Related neural networks underlie suppression of emotion, memory, motor processes as identified by data-driven analysis.

BACKGROUND: Goal-directed behavior benefits from self-regulation of cognitive and affective processes, such as emotional reactivity, memory retrieval, and prepotent motor response. Dysfunction in self-regulation is a common characteristic of many psychiatric disorders, such as PTSD and ADHD. This study sought to determine whether common intrinsic connectivity networks (ICNs; e.g. default mode network) are involved in the regulation of emotion, motor, and memory processes, and if a data-driven approach using independent component analysis (ICA) would successfully identify such ICNs that contribute to inhibitory regulation. METHODS: Eighteen participants underwent neuroimaging while completing an emotion regulation (ER) task, a memory suppression (Think/No-Think; TNT) task, and a motor inhibition (Stop Signal; SS) task. ICA (CONN; MATLAB) was conducted on the neuroimaging data from each task and corresponding components were selected across tasks based on interrelated patterns of activation. Subsequently, ICNs were correlated with behavioral performance variables from each task. RESULTS: ICA indicated a common medial prefrontal network, striatal network, and frontoparietal executive control network, as well as downregulation in task-specific ROIs. CONCLUSIONS: These results illustrate that common ICNs were exhibited across three distinct inhibitory regulation tasks, as successfully identified through a data-driven approach (ICA).

Explicit and Ambiguous Threat Processing: Functionally Dissociable Roles of the Amygdala and Bed Nucleus of the Stria Terminalis.

Highly influential models have proposed that responses to different types of threat are mediated by partially segregated neural systems, with the amygdala underlying phasic responses to explicit threat (fear) and the bed nucleus of the stria terminalis (BNST) mediating sustained responses to ambiguous threat (anxiety). However, newer models have suggested similar recruitment of both regions across a wide spectrum of threat. Therefore, to empirically test these models and further elucidate the activation profiles and connectivity patterns of the amygdala and the BNST during threat processing, 20 participants were scanned using high-resolution fMRI (1.5 mm3). Using fearful faces and human screams as aversive stimuli, two threat conditions were created: Explicit Threat in which threats were certain and predictable (fear) and Ambiguous Threat in which threats were uncertain and unpredictable (anxiety). Results indicated that, although the amygdala and the BNST both showed heightened engagement across both threat conditions, the amygdala showed preferential engagement during Explicit Threat and displayed functional connectivity with regions involved in stimulus processing and motor response. By contrast, the BNST preferentially responded during Ambiguous Threat and exhibited functional connectivity with prefrontal regions underlying interoception and rumination. Furthermore, correlations with questionnaires measuring trait anxiety, worry, and rumination suggested that individual differences in affective style play a modulatory role in regional recruitment and network connectivity during threat processing.

Bimanual coordination positively predicts episodic memory: A combined behavioral and MRI investigation.

Some people remember events more completely and accurately than other people, but the origins of individual differences in episodic memory are poorly understood. One way to advance understanding is by identifying characteristics of individuals that reliably covary with memory performance. Recent research suggests motor behavior is related to memory performance, with individuals who consistently use a single preferred hand for unimanual actions performing worse than individuals who make greater use of both hands. This research has relied on self-reports of behavior. It is unknown whether objective measures of motor behavior also predict memory performance. Here, we tested the predictive power of bimanual coordination, an important form of manual dexterity. Bimanual coordination, as measured objectively on the Purdue Pegboard Test, was positively related to correct recall on the California Verbal Learning Test-II and negatively related to false recall. Furthermore, MRI data revealed that cortical surface area in right lateral prefrontal regions was positively related to correct recall. In one of these regions, cortical thickness was negatively related to bimanual coordination. These results suggest that individual differences in episodic memory may partially reflect morphological variation in right lateral prefrontal cortex and suggest a relationship between neural correlates of episodic memory and motor behavior.

Daily marijuana use is not associated with brain morphometric measures in adolescents or adults.

