Network Connectivity Alterations across the MAPT Mutation Clinical Spectrum.

OBJECTIVE: Microtubule-associated protein tau (MAPT) mutations cause frontotemporal lobar degeneration, and novel biomarkers are urgently needed for early disease detection. We used task-free functional magnetic resonance imaging (fMRI) mapping, a promising biomarker, to analyze network connectivity in symptomatic and presymptomatic MAPT mutation carriers. METHODS: We compared cross-sectional fMRI data between 17 symptomatic and 39 presymptomatic carriers and 81 controls with (1) seed-based analyses to examine connectivity within networks associated with the 4 most common MAPT-associated clinical syndromes (ie, salience, corticobasal syndrome, progressive supranuclear palsy syndrome, and default mode networks) and (2) whole-brain connectivity analyses. We applied K-means clustering to explore connectivity heterogeneity in presymptomatic carriers at baseline. Neuropsychological measures, plasma neurofilament light chain, and gray matter volume were compared at baseline and longitudinally between the presymptomatic subgroups defined by their baseline whole-brain connectivity profiles. RESULTS: Symptomatic and presymptomatic carriers had connectivity disruptions within MAPT-syndromic networks. Compared to controls, presymptomatic carriers showed regions of connectivity alterations with age. Two presymptomatic subgroups were identified by clustering analysis, exhibiting predominantly either whole-brain hypoconnectivity or hyperconnectivity at baseline. At baseline, these two presymptomatic subgroups did not differ in neuropsychological measures, although the hypoconnectivity subgroup had greater plasma neurofilament light chain levels than controls. Longitudinally, both subgroups showed visual memory decline (vs controls), yet the subgroup with baseline hypoconnectivity also had worsening verbal memory and neuropsychiatric symptoms, and extensive bilateral mesial temporal gray matter decline. INTERPRETATION: Network connectivity alterations arise as early as the presymptomatic phase. Future studies will determine whether presymptomatic carriers' baseline connectivity profiles predict symptomatic conversion. ANN NEUROL 2023;94:632-646.

Brain volumetric deficits in MAPT mutation carriers: a multisite study.

OBJECTIVE: MAPT mutations typically cause behavioral variant frontotemporal dementia with or without parkinsonism. Previous studies have shown that symptomatic MAPT mutation carriers have frontotemporal atrophy, yet studies have shown mixed results as to whether presymptomatic carriers have low gray matter volumes. To elucidate whether presymptomatic carriers have lower structural brain volumes within regions atrophied during the symptomatic phase, we studied a large cohort of MAPT mutation carriers using a voxelwise approach. METHODS: We studied 22 symptomatic carriers (age 54.7 ± 9.1, 13 female) and 43 presymptomatic carriers (age 39.2 ± 10.4, 21 female). Symptomatic carriers' clinical syndromes included: behavioral variant frontotemporal dementia (18), an amnestic dementia syndrome (2), Parkinson's disease (1), and mild cognitive impairment (1). We performed voxel-based morphometry on T1 images and assessed brain volumetrics by clinical subgroup, age, and mutation subtype. RESULTS: Symptomatic carriers showed gray matter atrophy in bilateral frontotemporal cortex, insula, and striatum, and white matter atrophy in bilateral corpus callosum and uncinate fasciculus. Approximately 20% of presymptomatic carriers had low gray matter volumes in bilateral hippocampus, amygdala, and lateral temporal cortex. Within these regions, low gray matter volumes emerged in a subset of presymptomatic carriers as early as their thirties. Low white matter volumes arose infrequently among presymptomatic carriers. INTERPRETATION: A subset of presymptomatic MAPT mutation carriers showed low volumes in mesial temporal lobe, the region ubiquitously atrophied in all symptomatic carriers. With each decade of age, an increasing percentage of presymptomatic carriers showed low mesial temporal volume, suggestive of early neurodegeneration.

