Activity In Dorsal Anterior Cingulate Cortex Research Articles

359 Low-Intensity Focused Ultrasound to Human Dorsal Anterior Cingulate Cortex and Insula Attenuates Measures of Central Sensitization

INTRODUCTION: Central sensitization is the abnormal amplified response to pain and is associated with chronic pain. Increased insula and dorsal anterior cingulate cortex (dACC) activity is associated with central sensitization. Low-intensity focused ultrasound (LIFU) is a novel form of non-invasive neuromodulation that can precisely target the anterior insula (AI), posterior insula (PI) and dACC. METHODS: N = 18 healthy participants underwent conditioned pain modulation (CPM) and temporal summation of pain (TSP) tasks before and after 10 minutes of LIFU or sham stimulations. For CPM, the conditioning stimulus (CS) was a cold pressor test to the left hand and the test stimulus (TS) was a brief transient heat stimulus to the dorsum of the right hand. For TSP, 10 transient heat stimuli (>0.33 Hz) were administered to the dorsum of the right hand. The primary outcome measure for both tasks was perceived pain ratings (0-9). Electrodermal response and electrocardiogram was collected to evaluate the effect of LIFU on autonomic reactivity. RESULTS: LIFU to PI increased CPM 0.5 ± 0.181 compared to sham (p = 0.024). LIFU to PI also significantly reduced perceived pain during the TSP task compared to sham (p < 0.001). We also found a significant difference between dACC and sham conditions during TSP by -0.55 ± 0.05 (p < 0.001). LIFU to the AI increases frequency domain measures of heart-rate variability. CONCLUSIONS: LIFU to the insula and dACC affects pain processing in measures of central sensitization. This demonstrates the neuromodulation abilities of LIFU and is a promising tool to develop noninvasive clinical therapies for chronic pain conditions.

Gray matter associations with extinction-induced neural activation in patients with anxiety disorders

The relationship between structural characteristics and extinction-induced brain activations in anxiety disorders (ANX) remains a space for greater exploration. In this study, we assessed gray matter volume (GMV) and its associated functional activations during fear extinction memory recall in an ANX cohort. We performed voxel-based morphometry analysis to examine GMVs from ANX (n = 92) and controls (n = 73). We further examined the correlation between GMVs and extinction-induced neural activations during recall across groups. In the patients’ group, we observed decreased GMV in the anterior hippocampus and increased GMV in the dorsolateral prefrontal cortex (dlPFC). Hippocampal volume was positively correlated with ventromedial prefrontal cortex activation in healthy controls, while it was negatively correlated with dorsal anterior cingulate cortex (dACC) activation in ANX. The dlPFC volume was positively correlated with activations of dACC, pre- and post-central gyrus, and supramarginal gyrus only in healthy controls. Therefore, the link between structural and functional imbalance within the hippocampus and dlPFC might contribute to the pathophysiology of ANX. In the controls, the relationship between structural variance in the hippocampus and dlPFC and extinction-induced neural activations is consistent with a greater ability to regulate fear responding; associations that were absent in the ANX cohort. Furthermore, our findings of structure-function abnormalities within key nodes of emotional homeostasis in ANX point to dlPFC as a potential neural node to target using neuromodulation tools.

Behavioral pattern separation is associated with neural and electrodermal correlates of context-dependent fear conditioning

Hippocampus-dependent pattern separation is considered as a relevant factor for context discrimination and might therefore impact the contextual modulation of conditioned fear. However, the association between pattern separation and context-dependent fear conditioning has not been investigated so far. In the current study, 72 healthy female students completed the Mnemonic Similarity Task, a measure of behavioral pattern separation, in addition to a context-dependent fear conditioning paradigm during functional magnetic resonance imaging. The paradigm included fear acquisition in context A and extinction training in context B on a first day, as well as retrieval testing of the fear and extinction memories in the safe context B (extinction recall) and a novel context C (fear renewal) one day later. Main outcome measures comprised skin conductance responses (SCRs) and blood oxygen level-dependent responses in brain regions of the fear and extinction circuit. Regarding retrieval testing, pattern separation did not correlate with extinction recall, but with stronger dorsal anterior cingulate cortex activation and conditioned SCRs (trend) during fear renewal, indicating a stronger retrieval of the fear memory trace. Our findings suggest that behavioral pattern separation ability seems to be important for context-dependent fear modulation, which is impaired in patients with posttraumatic stress disorder.