Recent research has suggested that marijuana use is associated with volumetric and shape differences in subcortical structures, including the nucleus accumbens and amygdala, in a dose-dependent fashion. Replication of such results in well controlled studies is essential to clarify the effects of marijuana. To that end, this retrospective study examined brain morphology in a sample of adult daily marijuana users (n = 29) versus nonusers (n = 29) and a sample of adolescent daily users (n = 50) versus nonusers (n = 50). Groups were matched on a critical confounding variable, alcohol use, to a far greater degree than in previously published studies. We acquired high-resolution MRI scans, and investigated group differences in gray matter using voxel-based morphometry, surface-based morphometry, and shape analysis in structures suggested to be associated with marijuana use, as follows: the nucleus accumbens, amygdala, hippocampus, and cerebellum. No statistically significant differences were found between daily users and nonusers on volume or shape in the regions of interest. Effect sizes suggest that the failure to find differences was not due to a lack of statistical power, but rather was due to the lack of even a modest effect. In sum, the results indicate that, when carefully controlling for alcohol use, gender, age, and other variables, there is no association between marijuana use and standard volumetric or shape measurements of subcortical structures.

Resting-state networks predict individual differences in common and specific aspects of executive function.

The goal of the present study was to examine relationships between individual differences in resting state functional connectivity as ascertained by fMRI (rs-fcMRI) and performance on tasks of executive function (EF), broadly defined as the ability to regulate thoughts and actions. Unlike most previous research that focused on the relationship between rs-fcMRI and a single behavioral measure of EF, in the current study we examined the relationship of rs-fcMRI with individual differences in subcomponents of EF. Ninety-one adults completed a resting state fMRI scan and three separate EF tasks outside the magnet: inhibition of prepotent responses, task set shifting, and working memory updating. From these three measures, we derived estimates of common aspects of EF, as well as abilities specific to working memory updating and task shifting. Using Independent Components Analysis (ICA), we identified across the group of participants several networks of regions (Resting State Networks, RSNs) with temporally correlated time courses. We then used dual regression to explore how these RSNs covaried with individual differences in EF. Dual regression revealed that increased higher common EF was associated with connectivity of a) frontal pole with an attentional RSN, and b) Crus I and II of the cerebellum with the right frontoparietal RSN. Moreover, higher shifting-specific abilities were associated with increased connectivity of angular gyrus with a ventral attention RSN. The results of the current study suggest that the organization of the brain at rest may have important implications for individual differences in EF, and that individuals higher in EF may have expanded resting state networks as compared to individuals with lower EF.

Symptom-correlated brain regions in young adults with combined-type ADHD: their organization, variability, and relation to behavioral performance.

Attention Deficit Hyperactivity Disorder (ADHD) is a widely diagnosed psychiatric disorder of childhood that may continue to manifest itself during adulthood. Across adults and children, inattention appears to be the most developmentally stable symptomatology of ADHD. To determine the neural systems that may be linked to such symptoms, the association between brain activation in a group of young adults in the face of an attentional challenge (the Stroop task) and inattentive symptoms was examined with functional magnetic resonance imaging. The results implicated a broad array of brain regions that are linked to behaviors compromised in ADHD, including executive function/cognitive control (prefrontal cortex, dorsal striatum), reward and motivational circuitry (ventral striatum), and stimulus representation and timing (posterior cortex and cerebellum). Also implicating these regions as being important for the manifestation of ADHD symptoms, the variability in the size of the BOLD signal across individuals was significantly higher for the ADHD group than for the control group, and variability across the time series in individuals with ADHD was linked to symptom severity and behavioral performance. The results suggest that a diverse set of brain structures is linked to ADHD symptoms and that the variability of activation within these regions may contribute to compromised attentional control.

Behavioral performance predicts grey matter reductions in the right inferior frontal gyrus in young adults with combined type ADHD.

