Cognitive impairment and amygdala subregion volumes in elderly with cerebral small vessel disease: A large prospective cohort study.

Although the amygdala is associated with cognitive impairment resulting from cerebral small vessel disease, the relationship between alterations in amygdala structure and cerebral small vessel disease (CSVD) remains controversial. Given that the amygdala comprises several subregions, detecting subtle regional changes through total amygdala volume measurement is challenging. This study aimed to identify the patterns of amygdala subregion atrophy in cerebral small vessel disease patients and their relationship with cognitive impairment. A total of 114 participants diagnosed with cerebral small vessel disease and 129 healthy participants, aged 40 to 70, underwent 3 T magnetic resonance imaging scans. The amygdala subregions were automatically segmented using FreeSurfer. In the Propensity Score Matching (PSM)-matched cohort, Lasso regression was employed to identify subregions associated with cerebral small vessel disease, and restricted cubic splines (RCS) were used to explore their nonlinear relationship with cognitive abilities. Subsequently, multivariate linear regression models were used to investigate the impact of amygdala subregion volumes on various cognitive abilities. Compared to healthy controls (HC), the volume of the left cortical nucleus was significantly reduced in cerebral small vessel disease patients. The volume of the left cortical nucleus was significantly negatively correlated with cerebral small vessel disease progression, and atrophy in this region was also identified as an independent risk factor for decreased cognitive control and processing ability. Our findings suggest that patients with cerebral small vessel disease exhibit atrophy in specific amygdala subregions compared to healthy controls, which correlates with poorer cognitive control and processing abilities. These insights may advance our understanding of the pathogenesis of cerebral small vessel disease.

Intercalated amygdala dysfunction drives avoidance extinction deficits in the Sapap3 mouse model of obsessive-compulsive disorder.

BACKGROUND: The avoidance of aversive stimuli through negative reinforcement learning is critical for survival in real-world environments, which demand dynamic responding to both positive and negative stimuli that often conflict with each other. Individuals with obsessive-compulsive disorder (OCD) commonly exhibit impaired negative reinforcement and extinction, perhaps involving deficits in amygdala functioning. An amygdala subregion of particular interest is the intercalated nuclei of the amygdala (ITC) which has been linked to negative reinforcement and extinction, with distinct clusters mediating separate aspects of behavior. This study focuses on the dorsal ITC cluster (ITCd) and its role in negative reinforcement during a complex behavior that models real-world dynamic decision making. METHODS: We investigated the impact of ITCd function on negative reinforcement and extinction by applying fiber photometry measurement of GCamp6f signals and optogenetic manipulations during a platform-mediated avoidance task in a mouse model of OCD-like behavior: the Sapap3-null mouse. RESULTS: We find impaired neural activity in the ITCd of male and female Sapap3-null mice to the encoding of negative stimuli during platform-mediated avoidance. Sapap3-null mice also exhibit deficits in extinction of avoidant behavior, which is modulated by ITCd neural activity. CONCLUSIONS: Sapap3-null mice fail to extinguish avoidant behavior in platform-mediated avoidance, due to heightened ITCd activity. This deficit can be rescued by optogenetically inhibiting ITCd during extinction. Together, our results provide insight into the neural mechanisms underpinning negative reinforcement deficits in the context of OCD, emphasizing the necessity of ITCd in responding to negative stimuli in complex environments.

Astrocytic determinant of the fate of long-term memory.

