Prefrontal Function Research Articles

Working and short-term memory in children with ADHD: an examination of prefrontal cortical functioning using functional Near-Infrared Spectroscopy (fNIRS)

ABSTRACT Working memory impairments are an oft-reported deficit among children with ADHD, and complementary neuroimaging studies implicate reductions in prefrontal cortex (PFC) structure and function as a neurobiological explanation. Most imaging studies, however, rely on costly, movement-intolerant, and/or invasive methods to examine cortical differences. This is the first study to use a newer neuroimaging tool that overcomes these limitations, functional Near Infrared Spectroscopy (fNIRS), to investigate hypothesized prefrontal differences. Children (aged 8–12) with ADHD (N = 22) and typically developing (N = 18) children completed phonological working memory (PHWM) and short-term memory (PHSTM) tasks. Children with ADHD evinced poorer performance on both tasks, with greater differences observed in PHWM (Hedges’ g = 0.67) relative to PHSTM (g = 0.39). fNIRS revealed reduced hemodynamic response among children with ADHD in the dorsolateral PFC while completing the PHWM task, but not within the anterior or posterior PFC. No between-group fNIRS differences were observed during the PHSTM task. Findings suggest that children with ADHD exhibit an inadequate hemodynamic response in a region of the brain that underlies PHWM abilities. The study also highlights the use of fNIRS as a cost-effective, noninvasive neuroimaging technique to localize/quantify neural activation patterns associated with executive functions.

The need to change: Is there a critical role of midlife adaptation in mental health later in life?

Although late-life depression (LLD) is a serious health problem and more common than dementia in people over 60, it is underdiagnosed and undertreated. The cognitive-emotional etiology of LLD is particularly poorly understood. This is in contrast to the now extensive literature from psychology and cognitive neuroscience on the characteristics of emotionally healthy aging. This research consistently shows a change in emotional processing in older adults that is modulated by prefrontal regulation. Lifespan theories explain this change in terms of neurocognitive adaptation to limited opportunities and resources that typically occur in the second half of life. Epidemiological data on an increase in well-being after a low point around age 50 suggest that the majority of people seem quite capable of making this adaptation, even though empirical evidence for a causal modulation of this so called 'paradox of aging' and for the role of the midlife dip is still lacking. Intriguingly, LLD is associated with deficits in emotional, cognitive, and prefrontal functions similar to those shown to be crucial for healthy adaptation. Suspected causes of these deficits, such as white matter lesions or affective instability, become apparent as early as midlife when internal and external changes as well as daily challenges set in. Based on these findings, we propose that some individuals who develop depression at older ages may not have been able to successfully implement self-regulatory adaptation at midlife. Here, we review the current evidence and theories on successful aging, the neurobiology of LLD, and well-being across the lifespan. Drawing on recent advances in lifespan theories, emotion regulation research, and cognitive neuroscience, we propose a model of successful versus unsuccessful adaptation that emphasizes the increasing need for implicit habitual control and resource-based regulatory choice during midlife.

Later stages of acute stress impair reinforcement-learning and feedback sensitivity in decision making

Whereas the effects of the early stages of acute stress seem to improve learning and increase loss aversion in decision making, in later stages, the opposite has been found, an impairment in decision making probably due to higher reward-attraction, as the STARS approach suggests. This study aims to investigate the effects of the later stages of acute stress on decision making and its underlying processes using a computational model. We hypothesized that stress would affect underlying cognitive strategies during decision making. Ninety-five participants were randomly distributed into two groups, experimental (N = 46) and control (N = 49). A virtual version of The Trier Social Stress Test (TSST) was used as a laboratory stressor. After 20 min, decision making was assessed by using the Iowa Gambling Task (IGT). The Value-Plus-Preservation (VPP) RL computational model was used to extract decision-making components. As expected, the stressed participants showed deficits in IGT performance on reinforcement-learning and feedback sensitivity. However, there was no gains attraction. These results are discussed by considering that decision making in later stages of acute stress could be based on impairments in prefrontal cortex functioning.

Dopaminergic Modulation of Prefrontal Cortex Inhibition.

The prefrontal cortex is the highest stage of integration in the mammalian brain. Its functions vary greatly, from working memory to decision-making, and are primarily related to higher cognitive functions. This explains the considerable effort devoted to investigating this area, revealing the complex molecular, cellular, and network organization, and the essential role of various regulatory controls. In particular, the dopaminergic modulation and the impact of local interneurons activity are critical for prefrontal cortex functioning, controlling the excitatory/inhibitory balance and the overall network processing. Though often studied separately, the dopaminergic and GABAergic systems are deeply intertwined in influencing prefrontal network processing. This mini review will focus on the dopaminergic modulation of GABAergic inhibition, which plays a significant role in shaping prefrontal cortex activity.

