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Studies’ selection flow for the systematic review
Source publication
Generalized anxiety disorder (GAD) is a prevalent anxiety disorder, but is still poorly recognized in clinical practice. The aim of this review is to provide a coherent understanding of the functional neuroanatomy of GAD; second, to discuss the current theoretical cognitive models surrounding GAD; and finally to discuss the discrepancy between fund...
Citations
... Causes of anxiety disorders have widely been explored. Causes of generalized anxiety disorder include genetic factors (e.g., variations in the sub-type of the glutamic acid decarboxylase gene) 23 , a higher-than-average number of traumatic experiences and other undesirable life events in childhood 24 , threatening stimuli like verbal-linguistic threats 25 , difficulties in engaging the prefrontal cortex and anterior cingulate cortex during emotional regulation tasks 26 , etc. Panic disorder may result from disturbances in serotonergic neuro-transmission 27 , cholecystokinin receptors 28 , hyperventilation and hypocapnia 29 , disturbances in the coordination between cortical and brainstem functions 30 , and psychological factors like life stressors and conditioned stimuli 12,31 . Causes underlying social anxiety disorder may involve genetic components 32 and psychological factors like childhood temperament, parental psychopathology, neuroticism, peer criticism, heightened self-awareness and increased self-evaluation; biases in the processing of emotional information, and persistently negative expectations of social situations 33 . ...
Background
About one in four Chinese people might suffer or have already suffered from anxiety conditions, with a lifetime prevalence rate of 4.8%. However, many of those who could have benefited from psychological or pharmacological treatments fail to be recognized or treated due to the lack of timely recognition and accurate diagnosis.
Objective
This study used a topic modeling approach to explore people’s anxiety-related concerns raised on a computer-mediated Chinese health platform, YOU WEN BI DA (questioning and answering), to provide implications for accurate diagnosis, targeted education, tailored intervention, and informed policy-making in the course of addressing this condition of public concern.
Methods
First, we extracted data from YOU WEN BI DA between May 2022 and February 2023. After cleaning the extracted data both using the Python text processing tool spaCy and manually, we ascertained the optimal number of topics by drawing on the coherence scores and used latent Dirichlet allocation (LDA) topic modeling to generate the most salient topics and related terms. We then categorized the topics ascertained into different classes of themes by plotting them onto a 2D plane via multidimensional scaling using the pyLDAvis visualization tool. Finally, we analyzed these topics and themes qualitatively to better understand people’s anxiety-related concerns.
Results
5 topics with different overall prevalence were ascertained through data analysis. Topic 2 (tinnitus phobia-incurred concerns, n = 639) is the most popular dominant topic, occurring in 25.1% of the 2545 collected concerns, closely followed by Topics 1 (neurosis-incurred concerns, n = 512;) and 3 (sleep, dyskinesia, bipolar, cognitive, and somatic disorders-incurred concerns, n = 619), which appeared in 20.1% and 24.3% of the 2545 concerns respectively. Topic 5 (social phobia-incurred concerns, n = 428) ranks as the fourth most popular dominant topic, showing up in 16.8% of the 2545 concerns. Topic 4 (autonomic nerve dysfunction-incurred concerns, n = 347) accounts for 13.6% of the 2545 concerns. The t-distributed Stochastic Neighbor Embedding analysis reveals partial similarities between Topics 2 and 5 as well as between Topics 4 and 5 because many concerns involved in Topics 2 and 5 pertain to people’s psychological status of fear and anxiety and the relief and dispelling of such symptoms through medication, and many concerns involved in Topics 4 and 5 relate to people’s worries about the negative impact on their nerves and the adjustment and conditioning of such effects through medication.
Conclusion
This was the first study that investigated Chinese people’s anxiety-related concerns raised on YOU WEN BI DA using the topic modeling technique. The automatic text analysis and complementary manual interpretation of the collected data allowed for the discovery of the dominant topics hidden in the data and the categorization of these topics into different themes to reveal the overall status of people’s anxiety-related concerns. The research findings can provide some practice implications for health and medical educators, practitioners, and policy-makers to make joint efforts to address this common public concern effectively and efficiently.
... Greater increased activities in the left SFG in GAD were found compared with ID. Broad evidence from fMRI studies has revealed that the SFG are important part of the dorsolateral prefrontal cortex (DLPFC), which has been proved to be tightly linked to anxiety and depression (Goossen et al., 2019;Ma et al., 2019;B. Zhang et al., 2021aB. ...