While some vivid memories are unyielding and unforgettable, others fade with time. Astrocytes are recognized for their role in modulating the brain's environment and have recently been considered integral to the brain's information processing and memory formation. This suggests their potential roles in emotional perception and memory formation. In this study, we delve into the impact of amygdala astrocytes on fear behaviors and memory, employing astrocyte-specific optogenetic manipulations in mice. Our findings reveal that astrocytic photoactivation with channelrhodopsin-2 (ChR2) provokes aversive behavioral responses, while archaerhodopsin-T (ArchT) photoactivation diminishes fear perception. ChR2 photoactivation amplifies fear perception and fear memory encoding but obstructs its consolidation. On the other hand, ArchT photoactivation inhibits memory formation during intense aversive stimuli, possibly due to weakened fear perception. However, it prevents the decay of remote fear memory over three weeks. Crucially, these memory effects were observed when optogenetic manipulations coincided with the aversive experience, indicating a deterministic role of astrocytic states at the exact moment of fear experiences in shaping long-term memory. This research underscores the significant and multifaceted role of astrocytes in emotional perception, fear memory formation, and modulation, suggesting a sophisticated astrocyte-neuron communication mechanism underlying basic emotional state transitions of information processing in the brain.

Standardized weighted low-resolution electromagnetic tomography study of the amygdala activity in patients with comorbid major depressive disorder and anxiety symptoms.

Major depressive disorder (MDD) often coexists with anxiety disorders or symptoms, as identified by previous functional magnetic resonance imaging (fMRI) studies. These studies have found abnormal amplitudes of low-frequency fluctuations (ALFF) in the amygdala, which serve as traits and state markers of MDD. This study used standardized weighted low-resolution electromagnetic tomography (swLORETA) technology to explore amygdala markers in patients with comorbid MDD and anxiety. Participants included patients with MDD comorbid with anxiety symptoms (MDD group) and healthy controls (HC group) who completed the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory (BAI). EEG data collected under resting state, happiness recall, and depressive recall tasks were converted into current-source density (CSD) values using swLORETA to assess amygdala activation. The results indicated higher beta2, beta3, and high beta levels in both the left and right amygdalae during the resting state in the MDD group than in the HC group. Similarly, elevated levels of beta2, beta3, and high beta were observed in the left and right amygdalae of the MDD group during happiness and depressive recall tasks. These findings support the presence of hyperactivity in the amygdala under resting state and emotional tasks in patients with comorbid MDD and anxiety symptoms.

Unearthing the hidden links: Investigating the functional connectivity between amygdala subregions and brain networks in bipolar disorder through resting-state fMRI.

Introduction: Bipolar disorder is a multifaceted psychiatric condition characterized by fluctuating activity levels and dysfunctional mood states, oscillating between manic and depressive episodes. These mood disturbances are accompanied by persistent functional and cognitive impairments, even during periods of euthymia. Prior studies have underscored the critical role of amygdala activity in the pathophysiology of bipolar disorder. This research aims to utilize resting-state functional Magnetic Resonance Imaging (rs-fMRI) to explore the functional modifications in the six sub-regions that compose the amygdala of individuals diagnosed with bipolar disorder. Method: The study encompassed 80 participants, bifurcated into two groups: 40 individuals with bipolar disorder and 40 healthy controls. Each group comprised an equal gender distribution of 20 females and 20 males, ranging in age from 21 to 50 years. Using rs-fMRI, we examined the functional connectivity within six amygdala sub-regions across eight regional functional networks. Results: Comparative analysis between the control group and the bipolar patients revealed that all six amygdala sub-regions demonstrated connectivity with the eight functional brain networks. Notable similarities and disparities were observed in the connectivity patterns between the bipolar group and controls, particularly within the amygdala's sub-regions and other brain networks. The most significant functional connectivity alterations were found with the salience network and the default mode network. Additionally, alterations in the functional connectivity between the amygdala, sensory-motor, and visual networks were noted in bipolar patients. Conclusion: The study's findings highlight the distinct patterns of resting-state functional connectivity of the amygdala and various brain networks in differentiating bipolar patients from healthy controls. These variations suggest the existence of multiple pathophysiological mechanisms contributing to emotional dysregulation in bipolar disorder.

Alterations of subcortical structure volume in pediatric bipolar disorder patients with manic or depressive first-episode.

