 weeks. The findings support that epigenetic mechanisms act on neural and behavioral sensory acuity to increase the precision of associative cue memory, which can be revealed by studying the sensory characteristics of long-term associative memory formation with HDAC inhibitors.

Cognitive Behavior Classification From Scalp EEG Signals.

Electroencephalography (EEG) has become increasingly valuable outside of its traditional use in neurology. EEG is now used for neuropsychiatric diagnosis, neurological evaluation of traumatic brain injury, neurotherapy, gaming, neurofeedback, mindfulness, and cognitive enhancement training. The trend to increase the number of EEG electrodes, the development of novel analytical methods, and the availability of large data sets has created a data analysis challenge to find the "signal of interest" that conveys the most information about ongoing cognitive effort. Accordingly, we compare three common types of neural synchrony measures that are applied to EEG-power analysis, phase locking, and phase-amplitude coupling to assess which analytical measure provides the best separation between EEG signals that were recorded, while healthy subjects performed eight cognitive tasks-Hopkins Verbal Learning Test and its delayed version, Stroop Test, Symbol Digit Modality Test, Controlled Oral Word Association Test, Trail Marking Test, Digit Span Test, and Benton Visual Retention Test. We find that of the three analytical methods, phase-amplitude coupling, specifically theta (4-7 Hz)-high gamma (70-90 Hz) obtained from frontal and parietal EEG electrodes provides both the largest separation between the EEG during cognitive tasks and also the highest classification accuracy between pairs of tasks. We also find that phase-locking analysis provides the most distinct clustering of tasks based on their utilization of long-term memory. Finally, we show that phase-amplitude coupling is the least sensitive to contamination by intense jaw-clenching muscle artifact.

Acute Exercise Improves Prefrontal Cortex but not Hippocampal Function in Healthy Adults.

The effects of acute aerobic exercise on cognitive functions in humans have been the subject of much investigation; however, these studies are limited by several factors, including a lack of randomized controlled designs, focus on only a single cognitive function, and testing during or shortly after exercise. Using a randomized controlled design, the present study asked how a single bout of aerobic exercise affects a range of frontal- and medial temporal lobe-dependent cognitive functions and how long these effects last. We randomly assigned 85 subjects to either a vigorous intensity acute aerobic exercise group or a video watching control group. All subjects completed a battery of cognitive tasks both before and 30, 60, 90, or 120 min after the intervention. This battery included the Hopkins Verbal Learning Test-Revised, the Modified Benton Visual Retention Test, the Stroop Color and Word Test, the Symbol Digit Modalities Test, the Digit Span Test, the Trail Making Test, and the Controlled Oral Word Association Test. Based on these measures, composite scores were formed to independently assess prefrontal cortex- and hippocampal-dependent cognition. A three-way mixed Analysis of Variance was used to determine whether differences existed between groups in the change in cognitive function from pre- to post-intervention testing. Acute exercise improved prefrontal cortex- but not hippocampal-dependent functioning, with no differences found between delay groups. Vigorous acute aerobic exercise has beneficial effects on prefrontal cortex-dependent cognition and these effects can last for up to 2 hr after exercise.

Brief report: Effects of exercise and self-affirmation intervention after traumatic brain injury.

BACKGROUND: Physical exercise has been proven to be an effective method for improving cognition and mood, but little is known about its benefits among individuals with traumatic brain injury. OBJECTIVE: This pilot study investigated the feasibility of a combined exercise and self-affirmation intervention (IntenSati) for enhancing cognition and mood in individuals with TBI. It was hypothesized that this intervention would improve individuals' cognition and mood following the completion of the program. METHOD: This intervention was held at an outpatient rehabilitation department in an urban medical center. A wait-list control design was conducted. Twenty-one adult participants-at least 12-months post-TBI-enrolled in the study. Twelve of them completed the study. Assessment was conducted at three time-points throughout the study using neuropsychological and self-report measures to evaluate participants' cognition and mood. Following initial evaluation, participants were assigned into either the immediate intervention group or the waitlist control group. During the intervention, participants attended the program twice a week over the course of 8 weeks. Debriefing was conducted following the completion of the program. RESULTS: Both independent t tests and paired t tests were utilized. Results indicated that the intervention group experienced less depressive symptoms following the completion of the IntenSati program compared to the waitlist control group. Participants also reported having less depressive symptoms, experienced more positive affect, and had a higher quality of life following the completion of the program. Moderate-to-large effect sizes were found on decrease in negative affect. However, results associated with cognitive benefits were mixed. The participants tolerated the program well and reported satisfaction with the program. CONCLUSIONS: Results from this study indicated that the IntenSati exercise program is a feasible and beneficial intervention for individuals with TBI as supported by the positive impact on their mood and quality of life.