Dorsal anterior cingulate cortex activity during cognitive challenge in social anxiety disorder

BackgroundSocial anxiety disorder (SAD) is associated with aberrant emotional information processing while little is known about non-emotional cognitive processing biases. The dorsal anterior cingulate cortex (dACC) has been implicated in SAD neuropathology and is activated both by emotional and non-affective cognitive challenges like the Multisource Interference Task (MSIT). MethodsHere, we used fMRI to compare dACC activity and test performance during MSIT in 69 SAD patients and 38 healthy controls. In addition to patient-control comparisons, we examined whether neural activity in the dACC correlated with social anxiety, trait anxiety or depression levels. ResultsThe MSIT activated the dACC as expected but with no differences in task performance or neural reactivity between SAD patients and controls. There were no significant correlations between dACC activity and social or trait anxiety symptom severity. In patients, there was a significant negative correlation between dACC activity and depressive symptoms. ConclusionsIn absence of affective challenge, we found no disorder-related cognitive profile in SAD patients since neither MSIT task performance nor dACC neural activity deviated in patients relative to controls.

Altered dorsal anterior cingulate cortex activation in late-life depression and mild cognitive impairment during oddball task: an fmri study

Altered dorsal anterior cingulate cortex activation in late-life depression and mild cognitive impairment during oddball task: an fmri study

Comparison of behavioral and brain indices of fear renewal during a standard vs. novel immersive reality Pavlovian fear extinction paradigm in healthy adults

Pavlovian conditioning paradigms model the learned fear associations inherent in posttraumatic stress disorder, including the renewal of inappropriate fear responses following extinction learning. However, very few studies in humans investigate the underlying neural mechanisms involved in fear renewal despite its clinical importance. To address this issue, our lab designed a novel, immersive-reality Pavlovian fear acquisition, extinction, recall, and renewal paradigm. We utilized an ecological threat - a snake striking towards the participant - as the unconditioned stimulus (US). Context and background were dynamic and included both visual and auditory cues that are relevant to everyday life. Using functional magnetic resonance imaging and behavioral measures (US expectancy ratings), we examined the validity of this Novel paradigm in healthy adults (n = 49) and compared it to a Standard, well-validated 2D paradigm (n = 28). The Novel paradigm, compared to the Standard, was associated with greater hippocampal activation throughout the task. Participants who underwent the Standard paradigm, compared to the Novel, also displayed insula activation; however, this was not specific to stimulus or time. During fear renewal, the Novel paradigm was associated with dorsal anterior cingulate cortex activation to CS+ (> CS-). Overall, we found that our Novel, immersive-reality paradigm, which features an ecologically relevant US, elicited greater corticolimbic activation. These results suggest that immersive Pavlovian fear conditioning paradigms paired with innately fearful stimuli may improve translatability of preclinical paradigms to clinical interventions for fear-based disorders.

Anxiety disrupts performance monitoring: integrating behavioral, event-related potential, EEG microstate, and sLORETA evidence.

Anxiety impacts performance monitoring, though theory and past research are split on how and for whom. However, past research has often examined either trait anxiety in isolation or task-dependent state anxiety and has indexed event-related potential components, such as the error-related negativity or post-error positivity (Pe), calculated at a single node during a limited window of time. We introduced 2 key novelties to this electroencephalography research to examine the link between anxiety and performance monitoring: (i) we manipulated antecedent, task-independent, state anxiety to better establish the causal effect; (ii) we conducted moderation analyses to determine how state and trait anxiety interact to impact performance monitoring processes. Additionally, we extended upon previous work by using a microstate analysis approach to isolate and sequence the neural networks and rapid mental processes in response to error commission. Results showed that state anxiety disrupts response accuracy in the Stroop task and error-related neural processes, primarily during a Pe-related microstate. Source localization shows that this disruption involves reduced activation in the dorsal anterior cingulate cortex and compensatory activation in the right lateral prefrontal cortex, particularly among people high in trait anxiety. We conclude that antecedent anxiety is largely disruptive to performance monitoring.