Insomniacs show greater prefrontal activation during verbal fluency task compared to non-insomniacs: a functional near-infrared spectroscopy investigation of depression in patients

BackgroundPrevious studies have shown that insomnia affects human prefrontal function and that there are specific patterns of brain activation to counteract sleep and improve cognition. However, the effects of insomnia on the prefrontal cortex of MDD (major depressive disorder) patients and the patterns of activation to counteract sleep in MDD patients remain unclear. The aim of this study is to examine this using fNIRS (functional near-infrared spectroscopy).MethodsEighty depressed patients and 44 healthy controls were recruited for this study. fNIRS was used to assess changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the prefrontal cortex of all participants during the VFT (verbal fluency test) and to record the number of words created to assess cognitive ability. The Pittsburgh Sleep Quality Index was used to assess sleep quality, and the Hamilton Rating Scale for Depression (24-item) and Hamilton Rating Scale for Anxiety (14-item) were used to assess the severity of depression and anxiety.ResultsWhen comparing patients, the healthy control group had significantly higher [oxy-Hb] values in the bilateral prefrontal cortex during VFT than the MDD group. In the MDD group, the [oxy-Hb] values in all brain regions except the right DLPFC were significantly higher in the group with insomnia than in the group without insomnia, but their VFT performance was significantly lower than in the group without insomnia and the healthy group. PSQI scores were positively correlated with [oxy-Hb] values in some left-brain regions, whereas HAMD and HAMA scores were not correlated with [oxy-Hb] values.ConclusionThe PFC was significantly less active during VFT in those with MDD than in healthy controls. All brain regions, except the right DLPFC, were significantly more active in MDD patients with insomnia than in those without insomnia, suggesting that sleep quality needs to be an important indicator in fNIRS screening. In addition, there was a positive correlation between the severity of insomnia in the left VLPFC and the level of activation, suggesting a role for the left brain region in the neurophysiology of overcoming sleepiness in MDD patients. these findings may provide new ideas for the treatment of MDD patients in the future.Trial registrationOur experiment was registered in the China Clinical Trial Registry (registration number ChiCTR2200065622) on November 10.( The first patient was recruited in 10/11/2022.)

Anhedonia and sensitivity to punishment in schizophrenia, depression and opiate use disorder

BackgroundFrom a behavioural perspective anhedonia is defined as diminished interest in the engagement of pleasurable activities. Despite its presence across a range of psychiatric disorders, the cognitive processes that give rise to anhedonia remain unclear. MethodsHere we examine whether anhedonia is associated with learning from positive and negative outcomes in patients diagnosed with major depression, schizophrenia and opiate use disorder alongside a healthy control group. Responses in the Wisconsin Card Sorting Test – a task associated with healthy prefrontal cortex function – were fitted to the Attentional Learning Model (ALM) which separates learning from positive and negative feedback. ResultsLearning from punishment, but not from reward, was negatively associated with anhedonia beyond other socio-demographic, cognitive and clinical variables. This impairment in punishment sensitivity was also associated with faster responses following negative feedback, independently of the degree of surprise. LimitationsFuture studies should test the longitudinal association between punishment sensitivity and anhedonia also in other clinical populations controlling for the effect of specific medications. ConclusionsTogether the results reveal that anhedonic subjects, because of their negative expectations, are less sensitive to negative feedbacks; this might lead them to persist in actions leading to negative outcomes.

Applying Functional Imaging to Clinical Practice: Are We Making Progress Toward Its Promise?

Applying Functional Imaging to Clinical Practice: Are We Making Progress Toward Its Promise?

Inhibition of noradrenergic signalling in rodent orbitofrontal cortex impairs the updating of goal-directed actions.

