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ABSTRACT: Few standardized tools are available for time-efficient screening of emotional health status across diagnostic categories, especially in primary care. We evaluated the 45-question Brief Risk-resilience Index for SCreening (BRISC) and the 15-question mini-BRISC in identifying poor emotional health and coping capacity across a range of diagnostic groups - compared with a detailed clinical assessment - in a large sample of adult outpatients. Participants 18-60 years of age (n = 1079) recruited from 12 medical research and clinical sites completed the computerized assessments. Three index scores were derived from the full BRISC and the mini-BRISC: one for risk (negativity-positivity bias) and two for coping (resilience and social capacity). Summed answers were converted to standardized z-scores. BRISC scores were compared with detailed health assessment and diagnostic interview (for current psychiatric, psychological, and neurological conditions) by clinicians at each site according to diagnostic criteria. Clinicians were blinded to BRISC scores. Clinical assessment stratified participants as having "clinical" (n = 435) or "healthy" (n = 644) diagnostic status. Receiver operating characteristic analyses showed that a z-score threshold of -1.57 on the full BRISC index of emotional health provided an optimal classification of "clinical" versus "healthy" status (sensitivity: 81.2%, specificity: 92.7%, positive predictive power: 80.2%, and negative predictive power: 93.1%). Comparable findings were revealed for the mini-BRISC. Negativity-positivity bias index scores contributed the most to prediction. The negativity-positivity index of emotional health was most sensitive to classifying major depressive disorder (100%), posttraumatic stress disorder (95.8%), and panic disorder (88.7%). The BRISC and mini-BRISC both offer a brief, clinically useful screen to identify individuals at risk of disorders characterized by poor emotion regulation, from those with good emotional health and coping.
Brain and behavior. 09/2012; 2(5):576-89.
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ABSTRACT: This study tested the extent to which coached participants can simulate the neural responses of participants with posttraumatic
stress disorder (PTSD) when they are presented with signals of fear. Functional magnetic resonance imaging (fMRI) was used
to study blood oxygenation level-dependent signal during the presentations of fearful and neutral faces under both conscious
and nonconscious (masked) conditions. Participants comprised 12 patients with PTSD and 12 trauma-exposed controls who were
instructed to simulate PTSD. During conscious fear processing, simulators showed greater activation in the left amygdala and
medial prefrontal cortex (MPFC) than PTSD participants. By contrast, during nonconscious processing, PTSD participants had
greater MPFC activation than simulators. These findings suggest that coached simulators produce a profile of ‘over-responding’
to fear when controlled conscious processing is possible, but are not able to simulate the exaggerated medial prefrontal responses
observed in PTSD participants under conditions of nonconscious processing.
KeywordsFear-Neural networks-Posttraumatic stress disorder-Simulation
Psychological Injury and Law 04/2012; 3(2):111-117.
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ABSTRACT: This study investigated attention (P300 amplitude) and orienting (skin conductance amplitude) to auditory tones in a standard oddball task in early trauma-exposed groups (Acute Stress Disorder: ASD) (n=12) or no ASD (n=13), compared to individuals with chronic posttraumatic stress disorder (PTSD) (n=17) and non-trauma-exposed controls (n=17). Individuals with ASD displayed significantly higher SCR and P3 amplitudes to target tones than individuals with PTSD, non-traumatized controls, and traumatized controls. These findings suggest that attention and orienting responses are greater to neutral, task-relevant target tones in ASD than PTSD and traumatized and non-traumatized controls.