BACKGROUND: Bipolar disorder may begin as depression or mania, which can affect the treatment and prognosis. The physiological and pathological differences among pediatric bipolar disorder (PBD) patients with different onset symptoms are not clear. The aims of the present study were to investigate subcortical structural alterations in PBD patients with first-episode depressive (PBD-FED) and first-episode manic (PBD-FEM). METHODS: A total of 59 individuals including 28 PBD-FED, 13 PBD-FEM, and 18 healthy controls (HCs) underwent high-resolution structural magnetic resonance scans. FreeSurfer 7.2 was used to detect changes in subcortical volumes. Simultaneously, thalamic, hippocampal, and amygdala subregion volumes were compared between the three groups. RESULTS: Analysis of covariance controlling for age, sex, education, and estimated intracranial volume shows third and fourth ventricle enlargement in patients with PBD. Compared with the PBD-FED and HCs, the PBD-FEM group had reduced gray matter volume in the left thalamus, bilateral hippocampus, and right amygdala. Subsequent subregion analyses showed right cortico-amygdaloid transient, bilateral accessory-basal nucleus, left hippocampal tail, right hippocampal head, and body volume reduction in the PBD-FEM group. CONCLUSIONS: The present findings provided evidence of decreased subcortical structure in PBD-FEM patients, which might present its trait feature.

An overview of the pathophysiology of agitation in Alzheimer's dementia with a focus on neurotransmitters and circuits.

Alzheimer's dementia (AD) is a progressive, neurodegenerative disease often accompanied by neuropsychiatric symptoms that profoundly impact both patients and caregivers. Agitation is among the most prevalent and distressing of these symptoms and often requires treatment. Appropriate therapeutic interventions depend on understanding the biological basis of agitation and how it may be affected by treatment. This narrative review discusses a proposed pathophysiology of agitation in Alzheimer's dementia based on convergent evidence across research approaches. Available data indicate that agitation in Alzheimer's dementia is associated with an imbalance of activity between key prefrontal and subcortical brain regions. The monoamine neurotransmitter systems serve as key modulators of activity within these brain regions and circuits and are rendered abnormal in AD. Patients with AD who exhibited agitation symptoms during life have alterations in neurotransmitter nuclei and related systems when the brain is examined at autopsy. The authors present a model of agitation in Alzheimer's dementia in which noradrenergic hyperactivity along with serotonergic deficits and dysregulated striatal dopamine release contribute to agitated and aggressive behaviors.

Sex-dependent effects of ethanol withdrawal from a single- and repeated binge episode exposures on social anxiety-like behavior and neuropeptide gene expression in adolescent rats.

Ethanol withdrawal sensitivity is a risk factor for the development of alcohol use disorder. Heavy episodic drinking during adolescence often encompasses repeated periods of withdrawal. Adolescent intermittent ethanol exposure of laboratory rodents produces several neurobiological deficits that differ between sexes, but the sensitivity to withdrawal as a contributor to the observed sex differences is not clear. The current study assessed the impact of acute withdrawal from a single- and repeated binge ethanol episodes during adolescence as well as protracted abstinence from repeated binge episodes on social anxiety-like behavior (indexed via significant decreases of social investigation) as well as oxytocin (OXT) and vasopressin (AVP) system gene expression in the hypothalamus (HYP) and central amygdala (CeA) in male and female Sprague Dawley rats. Females displayed social anxiety-like behavior during withdrawal from a single binge episode, whereas both sexes showed social anxiety-like changes following acute withdrawal from repeated binge episodes. After a period of protracted abstinence, only males still displayed ethanol-associated social alterations. Analysis of gene expression in separate, non-socially tested subjects revealed that withdrawal from repeated binge episodes during adolescence increased AVP gene expression in the HYP of males and decreased it in females. Males also displayed increased AVP and OXTR gene expression during acute withdrawal from repeated binge episodes in the CeA, with these changes persisting into adulthood. Together, these findings suggest that adolescent females are sensitive to withdrawal from both acute and repeated ethanol exposures, whereas males are sensitive to withdrawal from repeated ethanol exposures, with affective and transcriptional changes persisting into adulthood.