Thalamo-cortical network hyperconnectivity in preclinical progranulin mutation carriers.

Mutations in progranulin (GRN) cause heterogeneous clinical syndromes, including behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), corticobasal syndrome (CBS) and Alzheimer-type dementia (AD-type dementia). Human studies have shown that presymptomatic GRN carriers feature reduced connectivity in the salience network, a system targeted in bvFTD. Mice with homozygous deletion of GRN, in contrast, show thalamo-cortical hypersynchrony due to aberrant pruning of inhibitory synapses onto thalamo-cortical projection neurons. No studies have systematically explored the intrinsic connectivity networks (ICNs) targeted by the four GRN-associated clinical syndromes, or have forged clear links between human and mouse model findings. We compared 17 preclinical GRN carriers (14 "presymptomatic" clinically normal and three "prodromal" with mild cognitive symptoms) to healthy controls to assess for differences in cognitive testing and gray matter volume. Using task-free fMRI, we assessed connectivity in the salience network, a non-fluent variant primary progressive aphasia network (nfvPPA), the perirolandic network (CBS), and the default mode network (AD-type dementia). GRN carriers and controls showed similar performance on cognitive testing. Although carriers showed little evidence of brain atrophy, markedly enhanced connectivity emerged in all four networks, and thalamo-cortical hyperconnectivity stood out as a unifying feature. Voxelwise assessment of whole brain degree centrality, an unbiased graph theoretical connectivity metric, confirmed thalamic hyperconnectivity. These results show that human GRN disease and the prevailing GRN mouse model share a thalamo-cortical network hypersynchrony phenotype. Longitudinal studies will determine whether this network physiology represents a compensatory response as carriers approach symptom onset, or an early and sustained preclinical manifestation of lifelong progranulin haploinsufficiency.

How Do You See Me? The Neural Basis of Motivated Meta-perception.

We cannot see the minds of others, yet people often spontaneously interpret how they are viewed by other people (i.e., meta-perceptions) and often in a self-flattering manner. Very little is known about the neural associations of meta-perceptions, but a likely candidate is the ventromedial pFC (VMPFC). VMPFC has been associated with both self- and other-perception as well as motivated self-perception. Does this function extend to meta-perceptions? The current study examined neural activity while participants made meta-perceptive interpretations in various social scenarios. A drift-diffusion model was used to test whether the VMPFC is associated with two processes involved in interpreting meta-perceptions in a self-flattering manner: the extent to which the interpretation process involves the preferential accumulation of evidence in favor of a self-flattering interpretation versus the extent to which the interpretation process begins with an expectation that favors a self-flattering outcome. Increased VMPFC activity was associated with the extent to which people preferentially accumulate information when interpreting meta-perceptions under ambiguous conditions and marginally associated with self-flattering meta-perceptions. Together, the present findings illuminate the neural underpinnings of a social cognitive process that has received little attention to date: how we make meaning of others' minds when we think those minds are pointed at us.

Intimate Partner Violence PTSD and Neural Correlates of Inhibition.

Posttraumatic stress disorder (PTSD) has been linked to deficits in response inhibition, and neuroimaging research suggests this may be due to differences in prefrontal cortex recruitment. The current study examined relationships between PTSD from intimate partner violence (IPV) and neural responses during inhibition. There were 10 women with PTSD from IPV and 12 female control subjects without trauma history who completed the stop signal task during functional magnetic resonance imaging. Linear mixed models were used to investigate group differences in activation (stop-nonstop and hard-easy trials). Those with PTSD exhibited greater differential activation to stop-nonstop trials in the right dorsolateral prefrontal cortex and the anterior insula and less differential activation in several default mode regions (d = 1.12-1.22). Subjects with PTSD exhibited less differential activation to hard-easy trials in the lateral frontal and the anterior insula regions (driven by less activation to hard trials) and several default mode regions (i.e., medial prefrontal cortex, posterior cingulate; driven by greater activation to easy trials; d = 1.23-1.76). PTSD was associated with difficulties disengaging default mode regions during cognitive tasks with relatively low cognitive demand, as well as difficulties modulating executive control and salience processing regions with increasing cognitive demand. Together, these results suggest that PTSD may relate to decreased neural flexibility during inhibition.

