•New approaches to reveal the neural interplay between anxiety and cognition.•Methylphenidate led differential activation across low and high cognitive load.•Load-based differential activation was ...linked to better task performance.
The reciprocal interplay between anxiety and cognition is well documented. Anxiety negatively impacts cognition, while cognitive engagement can down-regulate anxiety. The brain mechanisms and dynamics underlying such interplay are not fully understood. To study this question, we experimentally and orthogonally manipulated anxiety (using a threat of shock paradigm) and cognition (using methylphenidate; MPH). The effects of these manipulations on the brain and behavior were evaluated in 50 healthy participants (25 MPH, 25 placebo), using an n-back working memory fMRI task (with low and high load conditions). Behaviorally, improved response accuracy was observed as a main effect of the drug across all conditions. We employed two approaches to understand the neural mechanisms underlying MPH-based cognitive enhancement in safe and threat conditions. First, we performed a hypothesis-driven computational analysis using a mathematical framework to examine how MPH putatively affects cognitive enhancement in the face of induced anxiety across two levels of cognitive load. Second, we performed an exploratory data analysis using Topological Data Analysis (TDA)-based Mapper to examine changes in spatiotemporal brain activity across the entire cortex. Both approaches provided converging evidence that MPH facilitated greater differential engagement of neural resources (brain activity) across low and high working memory load conditions. Furthermore, load-based differential management of neural resources reflects enhanced efficiency that is most powerful during higher load and induced anxiety conditions. Overall, our results provide novel insights regarding brain mechanisms that facilitate cognitive enhancement under MPH and, in future research, may be used to help mitigate anxiety-related cognitive underperformance.
Background Attention Bias Modification Treatment (ABMT) is a newly emerging, promising treatment for anxiety disorders. Although recent randomized control trials (RCTs) suggest that ABMT reduces ...anxiety, therapeutic effects have not been summarized quantitatively. Methods Standard meta-analytic procedures were used to summarize the effect of ABMT on anxiety. With MEDLINE, January 1995 to February 2010, we identified RCTs comparing the effects on anxiety of ABMT and quantified effect sizes with Hedge’s d. Results Twelve studies met inclusion criteria, including 467 participants from 10 publications. Attention Bias Modification Treatment produced significantly greater reductions in anxiety than control training, with a medium effect (d = .61, p < .001). Age and gender did not moderate the effect of ABMT on anxiety, whereas several characteristics of the ABMT training did. Conclusions Attention Bias Modification Treatment shows promise as a novel treatment for anxiety. Additional RCTs are needed to fully evaluate the degree to which these findings replicate and apply to patients. Future work should consider the precise role for ABMT in the broader anxiety-disorder therapeutic armamentarium.
The triadic neural systems model is a heuristic tool, which was developed with the goal of providing a framework for neuroscience research into motivated behaviors. Unlike dual models that highlight ...dynamics between approach systems centered on striatal function and control systems centered on prefrontal cortex, the triadic model also includes an avoidance system, centered on amygdala-related circuits. A first application of this model has been to account for adolescent behavior.
Risk-taking behavior is a major cause of morbidity and mortality in adolescence. In the context of decision theory and motivated (goal-directed) behavior, risk-taking reflects a pattern of ...decision-making that favors the selection of courses of action with uncertain and possibly harmful consequences. We present a triadic, neuroscience systems-based model of adolescent decision-making.
We review the functional role and neurodevelopmental findings of three key structures in the control of motivated behavior, i.e. amygdala, nucleus accumbens, and medial/ventral prefrontal cortex. We adopt a cognitive neuroscience approach to motivated behavior that uses a temporal fragmentation of a generic motivated action. Predictions about the relative contributions of the triadic nodes to the three stages of a motivated action during adolescence are proposed.
The propensity during adolescence for reward/novelty seeking in the face of uncertainty or potential harm might be explained by a strong reward system (nucleus accumbens), a weak harm-avoidant system (amygdala), and/or an inefficient supervisory system (medial/ventral prefrontal cortex). Perturbations in these systems may contribute to the expression of psychopathology, illustrated here with depression and anxiety.
A triadic model, integrated in a temporally organized map of motivated behavior, can provide a helpful framework that suggests specific hypotheses of neural bases of typical and atypical adolescent behavior.
We present a temporal map of key processes that occur during decision making, which consists of three stages: 1) formation of preferences among options, 2) selection and execution of an action, and ...3) experience or evaluation of an outcome. This framework can be used to integrate findings of traditional choice psychology, neuropsychology, brain lesion studies, and functional neuroimaging. Decision making is distributed across various brain centers, which are differentially active across these stages of decision making. This approach can be used to follow developmental trajectories of the different stages of decision making and to identify unique deficits associated with distinct psychiatric disorders.
The central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST), two nuclei within the central extended amygdala, function as critical relays within the distributed neural ...networks that coordinate sensory, emotional, and cognitive responses to threat. These structures have overlapping anatomical projections to downstream targets that initiate defensive responses. Despite these commonalities, researchers have also proposed a functional dissociation between the CeA and BNST, with the CeA promoting responses to discrete stimuli and the BNST promoting responses to diffuse threat. Intrinsic functional connectivity (iFC) provides a means to investigate the functional architecture of the brain, unbiased by task demands. Using ultra-high field neuroimaging (7-Tesla fMRI), which provides increased spatial resolution, this study compared the iFC networks of the CeA and BNST in 27 healthy individuals. Both structures were coupled with areas of the medial prefrontal cortex, hippocampus, thalamus, and periaqueductal gray matter. Compared to the BNST, the bilateral CeA was more strongly coupled with the insula and regions that support sensory processing, including thalamus and fusiform gyrus. In contrast, the bilateral BNST was more strongly coupled with regions involved in cognitive and motivational processes, including the dorsal paracingulate gyrus, posterior cingulate cortex, and striatum. Collectively, these findings suggest that responses to sensory stimulation are preferentially coordinated by the CeA and cognitive and motivational responses are preferentially coordinated by the BNST.