Optimized voxel-based morphometry (VBM) was used in the present study to investigate morphometric differences between young adults with combined type Attention Deficit/Hyperactivity Disorder (ADHD) and a well-matched control group. Investigations examined differences on a between-group whole brain level, as well as how individual differences in behavioral performance predicted grey matter differences. Although a whole brain analysis revealed no significant differences between ADHD and control individuals, ADHD but not control individuals exhibited reduced grey matter volume in the right inferior frontal gyrus (rIFG), predicted by poorer behavioral performance on all three measures. A subsequent region-of-interest approach revealed lower grey matter volume in the rIFG in ADHD compared to control individuals. These results suggest that young adults with ADHD show morphometric differences in inferior prefrontal regions, as compared to controls. These morphometric differences are related to disruptions in performance on behavioral tasks that frequently have been reported to be affected in individuals with ADHD.

New Frontiers in Anxiety Research: The Translational Potential of the Bed Nucleus of the Stria Terminalis.

After decades of being overshadowed by the amygdala, new perspectives suggest that a tiny basal forebrain region known as the bed nucleus of the stria terminalis (BNST) may hold key insights into understanding and treating anxiety disorders. Converging research indicates that the amygdala and BNST play complementary but distinct functional roles during threat processing, with the BNST specializing in the detection of a potential threat to maintain hypervigilance and anxiety, while the amygdala responds to the perceived presence of an aversive stimulus (i.e., fear). Therefore, given that human anxiety is largely driven by future-oriented hypothetical threats that may never occur, studies involving the BNST stand at the forefront of essential future research with the potential to bring about profound insights for understanding and treating anxiety disorders. In this article, we present a narrative review on the BNST, summarizing its roles in anxiety and the stress response and highlighting the most recent advances in the clinical realm. Furthermore, we discuss oversights in the current state of anxiety research and identify avenues for future exploration.

Convergent Neural Correlates of Empathy and Anxiety During Socioemotional Processing.

Empathy is characterized by the ability to understand and share an emotional experience with another person and is closely tied to compassion and concern for others. Consequently, this increased emotional awareness and sensitivity may also be related to increased anxiety. Taken from another perspective, higher general anxiety may translate into increased concern for others, or concern for how one's actions might affect others, and therefore may be linked to increased empathy. Furthermore, self-reflection is positively related to perspective-taking and empathic concern, while rumination is closely tied to anxiety, thus providing an additional connecting point between empathy and anxiety through enhanced internally generated thought. While previous literature suggests a relationship between empathy and anxiety, this has yet to be empirically studied using neuroimaging tools aimed at investigating the underlying neural correlates that may support these convergent responses. We therefore conducted an functional magnetic resonance imaging (fMRI) study (N = 49) in which participants viewed fearful and neutral human faces and rated how the faces made them feel, to promote introspection. Participants also completed questionnaires assessing empathy Toronto Empathy Questionnaire (TEQ), trait anxiety State Trait Anxiety Inventory (STAI), worry Penn State Worry Questionnaire (PSWQ) and rumination Ruminative Responses Scale (RRS). Behaviorally, empathy positively correlated with worry, worry and rumination positively correlated with anxiety, and significant indirect relationships were found between empathy and anxiety through worry and rumination. Using the neuroimaging face processing task as a backdrop on which the neurobiological mechanisms of empathy and anxiety may interact, regressions of questionnaires with brain activations revealed that empathy related to activation in the temporoparietal junction (TPJ), anxiety related to bilateral insula activation, and worry related to medial prefrontal cortex (mPFC) activation, while rumination showed increased engagement of all three aforementioned regions. Functional connectivity (FC) analyses showed increased communication between the left amygdala and insula related to higher empathy, worry and rumination. Finally, whole-brain analysis using median split groups from questionnaires revealed that the lower halves of anxiety, worry and rumination exhibited increased activation in top-down attentional networks. In sum, empathy, worry and rumination related to enhanced bottom-up processing, while worry, rumination and anxiety exhibited decreased top-down attentional control, suggesting an indirect relationship between empathy and anxiety through the ruminative tendencies of worry.

Cortical morphometry and structural connectivity relate to executive function and estradiol level in healthy adolescents.

