Neuroscience Applied最新文献

Virtual Reality (VR) has emerged as a promising tool in the treatment of anxiety disorders, particularly for exposure-based interventions. This literature review summarizes recent research on the efficacy of Virtual Reality Exposure Therapy (VRET) for addressing public speaking anxiety (PSA) and Social Anxiety Disorder (SAD). VRET demonstrates comparable efficacy to traditional in vivo exposure. While VRET exhibits relatively low drop-out rates, challenges related to immersion and sense of presence in the virtual environment remain to be addressed. Additionally, patients' preferences for VRET over in vivo exposure could enhance treatment adherence. The accessibility and cost-effectiveness of VRET render it a valuable therapeutic option, particularly for individuals with limited access to or low acceptance towards traditional therapy options. Self-guided VRET shows promise as an effective treatment approach, but its efficacy and safety necessitate further investigation. Ethical considerations pertaining to data protection and quality control are crucial when employing VRET applications. Careful implementation and monitoring are necessary to ensure patient privacy and safety. In conclusion, VRET holds significant promise as an effective and accessible treatment modality for SAD and PSA, offering new opportunities for prevention and management in the field of anxiety disorders. Continued research and advancements in VRET technology are expected to enhance its potential as a valuable tool in the mental health care landscape.

The complex dyadic interaction of stress and resilience has received growing attention as a promising avenue for informing new diagnostic and prognostic models for human health. In this review, we present a selection of some of the most relevant data on translational models and biomarkers of stress and resilience in the field of mental health. Several critical aspects concerning the preclinical and clinical model development are addressed. The distance between preclinical and clinical disease models has widened with time across all fields of medicine, with psychiatry presenting additional hurdles represented by the inherent heterogeneity of the studied phenotypes. Capitalizing on technological advances in developing and consolidating sound theories for stress-resilience interaction models represents a promising avenue, possibly endowed with greater ecological validity compared to the sole socio-psychological assessment. Instrumental in advancing the field will be an increased level of integration between preclinical and clinical researchers' efforts in developing translational biomarkers, aiming to elucidate better the interindividual heterogeneity in the impact of stress exposure on individuals’ health and behavior.

Impaired neuroplasticity in neurons endowed in limbic circuits is considered a hallmark of chronic stress and depression. The reasons for this impairment are still partially unclear, but converging findings suggest that it can be reverted by exposure to rapid-acting antidepressants. In this study we revamped the hypothesis that the abnormal high circulating levels of cortisol observed in Major Depressive Disorders with anhedonia may contribute to drive the limbic circuit neuroplasticity impairment. Here we used an established in-vitro translational model based on human iPSC-derived dopaminergic neurons to extend the evidence obtained in rodents of glucocorticoid-induced hypotrophy of cortical dendrites. The predictive value of this model was tested by assessing the reversal potential of rapid-acting antidepressants on cortisol-induced hypotrophy. Human mesencephalic dopaminergic neurons were differentiated in-vitro from healthy donor iPSCs for 60–70 days. Cortisol effects were assessed by measuring maximal dendrite length, primary dendrite number and soma area 3 days after last exposure. Concentration- and time-response curves were initially established. Cortisol produced a concentration- and time-dependent reduction of dendritic arborization of human dopaminergic neurons, with maximal effects at 50 μM for 4-day dosing. These effects were reverted when followed by 1-hr exposure to ketamine or (2R,6R)-hydroxynorketamine at concentrations of 0.01 μM and 0.05 μM, respectively, resulting approximately 10- or 100-fold lower than those effective in neurons not exposed to cortisol. Overall, in this study high cortisol impaired dendritic arborization in human dopaminergic neurons and sensitized their neuroplasticity response to very low doses of rapid-acting antidepressants known to upregulate AMPA-mediated glutamatergic neurotransmission.

Glucocorticoid hormones cortisol and corticosterone (collectively called CORT), secreted as the end products of the hypothalamus-pituitary-adrenal (HPA)-axis, coordinate body and brain function over the circadian cycle and during adaptation to stress. For this purpose, the hormones bind to the mineralocorticoid receptors (MR) with the highest expression in the hippocampus/lateral septum neurons and a 10-fold lower affinity to the widely distributed glucocorticoid receptors (GR). MR and GR mediate opposing rapid non-genomic actions of CORT on neuronal excitability. MR and GR also mediate in a slower complementary manner the genomic actions on neuronal excitability, the management of energy resources, the control of defense reactions, and emotional, motivational, social, and valuation processes to gain control and adapt. The glucocorticoids perform this life-sustaining pleiotropic action in interaction with the neuropeptides of the HPA-axis, the central and autonomic nervous systems, and the immune system. Here, the progress is discussed in (i) detecting dysregulation and recovery in glucocorticoid secretion patterns, (ii) unraveling the complementary function of MR and GR in the mechanism underlying stress-coping and adaptation, and (iii) applying selective CORT receptor modulators for attenuating neurodegeneration and enhancing resilience.

Cognitive impairment is prevalent in affective disorders. Currently, there is a lack of effective treatment options, which is partly due to limited insight into their neural underpinnings and poor transfer to everyday life. Integrating neuroimaging measures in cognition trials to identify neurocircuitry biomarkers is crucial for treatment development. We pooled baseline data from two clinical trials to validate a novel functional magnetic resonance imaging (fMRI) paradigm simulating real-life verbal learning and memory tasks. Healthy participants with no psychiatric history (n = 34) underwent fMRI and an ecologically valid virtual reality-based verbal memory task. During fMRI, they performed an ecologically valid paradigm involving encoding and recognition of a grocery shopping list. Whole-brain analyses assessed task-related activation in key neural networks. Neural underpinnings of memory encoding involved the hippocampus, prefrontal, temporal, occipital, and parietal regions, and caudate. Recognition task activation encompassed a network of frontal, parietal, temporal, and occipital regions. Positive associations were found between encoding-related activity in the inferior temporal gyrus and lateral occipital cortex and the number of correctly recalled grocery items. This study introduces and validates a novel fMRI paradigm for assessing real-life verbal learning and memory abilities. The identified neural underpinnings highlight the involvement of diverse brain regions in encoding and recognition processes that may be implemented in future investigations of the neural correlates of memory impairment and improvement.

Anorexia nervosa is a serious mental illness characterized by voluntary restriction of food intake and avoidance of high-calorie food. Anxiety, highly comorbid with anorexia nervosa, appears to be a significant, yet underexplored, factor affecting core behavioural symptoms such as food restriction and compulsive physical exercise. The aims of this review are to disentangle the influence of anxiety in food decision-making in anorexia nervosa and to offer a comprehensive model connecting the mechanisms involved.

The shift from food approach to avoidance seems to be a conditioned response, underpinned by an activation of salience and fear circuitry. Altered neurotransmission (dopamine, serotonin) and neuroendocrine release (leptin, ghrelin, cortisol), aberrant neural structure activation (hyperactivation of the amygdala and hypoactivation of the insula-ventral striatum circuit) and cognitive and behavioural traits shared by anxiety and anorexia nervosa (rigidity, compulsiveness) contribute to these modifications. Animal models suggest a bidirectional relationship between food restriction and anorectic-like behaviours, strengthening yet complexifying the link between anxiety and food choice in anorexia nervosa. Therapeutic strategies focusing on anxiety and the conditioned response could contribute to restore healthy food choices and dissociate food stimuli from the anxious response elicited.