Attenuated Neural Processing of Risk in Young Adults at Risk for Stimulant Dependence.

OBJECTIVE: Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate), which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing. METHODS: 158 occasional stimulants users (OSU) and 50 comparison subjects (CS) performed a "risky gains" decision making task during which they could select safe options (cash in 20 cents) or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, "risky decisions"). The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42), or <50 lifetime marijuana uses (n = 32), were compared to CS with <50 lifetime uses (n = 46) to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed. RESULTS: There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC) and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options. DISCUSSION: Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions critical for performance monitoring, reward processing and interoceptive awareness. Marijuana had additive effects by diminishing neural risk differentiation.

Common and disorder-specific neural responses to emotional faces in generalised anxiety, social anxiety and panic disorders.

BACKGROUND: Although evidence exists for abnormal brain function across various anxiety disorders, direct comparison of neural function across diagnoses is needed to elicit abnormalities common across disorders and those distinct to a particular diagnosis. AIMS: To delineate common and distinct abnormalities within generalised anxiety (GAD), panic and social anxiety disorder (SAD) during affective processing. METHOD: Fifty-nine adults (15 with GAD, 15 with panic disorder, 14 with SAD, and 15 healthy controls) underwent functional magnetic resonance imaging while completing a facial emotion matching task with fearful, angry and happy faces. RESULTS: Greater differential right amygdala activation to matching fearful v. happy facial expressions related to greater negative affectivity (i.e. trait anxiety) and was heightened across all anxiety disorder groups compared with controls. Collapsing across emotional face types, participants with panic disorder uniquely displayed greater posterior insula activation. CONCLUSIONS: These preliminary results highlight a common neural basis for clinical anxiety in these diagnoses and also suggest the presence of disorder-specific dysfunction.

What do we know about positive appraisals? Low cognitive cost, orbitofrontal-striatal connectivity, and only short-term bolstering of resilience.

The PASTOR framework needs to be reconciled with existing research on positive illusions, which finds that positive appraisals of stressors have a short shelf life as a mechanism of resilience, do not draw on costly executive functioning, and rely on neural networks that are distinct from those found in studies of experimentally instructed reappraisal or value.

Cognitive-behavioral therapy for generalized anxiety disorder is associated with attenuation of limbic activation to threat-related facial emotions.

BACKGROUND: The neural processes underlying the benefits of cognitive behavioral treatment (CBT) for generalized anxiety disorder (GAD) are not well understood. METHODS: Twenty-one (n=21) adults with a principal diagnosis of GAD and eleven (n=11) non-anxious healthy controls (HC) underwent functional magnetic resonance imaging while completing a facial emotion processing task. Responses to threat-related emotionality (i.e., the contrast of fear and angry vs. happy faces) were assessed at pretreatment and again following 10 sessions of CBT in the GAD group and a comparable waiting period in the HC group. RESULTS: At pretreatment, GAD participants displayed blunted responses in the amygdala, insula, and anterior cingulate to the happy face-processing comparison condition, and greater amygdalo-insular connectivity. CBT was associated with attenuated amygdalar and subgenual anterior cingulate activation to fear/angry faces and heightened insular responses to the happy face comparison condition, but had no apparent effects on connectivity. Pre-treatment abnormalities and treatment-related changes were not associated with symptoms of worry. LIMITATIONS: There was no active control condition (e.g., treatment waitlist) for comparison of treatment effects. CONCLUSIONS: Taken together, these results provide evidence for a dual-process psychotherapeutic model of neural systems changes in GAD in which cingulo-amygdalar reactivity to threat-cues is attenuated while insular responses to positive facial emotions are potentiated. Future work is needed to determine the clinical implications of these changes and their specificity to CBT.

