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In the largest and most expansive lifespan magnetoencephalography (MEG) study to date (n = 434, 6 to 84 y), we provide critical data on the normative trajectory of resting-state spontaneous activity and its temporal dynamics. We perform cutting-edge analyses to examine age and sex effects on whole-brain, spatially-resolved relative and absolute power maps, and find significant age effects in all spectral bands in both types of maps. Specifically, lower frequencies showed a negative correlation with age, while higher frequencies positively correlated with age. These correlations were further probed with hierarchical regressions, which revealed significant nonlinear trajectories in key brain regions. Sex effects were found in absolute but not relative power maps, highlighting key differences between outcome indices that are generally used interchangeably. Our rigorous and innovative approach provides multispectral maps indicating the unique trajectory of spontaneous neural activity across the lifespan, and illuminates key methodological considerations with the widely used relative/absolute power maps of spontaneous cortical dynamics.

Alcohol and cannabis use disorder (AUD/CUD) are two of the most common addictive disorders. While studies are beginning to understand the neural changes related to acute and chronic use, few studies have examined the independent effects of AUD and CUD on neural oscillatory activity. We examined 45 adults who reported current use of both cannabis and alcohol. Participants underwent the SCID-V to determine whether they met criteria for AUD and/or CUD. Participants also completed a visual-spatial processing task while undergoing magnetoencephalography (MEG). ANCOVA with a 2 × 2 design was then used to identify the main effects of AUD and CUD on source-level oscillatory activity. Of the 45 adults, 17 met criteria for AUD, and 26 met criteria for CUD. All participants, including comparison groups, reported use of both cannabis and alcohol. Statistical analyses showed a main effect of AUD, such that participants with AUD displayed a blunted occipital alpha (8–16 Hz) response. Post-hoc testing showed this decreased alpha response was related to increased AUD symptoms, above and beyond amount of use. No effects of AUD or CUD were identified in visual theta or gamma activity. In conclusion, AUD was associated with reduced alpha responses and scaled with increasing severity, independent of CUD. These findings indicate that alpha oscillatory activity may play an integral part in networks affected by alcohol addiction.

Background: Cannabis is one of the most commonly used substances in the United States. Prior literature using task-based functional magnetic resonance imaging (fMRI) has identified that individuals with Cannabis use disorder (CUD) show impairments in emotion processing circuitry. However, whether the functional networks involving these regions are also altered in CUD remains poorly understood. Aims: Investigate changes in resting-state functional connectivity (rsFC) in regions related to emotional processing in CUD. Methods: Sixty-two participants completed resting-state fMRI, including 21 with CUD, 20 with histories of illicit substance use but no current CUD diagnosis, and 21 with no history of illicit substance use. Whole-brain seed-based connectivity analyses were performed and one-way analyses of covariance (ANCOVAs) were conducted to detect group differences in the bilateral amygdalae, hippocampi, and the anterior and posterior cingulate cortices. Results: The CUD group exhibited significant reductions in rsFC between the amygdala and the cuneus, paracentral lobule, and supplementary motor area, and between the cingulate cortices and the occipital and temporal lobes. There were no significant group differences in hippocampal functional connectivity. In addition, CUD symptom counts based on the Structured Clinical Interview for DSM-5 (SCID) and the Cannabis Use Disorders Identification Test (CUDIT) significantly correlated with multiple connectivity metrics. Conclusion: These data expand on emerging literature indicating that CUD is associated with dysfunction in the neural circuits underlying emotion processing. Dysfunction in emotion processing circuits may play a role in the behavioral impairments seen in emotion processing tasks in individuals with CUD, and the severity of CUD symptoms appears to be directly related to the degree of dysfunction in these circuits.