INTRODUCTION: Emotional and behavioral control is necessary self-regulatory processes to maintain stable goal-driven behavior. Studies indicate that variance in these executive function (EF) processes is related to morphological features of the brain and white matter (WM) differences. Furthermore, sex hormone level may modulate circuits in the brain important for cognitive function. METHODS: We aimed to investigate the structural neural correlates of EF behavior in gray matter (GM) and WM while taking into account estradiol level, in an adolescent population. The present study obtained neuroimaging behavioral and physiological data from the National Institute of Health's Pediatric Database (NIHPD). We analyzed the relationship between cortical morphometry and structural connectivity (N = 55), using a parent-administered behavioral monitoring instrument (Behavior Rating Inventory of Executive Function-BRIEF), estradiol level, as well as their interaction. RESULTS: Executive function behavior and estradiol level related to bidirectional associations with cortical morphometry in the right posterior dorsolateral prefrontal cortex (pDLPFC) and primary motor cortex (PMC), as well as fractional anisotropy (FA) in the forceps major and minor. Lastly, the interaction of EF behavior and estradiol level related to decreased volume in the right PMC and was linked to altered FA in the right inferior fronto-occipital fasciculus (iFOF). CONCLUSIONS: The study provides evidence that the relationship between EF behavior and estradiol level related to bidirectional GM and WM differences, implying estradiol level has an influence on the putative structural regions underlying EF behavior. The findings represent a crucial link between EF behavior and hormonal influence on brain structure in adolescence.

Behavioral and neural correlates of memory suppression in PTSD.

Previous work has shown that healthy individuals can actively suppress emotional memories through recruitment of the lateral prefrontal cortex. By contrast, individuals with posttraumatic stress disorder (PTSD) frequently experience unwanted memories of their traumatic experiences, even when making explicit efforts to avoid them. However, little is known regarding the behavioral and neural effects of memory suppression among individuals with PTSD. We examined memory suppression associated with PTSD using the Think-No-Think paradigm in an event-related functional magnetic resonance imaging (fMRI) study. We studied three groups: PTSD (n = 16), trauma exposure without PTSD (n = 19), and controls (i.e., no trauma exposure or PTSD; n = 13). There was a main effect of memory suppression such that participants remembered fewer face-picture pairs during the suppress condition than the remember condition. However, trauma-exposed participants (regardless of PTSD status) were less likely to successfully suppress memory than non-trauma-exposed controls. Neuroimaging data revealed that trauma-exposed individuals showed reduced activation in the right middle frontal gyrus during memory suppression. These results suggest that trauma exposure is associated with neural and behavioral disruptions in memory suppression and point to the possibility that difficulty in active suppression of memories may be just one of several likely factors contributing to the development of PTSD.

Lifetime PTSD and geriatric depression symptomatology relate to altered dorsomedial frontal and amygdala morphometry.

Posttraumatic stress disorder (PTSD) affects a large portion of combat deployed Veterans. Moreover, many individuals also suffer from comorbid late life depression (geriatric depression; GD). While a great deal of research has begun to characterize the morphometric features of PTSD and depression individually, few studies have investigated the interacting effect of these two disorders, specifically in a Veteran population. The current study used cortical and subcortical surface-based morphometry (SBM) in combination with psychological assessments of PTSD and GD symptom severity to examine morphometric alterations in Vietnam War Veterans. Our results indicated that increased GD severity, PTSD symptomatology, and their interaction, was related to decreased grey matter volume (GMV) in the left dorsomedial prefrontal cortex (dmPFC). Furthermore, increased symptomatology in the PTSD subscales of reexperiencing and hyperarousal were additionally found to be related to decreased GMV in this same dmPFC region. Subcortically, the interacting effect between PTSD and GD was also significantly related to regional shape variation in the left amygdala. These results suggest that morphometry of cortical (dmPFC) and non-neocortical regions (amygdala) putatively underlying emotional reactivity and the emotional components of memory is altered in PTSD and GD.

Reduced lateral prefrontal cortical volume is associated with performance on the modified Iowa Gambling Task: A surface based morphometric analysis of previously deployed veterans.