Biological psychology 03/2012; 90(3):224-7. · 4.36 Impact Factor
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ABSTRACT: White matter (WM) has been shown to be affected in elderly patients with major depressive disorders (MDD). There is only limited evidence of WM structural abnormalities in nongeriatric MDD patients. This study investigates WM microstructural integrity in nongeriatric MDD patients recruited as part of the International Study to Predict Optimized Treatment in Depression clinical trial and establishes the validity of diffusion tensor imaging measures for the investigation of depression. Baseline diffusion tensor imaging data from 29 nongeriatric MDD participants (11 with melancholia) and 39 healthy control participants were used in this analysis. We performed tract-based spatial statistics analyses to evaluate WM microstructural integrity (1) between all healthy controls and all MDD participants, (2) between melancholic and nonmelancholic MDD participants, and (3) between each subgroup (melancholic and nonmelancholic) and controls. Significant WM integrity deficits were seen only for the melancholic MDD participants compared with controls. Compared with controls, melancholic participants showed an average reduction of 7.8% in fractional anisotropy over WM regions associated with the limbic system, dorsolateral prefrontal cortex, thalamic projection fibers, corpus callosum, and other association fibers. These fractional anisotropy deficits were also associated with decreased axial and increased radial diffusivity in these WM regions, suggesting a pattern of decreased myelination or other degeneration change. Our findings of WM structural abnormalities associated with the limbic system, the frontal cortex, and the thalamus support the prevailing theory of limbic-dorsolateral prefrontal cortex-thalamic dysfunction in depression. Our results also suggest that these deficits are most prominent in the melancholic subtype of MDD.
Human Brain Mapping 12/2011; 32(12):2161-71. · 5.88 Impact Factor
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ABSTRACT: To examine resting awake EEG in adolescent AN participants before and after refeeding to determine if EEG abnormalities in Anorexia Nervosa (AN) are reversible.
In 37 adolescent first admission AN patients and 45 healthy controls, EEG was recorded during short duration "eyes open" and "eyes closed" awake resting conditions. Repeat testing occurred in 28 AN participants after refeeding and subsequent weight gain.
In "eyes open," underweight AN participants exhibit reduced relative alpha power and increased beta power in frontal brain regions. A significant increase in alpha, and decrease in beta and delta power was observed within participants after refeeding. In "eyes closed", underweight AN participants had elevated theta in parietal-occipital regions which remained after refeeding.
EEG abnormalities (reduced alpha/increased beta power) in AN normalizes with refeeding, while increased theta power persists in parietal-occipital regions in an eyes closed context.
International Journal of Eating Disorders 01/2011; 44(1):65-75. · 2.95 Impact Factor
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ABSTRACT: Clinically useful treatment moderators of Major Depressive Disorder (MDD) have not yet been identified, though some baseline predictors of treatment outcome have been proposed. The aim of iSPOT-D is to identify pretreatment measures that predict or moderate MDD treatment response or remission to escitalopram, sertraline or venlafaxine; and develop a model that incorporates multiple predictors and moderators.
The International Study to Predict Optimized Treatment - in Depression (iSPOT-D) is a multi-centre, international, randomized, prospective, open-label trial. It is enrolling 2016 MDD outpatients (ages 18-65) from primary or specialty care practices (672 per treatment arm; 672 age-, sex- and education-matched healthy controls). Study-eligible patients are antidepressant medication (ADM) naïve or willing to undergo a one-week wash-out of any non-protocol ADM, and cannot have had an inadequate response to protocol ADM. Baseline assessments include symptoms; distress; daily function; cognitive performance; electroencephalogram and event-related potentials; heart rate and genetic measures. A subset of these baseline assessments are repeated after eight weeks of treatment. Outcomes include the 17-item Hamilton Rating Scale for Depression (primary) and self-reported depressive symptoms, social functioning, quality of life, emotional regulation, and side-effect burden (secondary). Participants may then enter a naturalistic telephone follow-up at weeks 12, 16, 24 and 52. The first half of the sample will be used to identify potential predictors and moderators, and the second half to replicate and confirm.
First enrolment was in December 2008, and is ongoing. iSPOT-D evaluates clinical and biological predictors of treatment response in the largest known sample of MDD collected worldwide.