In a constantly changing environment, organisms must track the current relationship between actions and their specific consequences and use this information to guide decision-making. Such goal-directed behaviour relies on circuits involving cortical and subcortical structures. Notably, a functional heterogeneity exists within the medial prefrontal, insular, and orbitofrontal cortices (OFC) in rodents. The role of the latter in goal-directed behaviour has been debated, but recent data indicate that the ventral and lateral subregions of the OFC are needed to integrate changes in the relationships between actions and their outcomes. Neuromodulatory agents are also crucial components of prefrontal functions and behavioural flexibility might depend upon the noradrenergic modulation of the prefrontal cortex. Therefore, we assessed whether noradrenergic innervation of the OFC plays a role in updating action-outcome relationships in male rats. We used an identity-based reversal task and found that depletion or chemogenetic silencing of noradrenergic inputs within the OFC rendered rats unable to associate new outcomes with previously acquired actions. Silencing of noradrenergic inputs in the prelimbic cortex or depletion of dopaminergic inputs in the OFC did not reproduce this deficit. Together, our results suggest that noradrenergic projections to the OFC are required to update goal-directed actions.

Anti-LINGO-1 antibody protects neurons and synapses in the medial prefrontal cortex of APP/PS1 transgenic mice

The medial prefrontal cortex (mPFC), one of the most vulnerable brain regions in Alzheimer's disease (AD), plays a critical role in cognition. Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein-1 (LINGO-1) negatively affects nerve growth in the central nervous system; however, its role in the pathological damage to the mPFC remains to be studied in AD. In this study, an anti-LINGO-1 antibody was administered to 10-month-old APP/PS1 mice, and behavioral tests, stereological methods, immunohistochemistry and immunofluorescence were used to answer this question. Our results revealed that LINGO-1 was highly expressed in the neurons of the mPFC of AD mice, and the anti-LINGO-1 antibody improved prefrontal cortex-related function and reduced the protein level of LINGO-1, atrophy of the volume, Aβ deposition and massive losses of synapses and neurons in the mPFC of AD mice. Antagonizing LINGO-1 could effectively alleviate the pathological damage in the mPFC of AD mice, which might be an important structural basis for improving prefrontal cortex-related function. Abnormal expression of LINGO-1 in the mPFC may be one of the key targets of AD, and the effect initiated by the anti-LINGO-1 antibody may provide an important basis in the search for drugs for the prevention and treatment of AD.

클래스핏 트레이닝이 아동의 체력과 전전두엽 실행기능에 미치는 영향

Objectives The purpose of this study is to investigate the impact of the 12-week Class-fit training exercise program on physical fitness and prefrontal executive function in elementary school students and provide base data needed to use Class-fit training as physical fitness and prefrontal executive function improvement program of students.
 Methods In order to accomplish the purpose of this study, 36 sixth-grade students at E elementary school located in Seoul, were selected by convenience sampling and allocated 18 students each for the exercise group and the control group. Each group was measured for physical fitness and prefrontal executive function before and after the exercise. Class-fit training was implemented for 40 minutes of 3 times each week for 12 weeks.
 Results The results obtained through this study are as follows. First, muscle endurance, cardiovascular endurance, flexibility, power showed interaction effects in the group and time. Second, raw color-word score showed interaction effects in the group and time. Word raw score, color raw score showed significant differences in timing, particularly the post score of exercise group increased significantly.
 Conclusions In conclusion, 12-week Class-fit training had positive effect on elementary school students for physical fitness and prefrontal execution function. Class-fit training will make a contribution to the exercise program to help improve physical fitness and cognitive function.

Serotonergic and dopaminergic control of impulsivity in gambling disorder.

Gambling disorder (GD) is major public health issue. The disorder is often characterized by elevated impulsivity with evidence from analogous substance use disorders underlining prominent roles of brain monoamines in addiction susceptibility and outcome. Critically, GD allows the study of addiction mechanisms without the confounder of the effects of chronic substances. Here, we assessed the roles of striatal dopamine transporter binding and extrastriatal serotonin transporter binding in GD as a function of impulsivity using [123 I]FP-CIT SPECT imaging in 20 older adults with GD (DSM-5 criteria; mean age 64 years) and 40 non-GD age- and sex-matched controls. We focused on GD in older individuals because there are prominent age-related changes in neurotransmitter function and because there are no reported neuroimaging studies of GD in older adults. Volume-of-interest-based and voxelwise analyses were performed. GD patients scored clearly higher on impulsivity and had higher tracer binding in the ventromedial prefrontal cortex than controls (p < 0.001), likely reflecting serotonin transporter activity. The binding in the medial prefrontal cortex positively correlated with impulsivity over the whole sample (r = 0.62, p < 0.001) as well as separately in GD patients (r = 0.46, p = 0.04) and controls (r = 0.52, p < 0.001). Striatal tracer binding, reflecting dopamine transporter activity was also positively correlated with impulsivity but showed no group differences. These findings highlight the role of prefrontal serotonergic function in GD and impulsivity. They identify cerebral coordinates of a potential target for neuromodulation for both GD and high impulsivity, a core phenotypic dimensional cognitive marker in addictions.