Detecting emotion in others: increased insula and decreased medial prefrontal cortex activation during emotion processing in elite adventure racers.

Understanding the neural processes that characterize elite performers is a first step to develop a neuroscience model that can be used to improve performance in stressful circumstances. Adventure racers are elite athletes that operate in small teams in the context of environmental and physical extremes. In particular, awareness of team member's emotional status is critical to the team's ability to navigate high-magnitude stressors. Thus, this functional magnetic resonance imaging (fMRI) study examined the hypothesis that adventure racers would show altered emotion processing in brain areas that are important for resilience and social awareness. Elite adventure racers (n = 10) were compared with healthy volunteers (n = 12) while performing a simple emotion face-processing (modified Hariri) task during fMRI. Across three types of emotional faces, adventure racers showed greater activation in right insula, left amygdala and dorsal anterior cingulate. Additionally, compared with healthy controls adventure racers showed attenuated right medial prefrontal cortex activation. These results are consistent with previous studies showing elite performers differentially activate neural substrates underlying interoception. Thus, adventure racers differentially deploy brain resources in an effort to recognize and process the internal sensations associated with emotions in others, which could be advantageous for team-based performance under stress.

Neural correlates of a computerized attention modification program in anxious subjects.

Computerized attention modification is a relatively new and empirically validated treatment approach for different types of anxiety disorders. However, its neural basis and processes involved are poorly understood. This study examined the effect of a one-time application of an attention modification program (AMP) on neural substrates underlying emotion processing in individuals with high social anxiety. Fourteen individuals with elevated social anxiety symptoms completed an emotional face processing task during functional magnetic resonance imaging before and after AMP, and were subsequently exposed to a laboratory stressor. Results revealed the following: First, there was attenuated activation from pre- to post-AMP in the bilateral amygdala, bilateral insula and subgenual anterior cingulate cortex. Second, post-AMP, individuals exhibited increased activation in several regions of the prefrontal cortex (PFC). Third, those individuals with greater enhancement of ventromedial PFC activation after AMP showed diminished attentional allocation for threat and attenuated anxiety reactivity to the stressor. We conclude that AMP exerts effects that are similar to those previously reported for standard anxiolytics; however, it also appears to foster deployment of top-down brain processes aimed to regulate anxiety.

Three ways in which midline regions contribute to self-evaluation.

An integration of existing research and newly conducted psychophysiological interaction (PPI) connectivity analyses suggest a new framework for understanding the contribution of midline regions to social cognition. Recent meta-analyses suggest that there are no midline regions that are exclusively associated with self-processing. Whereas medial prefrontal cortex (MPFC) is broadly modulated by self-processing, subdivisions within MPFC are differentially modulated by the evaluation of close others (ventral MPFC: BA 10/32) and the evaluation of other social targets (dorsal MPFC: BA 9/32). The role of DMPFC in social cognition may also be less uniquely social than previously thought; it may be better characterized as a region that indexes certainty about evaluation rather than previously considered social mechanisms (i.e., correction of self-projection). VMPFC, a region often described as an important mediator of socioemotional significance, may instead perform a more cognitive role by reflecting the type of information brought to bear on evaluations of people we know well. Furthermore, the new framework moves beyond MPFC and hypothesizes that two other midline regions, ventral anterior cingulate cortex (VACC: BA 25) and medial orbitofrontal cortex (MOFC: BA 11), aid motivational influences on social cognition. Despite the central role of motivation in psychological models of self-perception, neural models have largely ignored the topic. Positive connectivity between VACC and MOFC may mediate bottom-up sensitivity to information based on its potential for helping us evaluate ourselves or others the way we want. As connectivity becomes more positive with striatum and less positive with middle frontal gyrus (BA 9/44), MOFC mediates top-down motivational influences by adjusting the standards we bring to bear on evaluations of ourselves and other people.

