The value of an anticipated rewarding event is a crucial component of the decision to engage in its pursuit. But little is known of the networks responsible for encoding and retrieving this value. By ...using biosensors and pharmacological manipulations, we found that basolateral amygdala (BLA) glutamatergic activity tracks and mediates encoding and retrieval of the state-dependent incentive value of a palatable food reward. Projection-specific, bidirectional chemogenetic and optogenetic manipulations revealed that the orbitofrontal cortex (OFC) supports the BLA in these processes. Critically, the function of ventrolateral and medial OFC→BLA projections is doubly dissociable. Whereas lateral OFC→BLA projections are necessary and sufficient for encoding of the positive value of a reward, medial OFC→BLA projections are necessary and sufficient for retrieving this value from memory. These data reveal a new circuit for adaptive reward valuation and pursuit and provide insight into the dysfunction in these processes that characterizes myriad psychiatric diseases.
ABSTRACT
Subjective cognitive decline (SCD) is a high‐risk yet less understood status before developing Alzheimer's disease (AD). This work included 76 SCD individuals with two (baseline and 7 years ...later) neuropsychological evaluations and a baseline T1‐weighted structural MRI. A machine learning‐based model was trained based on 198 baseline neuroimaging (morphometric) features and a battery of 25 clinical measurements to discriminate 24 progressive SCDs who converted to mild cognitive impairment (MCI) at follow‐up from 52 stable SCDs. The SCD progression was satisfactorily predicted with the combined features. A history of stroke, a low education level, a low baseline MoCA score, a shrunk left amygdala, and enlarged white matter at the banks of the right superior temporal sulcus were found to favor the progression. This is to date the largest retrospective study of SCD‐to‐MCI conversion with the longest follow‐up, suggesting predictable far‐future cognitive decline for the risky populations with baseline measures only. These findings provide valuable knowledge to the future neuropathological studies of AD in its prodromal phase.
In this article, we used a community‐based cohort of subjective cognitive decline (SCD) elderly subjects with 7‐year follow‐up and retrospectively identified individual SCD who had converted to mild cognitive impairment (MCI) during the follow‐up. After identifying progressive SCDs from stable SCDs, we constructed a machine learning‐based prediction model that successfully identified most progressive SCD individuals based on 198 morphometric features derived from structural MRI and 25 comprehensive clinical features. The striking finding is that as few as five neuroimaging and clinical features derived from baseline were able to predict cognitive impairment occurred 7 years later.
The study of human anxiety disorders has benefited greatly from functional neuroimaging approaches. Individual studies, however, vary greatly in their findings. The authors searched for common and ...disorder-specific functional neurobiological deficits in several anxiety disorders. The authors also compared these deficits to the neural systems engaged during anticipatory anxiety in healthy subjects.
Functional magnetic resonance imaging and positron emission tomography studies of posttraumatic stress disorder (PTSD), social anxiety disorder, specific phobia, and fear conditioning in healthy individuals were compared by quantitative meta-analysis. Included studies compared negative emotional processing to baseline, neutral, or positive emotion conditions.
Patients with any of the three disorders consistently showed greater activity than matched comparison subjects in the amygdala and insula, structures linked to negative emotional responses. A similar pattern was observed during fear conditioning in healthy subjects. Hyperactivation in the amygdala and insula were, of interest, more frequently observed in social anxiety disorder and specific phobia than in PTSD. By contrast, only patients with PTSD showed hypoactivation in the dorsal and rostral anterior cingulate cortices and the ventromedial prefrontal cortex-structures linked to the experience and regulation of emotion.
This meta-analysis allowed us to synthesize often disparate findings from individual studies and thereby provide neuroimaging evidence for common brain mechanisms in anxiety disorders and normal fear. Effects unique to PTSD furthermore suggested a mechanism for the emotional dysregulation symptoms in PTSD that extend beyond an exaggerated fear response. Therefore, these findings help refine our understanding of anxiety disorders and their interrelationships.
Childhood maltreatment (CM) is known to influence brain development. To obtain a better understanding of related brain alterations, recent research has focused on the influence of the type and timing ...of CM. We aimed to investigate the association between type and timing of CM and local brain volume. Anatomical magnetic resonance images were collected from 93 participants (79 female/14 male) with a history of CM. CM history was assessed with the German Interview Version of the "Maltreatment and Abuse Chronology of Exposure" scale, "KERF-40 + ". Random forest regressions were performed to assess the impact of CM characteristics on the volume of amygdala, hippocampus and anterior cingulate cortex (ACC). The volume of the left ACC was predicted by neglect at age 3 and 4 and abuse at age 16 in a model including both type and timing of CM. For the right ACC, overall CM severity and duration had the greatest impact on volumetric alterations. Our data point to an influence of CM timing on left ACC volume, which was most pronounced in early childhood and in adolescence. We were not able to replicate previously reported effects of maltreatment type and timing on amygdala and hippocampal volume.