People with HIV (PWH) use cannabis at a higher rate than the general population, but the influence on neural activity is not well characterized. Cannabis use among PWH may have a beneficial effect, as neuroinflammation is known to be a critical problem in PWH and cannabis use has been associated with a reduction in proinflammatory markers. Thus, it is important to understand the net impact of cannabis use on brain and cognitive function in PWH. In this study, we collected magnetoencephalographic (MEG) brain imaging data on 81 participants split across four demographically matched groups (i.e., PWH using cannabis, controls using cannabis, non‐using PWH, and non‐using controls). Participants completed a visuospatial processing task during MEG. Time–frequency resolved voxel time series were extracted to identify the dynamics of oscillatory and pre‐stimulus baseline neural activity. Our results indicated strong theta (4–8 Hz), alpha (10–16 Hz), and gamma (62–72 Hz) visual oscillations in parietal–occipital brain regions across all participants. PWH exhibited significant behavioral deficits in visuospatial processing, as well as reduced theta oscillations and elevated pre‐stimulus gamma activity in visual cortices, all of which replicate prior work. Strikingly, chronic cannabis use was associated with a significant reduction in pre‐stimulus gamma activity in the visual cortices, such that PWH no longer statistically differed from controls. These results provide initial evidence that cannabis use may normalize some neural aberrations in PWH. This study fills an important gap in understanding the impact of cannabis use on brain and cognitive function in PWH., This work used a visuospatial processing paradigm in combination with magnetoencephalographic (MEG) imaging. Voxel‐level timeseries analyses were applied to study the impact of cannabis use on behavior and neural activity in people with HIV (PWH).

Somatosensory cortical activity is altered in individuals with cerebral palsy (CP). However, previous studies have focused on the lower extremities in children with CP and have given less attention to structural changes that may contribute to these alterations. We used a multimodal neuroimaging approach to investigate the relationship between somatosensory cortical activity and cortical thickness in 17 adults with CP (age = 32.8 ± 9.3 years) and 18 healthy adult controls (age = 30.7 ± 9.8 years). Participants performed a median nerve paired-pulse stimulation paradigm while undergoing magnetoencephalography (MEG) to investigate somatosensory cortical activity and sensory gating. Participants also underwent magnetic resonance imaging to evaluate cortical thickness within the area of the somatosensory cortex that generated the MEG response. We found that the somatosensory responses were attenuated in the adults with CP (P = 0.004). The adults with CP also hypergated the second stimulation (P = 0.030) and had decreased cortical thickness in the somatosensory cortex (P = 0.015). Finally, the strength of the somatosensory response was significantly correlated with the cortical thickness (P = 0.023). These findings demonstrate that the aberrant somatosensory cortical activity in adults with CP extends to the upper extremities and appears to be related to cortical thickness.

HIV‐infection has been associated with widespread alterations in brain structure and function, although few studies have examined whether such aberrations are co‐localized and the degree to which clinical and cognitive metrics are related. We examine this question in the somatosensory system using high‐resolution structural MRI (sMRI) and magnetoencephalographic (MEG) imaging of neural oscillatory activity. Forty‐four participants with HIV (PWH) and 55 demographically‐matched uninfected controls completed a paired‐pulse somatosensory stimulation paradigm during MEG and underwent 3T sMRI. MEG data were transformed into the time‐frequency domain; significant sensor level responses were imaged using a beamformer. Virtual sensor time series were derived from the peak responses. These data were used to compute response amplitude, sensory gating metrics, and spontaneous cortical activity power. The T1‐weighted sMRI data were processed using morphological methods to derive cortical thickness values across the brain. From these, the cortical thickness of the tissue coinciding with the peak response was estimated. Our findings indicated both PWH and control exhibit somatosensory gating, and that spontaneous cortical activity was significantly stronger in PWH within the left postcentral gyrus. Interestingly, within the same tissue, PWH also had significantly reduced cortical thickness relative to controls. Follow‐up analyses indicated that the reduction in cortical thickness was significantly correlated with CD4 nadir and mediated the relationship between HIV and spontaneous cortical activity within the left postcentral gyrus. These data indicate that PWH have abnormally strong spontaneous cortical activity in the left postcentral gyrus and such elevated activity is driven by locally reduced cortical gray matter thickness., Forty‐four participants with HIV (PWH) and 55 demographically‐matched uninfected controls completed a paired‐pulse somatosensory stimulation paradigm during MEG and underwent 3T sMRI. These data were used to compute response amplitude, sensory gating metrics, and spontaneous cortical activity power. Our findings indicated both PWH and controls exhibit somatosensory gating, and that spontaneous cortical activity was significantly stronger in PWH within the left postcentral gyrus. Interestingly, within the same tissue, PWH also had significantly reduced cortical thickness relative to controls.