Experimental evidence for a child-to-adolescent switch in human amygdala-prefrontal cortex communication: A cross-sectional pilot study.

Interactions between the amygdala and prefrontal cortex are fundamental to human emotion. Despite the central role of frontoamygdala communication in adult emotional learning and regulation, little is known about how top-down control emerges during human development. In the present cross-sectional pilot study, we experimentally manipulated prefrontal engagement to test its effects on the amygdala during development. Inducing dorsal anterior cingulate cortex (dACC) activation resulted in developmentally-opposite effects on amygdala reactivity during childhood versus adolescence, such that dACC activation was followed by increased amygdala reactivity in childhood but reduced amygdala reactivity in adolescence. Bayesian network analyses revealed an age-related switch between childhood and adolescence in the nature of amygdala connectivity with the dACC and ventromedial PFC (vmPFC). Whereas adolescence was marked by information flow from dACC and vmPFC to amygdala (consistent with that observed in adults), the reverse information flow, from the amygdala to dACC and vmPFC, was dominant in childhood. The age-related switch in information flow suggests a potential shift from bottom-up co-excitatory to top-down regulatory frontoamygdala connectivity and may indicate a profound change in the circuitry supporting maturation of emotional behavior. These findings provide novel insight into the developmental construction of amygdala-cortical connections and implications for the ways in which childhood experiences may influence subsequent prefrontal function.

Cortisol before extinction generalization alters its neural correlates during retrieval

While generalization of fear seems to be naturally acquired as frequently observed in fear-related disorders, extinction learning appears to be stimulus-specific. Thus, treatments aiming to generalize extinction learning comprise the chance to overcome stimulus-specificity and consequently reduce relapse. One suggested candidate is the timing-dependent administration of the stress hormone cortisol.In the present pre-registered, three-day fear conditioning study, we aimed to create a generalized extinction memory trace in 60 healthy men and women using multiple sizes of one conditioned stimulus (CS+G; generalized) during extinction training, whereas the other CS (CS+N; non-generalized) and the CS- were solely presented in their original sizes. Extinction training took place either after pharmacological administration of 20 mg cortisol or placebo. Following successful fear acquisition on day one, generalization effects during extinction training and retrieval were investigated in the comparison of CS+G and CS+N. Insula and dorsal anterior cingulate cortex (dACC) activation for CS+G as compared to CS+N extending to the second half of extinction training indicated prolonged fear processing during extinction training for the CS+G on day two. During retrieval on day three, an activation of the anterior hippocampus occurred for CS+N minus CS+G in the cortisol but not in the placebo group. Additionally, a more posterior hippocampal activation (compared to the other hippocampal activation) was observed for the contrast CS+G minus CS+N. In accordance with our hypotheses, amygdala and dACC responding during reinstatement test was reduced for the CS+G as compared to CS+N. However, cortisol did not modulate amygdala responding, but abolished the CS+G/CS+N differentiation in the dACC relative to placebo. Generalization and cortisol effects were not mirrored in skin conductance responses. In conclusion, extinction generalization processes appear to rely on prolonged fear processing still present in the second half of extinction training that in turn leads to reduced fear-related processing after reinstatement. Cortisol administration prior to extinction training, however, selectively reduced fear-related activation for standard extinction but did not further reduce fear-related activation for extinction generalization.

