Sarcopenia and Sarcopenic Obesity on Body Composition Analysis is a Significant Predictor of Mortality in Severe Acute Pancreatitis: A Longitudinal Observational Study.

BACKGROUND: The prevalence and impact of sarcopenia and sarcopenic obesity noted on body composition analysis in severe acute pancreatitis (SAP) is unknown. This study investigates the prevalence of sarcopenia at different timepoints and its effect on post-pancreatitis complications and mortality. METHODS: A prospective database of SAP admissions with organ failure at a single institution from 2015 to 2019 were analysed. Sarcopenia was determined by IMAGE J software on CT. Database was further queried for post-pancreatitis complications and mortality. RESULTS: 141 patients with a median age of 59 (range 18-88) and M:F ratio 1.52:1 of were analysed. Sarcopenia was present in 111/141 (79%) patients at admission, 78/79 (99%) at 3 months and 26/36 (72%) at 12 months. 67/111 patients with sarcopenia on admission had sarcopenic obesity. The mortality at 30 days, 3 months and 12 months was 16/141 (11%), 30/141 (21%) and 42/141 (30%) respectively. Mortality was significantly higher in sarcopenic patients at admission (35.14%) compared to the non-sarcopenic group (10%), P = 0.008). Mortality in the sarcopenic obesity group was significantly higher (45%) compared to the sarcopenic non-obese group (20%), P = 0.009) at admission. Multivariate logistic regression identified sarcopenic obesity (OR: 2.880), age (OR: 1.048) and number of organ failures (OR: 3.225) as significant predictors of mortality. CONCLUSIONS: Sarcopenia and Sarcopenic obesity are highly prevalent in SAP patients on admission and during follow up. Furthermore, sarcopenic obesity was shown to be a significant predictor of mortality at admission, suggesting that body composition analysis could be a potential predictive marker of mortality in SAP patients.

Resting-state magnetoencephalography source magnitude imaging with deep-learning neural network for classification of symptomatic combat-related mild traumatic brain injury.

Combat-related mild traumatic brain injury (cmTBI) is a leading cause of sustained physical, cognitive, emotional, and behavioral disabilities in Veterans and active-duty military personnel. Accurate diagnosis of cmTBI is challenging since the symptom spectrum is broad and conventional neuroimaging techniques are insensitive to the underlying neuropathology. The present study developed a novel deep-learning neural network method, 3D-MEGNET, and applied it to resting-state magnetoencephalography (rs-MEG) source-magnitude imaging data from 59 symptomatic cmTBI individuals and 42 combat-deployed healthy controls (HCs). Analytic models of individual frequency bands and all bands together were tested. The All-frequency model, which combined delta-theta (1-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-80 Hz) frequency bands, outperformed models based on individual bands. The optimized 3D-MEGNET method distinguished cmTBI individuals from HCs with excellent sensitivity (99.9 ± 0.38%) and specificity (98.9 ± 1.54%). Receiver-operator-characteristic curve analysis showed that diagnostic accuracy was 0.99. The gamma and delta-theta band models outperformed alpha and beta band models. Among cmTBI individuals, but not controls, hyper delta-theta and gamma-band activity correlated with lower performance on neuropsychological tests, whereas hypo alpha and beta-band activity also correlated with lower neuropsychological test performance. This study provides an integrated framework for condensing large source-imaging variable sets into optimal combinations of regions and frequencies with high diagnostic accuracy and cognitive relevance in cmTBI. The all-frequency model offered more discriminative power than each frequency-band model alone. This approach offers an effective path for optimal characterization of behaviorally relevant neuroimaging features in neurological and psychiatric disorders.

MEG Working Memory N-Back Task Reveals Functional Deficits in Combat-Related Mild Traumatic Brain Injury.

Combat-related mild traumatic brain injury (mTBI) is a leading cause of sustained cognitive impairment in military service members and Veterans. However, the mechanism of persistent cognitive deficits including working memory (WM) dysfunction is not fully understood in mTBI. Few studies of WM deficits in mTBI have taken advantage of the temporal and frequency resolution afforded by electromagnetic measurements. Using magnetoencephalography (MEG) and an N-back WM task, we investigated functional abnormalities in combat-related mTBI. Study participants included 25 symptomatic active-duty service members or Veterans with combat-related mTBI and 20 healthy controls with similar combat experiences. MEG source-magnitude images were obtained for alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and low-frequency (1-7 Hz) bands. Compared with healthy combat controls, mTBI participants showed increased MEG signals across frequency bands in frontal pole (FP), ventromedial prefrontal cortex, orbitofrontal cortex (OFC), and anterior dorsolateral prefrontal cortex (dlPFC), but decreased MEG signals in anterior cingulate cortex. Hyperactivations in FP, OFC, and anterior dlPFC were associated with slower reaction times. MEG activations in lateral FP also negatively correlated with performance on tests of letter sequencing, verbal fluency, and digit symbol coding. The profound hyperactivations from FP suggest that FP is particularly vulnerable to combat-related mTBI.