Neural responses during emotional processing before and after cognitive trauma therapy for battered women.

Therapy for combat and accident-related posttraumatic stress disorder (PTSD) has been reported to influence amygdala and anterior cingulate cortex (ACC) response during emotional processing. It is not yet understood how therapy influences different phases of emotional processing, and whether previous findings generalize to other PTSD populations. We hypothesized that cognitive trauma therapy for battered women (CTT-BW) would alter insula, amygdala, and cingulate responses during anticipation and presentation of emotional images. Fourteen female patients with PTSD related to domestic violence completed the Clinician Administered PTSD Scale (CAPS) and functional magnetic resonance imaging (fMRI) before and after CTT-BW. The fMRI task involved cued anticipation followed by presentation of positive versus negative affective images. CTT-BW was associated with decreases in CAPS score, enhanced ACC and decreased anterior insula activation during anticipation, and decreased dorsolateral prefrontal cortex and amygdala response during image presentation (negative-positive). Pre-treatment ACC activation during anticipation and image presentation exhibited positive and negative relationships to treatment response, respectively. Results suggest that CTT-BW enhanced efficiency of neural responses during preparation for upcoming emotional events in a way that reduced the need to recruit prefrontal-amygdala responses during the occurrence of the event. Results also suggest that enhancing ACC function during anticipation may be beneficial for PTSD treatment.

Red brain, blue brain: evaluative processes differ in Democrats and Republicans.

Liberals and conservatives exhibit different cognitive styles and converging lines of evidence suggest that biology influences differences in their political attitudes and beliefs. In particular, a recent study of young adults suggests that liberals and conservatives have significantly different brain structure, with liberals showing increased gray matter volume in the anterior cingulate cortex, and conservatives showing increased gray matter volume in the in the amygdala. Here, we explore differences in brain function in liberals and conservatives by matching publicly-available voter records to 82 subjects who performed a risk-taking task during functional imaging. Although the risk-taking behavior of Democrats (liberals) and Republicans (conservatives) did not differ, their brain activity did. Democrats showed significantly greater activity in the left insula, while Republicans showed significantly greater activity in the right amygdala. In fact, a two parameter model of partisanship based on amygdala and insula activations yields a better fitting model of partisanship than a well-established model based on parental socialization of party identification long thought to be one of the core findings of political science. These results suggest that liberals and conservatives engage different cognitive processes when they think about risk, and they support recent evidence that conservatives show greater sensitivity to threatening stimuli.

The effects of temporal unpredictability in anticipation of negative events in combat veterans with PTSD.

BACKGROUND: Exposure to psychological stress during combat can lead to posttraumatic stress disorder (PTSD). Anticipation of aversive events is often associated with an intense emotional state in individuals with PTSD. Both the valence (i.e., positive or negative) of the anticipated event and the degree of temporal predictability (i.e., one's ability to predict when an event will occur) have profound effects on an individual's emotional experience. This investigation tested the hypothesis that individuals with combat-related PTSD would show increased activation in the insula and related emotion-processing circuitry when anticipating emotionally significant events such as portrayed in combat-related images, and this heighted response within the insula would be particularly enhanced during temporal unpredictability. METHODS: About 15 male veterans with PTSD and 15 male veterans with combat-exposure but no current or lifetime history of PTSD (combat exposed controls/CEC) performed a temporal unpredictability anticipation task of unpleasant (combat-related) and pleasant images during fMRI. RESULTS: As expected, greater activation in the bilateral anterior insulae was observed in the PTSD versus the CEC subjects during anticipation of combat-related images when the anticipatory period was of uncertain duration (p<0.05). Furthermore, activation in the right anterior insula was related to greater perceived threat in the CEC group (ρ=0.619). LIMITATIONS: The current study looks only at combat-related PTSD in a modest preliminary sized sample. CONCLUSIONS: These findings suggest that an excessive anticipatory reaction in individuals with PTSD to temporally unpredictable aversive stimulus may relate to greater perceived threat. These findings are concordant with psychological models of PTSD that focus on the association of PTSD with the experience of decreased predictability and control.