Adolescence is a critical period for the development and refinement of several higher-level cognitive functions, including visual selective attention. Clinically, it has been noted that adolescents with cerebral palsy (CP) may have deficits in selectively attending to objects within their visual field. This study aimed to evaluate the neural oscillatory activity in the ventral attention network while adolescents with CP performed a visual selective attention task. Adolescents with CP (N = 14; Age = 15.7 ± 4 years; MACS I–III; GMFCS I–IV) and neurotypical (NT) adolescents (N = 21; Age = 14.3 ± 2 years) performed the Eriksen flanker task while undergoing magnetoencephalographic (MEG) brain imaging. The participants reported the direction of a target arrow that was surrounded by congruent or incongruent flanking arrows. Compared with NT adolescents, adolescents with CP had slower responses and made more errors regarding the direction of the target arrow. The MEG results revealed that adolescents with CP had stronger alpha oscillations in the left insula when the flanking arrows were incongruent. Furthermore, participants that had more errors also tended to have stronger alpha oscillatory activity in this brain region. Altogether these results indicate that the aberrant activity seen in the left insula is associated with diminished visual selective attention function in adolescents with CP.

A major goal of many translational neuroimaging studies is the identification of biomarkers of disease. However, a prerequisite for any such biomarker is robust reliability, which for magnetoencephalography (MEG) and many other imaging modalities has not been established. In this study, we examined the reliability of visual (Experiment 1) and somatosensory gating (Experiment 2) responses in 19 healthy adults who repeated these experiments for three visits spaced 18 months apart. Visual oscillatory and somatosensory oscillatory and evoked responses were imaged, and intraclass correlation coefficients (ICC) were computed to examine the long-term reliability of these responses. In Experiment 1, ICCs showed good reliability for visual theta and alpha responses in occipital cortices, but poor reliability for gamma responses. In Experiment 2, the time series of somatosensory gamma and evoked responses in the contralateral somatosensory cortex showed good reliability. Finally, analyses of spontaneous baseline activity indicated excellent reliability for occipital alpha, moderate reliability for occipital theta, and poor reliability for visual/somatosensory gamma activity. Overall, MEG responses to visual and somatosensory stimuli show a high degree of reliability across 3 years and therefore may be stable indicators of sensory processing long term and thereby of potential interest as biomarkers of disease.

Introduction Resting-state oscillatory activity has been extensively studied across a wide array of disorders. Establishing which spectrally- and spatially-specific oscillatory components exhibit test-retest reliability is essential to move the field forward. While studies have shown short-term reliability of MEG resting-state activity, no studies have examined test-retest reliability across an extended period of time to establish the stability of these signals, which is critical for reproducibility. Methods We examined 18 healthy adults age 23 - 61 who completed three visits across three years. For each visit, participants completed both a resting state MEG and structural MRI scan. MEG data were source imaged, and the cortical power in canonical frequency bands (delta, theta, alpha, beta, low gamma, high gamma) was computed. Intra-class correlation coefficients (ICC) were then calculated across the cortex for each frequency band. Results Over three years, power in the alpha and beta bands displayed the highest reliability estimates, while gamma showed the lowest estimates of three-year reliability. Spatially, delta, alpha, and beta all showed the highest degrees of reliability in the parietal cortex. Interestingly, the peak signal for each of these frequency bands was located outside of the parietal cortex, suggesting that reliability estimates were not solely dependent on the signal-to-noise ratio. Conclusion Oscillatory resting-state power in parietal delta, posterior beta, and alpha across most of the cortex are reliable across three years and future MEEG studies may focus on these measures for the development of specific markers.

Cerebral palsy is the most common paediatric neurological disorder and results in extensive impairment to the sensorimotor system. However, these individuals also experience increased pain perception, resulting in decreased quality of life. In the present study, we utilized magnetoencephalographic brain imaging to examine whether alterations in spontaneous neural activity predict the level of pain experienced in a cohort of 38 individuals with spastic diplegic cerebral palsy and 67 neurotypical controls. Participants completed 5 min of an eyes closed resting-state paradigm while undergoing a magnetoencephalography recording. The magnetoencephalographic data were then source imaged, and the power within the delta (2–4 Hz), theta (5–7 Hz), alpha (8–12 Hz), beta (15–29 Hz), low gamma (30–59 Hz) and high gamma (60–90 Hz) frequency bands were computed. The resulting power spectral density maps were analysed vertex-wise to identify differences in spontaneous activity between groups. Our findings indicated that spontaneous cortical activity was altered in the participants with cerebral palsy in the delta, alpha, beta, low gamma and high gamma bands across the occipital, frontal and secondary somatosensory cortical areas (all pFWE