A pilot treatment study for mild traumatic brain injury: Neuroimaging changes detected by MEG after low-intensity pulse-based transcranial electrical stimulation.

BACKGROUND: Mild traumatic brain injury (mTBI) is a leading cause of sustained impairments in military service members, Veterans, and civilians. However, few treatments are available for mTBI, partially because the mechanism of persistent mTBI deficits is not fully understood. METHODS: We used magnetoencephalography (MEG) to investigate neuronal changes in individuals with mTBI following a passive neurofeedback-based treatment programme called IASIS. This programme involved applying low-intensity pulses using transcranial electrical stimulation (LIP-tES) with electroencephalography monitoring. Study participants included six individuals with mTBI and persistent post-concussive symptoms (PCS). MEG exams were performed at baseline and follow-up to evaluate the effect of IASIS on brain functioning. RESULTS: At the baseline MEG exam, all participants had abnormal slow-waves. In the follow-up MEG exam, the participants showed significantly reduced abnormal slow-waves with an average reduction of 53.6 ± 24.6% in slow-wave total score. The participants also showed significant reduction of PCS scores after IASIS treatment, with an average reduction of 52.76 ± 26.4% in PCS total score. CONCLUSIONS: The present study demonstrates, for the first time, the neuroimaging-based documentation of the effect of LIP-tES treatment on brain functioning in mTBI. The mechanisms of LIP-tES treatment are discussed, with an emphasis on LIP-tES's potentiation of the mTBI healing process.

Validation of the Modified Fatigue Impact Scale in mild to moderate traumatic brain injury.

OBJECTIVE: To evaluate the validity of the Modified Fatigue Impact Scale (MFIS) in veterans with a history of mild to moderate traumatic brain injury (TBI). PARTICIPANTS: Veterans (N = 106) with mild (92%) or moderate (8%) TBI. SETTING: Veterans Administration Health System. PROCEDURE: Factor structure, internal consistency, convergent validity, sensitivity, and specificity of the MFIS were examined. RESULTS: Principal component analysis identified 2 viable MFIS factors: a Cognitive subscale and a Physical/Activities subscale. Item analysis revealed high internal consistency of the MFIS Total scale and subscale items. Strong convergent validity of the MFIS scales was established with 2 Beck Depression Inventory II fatigue items. Receiver operating characteristic curve analysis revealed good to excellent accuracy of the MFIS in classifying fatigued versus nonfatigued individuals. CONCLUSION: The MFIS is a valid multidimensional measure that can be used to evaluate the impact of fatigue on cognitive and physical functioning in individuals with mild to moderate TBI. The psychometric properties of the MFIS make it useful for evaluating fatigue and provide the potential for improving research on fatigue in this population.

Altered insula activation during pain anticipation in individuals recovered from anorexia nervosa: evidence of interoceptive dysregulation.

OBJECTIVE: Recent evidence raises the possibility that symptoms of anorexia nervosa (AN) could be related to impaired interoception. Pain is an interoceptive process with well-characterized neuroanatomical pathways that may overlap to a large degree with neural systems that may be dysregulated in individuals with AN, such as the insula. METHOD: Functional magnetic resonance imaging (fMRI) was used to assess neural substrates of pain anticipation and processing in 10 healthy control women (CW) and 12 individuals recovered from AN (REC AN) in order to avoid the confounding effects of malnutrition. Painful heat stimuli were applied while different colors signaled the intensity of the upcoming stimuli. RESULTS: REC AN compared with CW showed greater activation within right anterior insula (rAI), dorsolateral prefrontal cortex (dlPFC) and cingulate during pain anticipation, and greater activation within dlPFC and decreased activation within posterior insula during painful stimulation. Greater anticipatory rAI activation correlated positively with alexithymic feelings in REC AN participants. DISCUSSION: REC AN showed a mismatch between anticipation and objective responses, suggesting altered integration and, possibly, disconnection between reported and actual interoceptive state. Alexithymia assessment provided additional evidence of an altered ability to accurately perceive bodily signals in women recovered from AN.