Mature parvalbumin interneuron function in prefrontal cortex requires activity during a postnatal sensitive period.

In their seminal findings, Hubel and Wiesel identified sensitive periods in which experience can exert lasting effects on adult visual cortical functioning and behavior via transient changes in neuronal activity during development. Whether comparable sensitive periods exist for non-sensory cortices, such as the prefrontal cortex, in which alterations in activity determine adult circuit function and behavior is still an active area of research. Here, using mice we demonstrate that inhibition of prefrontal parvalbumin (PV)-expressing interneurons during the juvenile and adolescent period, results in persistent impairments in adult prefrontal circuit connectivity, in vivo network function, and behavioral flexibility that can be reversed by targeted activation of PV interneurons in adulthood. In contrast, reversible suppression of PV interneuron activity in adulthood produces no lasting effects. These findings identify an activity-dependent sensitive period for prefrontal circuit maturation and highlight how abnormal PV interneuron activity during development alters adult prefrontal circuit function and cognitive behavior.

Prefrontal brain function in patients with chronic insomnia disorder: A pilot functional near-infrared spectroscopy study.

Insomnia is one of the most common diseases in elderly patients, which seriously affect the quality of life and psychological state of patients. The purpose of this study was to investigate the changes in the functional network pattern of the prefrontal cortex in patients with chronic insomnia disorder (CID) after taking drugs, using non-invasive and low-cost functional neuroimaging with multi-channel near-infrared spectroscopy (fNIRS). All subjects were assessed using the Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and fNIRS. The fNIRS assessment consists of two parts: the verbal fluency test (VFT) task state and the resting state, which assessed the differences in prefrontal activation and functional connectivity, respectively. A total of 30 patients with chronic insomnia disorder (CID) and 15 healthy peers completed the study. During the VFT task, a significantly lower PFC activation was observed in patients with insomnia compared to the control group (P < 0.05). However, the PFC activation in patients taking medication was higher than in patients who did not receive medication. Functional connectivity analysis showed a weaker mean PFC channel connectivity strength in patients with CID who did not receive drug treatment. Drug treatment resulted in enhanced functional connectivity of the prefrontal lobe, especially the DLPFC and frontal poles. A weak prefrontal cortex response was detected in patients with CID when performing the VFT task, which could be enhanced by taking hypnotics. The weakened right prefrontal lobe network may play a role in the development of CID. fNIRS may serve as a potential tool to assess sleep status and guide drug therapy.

Loss of GABA co-transmission from cholinergic neurons impairs behaviors related to hippocampal, striatal, and medial prefrontal cortex functions.

Introduction: Altered signaling or function of acetylcholine (ACh) has been reported in various neurological diseases, including Alzheimer's disease, Tourette syndrome, epilepsy among others. Many neurons that release ACh also co-transmit the neurotransmitter gamma-aminobutyrate (GABA) at synapses in the hippocampus, striatum, substantia nigra, and medial prefrontal cortex (mPFC). Although ACh transmission is crucial for higher brain functions such as learning and memory, the role of co-transmitted GABA from ACh neurons in brain function remains unknown. Thus, the overarching goal of this study was to investigate how a systemic loss of GABA co-transmission from ACh neurons affected the behavioral performance of mice. Methods: To do this, we used a conditional knock-out mouse of the vesicular GABA transporter (vGAT) crossed with the ChAT-Cre driver line to selectively ablate GABA co-transmission at ACh synapses. In a comprehensive series of standardized behavioral assays, we compared Cre-negative control mice with Cre-positive vGAT knock-out mice of both sexes. Results: Loss of GABA co-transmission from ACh neurons did not disrupt the animal's sociability, motor skills or sensation. However, in the absence of GABA co-transmission, we found significant alterations in social, spatial and fear memory as well as a reduced reliance on striatum-dependent response strategies in a T-maze. In addition, male conditional knockout (CKO) mice showed increased locomotion. Discussion: Taken together, the loss of GABA co-transmission leads to deficits in higher brain functions and behaviors. Therefore, we propose that ACh/GABA co-transmission modulates neural circuitry involved in the affected behaviors.

Parallel Pathways Provide Hippocampal Spatial Information to Prefrontal Cortex.