How the arts heal: a review of the neural mechanisms behind the therapeutic effects of creative arts on mental and physical health.

Background: The creative arts have long been known for their therapeutic potential. These modalities, which include dance, painting, and music, among others, appear to be effective in enhancing emotional expression and alleviating adverse physiological and psychological effects. Engagement in creative arts can be pursued as a personal hobby, in a classroom setting, or through a formal therapeutic intervention with a qualified therapist. Engagement can be active (i.e., creating) or passive (i.e., viewing, listening). Regardless of the modality and manner of engagement, the mechanisms explaining the therapeutic efficacy of creative arts remain poorly understood. Objective: This study aims to systematically review research investigating the neurological mechanisms activated during active or passive engagement in creative arts, with a specific emphasis on the roles of the medial prefrontal cortex (mPFC) and the amygdala in emotional regulation (ER) and creative behaviors. The review seeks to provide preliminary evidence for the possible existence of common neural mechanisms underlying both phenomena, which could inform the development of targeted therapeutic interventions leveraging creative arts for ER. Methods: A systematic review was conducted following the Cochrane Collaboration guideline and PRISMA standards to identify studies examining the neurological mechanisms underlying creative activities. Results: A total of six out of 85 records meet the inclusion criteria, with all being basic research studies. Preliminary findings suggest that active and passive engagement with creative arts consistently activate neural circuits implicated in adaptive emotional regulation, including the mPFC and amygdala. These activations mirror the neural pathways engaged in effective ER strategies, suggesting the possible existence of shared mechanisms between creative expression and emotional processing. Conclusion: The evidence underscores the potential of creative arts as a complementary therapeutic strategy alongside conventional care and other evidence-based mind-body modalities. By elucidating the shared neural mechanisms between creative arts engagement and ER, this review contributes to the theoretical and practical understanding of the role of creative arts in mental health. Future research is recommended to further explore these neural correlations and their implications for therapeutic practice.

On role models and Joe LeDoux.

Joseph LeDoux is a pioneering neuroscientist who has made profound discoveries that continue to impact our understanding of the neural basis of emotion and memory, particularly the role of the amygdala in threat conditioning. LeDoux's trailblazing and elegant studies were some of the first to examine the circuit basis of behavior. His work combined techniques to trace pathways into and out of the amygdala important for threat conditioning and related behaviors. Since that time, these types of circuit tracing studies have exploded in popularity across neuroscience, and I would argue, we all owe a debt to LeDoux for this. LeDoux has made numerous additional contributions to neuroscience and, by bringing emotion back to neuroscience, has helped unite neuroscience with psychology. A gifted writer with a knack for communicating complicated scientific ideas in an accessible manner, LeDoux has become an ambassador of science who uses his love of music to help educate and inspire. Perhaps more important than these laudable scientific achievements, LeDoux is also a true "gentleman" of science, showing that science need not be a contact sport. Here, I give a personal account on why Joseph LeDoux is one of my scientific role models.

Early childhood family threat and longitudinal amygdala-mPFC circuit development: Examining cortical thickness and gray matter-white matter contrast.

Early threat-associated cortical thinning may be interpreted as accelerated cortical development. However, non-adaptive processes may show similar macrostructural changes. Examining cortical thickness (CT) together with grey/white-matter contrast (GWC), a proxy for intracortical myelination, may enhance the interpretation of CT findings. In this prospective study, we examined associations between early life family-related threat (harsh parenting, family conflict, and neighborhood safety) and CT and GWC development from late childhood to middle adolescence. MRI was acquired from 4200 children (2069 boys) from the Generation R study at ages 8, 10 and 14 years (in total 6114 scans), of whom 1697 children had >1 scans. Linear mixed effect models were used to examine family factor-by-age interactions on amygdala volume, caudal and rostral anterior cingulate (ACC) and medial orbitofrontal cortex (mOFC) CT and GWC. A neighborhood safety-by-age-interaction was found for rostral ACC GWC, suggesting less developmental change in children from unsafe neighborhoods. Moreover, after more stringent correction for motion, family conflict was associated with greater developmental change in CT but less developmental change in GWC. Results suggest that early threat may blunt ACC GWC development. Our results, therefore, do not provide evidence for accelerated threat-associated structural development of the amygdala-mPFC circuit between ages 8-14 years.