An optimization method for stochastic reconstruction from empirical data - A limestone rock strain fields study-case using digital image correlation data.

Stochastic field reconstruction is a crucial technique to improve the accuracy of modern rock simulation. It allows explicit modelling of field conditions, often employed in uncertainty quantification analysis and upsampling and upscaling procedures. This paper presents a case-study of a framework for the stochastic reconstruction of rock's strain field using experimental data. The proposed framework is applied to a limestone outcrop in which the strain field is measured using Digital Image Correlation (DIC). Assuming that the strain fields of these rocks are well-represented by Gaussian random fields, we capitalize on the algorithms used for training Gaussian processes to estimate the correlation family and the parameters that best represent these fields. Although the spherical and exponential kernels often correspond to the best fit, our results depict that each field shall be analyzed separately and no general rule can be defined. We show that the method is versatile and can be employed in any measurable field reasonably represented by a Gaussian random field. Therefore, the present work aims to highlight the following topics:•A study-case of stochastic strain field reconstruction aims to contribute to uncertainty quantification of rock experimental procedures.•A stochastic minimization algorithm is presented to solve the maximum likelihood estimation to define the most suitable hyper-parameter: correlation length.•The calculated hyper-parameters of a set correlation functions are presented to best reproduce the strain fields of a rock sample.

Combat-exposed war veterans at risk for suicide show hyperactivation of prefrontal cortex and anterior cingulate during error processing.

OBJECTIVE: Suicide is a significant public health problem. Suicidal ideation (SI) increases the risk for completed suicide. However, the brain basis of SI is unknown. The objective of this study was to examine the neural correlates of self-monitoring in individuals at risk for suicide. We hypothesized that combat veterans with a history of SI relative to those without such a history would show altered activation in the anterior cingulate cortex and related circuitry during self-monitoring. METHODS: Two groups of combat-exposed war veterans (13 men with and 13 men without history of SI) were studied. Both the SI and non-SI participants had two or more of the following: a) current major depressive disorder, b) current posttraumatic stress disorder, and c) history of mild traumatic brain injury, and each subject performed a validated stop task during functional magnetic resonance imaging. Error-related activation was compared between the SI and non-SI groups. RESULTS: The SI group demonstrated more error-related activation of the anterior cingulate (8256 mm(3), t = 2.51) and prefrontal cortex (i.e., clusters >2048 mm(3), voxelwise p < .05). The SI and non-SI participants showed similar behavioral task performance (i.e., mean error rate, F values < 0.63, p values > .43; and mean reaction times, F = 0.27, p = .61). CONCLUSIONS: These findings suggest neural correlates of altered self-monitoring in individuals with a history of SI and may further suggest that functional magnetic resonance imaging could be used to identify individuals at risk for suicide before they engage in suicidal behavior.

fMRI differences between subjects with low and high responses to alcohol during a stop signal task.

BACKGROUND: A low level of response (i.e., a low LR) to alcohol is a genetically influenced phenotype that predicts later alcoholism. While the low LR reflects, at least in part, a low brain response to alcohol, the physiological underpinnings of the low LR have only recently been addressed. METHODS: Forty-nine drinking but not yet alcoholic matched pairs of 18- to 25-year-old subjects (N = 98; 53% women) with low and high LRs as established in separate alcohol challenges were evaluated in 2 event-related functional magnetic resonance imaging (fMRI) sessions (placebo and approximately 0.7 ml/kg of alcohol) while performing a validated stop signal task. The high and low LR groups had identical blood alcohol levels during the alcohol session. RESULTS: Significant high versus low LR group and LR group × condition effects were observed in blood oxygen level-dependent (BOLD) signal during error and inhibitory processing, despite similar LR group performance on the task. In most clusters with significant (corrected p < 0.05, clusters > 1,344 µl) LR group × alcohol/placebo condition interactions, the low LR group demonstrated relatively less, whereas the high LR group demonstrated more, error and inhibition-related activation after alcohol compared with placebo. CONCLUSIONS: This is one of the first fMRI studies to demonstrate significant differences between healthy groups with different risks of a future life-threatening disorder. The results may suggest a brain mechanism that contributes to how a low LR might enhance the risk of future heavy drinking and alcohol dependence.

Detection of Chronic Blast-Related Mild Traumatic Brain Injury with Diffusion Tensor Imaging and Support Vector Machines.