Neural functional and structural correlates of childhood maltreatment in women with intimate-partner violence-related posttraumatic stress disorder.

Childhood maltreatment (CM) is a strong risk factor for development of posttraumatic stress disorder (PTSD) upon adult exposure to extreme adverse events. However, the neural underpinnings of this relationship are not well understood. Here, we test the hypothesis that severity of CM history is positively correlated with emotion-processing limbic and prefrontal brain activation/connectivity and negatively correlated with prefrontal gray matter volumes in women with PTSD due to intimate-partner violence (IPV-PTSD). Thirty-three women with IPV-PTSD underwent structural and functional magnetic resonance imaging while completing a facial emotion processing task. Multivariate regressions examined the relationship of CM to patterns of activation, connectivity, and gray matter volumes. CM severity was: (a) positively correlated with ventral ACC activation while processing angry faces; (b) negatively correlated with dorsal ACC and insula activation while processing fear and angry faces, arising from positive correlations with the shape-matching baseline; (c) positively correlated with limbic-prefrontal connectivity while processing fear faces but negatively correlated with amygdalo-insular connectivity while processing fear and angry; and (d) negatively correlated with prefrontal gray matter volumes. These results suggest CM exposure may account for variability in limbic/prefrontal brain function and prefrontal structure in adulthood PTSD and offer one potential mechanism through which CM confers risk to future development of PTSD.

Young adults at risk for stimulant dependence show reward dysfunction during reinforcement-based decision making.

BACKGROUND: While stimulant-dependent individuals continue to make risky decisions, in spite of poor outcomes, much less is known about decision-making characteristics of occasional stimulant users (OSU) at risk for developing stimulant dependence. This study examines whether OSU exhibit inefficient learning and execution of reinforced decision-outcome contingencies. METHODS: Occasional stimulant users (n = 161) and stimulant-naïve comparison subjects (CTL) (n = 48) performed a Paper Scissors Rock task during functional magnetic resonance imaging. Selecting a particular option was associated with a predetermined probability of winning, which was altered repeatedly to examine neural and behavioral characteristics of reinforced contingencies. RESULTS: Occasional stimulant users displayed greater anterior insula, inferior frontal gyrus, and dorsal striatum activation than CTL during late trials when contingencies were familiar (as opposed to being learned) in the presence of comparable behavioral performance in both groups. Follow-up analyses demonstrated that during late trials: 1) OSU with high cannabis use displayed greater activation in these brain regions than CTL, whereas OSU with low cannabis use did not differ from the other two groups; and 2) OSU preferring cocaine exhibited greater anterior insula, inferior frontal gyrus, and dorsal striatum activation than CTL and also displayed higher activation in the former two regions than OSU who preferred prescription stimulants. CONCLUSIONS: Occasional stimulant users exhibit inefficient resource allocation during the execution of reinforced contingencies that may be a result of additive effects of cocaine and cannabis use. A critical next step is to establish whether this inefficiency predicts transition to stimulant dependence.

Pregabalin effects on neural response to emotional faces.