Patients with insomnia disorder (ID) usually experience a greater burden of comorbid anxiety symptoms. However, the neural mechanism under the mutual relationship between ID and anxiety remains largely unclear. The meta-analysis aimed to explore the concordance and distinction of regional brain functional activity in patients with ID and those with generalized anxiety disorder (GAD) using coordinate-based activation likelihood estimation approach. Studies using resting-state regional homogeneity, amplitude of low-frequency fluctuations (ALFF), or fractional ALFF in patients with ID or GAD were included by searching multiple databases up to May 24, 2024. Using meta-analytic approach, 21 studies of ID vs. healthy controls (HC) and 16 studies of GAD vs. HC were included to illuminate the common and distinct patterns between the two disorders. Results showed that ID and GAD shared increased brain activities in the left posterior cingulate cortex and left precuneus, as well as decreased brain activity in the left medial prefrontal cortex. Additionally, compared with ID, GAD showed greater increased activities in the left superior frontal gyrus. Our study reveals both common and different activation patterns between ID and GAD, which may provide novel insights for understanding the neural basis of the two disorders and enlighten the possibility of the development of more targeted treatment strategies for ID and GAD.
... Structural and functional (both task-dependent and resting-state) MRI, diffusion tensor imaging, and positron emission topography (PET) have all been employed to help elucidate the intricate relationship between PFC regions and clinical anxiety. They have revealed both structural and functional alterations across a network of prefrontal and cingulate regions, alongside the insula, amygdala, and hippocampus [30,[32][33][34][35][36], within the various clinical disorders of anxiety. A consistent finding of commonality is hyperactivity of the amygdala and insula, while activity in PFC and cingulate regions appear to have a more varied relationship with the diagnostic categories. ...
... There are inconsistencies across studies, however, not only with respect to which regions are reported but also the directionality of the activity in relation to any given anxiety disorder [30,32,33]. In general, phobias [38], GAD [34], and SAD [39] are characterised by findings of hyperactivity in circuitry associated with threat and threat responseincluding the amygdala, insula, and medial (m)PFCwhile PTSD is marked by select regional hypo-and hyperactivity changes [32,40,41]. Aside from activity changes in localised regions, altered activity in functional networks has also been reported. ...
Marked dysregulation of the human prefrontal cortex (PFC) and anterior cingulate cortex (ACC) characterises a variety of anxiety disorders, and its amelioration is a key feature of treatment success. Overall treatment response, however, is highly variable, and about a third of patients are resistant to treatment. In this review we hypothesise that a major contributor to this variation in treatment response are the multiple faces of anxiety induced by distinct forms of frontal cortex dysregulation. Comparison of findings from
humans and non-human primates reveals marked similarity in the functional organisation of threat regulation across the frontal lobes. This organisation is discussed in relation to the ‘predatory imminence continuum’ model of threat and the differential engagement of executive functions at the core of both emotion generation and regulation strategies.
... The intentional integration of task-based imaging paradigms alongside task-relevant behavior may be a clear path forward to boost power for effects of interest in psychiatry with smaller samples. However, many commonly used tasks (e.g., n-back for working memory, Stroop for executive function, monetary incentive tasks for reward/motivation, etc.), which tend to be implemented in large consortia studies, may not be enriched for associations with psychopathology per se [17]. Overcoming these shortcomings will require the creation and integration of novel task paradigms that target valid cognitive constructs associated with psychiatric disorders [7,18]. ...
Neuroimaging has been widely adopted in psychiatric research, with hopes that these non-invasive methods will provide important clues to the underpinnings and prediction of various mental health symptoms and outcomes. However, the translational impact of neuroimaging has not yet reached its promise, despite the plethora of computational methods, tools, and datasets at our disposal. Some have lamented that too many psychiatric neuroimaging studies have been underpowered with respect to sample size. In this review, we encourage this discourse to shift from a focus on sheer increases in sample size to more thoughtful choices surrounding experimental study designs. We propose considerations at multiple decision points throughout the study design, data modeling and analysis process that may help researchers working in psychiatric neuroimaging boost power for their research questions of interest without necessarily increasing sample size. We also provide suggestions for leveraging multiple datasets to inform each other and strengthen our confidence in the generalization of findings to both population-level and clinical samples. Through a greater emphasis on improving the quality of brain-based and clinical measures rather than merely quantity, meaningful and potentially translational clinical associations with neuroimaging measures can be achieved with more modest sample sizes in psychiatry.