Blast-related mild traumatic brain injury (bmTBI) often leads to long-term sequalae, but diagnostic approaches are lacking due to insufficient knowledge about the predominant pathophysiology. This study aimed to build a diagnostic model for future verification by applying machine-learning based support vector machine (SVM) modeling to diffusion tensor imaging (DTI) datasets to elucidate white-matter features that distinguish bmTBI from healthy controls (HC). Twenty subacute/chronic bmTBI and 19 HC combat-deployed personnel underwent DTI. Clinically relevant features for modeling were selected using tract-based analyses that identified group differences throughout white-matter tracts in five DTI metrics to elucidate the pathogenesis of injury. These features were then analyzed using SVM modeling with cross validation. Tract-based analyses revealed abnormally decreased radial diffusivity (RD), increased fractional anisotropy (FA) and axial/radial diffusivity ratio (AD/RD) in the bmTBI group, mostly in anterior tracts (29 features). SVM models showed that FA of the anterior/superior corona radiata and AD/RD of the corpus callosum and anterior limbs of the internal capsule (5 features) best distinguished bmTBI from HCs with 89% accuracy. This is the first application of SVM to identify prominent features of bmTBI solely based on DTI metrics in well-defined tracts, which if successfully validated could promote targeted treatment interventions.

A multimodal imaging study in U.S. veterans of Operations Iraqi and Enduring Freedom with and without major depression after blast-related concussion.

Although the exact number of affected individuals is unknown, it has been estimated that approximately 20% of U.S. veterans of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF) have experienced mild traumatic brain injury (mTBI) (i.e., concussion), which is defined as a brief loss or alteration of consciousness from a blow or jolt to the head. Blast exposure is among the most common causes of concussion in OEF-OIF warriors. Although the mechanism is unknown, major depressive disorder (MDD) after head injury is common. The purpose of this study was to use diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) to examine the structural and functional neural correlates of MDD in OEF-OIF combat veterans with a self-reported history of blast-related concussion. We hypothesized that subjects in the MDD group (i.e., individuals with a history of blast-related concussion who were experiencing current MDD) relative to individuals in the non-MDD group (i.e., individuals with a history of blast-related concussion but no current or lifetime history of MDD) would show amygdala hyperactivity and disruption of white matter tracts connecting prefrontal and limbic brain regions. To test these hypotheses, 11 MDD and 11 non-MDD individuals underwent DTI and performed a validated emotional face matching task during fMRI. MDD relative to non-MDD individuals showed greater activity during fear matching trials in the amygdala and other emotion processing structures, lower activity during fear matching trials in emotional control structures such as the dorsolateral prefrontal cortex and lower fractional anisotropy (FA) in several white matter tracts including the superior longitudinal fasciculus (SLF). Greater depressive symptom severity correlated negatively with FA in the SLF. These results suggest a biological basis of MDD in OEF-OIF veterans who have experienced blast-related concussion, and may contribute to the development of treatments aimed at improving the clinical care of this unique population of wounded warriors.

The effects of loss versus alteration of consciousness on inhibition-related brain activity among individuals with a history of blast-related concussion.

In this investigation, 27 individuals who experienced blast-related concussion, i.e., brief loss (LOC) or alteration (AOC) of consciousness, performed a stop task during functional magnetic resonance imaging. LOC versus AOC subjects displayed altered ventromedial prefrontal cortex activity, which correlated with somatic symptom severity-findings which may suggest a neural correlate of impaired self awareness after LOC.

Demand-specific alteration of medial prefrontal cortex response during an inhibition task in recovered anorexic women.

OBJECTIVE: It is well known that individuals with anorexia nervosa (AN) are inhibited and over-controlled. This study investigated a prefrontal-cingulate network that is involved in inhibitory control. METHOD: To avoid the confounds of malnutrition, 12 recovered (RAN) subjects were compared to 12 matched control women (CW) using a validated inhibition task (i.e., a stop signal task) during functional magnetic resonance imaging. RESULTS: Consistent with the a priori hypothesis, RAN subjects showed altered task-related activation in the medial prefrontal cortex (mPFC), a critical node of the inhibitory control network. Specifically, whereas RAN and CW showed similar mPFC activity during trials when inhibitory demand was low (i.e., easy trials), RAN relative to CW showed significantly less mPFC activation as inhibition trials became more difficult (i.e., hard trials), suggesting a demand-specific modulation of inhibitory control circuitry in RAN. DISCUSSION: These findings support a neural basis for altered impulse control symptoms in AN.

Alcohol attenuates activation in the bilateral anterior insula during an emotional processing task: a pilot study.