21.4 REWARD PROCESSING IN CHILDREN WITH DISRUPTIVE BEHAVIOR DISORDERS AND CALLOUS-UNEMOTIONAL TRAITS IN THE ABCD STUDY

Disrupted reward processing is implicated in the etiology of disruptive behavior disorders (DBDs) and callous-unemotional traits. However, neuroimaging investigations of reward processing underlying these phenotypes remain sparse. The authors examined neural sensitivity in response to reward anticipation and receipt among youths with DBDs, with and without callous-unemotional traits. Data were obtained from the ABCD study (mean age = 9.51 years [SD = 0.50]; 49% female). Reward-related activation during the monetary incentive delay task was examined across 16 brain regions, including the amygdala, anterior cingulate cortex (ACC), nucleus accumbens (NAcc), and orbitofrontal cortex (OFC). Latent variable modeling was used to examine network-level coactivation. The following diagnostic groups were compared: typically developing youths (N = 693) and youths with DBDs (N = 995), subdivided into those with callous-unemotional traits (DBD+CU, n = 198) and without callous-unemotional traits (DBD only, n = 276). During reward anticipation, youths in the overall DBD group (with and without callous-unemotional traits) showed decreased dorsal ACC activation compared with typically developing youths. The DBD-only group exhibited reduced ventral and dorsal striatal activity compared with the DBD+CU and typically developing groups. During reward receipt, youths with DBDs showed increased cortical (eg, OFC) and subcortical (eg, NAcc) regional activation compared with typically developing youths. The DBD+CU group demonstrated greater activation in several regions compared with those in the typically developing (eg, amygdala) and DBD-only (eg, dorsal ACC) groups. At the network level, the DBD-only group showed reduced anticipatory reward activation compared with the typically developing and DBD+CU groups, whereas youths in the DBD+CU group showed increased activation during reward receipt compared with those in the typically developing group. These findings advance our understanding of unique neuroetiologic pathways to DBDs and callous-unemotional traits.

Relationships Between Early Maternal Warmth and Social Connection: A Randomized Clinical Trial With Naltrexone.

Early experiences of having received maternal warmth predict responses to opportunities to connect with others later in life. However, the understanding of neurochemical mechanisms by which such relationships emerge remains incomplete. Endogenous opioids, involved in social connection in both animals and humans, may contribute to this link. Therefore, the current study examined a) relationships between early maternal warmth and brain and self-report responses to novel social targets (i.e., outcomes that may promote social connection) and b) the effect of the opioid antagonist, naltrexone, on such relationships. Eighty-two adult participants completed a retrospective report of early maternal warmth. On a second visit, participants were randomized to 50 mg of oral naltrexone (n = 42) or placebo (n = 40), followed by a magnetic resonance imaging scan where functional brain activity in response to images of novel social targets (strangers) was assessed. Approximately 24 hours later, participants reported on their feelings of social connection since leaving the scanner. In the placebo condition, greater early maternal warmth was associated with less dorsal anterior cingulate cortex, anterior insula, ventral striatum, and amygdala activity in response to images of novel social targets (r values ≥ -0.360, p values ≤ .031), and greater feelings of social connection (r = 0.524, p < .001) outside of the laboratory. The same relationships, however, were not present in the naltrexone condition. Results highlight relationships between early maternal warmth and responses to the social world at large and suggest that opioids might contribute to social connection by supporting the buffering effects of warm early life experiences on social connection later in life.Trial Registration: Clinical Trials NCT02818036.

A common genetic variant in fatty acid amide hydrolase is linked to alterations in fear extinction neural circuitry in a racially diverse, nonclinical sample of adults.

Poor fear extinction learning and recall are linked to the development of fear-based disorders, like posttraumatic stress disorder, and are associated with aberrant activation of fear-related neural circuitry. This includes greater amygdala activation during extinction learning and lesser hippocampal and ventromedial prefrontal cortex (vmPFC) activation during recall. Emerging data indicate that genetic variation in fatty acid amide hydrolase (FAAH C385A; rs324420) is associated with increased peripheral endocannabinoid (eCB) levels and lesser threat-related amygdala reactivity. Preclinical studies link increased eCB signaling to better extinction learning and recall, thus FAAH C385A may protect against the development of trauma-related psychopathology by facilitating extinction learning. However, how this FAAH variant affects fear extinction neural circuitry remains unknown. In the present study, we used a novel, immersive-reality fear extinction paradigm paired with functional neuroimaging to assess FAAH C385A effects on fear-related neural circuitry and conditioned fear responding (US expectancy ratings, subjective units of distress, and skin conductance responding) in healthy adults from an urban area (Detroit, MI; N=59; C/C=35, A-carrier=24). We found lesser amygdala activation in A-allele carriers, compared to C/C homozygotes, during early extinction recall. Likewise, we found lesser dorsal anterior cingulate cortex and greater hippocampus activation in early extinction learning in A-carriers compared to C/C homozygotes. We found no effects of FAAH C385A on vmPFC activation or behavioral fear indices. These data support and extend previous findings that FAAH genetic variation, associated with increased eCB signaling and subsequent enhanced fear extinction, may predict individual differences in successful fear learning.