Dynamically allocating neural resources to salient features or objects within our visual space is fundamental to making rapid and accurate decisions. Impairments in such visuospatial abilities have been consistently documented in the clinical literature on individuals with cerebral palsy (CP), although the underlying neural mechanisms are poorly understood. In this study, we used magnetoencephalography (MEG) and oscillatory analysis methods to examine visuospatial processing in children with CP and demographically matched typically developing (TD) children. Our results indicated robust oscillations in the theta (4–8 Hz), alpha (8–14 Hz), and gamma (64–80 Hz) frequency bands in the occipital cortex of both groups during visuospatial processing. Importantly, the group with CP exhibited weaker cortical oscillations in the theta and gamma frequency bands, as well as slower response times and worse accuracy during task performance compared to the TD children. Furthermore, we found that weaker theta and gamma oscillations were related to greater visuospatial performance deficits across both groups. We propose that the weaker occipital oscillations seen in children with CP may reflect poor bottom-up processing of incoming visual information, which subsequently affects the higher-order visual computations essential for accurate visual perception and integration for decision-making.

A growing literature suggests a relationship between HIV-infection and a molecular profile of age acceleration. However, despite the widely known high prevalence of HIV-related brain atrophy and HIV-associated neurocognitive disorder (HAND), epigenetic age acceleration has not been linked to HIV-related changes in structural MRI. We applied morphological MRI methods to study the brain structure of 110 virally suppressed participants with HIV infection and 122 uninfected controls age 22–72. All participants were assessed for cognitive impairment, and blood samples were collected from a subset of 86 participants with HIV and 83 controls to estimate epigenetic age. We examined the group-level interactive effects of HIV and chronological age and then used individual estimations of epigenetic age to understand the relationship between age acceleration and brain structure. Finally, we studied the effects of HAND. HIV-infection was related to gray matter reductions, independent of age. However, using epigenetic age as a biomarker for age acceleration, individual HIV-related age acceleration was associated with reductions in total gray matter. HAND was associated with decreases in thalamic and hippocampal gray matter. In conclusion, despite viral suppression, accentuated gray matter loss is evident with HIV-infection, and greater biological age acceleration specifically relates to such gray matter loss.

Background: Despite living a normal lifespan, at least 35% of persons with HIV (PWH) in resource-rich countries develop HIV-associated neurocognitive disorder (HAND). This high prevalence of cognitive decline may reflect accelerated ageing in PWH, but the evidence supporting an altered ageing phenotype in PWH has been mixed. Methods: We examined the impact of ageing on the orienting of visual attention in PWH using dynamic functional mapping with magnetoencephalography (MEG) in 173 participants age 22–72 years-old (94 uninfected controls, 51 cognitively-unimpaired PWH, and 28 with HAND). All MEG data were imaged using a state-of-the-art beamforming approach and neural oscillatory responses during attentional orienting were examined for ageing, HIV, and cognitive status effects. Findings: All participants responded slower during trials that required attentional reorienting. Our functional mapping results revealed HIV-by-age interactions in left prefrontal theta activity, alpha oscillations in the left parietal, right cuneus, and right frontal eye-fields, and left dorsolateral prefrontal beta activity (p

ObjectiveTo identify the neural markers of attention dysfunction in patients with HIV-associated neurocognitive disorder (HAND).MethodsSixty participants, including 40 HIV-infected adults (half with HAND) and 20 demographically matched controls performed a visual selective attention task while undergoing high-density magnetoencephalography. Neuronal activity related to selective attention processing was quantified and compared across the 3 groups, and correlated with neuropsychological measures of attention and executive function. Spontaneous neural activity was also extracted from these attention-related cortical areas and examined with respect to HAND status.ResultsHIV-infected participants with and without HAND exhibited behavioral selective attention deficits on the magnetoencephalography task, as indicated by an increased flanker effect. Neuronal measures of flanker interference activity in the alpha and theta range revealed differential dynamics in attention-related brain areas across the 3 groups, especially in those with HAND. In addition, theta range flanker interference activity in the left inferior frontal and dorsolateral prefrontal cortex was associated with executive function and attention composite scores, respectively. Progressively stronger spontaneous alpha and theta activity was also found in unimpaired HIV-infected and HAND participants relative to controls across brain regions implicated in different components of attention processing.ConclusionsBehavioral and neuronal metrics of selective attention performance distinguish participants with HAND from controls and unimpaired HIV-infected participants. These metrics, along with measures of local spontaneous neural activity, may hold promise as early markers of cognitive decline in participants with HIV infection and be useful prognostic indicators for HAND.