Pregabalin has shown promise in the treatment of anxiety disorders. Previous functional magnetic resonance imaging (fMRI) studies indicate agents used to treat anxiety, e.g., SSRIs and benzodiazepines, attenuate amygdala, insula, and medial prefrontal cortex (mPFC) activation during emotional processing. Our prior study has shown that during anticipation of an emotional stimulus, pregabalin attenuates amygdala and insula activation but increases medial PFC activation. In this study, we examined whether, similar to SSRIs and benzodiazepines, pregabalin attenuates amygdala, insula, and medial PFC during emotional face processing. Sixteen healthy volunteers underwent a double-blind within-subjects fMRI study investigating effects of placebo, 50 mg, and 200 mg pregabalin on neural activation during an emotional face-matching task. Linear mixed model analysis revealed that pregabalin dose-dependently attenuated left amygdala activation during fearful face-matching and left anterior insula activation during angry face-matching. The 50 mg dose exhibited more robust effects than the 200 mg dose in the right anterior insula and ventral ACC. Thus, pregabalin shares some similarity to SSRIs and benzodiazepines in attenuating anger and fear-related insula and amygdala activation during emotional face processing. However, there is evidence that a subclinical 50 mg dose of pregabalin produced more robust and widespread effects on neural responses in this paradigm than the more clinically relevant 200 mg dose. Taken together, pregabalin has a slightly different effect on brain activation as it relates to anticipation and emotional face processing, which may account for its unique characteristic as an agent for the treatment of anxiety disorders.

Dorsolateral prefrontal cortex activation during emotional anticipation and neuropsychological performance in posttraumatic stress disorder.

CONTEXT: Posttraumatic stress disorder (PTSD) has been associated with executive or attentional dysfunction and problems in emotion processing. However, it is unclear whether these two domains of dysfunction are related to common or distinct neurophysiological substrates. OBJECTIVE: To examine the hypothesis that greater neuropsychological impairment in PTSD relates to greater disruption in prefrontal-subcortical networks during emotional anticipation. DESIGN: Case-control, cross-sectional study. SETTING: General community and hospital and community psychiatric clinics. PARTICIPANTS: Volunteer sample of 37 women with PTSD related to intimate partner violence and 34 age-comparable healthy control women. MAIN OUTCOME MEASURES: We used functional magnetic resonance imaging (fMRI) to examine neural responses during anticipation of negative and positive emotional images. The Clinician-Administered PTSD Scale was used to characterize PTSD symptom severity. The Wechsler Adult Intelligence Scale, Third Edition, Digit Symbol Test, Delis-Kaplan Executive Function System Color-Word Interference Test, and Wisconsin Card Sorting Test were used to characterize neuropsychological performance. RESULTS: Women with PTSD performed worse on complex visuomotor processing speed (Digit Symbol Test) and executive function (Color-Word Interference Inhibition/Switching subtest) measures compared with control subjects. Posttraumatic stress disorder was associated with greater anterior insula and attenuated lateral prefrontal cortex (PFC) activation during emotional anticipation. Greater dorsolateral PFC activation (anticipation of negative images minus anticipation of positive images) was associated with lower PTSD symptom severity and better visuomotor processing speed and executive functioning. Greater medial PFC and amygdala activation related to slower visuomotor processing speed. CONCLUSIONS: During emotional anticipation, women with PTSD show exaggerated activation in the anterior insula, a region important for monitoring internal bodily state. Greater dorsolateral PFC response in PTSD patients during emotional anticipation may reflect engagement of cognitive control networks that are beneficial for emotional and cognitive functioning. Novel treatments could be aimed at strengthening the balance between cognitive control (dorsolateral PFC) and affective processing (medial PFC and amygdala) networks to improve overall functioning for PTSD patients.

Neural basis of egalitarian behavior.

Individuals are willing to sacrifice their own resources to promote equality in groups. These costly choices promote equality and are associated with behavior that supports cooperation in humans, but little is known about the brain processes involved. We use functional MRI to study egalitarian preferences based on behavior observed in the "random income game." In this game, subjects decide whether to pay a cost to alter group members' randomly allocated incomes. We specifically examine whether egalitarian behavior is associated with neural activity in the ventromedial prefrontal cortex and the insular cortex, two regions that have been shown to be related to social preferences. Consistent with previous studies, we find significant activation in both regions; however, only the insular cortex activations are significantly associated with measures of revealed and expressed egalitarian preferences elicited outside the scanner. These results are consistent with the notion that brain mechanisms involved in experiencing the emotional states of others underlie egalitarian behavior in humans.