Post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are two of the most common consequences of combat deployment. Estimates of comorbidity of PTSD and mTBI are as high as 42% in combat exposed Operation Enduring Freedom, Operation Iraqi Freedom and Operation New Dawn (OEF/OIF/OND) Veterans. Combat deployed Veterans with PTSD and/or mTBI exhibit deficits in classic executive function (EF) tasks. Similarly, the extant neuroimaging literature consistently indicates abnormalities of the ventromedial prefrontal cortex (vmPFC) and amygdala/hippocampal complex in these individuals. While studies examining deficits in classical EF constructs and aberrant neural circuitry have been widely replicated, it is surprising that little research examining reward processing and decision-making has been conducted in these individuals, specifically, because the vmPFC has long been implicated in underlying such processes. Therefore, the current study employed the modified Iowa Gambling Task (mIGT) and structural neuroimaging to assess whether behavioral measures related to reward processing and decision-making were compromised and related to cortical morphometric features of OEF/OIF/OND Veterans with PTSD, mTBI, or co-occurring PTSD/mTBI. Results indicated that gray matter morphometry in the lateral prefrontal cortex (lPFC) predicted performance on the mIGT among all three groups and was significantly reduced, as compared to the control group.

Brain activation underlying threat detection to targets of different races.

The current study examined blood oxygen level-dependent signal underlying racial differences in threat detection. During functional magnetic resonance imaging, participants determined whether pictures of Black or White individuals held weapons. They were instructed to make shoot responses when the picture showed armed individuals but don't shoot responses to unarmed individuals, with the cost of not shooting armed individuals being greater than that of shooting unarmed individuals. Participants were faster to shoot armed Blacks than Whites, but faster in making don't shoot responses to unarmed Whites than Blacks. Brain activity differed to armed versus unarmed targets depending on target race, suggesting different mechanisms underlying threat versus safety decisions. Anterior cingulate cortex was preferentially engaged for unarmed Whites than Blacks. Parietal and visual cortical regions exhibited greater activity for armed Blacks than Whites. Seed-based functional connectivity of the amygdala revealed greater coherence with parietal and visual cortices for armed Blacks than Whites. Furthermore, greater implicit Black-danger associations were associated with increased amygdala activation to armed Blacks, compared to armed Whites. Our results suggest that different neural mechanisms may underlie racial differences in responses to armed versus unarmed targets.

Multiple modes of clearing one's mind of current thoughts: overlapping and distinct neural systems.

This study used the power of neuroimaging to identify the neural systems that remove information from working memory, a thorny issue to examine because it is difficult to confirm that individuals have actually modified their thoughts. To overcome this problem, brain activation as measured via fMRI was assessed when individuals had to clear their mind of all thought (global clear), clear their mind of a particular thought (targeted clear), or replace the current thought (replace), relative to maintaining an item in working memory. The pattern of activity in posterior sensory regions across these conditions confirmed compliance with task demands. A hierarchy of brain regions involved in cognitive control, including parietal, dorsolateral prefrontal and frontopolar regions, were engaged to varying degrees depending on the manner in which information was removed from working memory. In addition, individuals with greater difficulty in controlling internal thoughts exhibited greater activity in prefrontal brain regions associated with cognitive control, as well as in left lateral prefrontal areas including Broca's area, which is associated with inner speech.

Familial risk and ADHD-specific neural activity revealed by case-control, discordant twin pair design.

Individuals with ADHD, as well as their family members who do not meet clinical criteria, have shown deficits in executive function. However, it remains unclear whether underlying neural alterations are familial or ADHD-specific. To investigate this issue, neural activation underlying executive function was assessed using functional magnetic resonance imaging during performance of a Stroop task in three groups of individuals: 20 young adults who were diagnosed with ADHD in childhood, their 20 dizygotic co-twins without ADHD in childhood, and 20 unrelated controls selected from dizygotic twin pairs in which neither twin had ADHD in childhood (total n=60). Implicating the frontoparietal network as a location of effects specific to ADHD, activation in the superior frontal (Brodmann's Area - BA 6) and parietal regions (BA 40) was significantly reduced in twins with childhood ADHD compared to both their control co-twins and unrelated control twins. Consistent with familial influences, activity in the anterior cingulate and insula was significantly reduced in both the twins with ADHD and their co-twins compared to the unrelated controls. These results show that both ADHD-specific and familial influences related to an ADHD diagnosis impact neural systems underlying executive function.