AIMS: Alcohol acutely reduces agitation and is widely used in social situations, but the neural substrates of emotion processing during its intoxication are not well understood. We examine whether alcohol's social stress dampening effect may be via reduced activity in the cortical systems that subserve awareness of bodily sensations, and are associated with affective distress. METHODS: Blood oxygen level-dependent activation was measured through 24 functional magnetic resonance imaging sessions in 12 healthy volunteers during an emotional face-processing task following ingestion of a moderate dose of alcohol and a placebo beverage. RESULTS: Results revealed that bilateral anterior insula response to emotional faces was significantly attenuated following consumption of alcohol, when compared with placebo (clusters >1472 µl; corrected P < 0.05). CONCLUSION: Attenuated response in the anterior insula after alcohol intake may explain some of the decreased interoceptive awareness described during intoxication.

Right anterior insula hypoactivity during anticipation of homeostatic shifts in major depressive disorder.

OBJECTIVE: To use functional magnetic resonance imaging (fMRI) to examine how shifts in homeostatic state affect anticipatory insular activity in major depressive disorder (MDD). An intact ability to mount preparatory emotional, cognitive, and bodily responses to anticipated environmental change is necessary for adaptive responding. Although abnormal insula activity during aversive anticipation has been observed in individuals with MDD, the extent to which shifts in homeostatic state during anticipation affect insular activity in MDD subjects has not been reported. METHODS: Cued hot and warm stimuli were delivered as subjects either passively viewed a fixation cross or performed an attentional task during fMRI. The task was designed so that anticipatory brain activation related to the following three types of shifts could be measured: 1) anticipatory shifts in stimulus intensity; 2) anticipatory shifts in cognitive demand; and 3) dual anticipatory shifts (i.e., shifts in both stimulus intensity and cognitive demand). Brain activation related to each of these three contrasts was compared between 15 (12 females) unmedicated subjects with current MDD and 17 (10 females) age- and education-comparable healthy control (HC) subjects. RESULTS: MDD vs. HC subjects showed lower right anterior insula activity related to anticipatory shifts in stimulus intensity, and altered brain activation during anticipatory shifts in cognitive demand and dual anticipatory shifts. CONCLUSIONS: These results indicate that MDD individuals show altered brain responses to shifts in homeostatic state during anticipation, and may suggest that MDD is associated with an impaired ability to effectively prepare for changes in the environment.

Acute ethanol effects on brain activation in low- and high-level responders to alcohol.

BACKGROUND: A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk of alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol. This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption. METHODS: A total of 30 matched high- and low-LR pairs (N = 60 healthy young adults) were recruited from the University of California, San Diego, and administered a structured diagnostic interview and laboratory alcohol challenge followed by two functional magnetic resonance imaging (fMRI) sessions under placebo and alcohol conditions, in randomized order. Task performance and blood oxygen level-dependent response contrast to high relative to low working memory load in an event-related visual working memory (VWM) task were examined across 120 fMRI sessions. RESULTS: Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p < 0.05). The LR group by condition effect remained even after controlling for cerebral blood flow, age, and typical drinking quantity. CONCLUSIONS: Alcohol had differential effects on brain activation for low- and high-LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR and identify brain regions that may be associated with the low LR response.

Escitalopram attenuates posterior cingulate activity during self-evaluation in healthy volunteers.

Medial cortex is critically involved in self-referential processing. Little is known about how selective serotonin reuptake inhibitors (SSRIs) affect medial cortical activity during self-assessment. We hypothesized that a 3-week oral course of escitalopram,10 mg/day, would alter activity related to self-referential processing in medial cortex. Fifteen healthy females performed a self-assessment task during functional magnetic resonance imaging on two occasions--once after 3 weeks of placebo and once at the end of 3 weeks of escitalopram. Task conditions involved responding "yes" or "no" to whether various positive and negative adjectives described the subject (i.e., "self" evaluation trials) or the subject's best friend (i.e., "other" evaluation trials), whereas the comparison condition involved responding whether the valence of various adjectives was positive or negative (i.e., "word" evaluation trials). Behaviorally after escitalopram, subjects less frequently endorsed that negative adjectives described themselves. Three main neuroimaging results were observed: (1) increased activation in medial prefrontal cortex and posterior cingulate related to self minus word evaluation trials, (2) increased activation in posterior cingulate related to escitalopram minus placebo for self and word evaluation trials, and (3) drug by task interactions in the insula, cerebellum and prefrontal cortex. These results show that SSRIs change medial cortical activity and may alter self-evaluation.