Counteracting Effects of Glutathione on the Glutamate-Driven Excitation/Inhibition Imbalance in First-Episode Schizophrenia: A 7T MRS and Dynamic Causal Modeling Study.

Oxidative stress plays a key role in the pathophysiology of schizophrenia. While free radicals produced by glutamatergic excess and oxidative metabolism have damaging effects on brain tissue, antioxidants such as glutathione (GSH) counteract these effects. The interaction between glutamate (GLU) and GSH is centered on N-Methyl-D-aspartate (NMDA) receptors. GSH levels increase during glutamate-mediated excitatory neuronal activity, which serves as a checkpoint to protect neurons from oxidative damage and reduce excitatory overdrive. We studied the possible influence of GSH on the glutamate-mediated dysconnectivity in 19 first-episode schizophrenia (FES) patients and 20 healthy control (HC) subjects. Using ultra-high field (7 Tesla) magnetic resonance spectroscopy (MRS) and resting state functional magnetic resonance imaging (fMRI), we measured GSH and GLU levels in the dorsal anterior cingulate cortex (dACC) and blood-oxygenation level-dependent activity in both the dACC and the anterior insula (AI). Using spectral dynamic causal modeling, we found that when compared to HCs, in FES patients inhibitory activity within the dACC decreased with GLU levels whereas inhibitory activity in both the dACC and AI increased with GSH levels. Our model explains how higher levels of GSH can reverse the downstream pathophysiological effects of a hyperglutamatergic state in FES. This provides an initial insight into the possible mechanistic effect of antioxidant system on the excitatory overdrive in the salience network (dACC-AI).

Impaired error awareness in healthy older adults: an age group comparison study

Aging is associated with reduced conscious error detection but the brain regions mediating these changes have yet to be clarified. The present study examined the neural correlates of error awareness in healthy older adults. Sixteen older participants (mean age = 75.5 years) and sixteen younger controls (mean age = 27.9 years) were administered the error awareness task, a go/no-go response inhibition paradigm, in which participants were required to signal commission errors. Compared with young adults, older adults were significantly poorer at consciously detecting performance errors, despite both groups being matched for overall accuracy. This age-related behavioral effect was associated with differences in error-related dorsal anterior cingulate cortex and insula activation, with younger adults showing significant differences between errors made with versus without awareness compared with older adults. By contrast, an age-specific modulation in right inferior parietal lobule activation emerged, with increased right inferior parietal lobule activity occurring in older adults during errors made with awareness compared with younger adults. These findings are consistent with theories of age-related deterioration in error processing mechanisms.

Reward Processing in Children With Disruptive Behavior Disorders and Callous-Unemotional Traits in the ABCD Study.

Disrupted reward processing is implicated in the etiology of disruptive behavior disorders (DBDs) and callous-unemotional traits. However, neuroimaging investigations of reward processing underlying these phenotypes remain sparse. The authors examined neural sensitivity in response to reward anticipation and receipt among youths with DBDs, with and without callous-unemotional traits. Data were obtained from the Adolescent Brain and Cognitive Development Study (mean age=9.51 years [SD=0.50]; 49% female). Reward-related activation during the monetary incentive delay task was examined across 16 brain regions, including the amygdala, anterior cingulate cortex (ACC), nucleus accumbens (NAcc), and orbitofrontal cortex (OFC). Latent variable modeling was used to examine network-level coactivation. The following diagnostic groups were compared: typically developing youths (N=693) and youths with DBDs (N=995), subdivided into those with callous-unemotional traits (DBD+CU, N=198) and without callous-unemotional traits (DBD only, N=276). During reward anticipation, youths in the overall DBD group (with and without callous-unemotional traits) showed decreased dorsal ACC activation compared with typically developing youths. The DBD-only group exhibited reduced ventral and dorsal striatal activity compared with the DBD+CU and typically developing groups. During reward receipt, youths with DBDs showed increased cortical (e.g., OFC) and subcortical (e.g., NAcc) regional activation compared with typically developing youths. The DBD+CU group demonstrated greater activation in several regions compared with those in the typically developing (e.g., amygdala) and DBD-only (e.g., dorsal ACC) groups. At the network level, the DBD-only group showed reduced anticipatory reward activation compared with the typically developing and DBD+CU groups, whereas youths in the DBD+CU group showed increased activation during reward receipt compared with those in the typically developing group. These findings advance our understanding of unique neuroetiologic pathways to DBDs and callous-unemotional traits.