International Study to Predict Optimised Treatment - in Depression (iSPOT-D) ClinicalTrials.gov Identifier: NCT00693849. URL: http://clinicaltrials.gov/ct2/show/NCT00693849?term=International+Study+to+Predict+Optimized+Treatment+for+Depression&rank=1
Trials 01/2011; 12:4. · 2.02 Impact Factor
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ABSTRACT: Abstract Background Clinically useful treatment moderators of Major Depressive Disorder (MDD) have not yet been identified, though some baseline predictors of treatment outcome have been proposed. The aim of iSPOT-D is to identify pretreatment measures that predict or moderate MDD treatment response or remission to escitalopram, sertraline or venlafaxine; and develop a model that incorporates multiple predictors and moderators. Methods/Design The International Study to Predict Optimized Treatment - in Depression (iSPOT-D) is a multi-centre, international, randomized, prospective, open-label trial. It is enrolling 2016 MDD outpatients (ages 18-65) from primary or specialty care practices (672 per treatment arm; 672 age-, sex- and education-matched healthy controls). Study-eligible patients are antidepressant medication (ADM) naïve or willing to undergo a one-week wash-out of any non-protocol ADM, and cannot have had an inadequate response to protocol ADM. Baseline assessments include symptoms; distress; daily function; cognitive performance; electroencephalogram and event-related potentials; heart rate and genetic measures. A subset of these baseline assessments are repeated after eight weeks of treatment. Outcomes include the 17-item Hamilton Rating Scale for Depression (primary) and self-reported depressive symptoms, social functioning, quality of life, emotional regulation, and side-effect burden (secondary). Participants may then enter a naturalistic telephone follow-up at weeks 12, 16, 24 and 52. The first half of the sample will be used to identify potential predictors and moderators, and the second half to replicate and confirm. Discussion First enrolment was in December 2008, and is ongoing. iSPOT-D evaluates clinical and biological predictors of treatment response in the largest known sample of MDD collected worldwide. Trial registration International Study to Predict Optimised Treatment - in Depression (iSPOT-D) ClinicalTrials.gov Identifier: NCT00693849 URL: http://clinicaltrials.gov/ct2/show/NCT00693849?term=International+Study+to+Predict+Optimized+Treatment+for+Depression&rank=1
Trials. 01/2011;
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ABSTRACT: Depression will be the second largest burden of disease by 2020. Developing new tools for identifying risk and ultimately prevention of depression relies on elucidating the integrative relationships between susceptibility markers from gene-stress interactions and how they impact emotional brain and arousal systems. They have largely been studied in isolation.
We examined how genetic (brain-derived neurotrophic factor [BDNF] valine 66 to methionine [Val66Met] and serotonin receptor gene 3A [HTR3A]) and early life stress susceptibility factors interact in predicting electroencephalogram (EEG) asymmetry, emotion-elicited heart rate, and self-reported negativity bias, each correlates of risk for depression. Caucasian volunteers (n = 363) were derived from the Brain Resource International Database, via the Brain Research And Integrative Neuroscience Network.
Individuals with both BDNF methionine and HTR3A CC risk genotypes and early life stressors demonstrated a profile of elevated emotion-elicited heart rate and right frontal hyper-activation with right parietotemporal hypoactivation in EEG asymmetry. Elevations in heart rate were a moderator of negativity bias.
The findings provide new evidence that these gene-stress susceptibility factors contribute to a brain-arousal profile indicative of risk for depression. They are a step toward identifying biological markers for detecting risk before overt symptoms. It would be valuable for future studies to examine comorbidity and specificity issues; for instance, whether these gene-stress factors contribute in different ways to the partially distinct EEG asymmetry profiles found with anxiety.
Biological psychiatry 11/2010; 68(9):818-24. · 8.93 Impact Factor
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ABSTRACT: Models of laterality infer distinct aspects of EEG alpha asymmetry in clinical disorders, which has been replicated for over three decades. This biomarker now requires a more fine-grained assessment of its clinical utility as a diagnostic and treatment predictive marker. Here, within the same study we assessed resting brain laterality across six clinical disorders, for which deviant laterality has been implicated as core dysfunction. These disorders were evaluated in comparison to a large normative dataset (approximately 1,900) from the Brain Resource International Database. EEG alpha asymmetry was assessed in the frontocentral region, for resting Eyes Closed and Eyes Open conditions. Schizophrenia was characterized by significantly greater left lateralized alpha power than controls, indicating a deficit in left frontal activity at rest, which may relate to "disconnections" across wider fronto-temporal networks. The depression group showed a trend-level tendency towards the opposite pattern of greater right-lateralized activity than controls. The remaining anxiety and behavioral disorders did not show any significant deviance in alpha asymmetry from the normative control group. However, at a non-significant level laterality for these groups was generally consistent with expected directions, suggesting a propensity towards a particular lateralization but still remaining within the normative range. Overall, the results of the current study indicate that EEG alpha asymmetry may show the most clinical utility as a biomarker for schizophrenia and depression in comparison to other clinical disorders.
Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS) 10/2010; 41(4):178-83. · 1.73 Impact Factor
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ABSTRACT: The risk for mental illnesses such as depression is increasingly conceptualized as the product of gene-environment interactions and their impact on brain structure and function. The role of serotonin 3A receptor gene (HTR3A -42C>T polymorphism) and its interaction with early life stress (ELS) was investigated in view of the receptor's localization to brain regions central to emotion processing.
Fronto-limbic grey matter (GM) loss was measured using magnetic resonance imaging and assessed using voxel-based morphometry analysis in 397 nonclinical individuals from the Brain Resource International Database. Negative mood symptoms were also assessed.
The HTR3A CC genotype group, compared to the T carriers, demonstrated comparative loss to GM in hippocampal structures, which extended to the frontal cortices for those CC genotype individuals also exposed to ELS. Elevations in depressed mood were also evident.
These findings suggest that the HTR3A CC genotype may be associated with alterations in brain structures central to emotion processing, particularly when exposed to stress, and further highlight the potential role of the serotonin system in the pathophysiology of affective disorders. In contrast, those individuals with the T allele, in particular the TT genotype, may be more protected from such alterations combined with minimal exposure to ELS events.
Depression and Anxiety 08/2010; 27(8):752-9. · 4.18 Impact Factor
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ABSTRACT: Identification of the biological markers of anorexia nervosa (AN) is crucial for the development of new treatments. We aimed to determine whether AN is associated with disturbances in the nonconscious neural processing of innate signals of emotion and whether these disturbances persist after weight gain.
In a retest design, 28 adolescent females with AN were tested at first ad not mission to hospital and again after they had gained weight. Matched healthy control participants were tested at the same times. We assessed emotion-elicited event-related potentials (ERPs) during overt and covert presentation of emotion expressions, scores on an emotion-identification behavioural task, and symptom measures. We performed between and within group analyses.
Individuals with AN had a marked alteration in ERPs relative to healthy controls. Irrespective of the form of stimulus, early and late ERP componotnents were significantly reduced in AN patients at baseline (when underweight) and on retest (after weight gain), especially in the temporo-occipital regions, suggesting a persistent disruption of the early automatic appraisal of salient emotional signals.
This study could have been improved with a longer standardized retest interval.
There is likely a core, generic disturbance in AN in the early "automatic" neural processing of emotion irrespective of weight or nutritional status. New innovative emotion-based psychologic or pharmacologic treatments targeting these nonconscious processes may prove beneficial.
Journal of psychiatry & neuroscience: JPN 07/2010; 35(4):267-74. · 5.34 Impact Factor
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ABSTRACT: Novelty and routinization-related information processing disturbances were examined in adolescent males with ADHD using an oddball paradigm and electrophysiological measurement of theta (4-7Hz) activity.
Fifty-four unmedicated adolescent males (12-18years) with Attention Deficit Hyperactivity Disorder (ADHD) and matched controls performed an auditory oddball task. Theta activity was sub-averaged, and Fourier Integrals with simultaneous measurement of electrodermal activity (EDA) was used to index response to stimulus novelty and routinization.
ADHD participants showed an overall increase in theta activity to both novel and routine stimuli relative to controls. While controls showed increased theta activity in response to novel compared to routine targets across the brain, ADHD participants did not show this novelty-related increase in theta activity in the right anterior/frontal brain.
The findings of this study are consistent with disturbances in theta activity and the brain substrates of novelty relative to routinization-related processing in ADHD.