Highlights • IFS produces a long-term reduction of the response to a novel environment in rats. • IFS increases evoked noradrenaline release in the amygdala. • Amygdala propranolol injections ...normalize the behavior of IFS exposed rats.
Amygdala Modulation of Cerebellar Learning Farley, Sean J; Radley, Jason J; Freeman, John H
The Journal of neuroscience,
2016-Feb-17, 2016-02-17, 20160217, Volume:
36, Issue:
7
Journal Article
Peer reviewed
Open access
Previous studies showed that amygdala lesions or inactivation slow the acquisition rate of cerebellum-dependent eyeblink conditioning, a type of associative motor learning. The current study was ...designed to determine the behavioral nature of amygdala-cerebellum interactions, to identify the neural pathways underlying amygdala-cerebellum interactions, and to examine how the amygdala influences cerebellar learning mechanisms in rats. Pharmacological inactivation of the central amygdala (CeA) severely impaired acquisition and retention of eyeblink conditioning, indicating that the amygdala continues to interact with the cerebellum after conditioning is consolidated (Experiment 1). CeA inactivation also substantially reduced stimulus-evoked and learning-related neuronal activity in the cerebellar anterior interpositus nucleus during acquisition and retention of eyeblink conditioning (Experiment 2). A very small proportion of cerebellar neurons responded to the conditioned stimulus (CS) during CeA inactivation. Finally, retrograde and anterograde tracing experiments identified the basilar pontine nucleus at the confluence of outputs from CeA that may support amygdala modulation of CS input to the cerebellum (Experiment 3). Together, these results highlight a role for the CeA in the gating of CS-related input to the cerebellum during motor learning that is maintained even after the conditioned response is well learned.
The current study is the first to demonstrate that the amygdala modulates sensory-evoked and learning-related neuronal activity within the cerebellum during acquisition and retention of associative learning. The findings suggest a model of amygdala-cerebellum interactions in which the amygdala gates conditioned stimulus inputs to the cerebellum through a direct projection from the medial central nucleus to the basilar pontine nucleus. Amygdala gating of sensory input to the cerebellum may be an attention-like mechanism that facilitates cerebellar learning. In contrast to previous theories of amygdala-cerebellum interactions, the sensory gating hypothesis posits that the gating mechanism continues to be necessary for retrieval of cerebellar memory after learning is well established.
Although seasonal changes in amygdala volume have been demonstrated in animals, seasonal differences in human amygdala subregion volumes have yet to be investigated. Amygdala volume has also been ...linked to depressed mood. Therefore, we hypothesised that differences in photoperiod would predict differences in amygdala or subregion volumes and that this association would be linked to depressed mood. 10,033 participants ranging in age from 45 to 79 years were scanned by MRI in a single location. Amygdala subregion volumes were obtained using automated processing and segmentation algorithms. A mediation analysis tested whether amygdala volume mediated the relationship between photoperiod and mood. Photoperiod was positively associated with total amygdala volume (p < .001). Multivariate (GLM) analyses revealed significant effects of photoperiod across all amygdala subregion volumes for both hemispheres (p < .001). Post hoc univariate regression analyses revealed significant associations of photoperiod with each amygdala subregion volume (p < .001). PLS showed the highest loadings of amygdala subregions in lateral nucleus, ABN, basal nucleus, CAT, PLN, AAA, central nucleus, cortical nucleus and medial nucleus for left hemisphere and ABN, lateral nucleus, CAT, PLN, cortical nucleus, AAA, central nucleus and medial nucleus for right hemisphere. There were no significant associations between photoperiod and mood nor between mood scores and amygdala volumes, and due to the lack of these associations, the mediation hypothesis was not supported. This study is the first to demonstrate an association between photoperiod and amygdala volume. These findings add to the evidence supporting the role of photoperiod on brain structural plasticity.
This research found a novel association between photoperiod and amygdala volumes but not with depressive symptoms. The findings add to the evidence supporting the role of photoperiod on brain structural plasticity that may have implications for future investigations of changes in mood associated with human exposure to variations in light. The findings point to the importance of documenting photoperiod of scan day to ensure detected volume differences were a result of the intended intervention.