... Whether certain populations benefit more by applying rehabilitation practices that target one of these processes, more so than the other, needs be clarified in future work. Finally, recent developments in neuroimaging strategies have produced sophisticated approaches to understand cognitive processes and emotional states (Goossen et al., 2019;Sui et al., 2020). Applying these methods to understand biomarkers for skilled proprioceptive ability would provide important insight that could be used to understand how it is affected in other populations (e.g. ...
Historically, research aimed at improving motor performance has largely focused on the neural processes involved in motor execution due to their role in muscle activation. However, accompanying somatosensory and proprioceptive sensory information is also vitally involved in performing motor skills. Here we review research from interdisciplinary fields to provide a description for how somatosensation informs the successful performance of motor skills as well as emphasize the need for careful selection of study methods to isolate the neural processes involved in somatosensory perception. We also discuss upcoming strategies of intervention that have been used to improve performance via somatosensory targets. We believe that a greater appreciation for somatosensation's role in motor learning and control will enable researchers and practitioners to develop and apply methods for the enhancement of human performance that will benefit clinical, healthy, and elite populations alike.
... Differential activation of frontal cortical areas such as the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC) is evident between men and women depending on the emotional valence of presented stimuli, induced stress levels or prior adverse childhood experiences (Thomas et al., 2019;Javanbakht et al., 2016;Seo et al., 2017;Stevens and Hamann, 2012). Accordingly, a dysfunctional activation of those cortical regions and their interaction with the amygdala and the hippocampal formation are observed during emotion regulation in anxiety patients (Mochcovitch et al., 2014;Goossen et al., 2019;Kim and Kim, 2021). This matches the basic function of these areas and their homologous structures in rodents regulating fear and anxiety as well as emotional affect, attention and decision making (Admon et al., 2013;Tovote et al., 2015;van Heukelum et al., 2020;Chen et al., 2022). ...
Anxiety disorders have been linked to a disbalance of excitation and inhibition in a network of brain structures comprising frontal cortical regions, the amygdala and the hippocampus, among others. Recent imaging studies suggest sex differences in the activation of this anxiety network during the processing of emotional information. Rodent models with genetically altered ϒ-amino butyric acid (GABA) neurotransmission allow studying the neuronal basis of such activation shifts and their relation to anxiety endophenotypes, but to date sex effects have rarely been addressed. Using mice with a null mutation of the GABA synthetizing enzyme glutamate decarboxylase 65 (GAD65-/-), we started to compare anxiety-like behavior and avoidance in male vs. female GAD65-/- mice and their wildtype littermates. In an open field, female GAD65-/- mice displayed increased activity, while male GAD65-/- mice showed an increased adaptation of anxiety-like behavior over time. GAD65-/- mice of both sexes had a higher preference for social interaction partners, which was further heightened in male mice. In male mice higher escape responses were observed during an active avoidance task. Together, female mice showed more stable emotional responses despite GAD65 deficiency. To gain insights into interneuron function in network structures controlling anxiety and threat perception, fast oscillations (10-45 Hz) were measured in ex vivo slice preparations of the anterior cingulate cortex (ACC). GAD65-/- mice of both sexes displayed increased gamma power in the ACC and a higher density of PV-positive interneurons, which are crucial for generating such rhythmic activity. In addition, GAD65-/- mice had lower numbers of somatostatin-positive interneurons in the basolateral amygdala and in the dorsal dentate gyrus especially in male mice, two key regions important for anxiety and active avoidance responses. Our data suggest sex differences in the configuration of GABAergic interneurons in a cortico-amygdala-hippocampal network controlling network activity patterns, anxiety and threat avoidance behavior.
... Differential activation of frontal cortical areas such as the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC) is evident between men and women depending on the emotional valence of presented stimuli, induced stress levels or prior adverse childhood experiences (Thomas et al., 2019;Javanbakht et al., 2016;Seo et al., 2017;Stevens & Hamann 2012). Accordingly, a dysfunctional activation of those cortical regions and their interaction with the amygdala and the hippocampal formation are observed during emotion regulation in anxiety patients (Mochkovotich et al., 2014;Goossen et al., 2019;Kim & Kim, 2021). This matches the basic function of these areas and their homologous structures in rodents regulating fear and anxiety as well as emotional affect, attention and decision making (Admon et al., 2013;Tovote et al., 2015;van Heukelum et al., 2020;Chen et al., 2022). ...