Yeast-encapsulated essential oils: a new perspective as an environmentally friendly larvicide.

BACKGROUND: Effective mosquito control approaches incorporate both adult and larval stages. For the latter, physical, biological, and chemical control have been used with varying results. Successful control of larvae has been demonstrated using larvicides including insect growth regulators, e.g. the organophosphate temephos, as well as various entomopathogenic microbial species. However, a variety of health and environmental issues are associated with some of these. Laboratory trials of essential oils (EO) have established the larvicidal activity of these substances, but there are currently no commercially available EO-based larvicides. Here we report on the development of a new approach to mosquito larval control using a novel, yeast-based delivery system for EO. METHODS: Food-grade orange oil (OO) was encapsulated into yeast cells following an established protocol. To prevent environmental contamination, a proprietary washing strategy was developed to remove excess EO that is adsorbed to the cell exterior during the encapsulation process. The OO-loaded yeast particles were then characterized for OO loading, and tested for efficacy against Aedes aegypti larvae. RESULTS: The composition of encapsulated OO extracted from the yeast microparticles was demonstrated not to differ from that of un-encapsulated EO when analyzed by high performance liquid chromatography. After lyophilization, the oil in the larvicide comprised 26-30 percentage weight (wt%), and is consistent with the 60-65% reduction in weight observed after the drying process. Quantitative bioassays carried with Liverpool and Rockefeller Ae. aegypti strains in three different laboratories presented LD50 of 5.1 (95% CI: 4.6-5.6) to 27.6 (95% CI: 26.4-28.8) mg/l, for L1 and L3/L4 mosquito larvae, respectively. LD90 ranged between 18.9 (95% CI: 16.4-21.7) mg/l (L1 larvae) to 76.7 (95% CI: 69.7-84.3) mg/l (L3/L4 larvae). CONCLUSIONS: The larvicide based on OO encapsulated in yeast was shown to be highly active (LD50 < 50 mg/l) against all larval stages of Ae. aegypti. These results demonstrate its potential for incorporation in an integrated approach to larval source management of Ae. aegypti. This novel approach can enable development of affordable control strategies that may have significant impact on global health.

Initial evidence of a failure to activate right anterior insula during affective set shifting in posttraumatic stress disorder.

OBJECTIVE: Interoception is the sense of one's internal physiological, sensory, and emotional status. Extensive evidence supports a link between interoception and subjective experience. An altered ability to monitor or modulate interoception as it relates to subjective experience may provide a mechanistic explanation for the development of some forms of psychiatric illness. METHODS: We investigated which neural networks are activated when anticipating a change in affective (and thus interoceptive) state, which we term "affective set-shifting," in 15 women with posttraumatic stress disorder (PTSD) related to intimate partner violence, and in 15 nontraumatized healthy volunteers. RESULTS: Although both groups activated the dorsolateral prefrontal cortex during affective set shifting, the PTSD group showed significantly less activation in the right anterior insula than did the controls. CONCLUSIONS: These findings may suggest that although individuals with PTSD are cognitively aware of the impending shift in interoceptive state, they fail to appropriately activate neural circuitry involved in modulating interoceptive responses.

Inhibition-related activity in subgenual cingulate is associated with symptom severity in major depression.

Individuals with major depressive disorder (MDD) show impaired inhibitory control over negative thoughts. However, the brain mechanism underlying impaired inhibitory control in MDD has been incompletely described. The objective of this study was to examine brain function during inhibitory and error processing in a unique population of young, healthy, unmedicated MDD individuals. We hypothesized that MDD subjects would show clinically relevant alterations in brain activation in medial prefrontal and anterior cingulate cortex (ACC) during both inhibitory and error processing. Subjects performed an individualized parametric stop-signal task during functional magnetic resonance imaging (fMRI). MDD subjects (n=15) met DSM-IV criteria for current MDD. Healthy control (HC) subjects (n=16) had no lifetime history of MDD or other psychiatric disorder. The groups were not significantly different in several socio-demographic variables or in behavioral performance. A group by trial difficulty interaction on error-related activation in bilateral inferior frontal gyrus and left supragenual ACC was observed, suggesting a demand-specific failure of this circuitry in MDD. Additionally, a group by trial difficulty interaction on inhibition-related activation in subgenual ACC was observed. Among MDD individuals, inhibition-related subgenual activation correlated with depressive symptom severity, implicating subgenual ACC in inhibitory control processes related to clinical depression.