Association of neuroimaging measures with facial emotional processing in healthy adults: a task fMRI study.

Investigating the neural processing of emotion-related neural circuits underlying emotional facial processing may help in understanding mental disorders. We used two subscales of the Toronto Alexithymia Scale to assess the emotional cognitive of 25 healthy participants. A higher score indicates greater difficulty in emotional perception. In addition, participants completed a n-back task during functional magnetic resonance imaging. Psychophysiological interaction analysis was used to explore the functional connectivity (FC) of neural circuits. Next, we used elastic-net regression analysis for feature selection and conducted correlation analysis between the neuroimaging measures and questionnaire scores. Following a 3-fold cross-validation, 5 neuroimaging measures emerged as significant features. Results of correlation analysis demonstrated that participants with higher TAS scores exhibited increased FC between the amygdala and occipital face area (OFA) during facial stimulus processing, but decreased connectivity during emotional processing. These findings suggested that individuals with poor emotional recognition exhibited increased connectivity among face-related brain regions during facial processing. However, during emotional processing, decreasing neural synchronization among neural circuits involved in emotional processing affects facial expression processing. These findings suggest potential neural marker related to subjective emotional perception, which may contribute to the diagnosis and treatment of emotional dysregulation in individuals with psychiatric conditions.

Behavioral and Amygdala Biochemical Damage Induced by Alternating Mild Stress and Ethanol Intoxication in Adolescent Rats: Reversal by Argan Oil Treatment?

Adolescence is a critical period when the effects of ethanol and stress exposure are particularly pronounced. Argan oil (AO), a natural vegetable oil known for its diverse pharmacological benefits, was investigated for its potential to mitigate addictive-like behaviors and brain damage induced by adolescent intermittent ethanol intoxication (IEI) and unpredictable mild stress (UMS). From P30 to P43, IEI rats received a daily ip ethanol (3 g/kg) on a two-day on/two-day off schedule. On alternate days, the rats were submitted to UMS protocol. Next, a two-bottle free access paradigm was performed over 10 weeks to assess intermittent 20% ethanol voluntary consumption. During the same period, the rats were gavaged daily with AO (15 mL/kg). Our results show that IEI/UMS significantly increased voluntary alcohol consumption (from 3.9 g/kg/24 h to 5.8 g/kg/24 h) and exacerbated withdrawal signs and relapse-like drinking in adulthood. Although AO treatment slightly reduced ethanol intake, it notably alleviated withdrawal signs during abstinence and relapse-like drinking in adulthood. AO's effects were associated with its modulation of the HPA axis (elevated serum corticosterone), restoration of amygdala oxidative balance, BDNF levels, and attenuation of neurodegeneration. These findings suggest that AO's neuroprotective properties could offer a potential therapeutic avenue for reducing ethanol/stress-induced brain damage and addiction. Further research is needed to explore its mechanisms and therapeutic potential in alcohol use disorders.

Persistent activity during working memory maintenance predicts long-term memory formation in the human hippocampus.

Working memory (WM) and long-term memory (LTM) are often viewed as separate cognitive systems. Little is known about how these systems interact when forming memories. We recorded single neurons in the human medial temporal lobe while patients maintained novel items in WM and completed a subsequent recognition memory test for the same items. In the hippocampus, but not in the amygdala, the level of WM content-selective persistent activity during WM maintenance was predictive of whether the item was later recognized with high confidence or forgotten. By contrast, visually evoked activity in the same cells was not predictive of LTM formation. During LTM retrieval, memory-selective neurons responded more strongly to familiar stimuli for which persistent activity was high while they were maintained in WM. Our study suggests that hippocampal persistent activity of the same cells supports both WM maintenance and LTM encoding, thereby revealing a common single-neuron component of these two memory systems.