... One of those variants results in increased GABA levels especially in the ACC, as revealed by fMRI-SPECT, and was associated to increased harm avoidance behavior in females but not males as an anxietyrelated trait (Colic, 2018). While functional imaging studies indeed pinpoint to the ACC as an important region for emotion regulation (Mochkovotich et al., 2014;Goossen et al., 2019;Kim & Kim, 2021), sex-specific regulation differences are not well studied. Interestingly in female, but not male healthy volunteers ACC volume and positive coping style predicted lower anxiety-or depression-related psychopathologies (Holz et al., 2016). ...
Anxiety disorders have been linked to a disbalance of excitation and inhibition in a network of brain structures comprising frontal cortical regions, the amygdala and the hippocampus, among others. Recent imaging studies suggest sex differences in the activation of this anxiety network during the processing of emotional information. Rodent models with genetically altered ϒ-amino butyric acid (GABA) neurotransmission allow studying the neuronal basis of such activation shifts and their relation to anxiety endophenotypes, but to date sex effects have rarely been addressed. Using mice with a null mutation of the GABA synthetizing enzyme glutamate decarboxylase 65 (GAD65-/-), we started to compare anxiety-like behavior and avoidance in male vs. female GAD65-/- mice and their wildtype littermates. In an open field, female GAD65-/- mice displayed increased activity, while male GAD65-/- mice showed an increased adaptation of anxiety-like behavior over time. GAD65-/- mice of both sexes had a higher preference for social interaction partners, which was further heightened in male mice. In male mice higher escape responses were observed during an active avoidance task. Together, female mice showed more stable emotional responses despite GAD65 deficiency. To gain insights into interneuron function in network structures controlling anxiety and threat perception, fast oscillations (10-45 Hz) were measured in ex vivo slice preparations of the anterior cingulate cortex (ACC). GAD65-/- mice of both sexes displayed increased gamma power in the ACC and a higher density of PV-positive interneurons, which are crucial for generating such rhythmic activity. In addition, GAD65-/- mice had lower numbers of somatostatin-positive interneurons in the basolateral amygdala and in the dorsal dentate gyrus especially in male mice, two key regions important for anxiety and active avoidance responses. Our data suggest sex differences in the configuration of GABAergic interneurons in a cortico-amygdala-hippocampal network controlling network activity patterns, anxiety and threat avoidance behavior.
Highlights
Role of GABA in sex-specific anxiety endophenotypes demonstrated in GAD65-/- mice
Sex- and GAD65-dependent alterations in anxiety, social preference and avoidance
Enhanced in vitro gamma-beta oscillations in ACC slices of GAD65-/- mice
Increased parvalbumin(+) interneuron counts in ACC slices of GAD65-/- mice
Reduced somatostatin(+) interneuron counts in dorsal DG and BLA of male GAD65-/- mice
Graphical Abstract
... [19][20][21][22][23][24] However, they have been tested primarily in nonclinical populations, contributing to normative understandings of the behavioural and neural patterns that underlie AAC decision-making, but not yet contributing to an understanding of the disruptions relevant to mental health disorders. 25,26 Further, determining the functional relationships between task behaviours and neural activations and how they might differ for those with anxiety or depression could facilitate a more nuanced understanding of AAC decision-making as a potential contributor to anxiety or depression, 27,28 similarly or differentially across the disorders and for people living with these disorders. ...
Background: We have previously reported activation in reward, salience and executive control regions during functional MRI (fMRI) using an approach–avoidance conflict (AAC) decision-making task with healthy adults. Further investigations into how anxiety and depressive disorders relate to differences in neural responses during AAC can inform their understanding and treatment. We tested the hypothesis that people with anxiety or depression have altered neural activation during AAC.
Methods: We compared 118 treatment-seeking adults with anxiety or depression and 58 healthy adults using linear mixed-effects models to examine group-level differences in neural activation (fMRI) during AAC decision-making. Correlational analyses examined relationships between behavioural and neural measures.