Temporal Dynamics of Large-Scale Networks Predict Neural Cue Reactivity and Cue-Induced Craving

BackgroundCue reactivity, a core characteristic of substance use disorders, commonly recruits brain regions that are key nodes in neurocognitive networks, including the default mode network (DMN) and salience network (SN). Whether resting-state temporal dynamic properties of these networks relate to subsequent cue reactivity and cue-induced craving is unknown. MethodsThe resting-state data of 46 nicotine-dependent participants were assessed to define temporal dynamic properties of DMN and SN states. Temporal dynamics focused on the total time across the scan session that brain activity resides in these specific states. Using regression models, we examined how the total time in each state related to neural reactivity to smoking cues within key DMN (posterior cingulate cortex, medial prefrontal cortex) or SN (anterior insula, dorsal anterior cingulate cortex) nodes. Mediation analyses were subsequently conducted to study how neural cue reactivity mediates the relationship between total time in state at rest and subjective cue-induced craving. ResultsIncreased time spent in the DMN state and decreased time spent in the SN state predicted subsequent cue-induced increases in the anterior insula and dorsal anterior cingulate cortex, respectively. Cue-induced anterior insula and dorsal anterior cingulate cortex activity significantly mediated the relationship between time spent in DMN/SN and cue-induced subjective craving. ConclusionsOur findings showed a significant relationship between resting-state dynamics of the DMN/SN and task-activated SN nodes that together predicted cue-induced craving changes in nicotine-dependent individuals. These findings propose a neurobiological pathway for cue-induced craving that begins with resting-state temporal dynamics, suggesting that brain responding to external stimuli is driven by resting temporal dynamics.

Nicotine dependence (trait) and acute nicotinic stimulation (state) modulate attention but not inhibitory control: converging fMRI evidence from Go-Nogo and Flanker tasks.

Cognitive deficits during nicotine withdrawal may contribute to smoking relapse. However, interacting effects of chronic nicotine dependence and acute nicotine withdrawal on cognitive control are poorly understood. Here we examine the effects of nicotine dependence (trait; smokers (n = 24) vs. non-smoking controls; n = 20) and acute nicotinic stimulation (state; administration of nicotine and varenicline, two FDA-approved smoking cessation aids, during abstinence), on two well-established tests of inhibitory control, the Go-Nogo task and the Flanker task, during fMRI scanning. We compared performance and neural responses between these four pharmacological manipulations in a double-blind, placebo-controlled crossover design. As expected, performance in both tasks was modulated by nicotine dependence, abstinence, and pharmacological manipulation. However, effects were driven entirely by conditions that required less inhibitory control. When demand for inhibitory control was high, abstinent smokers showed no deficits. By contrast, acutely abstinent smokers showed performance deficits in easier conditions and missed more trials. Go-Nogo fMRI results showed decreased inhibition-related neural activity in right anterior insula and right putamen in smokers and decreased dorsal anterior cingulate cortex activity on nicotine across groups. No effects were found on inhibition-related activity during the Flanker task or on error-related activity in either task. Given robust nicotinic effects on physiology and behavioral deficits in attention, we are confident that pharmacological manipulations were effective. Thus findings fit a recent proposal that abstinent smokers show decreased ability to divert cognitive resources at low or intermediate cognitive demand, while performance at high cognitive demand remains relatively unaffected, suggesting a primary attentional deficit during acute abstinence.

Individual differences in resting-state connectivity and giving social support: implications for health.