Long-range synaptic connections define how information flows through neuronal networks. Here, we combined retrograde and anterograde trans-synaptic viruses to delineate areas that exert direct and indirect influence over the dorsal and ventral prefrontal cortex (PFC) of the rat (both sexes). Notably, retrograde tracing using pseudorabies virus (PRV) revealed that both dorsal and ventral areas of the PFC receive prominent disynaptic input from the dorsal CA3 (dCA3) region of the hippocampus. The PRV experiments also identified candidate anatomical relays for this disynaptic pathway, namely, the ventral hippocampus, lateral septum, thalamus, amygdala, and basal forebrain. To determine the viability of each of these relays, we performed three additional experiments. In the first, we injected the retrograde monosynaptic tracer Fluoro-Gold into the PFC and the anterograde monosynaptic tracer Fluoro-Ruby into the dCA3 to confirm the first-order connecting areas and revealed several potential relay regions between the PFC and dCA3. In the second, we combined PRV injection in the PFC with polysynaptic anterograde viral tracer (HSV-1) in the dCA3 to reveal colabeled connecting neurons, which were evident only in the ventral hippocampus. In the third, we combined retrograde adeno-associated virus (AAV) injections in the PFC with an anterograde AAV in the dCA3 to reveal anatomical relay neurons in the ventral hippocampus and dorsal lateral septum. Together, these findings reveal parallel disynaptic pathways from the dCA3 to the PFC, illuminating a new anatomical framework for understanding hippocampal-prefrontal interactions. We suggest that the representation of context and space may be a universal feature of prefrontal function.SIGNIFICANCE STATEMENT The known functions of the prefrontal cortex are shaped by input from multiple brain areas. We used transneuronal viral tracing to discover multiple prominent disynaptic pathways through which the dorsal hippocampus (specifically, the dorsal CA3) has the potential to shape the actions of the prefrontal cortex. The demonstration of neuronal relays in the ventral hippocampus and lateral septum presents a new foundation for understanding long-range influences over prefrontal interactions, including the specific contribution of the dorsal CA3 to prefrontal function.

Effects of trihexyphenidyl on prefrontal executive function and spontaneous neural activity in patients with tremor-dominant Parkinson's disease: An fNIRS study

IntroductionThe use of the anti-parkinsonian drug trihexyphenidyl (THP) to treat patients with Parkinson's disease (PD), particularly those with tremor-dominant PD (tdPD), has been well documented. Despite growing concerns about THP causing cognitive decline in tdPD patients, the underlying neural correlates remain unclear. Therefore, we investigated the effects of THP on prefrontal executive function and spontaneous neural activity in patients with tdPD by utilizing functional near-infrared spectroscopy (fNIRS). MethodsWe recruited 30 patients with tdPD, including 15 patients receiving THP and 15 patients not receiving THP. We performed comprehensive neuropsychological and clinical assessments to evaluate each patient's cognitive function, mental status, and clinical symptoms. We measured brain activation elicited from the verbal fluency task (VFT) and changes in amplitude of low-frequency fluctuations (ALFF) at rest to investigate executive function and spontaneous neural activity, respectively. In addition, we examined the relationship between altered activation during task and resting state and neuropsychological and clinical data. ResultsCompared with tdPD patients not taking THP, tdPD patients taking THP showed no differences on neuropsychological tests. However, there was insufficient activity of the dorsolateral prefrontal cortex (DLPFC) during VFT and reduced ALFF values for the DLPFC, ventrolateral prefrontal cortex (VLPFC), and the orbitofrontal cortex (OFC) related to the frontoparietal network (FPN) at rest. Furthermore, ALFF values of the VLPFC were positively correlated with scores of multiple cognitive domain functions. ConclusionThese findings suggest that THP treatment may lead to prefrontal dysfunction in tdPD patients, attenuating brain activation in executive function and cognition-related spontaneous neural activity.

The role of dopamine and endocannabinoid systems in prefrontal cortex development: Adolescence as a critical period.

The prefrontal cortex plays a central role in the control of complex cognitive processes including action control and decision making. It also shows a specific pattern of delayed maturation related to unique behavioral changes during adolescence and allows the development of adult cognitive processes. The adolescent brain is extremely plastic and critically vulnerable to external insults. Related to this vulnerability, adolescence is also associated with the emergence of numerous neuropsychiatric disorders involving alterations of prefrontal functions. Within prefrontal microcircuits, the dopamine and the endocannabinoid systems have widespread effects on adolescent-specific ontogenetic processes. In this review, we highlight recent advances in our understanding of the maturation of the dopamine system and the endocannabinoid system in the prefrontal cortex during adolescence. We discuss how they interact with GABA and glutamate neurons to modulate prefrontal circuits and how they can be altered by different environmental events leading to long-term neurobiological and behavioral changes at adulthood. Finally, we aim to identify several future research directions to help highlight gaps in our current knowledge on the maturation of these microcircuits.