Background While numerous studies have examined the developmental trajectory of task-based neural oscillations during childhood and adolescence, far less is known about the evolution of spontaneous cortical activity during this time period. Likewise, many studies have shown robust sex differences in task-based oscillations during this developmental period, but whether such sex differences extend to spontaneous activity is not understood. Methods Herein, we examined spontaneous cortical activity in 111 typically-developing youth (ages 9–15 years; 55 male). Participants completed a resting state magnetoencephalographic (MEG) recording and a structural MRI. MEG data were source imaged and the power within five canonical frequency bands (delta, theta, alpha, beta, gamma) was computed. The resulting power spectral density maps were analyzed via vertex-wise ANCOVAs to identify spatially-specific effects of age, sex, and their interaction. Results We found robust increases in power with age in all frequencies except delta, which decreased over time, with findings largely confined to frontal cortices. Sex effects were distributed across frontal and temporal regions; females tended to have greater delta and beta power, whereas males had greater alpha. Importantly, there was a significant age-by-sex interaction in theta power, such that males exhibited decreasing power with age while females showed increasing power with age in the bilateral superior temporal cortices. Discussion These data suggest that the strength of spontaneous activity undergoes robust change during the transition from childhood to adolescence (i.e., puberty onset), with intriguing sex differences in some cortical areas. Future developmental studies should probe task-related oscillations and spontaneous activity in parallel.

Highlights • Visual processing dynamics continue to develop throughout childhood and adolescence. • Visual alpha response power differed between males and females. • Sex and age interacted to modulate visual gamma responses. • Peak frequency predicted response power above and beyond the effects of age and sex., Successful interaction with one’s visual environment is paramount to developing and performing many basic and complex mental functions. Although major aspects of visual development are completed at an early age, other structural and functional components of visual processing appear to be dynamically changing across a much more protracted period extending into late childhood and adolescence. However, the underlying neurophysiological changes and cortical oscillatory dynamics that support maturation of the visual system during this developmental period remain poorly understood. The present study utilized magnetoencephalography (MEG) to investigate maturational changes in the neural dynamics serving basic visual processing during childhood and adolescence (ages 9–15, n = 69). Our key results included robust sex differences in alpha oscillatory activity within the left posterior parietal cortex, and sex-by-age interactions in gamma activity in the right lingual gyrus and superior parietal lobule. Hierarchical regression revealed that the peak frequency of both the alpha and gamma responses predicted response power in parietal regions above and beyond the noted effects of age and sex. These findings affirm the view that neural oscillations supporting visual processing develop over a much more protracted period, and illustrate that these maturational trajectories are influenced by numerous elements, including age, sex, and individual variation.

Background: Visual-spatial processing deficits have been previously linked to heavy alcohol use, but the underlying neurological mechanisms are poorly understood. Neuroimaging studies have shown alcohol-related aberrations in occipital cortices that appear to be associated with these neuropsychological deficits in visual-spatial processing, however the neural dynamics underlying this altered processing remains unknown. Methods: Twenty-three adults with high scores on the Alcohol Use Disorders Identification Test – Consumption (male: ⩾5, female: ⩾4) were compared to 30 demographically-matched controls with low Alcohol Use Disorders Identification Test – Consumption scores (⩽2). All participants completed a visual-spatial processing task while undergoing high-density magnetoencephalography. Time-frequency windows of interest were determined using a data-driven method, and spectrally-specific neural activity was imaged using a beamforming approach. Permutation testing of peak voxel time series was then used to statistically compare across groups. Results: Participants with heavy alcohol use responded slower on the task and their performance was more variable. The magnetoencephalography data indicated strong theta (4–8 Hz), alpha (10–16 Hz), and gamma (62–72 Hz) responses in posterior brain regions across both groups. Following voxel time-series extraction, significant group differences were found in the left and right visual association cortices from about 375–550 ms post-stimulus, such that adults with heavy alcohol use had blunted alpha responses compared to controls. Conclusion: Individuals with heavy alcohol use exhibited aberrant occipital alpha activity during visual-spatial processing. These data are the first to show spectrally-specific differences during visual-spatial processing related to heavy alcohol use, and highlight alcohol’s effect on systems-level neural activity.