There is a growing appreciation for the health benefits of giving support, though variability in such behavior exists. Based on the possibility that the dorsomedial (DMPFC) default network subsystem is associated with social thinking and behavior, integrity of this subsystem may facilitate giving support to others. The current study tested associations between DMPFC subsystem connectivity at rest and tendencies related to giving support. During a functional magnetic resonance imaging session, 45 participants completed an emotional social cues task, a resting-state scan and self-report measures of social support. Supportive behavior during the month following the scan was also assessed. Greater DMPFC subsystem connectivity at rest was associated with greater support giving (though not receiving or perceiving support) at the time of the scan and one month later. Results held after adjusting for extraversion. In addition, greater resting-state DMPFC subsystem connectivity was associated with attenuated dorsal anterior cingulate cortex, anterior insula and amygdala activity to others’ negative emotional social cues, suggesting that DMPFC subsystem integrity at rest is also associated with the dampened withdrawal response proposed to facilitate care for others in need. Together, results begin to hint at an additional role for the ‘default’ social brain: giving support to others.

Behavioral and neural sensitivity to uncertain threat in individuals with alcohol use disorder: Associations with drinking behaviors and motives.

A developing theory is that individuals with alcohol use disorder (AUD) display exaggerated reactivity to threats that are uncertain (U-threat), which facilitates excessive drinking as a means of avoidance-based coping. There is a promising initial behavioral evidence supporting this theory; however, the neural bases of reactivity to U-threat in individuals with AUD have not been examined. The extent to which biomarkers of U-threat reactivity map onto drinking behaviors and coping motives for alcohol use is also unknown. The current study therefore examined group differences in behavioral and neural reactivity to U-threat in adults with and without AUD. The study also tested whether behavior and brain responses to U-threat correlate with problematic drinking and coping motivated drinking. Volunteers (n = 65) with and without a history of AUD (38 AUD, 27 controls) were included and completed a well-validated threat-of-shock task to probe responses to U-threat and predictable threat (P-threat) while startle eyeblink potentiation was collected. Individuals also completed a newly designed, analogous version of the task during functional magnetic resonance imaging (fMRI). Results indicated that individuals with AUD displayed greater startle magnitude during U-threat, but not P-threat, and greater right insula and dorsal anterior cingulate cortex (dACC) activation during both forms of threat compared with controls. Startle magnitude and insula activation during U-threat positively correlated with self-reported problem drinking and coping motives for alcohol use. Findings demonstrate that individuals with AUD display exaggerated sensitivity to U-threat at the behavioral and neural level and that these multimethod biomarkers tap into negative reinforcement processes of alcohol abuse.

Attentional control abnormalities in posttraumatic stress disorder: Functional, behavioral, and structural correlates

BackgroundAttentional disruptions are common in PTSD, but findings across neuropsychological and neuroimaging studies have been variable. Few PTSD studies have investigated abnormalities in attention networks using a multi-modal imaging approach and attentional tasks that include emotionally-salient images. This study combined a behavioral task that included these images (emotional Stroop) with functional and structural neuroimaging (fMRI and diffusion tensor imaging; DTI) methods to comprehensively investigate attentional control abnormalities in a highly-traumatized civilian sample. Methods48 traumatized women with and without PTSD received clinical assessments, fMRI and DTI. During fMRI, the Affective Stroop (AS), an attentional control task that includes emotionally-salient distractor images (trauma-relevant, positive, neutral) and variable task demands, was administered. ResultsIn response to more difficult AS trials, participants with PTSD demonstrated lower activation in the dorsal and rostral anterior cingulate cortex and greater activation in the insula. This group also showed comparatively poorer performance on positive AS distractor trials, even after adjusting for trauma exposure. Performance on these trials inversely correlated with structural integrity of the cingulum bundle and uncinate fasciculus. ConclusionsEven after adjusting for trauma exposure, participants with PTSD showed worse performance on an attentional control task in the context of emotional stimuli. They also showed relatively lower cognitive control network activation and greater salience network activation. Fronto-parietal and fronto-limbic white matter connectivity corresponded with AS performance. Our findings indicate that attentional control impairments in PTSD are most evident in the context of emotional cues, and are related to decrements in function and structure of cognitive control and salience networks.