Disrupted-in-schizophrenia-1 is required for normal pyramidal cell-interneuron communication and assembly dynamics in the prefrontal cortex.

We interrogated prefrontal circuit function in mice lacking Disrupted-in-schizophrenia-1 (Disc1-mutant mice), a risk factor for psychiatric disorders. Single-unit recordings in awake mice revealed reduced average firing rates of fast-spiking interneurons (INTs), including optogenetically identified parvalbumin-positive cells, and a lower proportion of INTs phase-coupled to ongoing gamma oscillations. Moreover, we observed decreased spike transmission efficacy at local pyramidal cell (PYR)-INT connections in vivo, suggesting a reduced excitatory effect of local glutamatergic inputs as a potential mechanism of lower INT rates. On the network level, impaired INT function resulted in altered activation of PYR assemblies: While assembly activations defined as coactivations within 25 ms were observed equally often, the expression strength of individual assembly patterns was significantly higher in Disc1-mutant mice. Our data, thus, reveal a role of Disc1 in shaping the properties of prefrontal assembly patterns by setting INT responsiveness to glutamatergic drive.

A ventral stream-prefrontal cortex processing cascade enables working memory gating dynamics

The representation of incoming information, goals and the flexible processing of these are required for cognitive control. Efficient mechanisms are needed to decide when it is important that novel information enters working memory (WM) and when these WM ‘gates’ have to be closed. Compared to neural foundations of maintaining information in WM, considerably less is known about what neural mechanisms underlie the representational dynamics during WM gating. Using different EEG analysis methods, we trace the path of mental representations along the human cortex during WM gate opening and closing. We show temporally nested representational dynamics during WM gate opening and closing depending on multiple independent neural activity profiles. These activity profiles are attributable to a ventral stream-prefrontal cortex processing cascade. The representational dynamics start in the ventral stream during WM gate opening and WM gate closing before prefrontal cortical regions are modulated. A regional specific activity profile is shown within the prefrontal cortex depending on whether WM gates are opened or closed, matching overarching concepts of prefrontal cortex functions. The study closes an essential conceptual gap detailing the neural dynamics underlying how mental representations drive the WM gate to open or close to enable WM functions such as updating and maintenance.

Diverging Effects of Adolescent Ethanol Exposure on Tripartite Synaptic Development across Prefrontal Cortex Subregions.

Adolescence is a developmental period that encompasses, but is not limited to, puberty and continues into early adulthood. During this period, maturation and refinement are observed across brain regions such as the prefrontal cortex (PFC), which is critical for cognitive function. Adolescence is also a time when excessive alcohol consumption in the form of binge drinking peaks, increasing the risk of long-term cognitive deficits and the risk of developing an alcohol use disorder later in life. Animal models have revealed that adolescent ethanol (EtOH) exposure results in protracted disruption of neuronal function and performance on PFC-dependent tasks that require higher-order decision-making. However, the role of astrocytes in EtOH-induced disruption of prefrontal cortex-dependent function has yet to be elucidated. Astrocytes have complex morphologies with an extensive network of peripheral astrocyte processes (PAPs) that ensheathe pre- and postsynaptic terminals to form the ‘tripartite synapse.’ At the tripartite synapse, astrocytes play several critical roles, including synaptic maintenance, dendritic spine maturation, and neurotransmitter clearance through proximity-dependent interactions. Here, we investigate the effects of adolescent binge EtOH exposure on astrocyte morphology, PAP-synaptic proximity, synaptic stabilization proteins, and dendritic spine morphology in subregions of the PFC that are important in the emergence of higher cognitive function. We found that adolescent binge EtOH exposure resulted in subregion specific changes in astrocyte morphology and astrocyte-neuronal interactions. While this did not correspond to a loss of astrocytes, synapses, or dendritic spines, there was a corresponding region-specific and EtOH-dependent shift in dendritic spine phenotype. Lastly, we found that changes in astrocyte-neuronal interactions were not a consequence of changes in the expression of key synaptic structural proteins neurexin, neuroligin 1, or neuroligin 3. These data demonstrate that adolescent EtOH exposure results in enduring effects on neuron-glia interactions that persist into adulthood in a subregion-specific PFC manner, suggesting selective vulnerability. Further work is necessary to understand the functional and behavioral implications.