Magnetoencephalography (MEG) is a noninvasive, silent, and totally passive neurophysiological imaging method with excellent temporal resolution (~1 ms) and good spatial precision (~3–5 mm). While MEG studies of neuroHIV remain relatively rare, the number of studies per year has sharply increased recently and this trend will likely continue into the foreseeable future. The current in-depth review focuses on the studies that have been conducted to date, which include investigations of somatosensory and visual modalities, resting-state, as well as motor control and higher-level functions such as working memory and visual attention. The review begins with an introduction to the principles and methods of MEG, and then transitions to a review of each of the empirical studies that have been conducted to date, separated by sensory modality for the basic studies and cognitive domain for the higher-level investigations. As such, this review attempts to be exhaustive in its coverage of empirical MEG studies of neuroHIV. Across studies major themes emerge including aberrant neural oscillatory activity in HIV-infected adults, both in primary sensory regions of the brain and higher-order executive regions. Many studies have also connected the amplitude of neural oscillations to behavioral and/or neuropsychological function in the study population, making a vital connection to performance and improving the veracity of the findings. One conspicuous emerging area is the use of MEG to distinguish cognitively-impaired from unimpaired HIV-infected adults, with major success reported and future studies sure to come. The review concludes with a summary of findings and suggested focus areas for future studies.

Highlights • HIV-associated neurocognitive disorders (HAND) are common in people with HIV. • HAND is typically diagnosed using a neuropsychological assessment battery. • We examined whether gray matter volumes can be used to identify HAND cases. • Gray matter volumes accurately discriminated people with and without HAND. • Stratifying by sex improved discriminability, revealing sex differences in HAND., Background Current diagnostic criteria of HIV-associated neurocognitive disorders (HAND) rely on neuropsychological assessments. The aim of this study was to evaluate if gray matter volumes (GMV) can distinguish people with HAND, neurocognitively unimpaired people with HIV (unimpaired PWH), and uninfected controls using linear discriminant analyses. Methods A total of 231 participants, including 110 PWH and 121 uninfected controls, completed a neuropsychological assessment and an MRI protocol. Among PWH, HAND (n = 48) and unimpaired PWH (n = 62) designations were determined using the widely accepted Frascati criteria. We then assessed the extent to which GMV, corrected for intracranial volume, could accurately distinguish the three groups using linear discriminant analysis. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, area under the curve (AUC), and accuracy were computed for each model using the classification results based on GMV compared to the neuropsychological assessment. Results The best performing model was comprised of bilaterally combined GMV and was stratified by sex. Among males, sensitivity was 85.2% (95% CI: 66.3%–95.8%), specificity was 97.0% (95% CI: 91.6%-99.4%), and the AUC was 0.91 (95% CI: 0.83–0.99). Among females, sensitivity was 100.0% (95% CI: 83.9%–100.0%), specificity was 98.8% (95% CI: 93.4%-100.0%), and the AUC was 0.99 (95% CI: 0.98–1.00). Conclusions GMV accurately discriminated HAND from unimpaired PWH and controls. Measures of GMV may be highly sensitive to HAND, and revisions to the Frascati criteria should consider including GMV in conjunction with a neuropsychological assessment to diagnose HAND.

Chronic intermittent exposure to ethanol (EtOH; CIE) that produces binge-like levels of intoxication has been associated with age-dependent deficits in cognitive functioning. Male Sprague-Dawley rats were exposed to CIE (5 g/kg, 25% EtOH, 13 intragastric gavages) beginning at three ages: early adolescence (postnatal day [PD] 28), mid-adolescence (PD35) and adulthood (PD72). In experiment 1, rats were behaviorally tested following CIE. Spatial memory was not affected by CIE, but adult CIE rats were impaired at acquiring a non-spatial discrimination task and subsequent reversal tasks. Rats exposed to CIE during early or mid-adolescence were impaired on the first reversal, demonstrating transient impairment in behavioral flexibility. Blood EtOH concentrations negatively correlated with performance on reversal tasks. Experiment 2 examined changes in brain derived neurotrophic factor (BNDF) levels within the frontal cortex (FC) and hippocampus (HPC) at four time points: during intoxication, 24-hrs after the final EtOH exposure (acute abstinence), 3-weeks following abstinence (recovery) and after behavioral testing. HPC BDNF levels were not affected by CIE at any time point. During intoxication, BDNF was suppressed in the FC, regardless of the age of exposure. However, during acute abstinence, reduced FC BDNF levels persisted in early adolescent CIE rats, whereas adult CIE rats displayed an increase in BDNF levels. Following recovery, neurotrophin levels in all CIE rats recovered. Our results indicate that intermittent binge-like EtOH exposure leads to acute disruptions in FC BDNF levels and long-lasting behavioral deficits. However, the type of cognitive impairment and its duration differ depending on the age of exposure.