These findings show that there are distinct alterations in theta activity related to stimulus novelty and routinization during an auditory oddball task in ADHD, and they highlight the value of using an event-related approach to elucidate the neural substrates of stimulus processing in ADHD.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 04/2010; 121(8):1336-42. · 3.12 Impact Factor
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ABSTRACT: Measures of cognition support diagnostic and treatment decisions in attention deficit hyperactivity disorder. We used an integrative neuroscience framework to assess cognition and associated brain-function correlates in large attention deficit hyperactivity disorder and healthy groups. Matched groups of 175 attention deficit hyperactivity disorder children/adolescents and 175 healthy control subjects were assessed clinically, with the touch screen-based cognitive assessment battery "IntegNeuro" (Brain Resource Ltd., Sydney, Australia) and the "LabNeuro" (Brain Resource Ltd., Sydney, Australia) platform for psychophysiologic recordings of brain function and body arousal. IntegNeuro continuous performance task measures of sustained attention classified 68% of attention deficit hyperactivity disorder patients with 76% specificity, consistent with previous reports. Our additional cognitive measures of impulsivity, intrusive errors, inhibition, and response variability improved sensitivity to 88%, and specificity to 91%. Positive predictive power was 96%, and negative predictive power, 88%. These metrics were stable across attention deficit hyperactivity disorder subtypes and age. Consistent with their brain-based validity, cognitive measures were correlated with corresponding brain-function and body-arousal measures. We propose a combination of candidate cognitive "markers" that define a signature for attention deficit hyperactivity disorder: "sustained attention," "impulsivity," "inhibition," "intrusions," and "response variability." These markers offer a frame of reference to support diagnostic and treatment decisions, and an objective benchmark for monitoring outcomes of interventions.
Pediatric Neurology 02/2010; 42(2):118-26. · 1.52 Impact Factor
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ABSTRACT: Biases toward processing negative versus positive information vary as a function of level of awareness, and are modulated by monoamines. Excessive biases are associated with individual differences in mood and emotional stability, and emotional disorder. Here, we examined the impact of the catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism, involved in dopamine and norepinephrine catabolism, on both emotional brain function and self-reported negativity bias. COMT genotyping and self-reported level of negativity bias were completed for 46 healthy participants taking part in the Brain Resource International Database. Functional MRI was undertaken during perception of facial expressions of fear and happiness presented under unmasked (consciously identified) and masked (to prevent conscious detection) conditions. Structural MR images were also acquired. A greater number of COMT Met alleles predicted increased activation in brainstem, amygdala, basal ganglia and medial prefrontal regions for conscious fear, but decreased activation for conscious happiness. This pattern was also apparent for brainstem activation for the masked condition. Effects were most apparent for females. These differences could not be explained by gray matter variations. The Met-related profile of activation, particularly prefrontally, predicted greater negativity bias associated with risk for emotional disorder. The findings suggest that the COMT Met allele modulates neural substrates of negative versus positive emotion processing. This effect may contribute to negativity biases, which confer susceptibility for emotional disorders.
NeuroImage 02/2010; 53(3):918-25. · 5.89 Impact Factor
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ABSTRACT: There is overlap between the behavioural symptoms and disturbances associated with Attention-Deficit/Hyperactivity Disorder (AD/HD) and sleep problems. The aim of this study was to examine the extent of overlap in cognitive and electrophysiological disturbances identified in children experiencing sleep problems and children with AD/HD or both. Four groups (aged 7-18) were compared: children with combined AD/HD and sleep problems (n=32), children with AD/HD (n=52) or sleep problems (n=36) only, and children with neither disorder (n=119). Electrophysiological and cognitive function measures included: absolute EEG power during eyes open and eyes closed, event-related potential (ERP) components indexing attention and working memory processes (P3), and a number of standard neuropsychological tests. Children with symptoms of both AD/HD and sleep problems had a different profile from those of children with either AD/HD or sleep problems only. These findings suggest it is unlikely that disturbances in brain and cognitive functioning associated with sleep problems also give rise to AD/HD symptomatology and consequent diagnosis. Furthermore, findings suggest that children with symptoms of both AD/HD and sleep problems may have a different underlying aetiology than children with AD/HD-only or sleep problems-only, perhaps requiring unique treatment interventions.
Psychiatry Research 10/2009; 170(2-3):183-91. · 2.52 Impact Factor
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ABSTRACT: Schizophrenia may be understood as a disorder of neural synchrony. There is also increasing evidence that emotional and social cognitive impairments are central to this disorder. In patients with first-episode schizophrenia, we examined whether emotion perception is associated with disruptions to high-frequency (40 Hz) gamma synchrony and whether these disruptions predict self-regulatory adaptive compensations reflected in social cognitive behaviours.
We obtained electroencephalography recordings from 28 patients with first-episode schizophrenia and matched healthy controls during perception of facial emotion under both conscious and nonconscious conditions. We extracted gamma-band synchrony from the electroencephalogram. We also used behavioural measures of emotion identification, emotional intelligence, negativity bias and social function, along with ratings of first-episode schizophrenia symptoms. We analyzed group differences and predicted social cognition to assess the potential contribution of medication.