•The CeA and BNST have overlapping functional connections.•The CeA is more strongly connected to regions involved in sensory processing.•The BNST is more strongly connected to regions involved in motivational processing.
Background
Anxiety patients exhibit deficits in cognitive tasks that require prefrontal control of attention, including those that tap working memory (WM). However, it is unclear whether these ...deficits reflect threat‐related processes or symptoms of the disorder. Here, we distinguish between these hypotheses by determining the effect of shock threat versus safety on the neural substrates of WM performance in anxiety patients and healthy controls.
Methods
Patients, diagnosed with generalized and/or social anxiety disorder, and controls performed blocks of an N‐back WM task during periods of safety and threat of shock. We recorded blood‐oxygen‐level dependent (BOLD) activity during the task, and investigated the effect of clinical anxiety (patients vs. controls) and threat on WM load‐related BOLD activation.
Results
Behaviorally, patients showed an overall impairment in both accuracy and reaction time compared to controls, independent of threat. At the neural level, patients showed less WM load‐related activation in the dorsolateral prefrontal cortex, a region critical for cognitive control. In addition, patients showed less WM load‐related deactivation in the ventromedial prefrontal cortex and posterior cingulate cortex, which are regions of the default mode network. Most importantly, these effects were not modulated by threat.
Conclusions
This work suggests that the cognitive deficits seen in anxiety patients may represent a key component of clinical anxiety, rather than a consequence of threat.
Transcranial magnetic stimulation (TMS) is a noninvasive method to stimulate the cerebral cortex that has applications in psychiatry, such as in the treatment of depression and anxiety. Although many ...TMS targeting methods that use figure-8 coils exist, many do not account for individual differences in anatomy or are not generalizable across target sites. This protocol combines functional magnetic resonance imaging (fMRI) and iterative electric-field (E-field) modeling in a generalized approach to subject-specific TMS targeting that is capable of optimizing the stimulation site and TMS coil orientation. To apply this protocol, the user should (i) operationally define a region of interest (ROI), (ii) generate the head model from the structural MRI data, (iii) preprocess the functional MRI data, (iv) identify the single-subject stimulation site within the ROI, and (iv) conduct E-field modeling to identify the optimal coil orientation. In comparison with standard targeting methods, this approach demonstrates (i) reduced variability in the stimulation site across subjects, (ii) reduced scalp-to-cortical-target distance, and (iii) reduced variability in optimal coil orientation. Execution of this protocol requires intermediate-level skills in structural and functional MRI processing. This protocol takes ~24 h to complete and demonstrates how constrained fMRI targeting combined with iterative E-field modeling can be used as a general method to optimize both the TMS coil site and its orientation.
The habenula, a portion of the epithalamus, is implicated in the pathophysiology of depression, anxiety and addiction disorders. Its small size and connection to other small regions prevent standard ...human imaging from delineating its structure and connectivity with confidence. Resting state functional connectivity is an established method for mapping connections across the brain from a seed region of interest. The present study takes advantage of 7T fMRI to map, for the first time, the habenula resting state network with very high spatial resolution in 32 healthy human participants. Results show novel functional connections in humans, including functional connectivity with the septum and bed nucleus of the stria terminalis (BNST). Results also show many habenula connections previously described only in animal research, such as with the nucleus basalis of Meynert, dorsal raphe, ventral tegmental area (VTA), and periaqueductal grey (PAG). Connectivity with caudate, thalamus and cortical regions such as the anterior cingulate, retrosplenial cortex and auditory cortex are also reported. This work, which demonstrates the power of ultra-high field for mapping human functional connections, is a valuable step toward elucidating subcortical and cortical regions of the habenula network.
Background Unipolar major depressive disorder (MDD) is characterized by anomalous neurobiological responses to pleasant stimuli, a pattern that may be linked to symptoms of anhedonia. However, the ...potential for psychotherapy to normalize neurobiological responses to pleasant stimuli has not been evaluated. Methods Twelve adults with and 15 adults without MDD participated in two identical functional magnetic resonance imaging scans that used a Wheel of Fortune task. Between scans, MDD outpatients received Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. Results Seventy-five percent of adults with MDD were treatment responders, achieving post-treatment Hamilton Rating Scale for Depression score of six or below. Relative to changes in brain function in the matched nondepressed group, psychotherapy resulted in functional changes in structures that mediate responses to rewards, including the paracingulate gyrus during reward selection, the right caudate nucleus (i.e., the dorsal striatum), during reward anticipation, and the paracingulate and orbital frontal gyri during reward feedback. There was no effect of diagnostic status or psychotherapy on in-scanner task-related behavioral responses. Conclusions Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors, results in improved functioning of unique reward structures during different temporal phases of responses to pleasurable stimuli, including the dorsal striatum during reward anticipation.
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