•The amygdala has a long-standing history of hemispheric lateralization in emotion.•The CeA’s unique role in pain processing is thought to be right hemisphere dominant.•Recent findings suggest the ...left CeA also plays an important role in pain processing.•Growing evidence reveals CeA lateralization across a variety of pain models.•CeA lateralization should be examined in future pain studies.
Hemispheric asymmetries within the brain have been identified across taxa and have been extensively studied since the early 19th century. Here, we discuss lateralization of a brain structure, the amygdala, and how this lateralization is reshaping how we understand the role of the amygdala in pain processing. The amygdala is an almond-shaped, bilateral brain structure located within the limbic system. Historically, the amygdala was known to have a role in the processing of emotions and attaching emotional valence to memories and other experiences. The amygdala has been extensively studied in fear conditioning and affect but recently has been shown to have an important role in processing noxious information and impacting pain. The amygdala is composed of multiple nuclei; of special interest is the central nucleus of the amygdala (CeA). The CeA receives direct nociceptive inputs from the parabrachial nucleus (PBN) through the spino-parabrachio-amygdaloid pathway as well as more highly processed cortical and thalamic input via the lateral and basolateral amygdala. Although the amygdala is a bilateral brain region, most data investigating the amygdala’s role in pain have been generated from the right CeA, which has an overwhelmingly pro-nociceptive function across pain models. The left CeA has often been characterized to have no effect on pain modulation, a dampened pro-nociceptive function, or most recently an anti-nociceptive function. This review explores the current literature on CeA lateralization and the hemispheres’ respective roles in the processing and modulation of different forms of pain.
Abuse during early life, especially from the caregiver, increases vulnerability to develop later-life psychopathologies such as depression. Although signs of depression are typically not expressed ...until later life, signs of dysfunctional social behavior have been found earlier. How infant abuse alters the trajectory of brain development to produce pathways to pathology is not completely understood. Here we address this question using two different but complementary rat models of early-life abuse from postnatal day 8 (P8) to P12: a naturalistic paradigm, where the mother is provided with insufficient bedding for nest building; and a more controlled paradigm, where infants undergo olfactory classical conditioning. Amygdala neural assessment (c-Fos), as well as social behavior and forced swim tests were performed at preweaning (P20) and adolescence (P45). Our results show that both models of early-life abuse induce deficits in social behavior, even during the preweaning period; however, depressive-like behaviors were observed only during adolescence. Adolescent depressive-like behavior corresponds with an increase in amygdala neural activity in response to forced swim test. A causal relationship between the amygdala and depressive-like behavior was suggested through amygdala temporary deactivation (muscimol infusions), which rescued the depressive-like behavior in the forced swim test. Our results indicate that social behavior deficits in infancy could serve as an early marker for later psychopathology. Moreover, the implication of the amygdala in the ontogeny of depressive-like behaviors in infant abused animals is an important step toward understanding the underlying mechanisms of later-life mental disease associated with early-life abuse.
Medications that target the noradrenergic system are important therapeutics for depression and anxiety disorders. More recently, clinical studies have shown that the α2-noradrenergic receptor (α2AR) ...agonist guanfacine can decrease stress-induced smoking relapse during acute abstinence, suggesting that targeting the noradrenergic system may aid in smoking cessation through effects on stress pathways in the brain. Acetylcholine (ACh), like the nicotine in tobacco, acts at nicotinic acetylcholine receptors (nAChRs) to regulate behaviors related to anxiety and depression. We therefore investigated interactions between guanfacine and ACh signaling in tests of anxiolytic and antidepressant efficacy in female and male C57BL/6J mice, focusing on the amygdala as a potential site of noradrenergic/cholinergic interaction. The antidepressant-like effects of guanfacine were blocked by shRNA-mediated knockdown of α2AR in amygdala. Knockdown of the high-affinity β2 nAChR subunit in amygdala also prevented antidepressant-like effects of guanfacine, suggesting that these behavioral effects require ACh signaling through β2-containing nAChRs in this brain area. Ablation of NE terminals prevented the anxiolytic- and antidepressant-like effects of the nicotinic partial agonist cytisine, whereas administration of the cholinesterase antagonist physostigmine induced a depression-like phenotype that was not altered by knocking down α2AR in the amygdala. These studies suggest that ACh and NE have opposing actions on behaviors related to anxiety and depression and that cholinergic signaling through β2-containing nAChRs and noradrenergic signaling through α2a receptors in neurons of the amygdala are critical for regulation of these behaviors.