Within 200 ms poststimulus, patients with first-episode schizophrenia showed alterations in gamma synchrony during both conscious and nonconscious emotion perception. Stimulus-locked synchrony was reduced in patients, particularly over the temporal cortex, whereas complementary enhancements in absolute gamma synchrony (independent of stimuli) were more distributed over temporal and left parieto-occipital regions. This pattern of altered synchrony predicted poor performance on each measure of social cognition among these patients. Medication dosage did not correlate significantly with either gamma synchrony or behavioural measures in this group.
Limitations to our study include the lack of comparison between medicated and unmedicated patients or between types of medication.
These findings suggest that disruptions in integrative processing of motivationally important stimuli show promise as a potential biological marker of social cognitive impairments, present from the first episode of schizophrenia, and their outcomes.
Journal of psychiatry & neuroscience: JPN 08/2009; 34(4):303-13. · 5.34 Impact Factor
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ABSTRACT: This study explores the possibility that the more favourable clinical prognosis in females with schizophrenia may be associated with their greater network interconnectedness, which is possibly reflected in enhanced “Gamma” (40 Hz) electrical brain activity. An auditory “oddball” task was administered to 35 patients with schizophrenia and 35 age and sex matched controls (25 males and 10 females). Peak Gamma amplitude (from a time series of Gamma activity averaged for 40 target stimuli, as well as the immediately preceding 40 background tones) was examined across 19 sites. Peak Gamma activity occurred 250 to 450 ms in targets and 350 to 550 ms in backgrounds. Multiple within and between group MANOVAs were undertaken analysing both Peak Gamma amplitude (microvolts) and latency (milliseconds). Within-group, the control males showed a pattern of earlier Gamma latency in the right compared with the left hemisphere (F(1, 33) = 3.70, p <. 06), while control females exhibited delayed latency frontally compared with the posterior region (F(1, 33) = 6.25, p <. 04). This male lateralization finding and the anterior/posterior gradient in females is consistent with Goldberg's model. The patient group however, failed to show this male lateralized and female frontal-posterior pattern of Gamma activity, suggesting suboptimal network integration in the patient group, in both males and females.
07/2009; 107(1-2):131-144.
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ABSTRACT: A 43 year old man with a traumatic amnesic syndrome experienced only a brief, if any, loss of consciousness following an injury to the head. Four years after this injury, his results on standard psychometric assessment were normal. Long-latency evoked response potentials results were normal, and the neurological examination and computed tomography scans were unhelpful in explaining his amnesic symptoms. He had no history of alcohol abuse, yet his neuropsychological profile was that of a Korsakoff-like amnesia with frontal lobe features. Magnetic-resonance images demonstrated evidence of extensive frontal lobe damage, while cerebral blood flow studies provided additional evidence of bilateral frontal lobe dysfunction. The case highlights the need for those giving opinions in medico-legal head trauma cases to go beyond a reliance on routine indicators, such as duration of coma, results of standard psychometric assessment and computed tomography scans, to more specialised neuropsychological evaluations and magnetic-resonance imaging scans.
07/2009; 24(1):133-138.
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ABSTRACT: Reduced ventral anterior cingulate (vACC) activity to threat is thought to reflect an impairment in regulating arousal networks in posttraumatic stress disorder (PTSD). Concurrent functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) recording were used to examine neural functioning when arousal networks are engaged. Eleven participants with PTSD and 11 age- and sex-matched non-traumatized controls performed an oddball task that required responding to salient, non-trauma-related auditory target tones embedded in lower frequency background tones. Averaged target-background analyses revealed significantly greater dorsal ACC, supramarginal gyrus, and hippocampal activity in PTSD relative to control participants.With-SCR target responses resulted in increased vACC activity in controls, and dorsal ACC activity in PTSD. PTSD participants had reduced vACC activity relative to controls to target tones when SCR responses were present. This reduction in vACC in PTSD relative to controls was not apparent in without-SCR responses. These findings suggest that a reduction in vACC in PTSD occurs specifically when arousal networks are engaged.
Psychiatry Research 06/2009; 173(1):59-62. · 2.52 Impact Factor