A neuroanatomical model of prefrontal inhibitory modulation of memory retrieval.

Memory of past experience is essential for guiding goal-related behavior. Being able to control accessibility of memory through modulation of retrieval enables humans to flexibly adapt to their environment. Understanding the specific neural pathways of how this control is achieved has largely eluded cognitive neuroscience. Accordingly, in the current paper I review literature that examines the overt control over retrieval in order to reduce accessibility. I first introduce three hypotheses of inhibition of retrieval. These hypotheses involve: (i) attending to other stimuli as a form of diversionary attention, (ii) inhibiting the specific individual neural representation of the memory, and (iii) inhibiting the hippocampus and retrieval process more generally to prevent reactivation of the representation. I then analyze literature taken from the White Bear Suppression, Directed Forgetting and Think/No-Think tasks to provide evidence for these hypotheses. Finally, a neuroanatomical model is developed to indicate three pathways from PFC to the hippocampal complex that support inhibition of memory retrieval. Describing these neural pathways increases our understanding of control over memory in general.

A unified framework for inhibitory control.

Inhibiting unwanted thoughts, actions and emotions figures centrally in daily life, and the prefrontal cortex (PFC) is widely viewed as a source of this inhibitory control. We argue that the function of the PFC is best understood in terms of representing and actively maintaining abstract information, such as goals, which produces two types of inhibitory effects on other brain regions. Inhibition of some subcortical regions takes a directed global form, with prefrontal regions providing contextual information relevant to when to inhibit all processing in a region. Inhibition within neocortical (and some subcortical) regions takes an indirect competitive form, with prefrontal regions providing excitation of goal-relevant options. These distinctions are crucial for understanding the mechanisms of inhibition and how they can be impaired or improved.

Attentional control activation relates to working memory in attention-deficit/hyperactivity disorder.

BACKGROUND: Attentional control difficulties in individuals with attention-deficit/hyperactivity disorder (ADHD) might reflect poor working memory (WM) ability, especially because WM ability and attentional control rely on similar brain regions. The current study examined whether WM ability might explain group differences in brain activation between adults with ADHD and normal control subjects during attentional demand. METHODS: Participants were 20 adults with ADHD combined subtype with no comorbid psychiatric or learning disorders and 23 control subjects similar in age, IQ, and gender. The WM measures were obtained from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-Revised. Brain activation was assessed with functional magnetic resonance imaging (fMRI) while performing a Color-Word Stroop task. RESULTS: Group differences in WM ability explained a portion of the activation in left dorsolateral prefrontal cortex (DLPFC), which has been related to the creation and maintenance of an attentional set for task-relevant information. In addition, greater WM ability predicted increased activation of brain regions related to stimulus-driven attention and response selection processes in the ADHD group but not in the control group. CONCLUSIONS: The inability to maintain an appropriate task set in young adults with combined type ADHD, associated with decreased activity in left DLPFC, might in part be due to poor WM ability. Furthermore, in individuals with ADHD, higher WM ability might relate to increased recruitment of stimulus-driven attention and response selection processes, perhaps as a compensatory strategy.

Cognitive control mechanisms, emotion and memory: a neural perspective with implications for psychopathology.

In this paper we provide a focused review of the literature examining neural mechanisms involved in cognitive control over memory processes that can influence, and in turn are influenced by, emotional processes. The review is divided into two parts, the first focusing on working memory and the second on long-term memory. With regard to working memory, we discuss the neural bases of (1) control mechanisms that can select against distracting emotional information, (2) mechanisms that can regulate emotional reactions or responses, (3) how mood state influences cognitive control, and (4) individual differences in control mechanisms. For long-term memory, we briefly review (1) the neural substrates of emotional memory, (2) the cognitive and neural mechanisms that are involved in controlling emotional memories and (3) how these systems are altered in post-traumatic stress disorder. Finally, we consider tentative generalizations that can be drawn from this relatively unexplored conjunction of research endeavors.