The multi-stage plasticity in the aggression circuit underlying the winner effect.

Winning increases the readiness to attack and the probability of winning, a widespread phenomenon known as the "winner effect." Here, we reveal a transition from target-specific to generalized aggression enhancement over 10 days of winning in male mice. This behavioral change is supported by three causally linked plasticity events in the ventrolateral part of the ventromedial hypothalamus (VMHvl), a critical node for aggression. Over 10 days of winning, VMHvl cells experience monotonic potentiation of long-range excitatory inputs, transient local connectivity strengthening, and a delayed excitability increase. Optogenetically coactivating the posterior amygdala (PA) terminals and VMHvl cells potentiates the PA-VMHvl pathway and triggers the same cascade of plasticity events observed during repeated winning. Optogenetically blocking PA-VMHvl synaptic potentiation eliminates all winning-induced plasticity. These results reveal the complex Hebbian synaptic and excitability plasticity in the aggression circuit during winning, ultimately leading to increased "aggressiveness" in repeated winners.

Amygdala self-neuromodulation capacity as a window for process-related network recruitment.

Neurofeedback (NF) has emerged as a promising avenue for demonstrating process-related neuroplasticity, enabling self-regulation of brain function. NF targeting the amygdala has drawn attention to therapeutic potential in psychiatry, by potentially harnessing emotion-regulation processes. However, not all individuals respond equally to NF training, possibly owing to varying self-regulation abilities. This underscores the importance of understanding the mechanisms behind successful neuromodulation (i.e. capacity). This study aimed to investigate the establishment and neural correlates of neuromodulation capacity using data from repeated sessions of amygdala electrical fingerprint (Amyg-EFP)-NF and post-training functional magnetic resonance imaging (fMRI)-NF sessions. Results from 97 participants (healthy controls and post-traumatic stress disorder and fibromyalgia patients) revealed increased Amyg-EFP neuromodulation capacity over training, associated with post-training amygdala-fMRI modulation capacity and improvements in alexithymia. Individual differenaces in this capacity were associated with pre-training amygdala reactivity and initial neuromodulation success. Additionally, amygdala downregulation during fMRI-NF co-modulated with other regions such as the posterior insula and parahippocampal gyrus. This combined modulation better explained EFP-modulation capacity and improvement in alexithymia than the amygdala modulation alone, suggesting the relevance of this broader network to gained capacity. These findings support a network-based approach for NF and highlight the need to consider individual differences in brain function and modulation capacity to optimize NF interventions. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Understanding Depression in Autism: The Role of Subjective Perception and Anterior Cingulate Cortex Volume.

Background: The prevalence of depression is elevated in individuals with autism spectrum disorder (ASD) compared to the general population, yet the reasons for this disparity remain unclear. While social deficits central to ASD may contribute to depression, it is uncertain whether social interaction behavior themselves or individuals' introspection about their social behaviors are more impactful. Although the anterior cingulate cortex (ACC) and amygdala are frequently implicated in ASD, depression, and social functioning, it is unknown if these regions explain differences between ASD adults with and without co-occurring depression. Methods: The present study contrasted observed vs. subjective perception of autism symptoms and social performances assessed with both standardized measures and a lab task, in 65 sex-balanced (52.24% male) autistic young adults. We also quantified ACC and amygdala volume with 7-Tesla structural neuroimaging to examine correlations with depression and social functioning. Results: We found that ASD individuals with depression exhibited differences in subjective evaluations including heightened self-awareness of ASD symptoms, lower subjective satisfaction with social relations, and less perceived affiliation during the social interaction task, yet no differences in corresponding observed measures, compared to those without depression. Larger ACC volume was related to depression, greater self-awareness of ASD symptoms, and worse subjective satisfaction with social interactions. In contrast, amygdala volume, despite its association with clinician-rated ASD symptoms, was not related to depression. Limitations: Due to the cross-sectional nature of our study, we cannot determine the directionality of the observed relationships. Additionally, we included only individuals with an IQ over 60 to ensure participants could complete the social task, which excluded many on the autism spectrum. We also utilized self-reported depression indices instead of clinically diagnosed depression, which may limit the comprehensiveness of the findings. Conclusions: Our approach highlights the unique role of subjective perception of autism symptoms and social interactions, beyond the observable manifestation of social interaction in ASD, in contributing to depression, with the ACC playing a crucial role. These findings imply possible heterogeneity of ASD concerning co-occurring depression. Using neuroimaging, we were able to demarcate depressive phenotypes co-occurring alongside autistic phenotypes.