Results: Adults with anxiety or depression had greater striatal engagement when reacting to affective stimuli (p = 0.008, d = 0.31) regardless of valence, and weaker striatal engagement during reward feedback (p = 0.046, d = −0.27) regardless of the presence of monetary reward. They also had blunted amygdala activity during decision-making (p = 0.023, d = −0.32) regardless of the presence of conflict. Across groups, approach behaviour during conflict decision-making was inversely correlated with striatal activation during affective stimuli (p < 0.001, r = −0.28) and positively related to striatal activation during reward feedback (p < 0.001, r = 0.27).
Limitations: Our transdiagnostic approach did not allow for comparisons between specific anxiety disorders, and our cross-sectional approach did not allow for causal inference.
Conclusion: Anxiety and depression were associated with altered neural responses to AAC. Findings were consistent with the role of the striatum in action selection and reward responsivity, and they point toward striatal reactivity as a future treatment target. Blunting of amygdala activity in anxiety or depression may indicate a compensatory response to inhibit affective salience and maintain approach.
... Studies using the reappraisal paradigm tend to show prefrontal hypoactivation and increased prefrontal cortex amygdala connectivity [3,4]. Thus, the most prevalent pathophysiological model postulates that the disorder is caused by abnormal activation along a circuit encompassing the prefrontal cortex, the basal ganglia, and the thalamus, resulting in a disinhibition of abnormal maladaptive habits, over which patients are unable to exert sufficient cognitive control [5]. ...
According to DSM 5, generalized anxiety disorder (GAD) is characterized by excessive, uncontrollable worry about various topics that occupies the majority of the subject’s time for a period of at least six months. The aforementioned state causes distress and/or functional impairments. This paper presents the outcomes of a pilot study that evaluated the implementation of cognitive behavioral therapy (CBT) and CBT with an SSRIs intervention program. The participants comprised 16 children and adolescents with GAD (8 males and 8 females) matched with 16 typically developing peers (8 males and 8 females) aged from 10 to 16 years old (M = 12.56 SD = 2.18). Baseline assessment consisted of event related potentials (ERPs), which indicated that participants with GAD presented cognitive deficits in attention and memory, as they exhibited longer P300 latencies. Following treatment with the CBT program and/or medication, children and adolescents with GAD did not present statistically significantly longer P300 latencies and reaction times in comparison to the control group. Lastly, children and adolescents who followed the CBT program or the CBT program with psychopharmacological assistance did not reveal statistically significant differences in 13 out of 15 topographic brain areas and in reaction time.
... The results match those of a previous study in which the researchers found that HTAs have general inhibitory deficits by using emotional and numberical Stroop tasks (Zhang et al., 2019). Similar results were observed in patients with panic disorders (Boshuisen et al., 2002;Bystritsky et al., 2001), trait anxiety (Basten et al., 2011;Bishop, 2009), posttraumatic stress disorder (Ansari and Derakshan, 2011), and generalized anxiety disorder (Goossen et al., 2019). ...
Background
Individuals with high test anxiety (HTA) have deficits in attentional control and in stress responses when faced with tests. However, little is known about the underlying neural mechanism. Anterior cingulate cortex (ACC) is involved in both attention and emotion networks, therefore this study examined the neural functional dysregulation in test anxiety from the perspective of functional connectivity (FC) using bilateral ACC as the regions of interest.
Methods
Fifty-one participants were divided into HTA (n = 23) and low test anxiety (LTA, n = 28) group according to their Test Anxiety Scale (TAS) scores. Brain imaging data in resting, preparing, and recovering phases of a modified social evaluative threat task were collected, and emotional changes were assessed.
Results
Compared with the LTA group, the HTA group exhibited significantly lower FCs between the ACC and superior frontal gyrus (SFG) in all 3 phases, significantly lower FCs between the ACC and inferior parietal gyrus (IPG), and significantly higher FCs between the ACC superior temporal gyrus (STG) in the preparing phase. Moreover, in the HTA group, the resting state IPG-ACC FC was associated with their TAS score, the preparing state STG-ACC FC was associated with the increased anxiety. Conclusions: Individuals with HTA have general prefrontal control deficits. When facing a test, they tend to recruit more resources to deal with high emotional interference. The dysregulated control of the ACC by the frontal-parietal network may underlie the pathophysiology of test anxiety.
