Social anxiety disorder (SAD) is characterized by over-reactivity of fear-related circuits in social or performance situations and associated with marked social impairment. We used dynamic causal modeling (DCM), a method to evaluate effective connectivity, to test our hypothesis that SAD patients would exhibit dysfunctions in the amygdala–prefrontal emotion regulation network. Thirteen unmedicated SAD patients and 13 matched healthy controls performed a series of facial emotion and object discrimination tasks while undergoing fMRI. The emotion-processing network was identified by a task-related contrast and motivated the selection of the right amygdala, OFC, and DLPFC for DCM analysis. Bayesian model averaging for DCM revealed abnormal connectivity between the OFC and the amygdala in SAD patients. In healthy controls, this network represents a negative feedback loop. In patients, however, positive connectivity from OFC to amygdala was observed, indicating an excitatory connection. As we did not observe a group difference of the modulatory influence of the FACE condition on the OFC to amygdala connection, we assume a context-independent reduction of prefrontal control over amygdalar activation in SAD patients. Using DCM, it was possible to highlight not only the neuronal dysfunction of isolated brain regions, but also the dysbalance of a distributed functional network.
Reflecting one's mental self is a fundamental process for evaluating the personal relevance of life events and for moral decision making and future envisioning. Although the corresponding network has been receiving growing attention, the driving neurochemical mechanisms of the default mode network (DMN) remain unknown. Here we combined positron emission tomography and functional magnetic resonance imaging to investigate modulations of the DMN via serotonin-1A receptors (5-HT 1A ), separated for 5-HT autoinhibition (dorsal raphe nucleus) and local inhibition (heteroreceptors in projection areas). Using two independent approaches, regional 5-HT 1A binding consistently predicted DMN activity in the retrosplenial cortex for resting-state functional magnetic resonance imaging and the Tower of London task. On the other hand, both local and autoinhibitory 5-HT 1A binding inversely modulated the posterior cingulate cortex, the strongest hub in the resting human brain. In the frontal part of the DMN, a negative association was found between the dorsal medial prefrontal cortex and local 5-HT 1A inhibition. Our results indicate a modulation of key areas involved in self-referential processing by serotonergic neurotransmission, whereas variations in 5-HT 1A binding explained a considerable amount of the individual variability in the DMN. Moreover, the brain regions associated with distinct introspective functions seem to be specifically regulated by the different 5-HT 1A binding sites. Together with previously reported modulations of dopamine and GABA, this regional specialization suggests complex interactions of several neurotransmitters driving the default mode network.functional connectivity | resting-state networks | neurotransmitter modulation
Pleasure and motivation are important factors for goal-directed behaviour and wellbeing in both animals and humans. Intact hedonic capacity requires an undisturbed interplay between a number of different brain regions and transmitter systems. Concordantly, dysfunction of networks encoding for reward have been shown in depression and other psychiatric disorders. The development of technological possibilities to investigate connectivity on a functional level in humans and to directly influence networks in animals using optogenetics among other techniques has provided new important insights in this field of research (Lenz and Lobo, 2013; Ferenczi et al., 2016).In this review we aim to provide an overview on the neurobiological substrates of anhedonia on a network level. For this purpose definition of anhedonia and the involved reward components are described first, then current data on reward networks in healthy individuals and in depressed patients are summarized and the roles of different neurotransmitter systems involved in reward processing are specified. Based on this information, the impact of different therapeutic approaches on reward processing is described with a particular focus on deep brain stimulation (DBS) as a possibility for a direct modulation of human brain structures in vivo.Overall, results of current studies emphasize on the importance of anhedonia in psychiatric disorders and the relevance of targeting this phenotype for a successful psychiatric treatment. However, more data incorporating these results for the refinement of methodological approaches are needed in order to be able to develop individually tailored therapeutic concepts based on both clinical and neurobiological profiles of patients.
Background:Schizophrenia has been associated with disturbances of thalamic functioning. In light of recent evidence suggesting a significant impact of the glutamatergic system on key symptoms of schizophrenia, we assessed whether modulation of the glutamatergic system via blockage of the N-methyl-d-aspartate (NMDA)-receptor might lead to changes of thalamic functional connectivity.Methods:Based on the ketamine model of psychosis, we investigated changes in cortico-thalamic functional connectivity by intravenous ketamine challenge during a 55-minute resting-state scan. Thirty healthy volunteers were measured with pharmacological functional magnetic resonance imaging using a double-blind, randomized, placebo-controlled, crossover design.Results:Functional connectivity analysis revealed significant ketamine-specific changes within the thalamus hub network, more precisely, an increase of cortico-thalamic connectivity of the somatosensory and temporal cortex.Conclusions:Our results indicate that changes of thalamic functioning as described for schizophrenia can be partly mimicked by NMDA-receptor blockage. This adds substantial knowledge about the neurobiological mechanisms underlying the profound changes of perception and behavior during the application of NMDA-receptor antagonists.
Functional magnetic resonance imaging (fMRI) has become the primary non-invasive method for investigating the human brain function. With an increasing number of ultra-high field MR systems worldwide possibilities of higher spatial and temporal resolution in combination with increased sensitivity and specificity are expected to advance detailed imaging of distinct cortical brain areas and subcortical structures. One target region of particular importance to applications in psychiatry and psychology is the amygdala. However, ultra-high field magnetic resonance imaging of these ventral brain regions is a challenging endeavor that requires particular methodological considerations. Ventral brain areas are particularly prone to signal losses arising from strong magnetic field inhomogeneities along susceptibility borders. In addition, physiological artifacts from respiration and cardiac action cause considerable fluctuations in the MR signal. Here we show that, despite these challenges, fMRI data from the amygdala may be obtained with high temporal and spatial resolution combined with increased signal-to-noise ratio. Maps of neural activation during a facial emotion discrimination paradigm at 7 T are presented and clearly show the gain in percental signal change compared to 3 T results, demonstrating the potential benefits of ultra-high field functional MR imaging also in ventral brain areas.
A characterizing symptom of social anxiety disorder (SAD) is increased emotional reactivity towards potential social threat in combination with impaired emotion and stress regulation. While several neuroimaging studies have linked SAD with hyperreactivity in limbic brain regions when exposed to emotional faces, little is known about habituation in both the amygdala and neocortical regulation areas. 15 untreated SAD patients and 15 age- and gender-matched healthy controls underwent functional magnetic resonance imaging during repeated blocks of facial emotion () and object discrimination tasks (). Emotion processing networks were defined by a task-related contrast (). Linear regression was employed for assessing habituation effects in these regions. In both groups, the employed paradigm robustly activated the emotion processing and regulation network, including the amygdalae and orbitofrontal cortex (OFC). Statistically significant habituation effects were found in the amygdalae, OFC, and pulvinar thalamus of SAD patients. No such habituation was found in healthy controls. Concurrent habituation in the medial OFC and the amygdalae of SAD patients as shown in this study suggests intact functional integrity and successful short-term down-regulation of neural activation in brain areas responsible for emotion processing. Initial hyperactivation may be explained by an insufficient habituation to new stimuli during the first seconds of exposure. In addition, our results highlight the relevance of the orbitofrontal cortex in social anxiety disorders.
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