Abnormal developmental of hippocampal subfields and amygdalar subnuclei volumes in young adults with heavy cannabis use: A three-year longitudinal study.

BACKGROUND: Differences in the volumes of the hippocampus and amygdala have consistently been observed between young adults with heavy cannabis use relative to their non-using counterparts. However, it remains unclear whether the subfields of these functionally and structurally heterogenous regions exhibit similar patterns of change in young adults with long-term heavy cannabis use disorder (CUD). OBJECTIVES: This study aims to investigate the effects of long-term heavy cannabis use in young adults on the subregional structures of the hippocampus and amygdala, as well as their longitudinal alterations. METHODS: The study sample comprised 20 young adults with heavy cannabis use and 22 matched non-cannabis using healthy volunteers. All participants completed the Cannabis Use Disorder Identification Test (CUDIT) and underwent two T1-structural magnetic resonance imaging (MRI) scans, one at baseline and another at follow-up 3 years later. The amygdala, hippocampus, and their subregions were segmented on T1-weighted anatomical MRI scans, using a previously validated procedure. RESULTS: At baseline, young adults with heavy CUD exhibited significantly larger volumes in several hippocampal (bilateral presubiculum, subiculum, Cornu Ammonis (CA) regions CA1, CA2-CA3, and right CA4-Dentate Gyrus (DG)) and amygdala (bilateral paralaminar nuclei, right medial nucleus, and right lateral nucleus) subregions compared to healthy controls, but these differences were attenuated at follow-up. Longitudinal analysis revealed an accelerated volumetric decrease in these subregions in young adults with heavy CUD relative to controls. Particularly, compared to healthy controls, significant accelerated volume decreases were observed in the right hippocampal subfields of the parasubiculum, subiculum, and CA4-DG. In the amygdala, similar trends of accelerated volumetric decreases were observed in the left central nucleus, right paralaminar nucleus, right basal nucleus, and right accessory basal nucleus. CONCLUSIONS: The current findings suggest that long-term heavy cannabis use impacts maturational process of the amygdala and hippocampus, especially in subregions with high concentrations of cannabinoid type 1 receptors (CB1Rs) and involvement in adult neurogenesis.

Gateway to the study of the amygdala and emotion.

The study of the amygdala and its role in the processing of emotions has become a common focus in neuroscience. The modern expansion of research in this area is partly due to the discovery of a subcortical pathway for the transmission of emotional information and the experimental paradigm that was developed to study it. Groundbreaking experiments during the 90s utilized anatomical, neurophysiological, and behavioral lesion studies in a rodent animal model to uncover the neural circuitry of a simple emotional memory. These studies demonstrated the essential role of a specific monosynaptic pathway in emotional memory, using traditional tools and behavioral methods. The development of an animal model with a simple and appropriate classical conditioning paradigm made experimental investigations into the neural basis of emotion tenable and available to a generation of neuroscientists. These tools and a focus on the amygdala's neural connections and their essential role in emotional memory were a driving force in the explosion of research regarding the amygdala and emotion.