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Moores KA, Clark CR, McFarlane AC, Brown GC, Puce A, Taylor DJ. Abnormal recruitment of working memory updating networks during maintenance of trauma-neutral information in post-traumatic stress disorder. Psychiatry Res 163: 156-170

Cognitive Neuroscience Laboratory, School of Psychology, Flinders University, Adelaide, SA, Australia.
Psychiatry Research (Impact Factor: 2.47). 08/2008; 163(2):156-70. DOI: 10.1016/j.pscychresns.2007.08.011
Source: PubMed

ABSTRACT

Post-traumatic stress disorder (PTSD) is characterised by disturbances in concentration and memory, symptoms which are a source of further distress for patients. Related to this, abnormalities in underlying working memory (WM) systems have been identified [Clark, C.R., McFarlane, A.C., Morris, P., Weber, D.L., Sonkkilla, C., Shaw, M.E., Marcina, J., Tochon-Danguy, H.J., Egan, G.F., 2003. Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Biological Psychiatry 53, 474-481.], indicating dysfunction in left hemisphere brain regions. In this study, we performed functional magnetic resonance imaging (fMRI) in 13 patients with severe PTSD and matched non-traumatized Controls, during performance of visuo-verbal tasks that involved either maintenance or continual updating of word stimuli in WM. The PTSD group failed to show differential activation during WM updating, and instead appeared to show abnormal recruitment of WM updating network regions during WM maintenance. These regions included the bilateral dorsolateral prefrontal cortex (DLPFC) and the inferior parietal lobe (IPL). Several other regions were significantly more activated in Controls than in PTSD during WM updating, including the hippocampus, the anterior cingulate (AC), and the brainstem pons, key regions that are consistently implicated in the neurobiology of PTSD. These findings suggest compensatory recruitment of networks in PTSD normally only deployed during updating of WM and may reflect PTSD patients' difficulty engaging with their day-to-day environment.

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    • "Since ELS is also strongly associated with the development of these illnesses, results from this study suggest that at least a component of the previous findings in the WM literature may be due to the common denominator of ELS exposure. This theory is supported by results from this study, which found WM-related activations in the ELS group overlapping with some regions reported in previous WM imaging studies of various psychiatric disorders (e.g., the IPL, found in Moores et al. 2008 and Daniels et al. 2010), but not overlapping in lateral and medial prefrontal regions found in these studies. "
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    ABSTRACT: Previous research suggests that a history of early life stress (ELS) impacts working memory (WM) in adulthood. Despite the widespread use of WM paradigms, few studies have evaluated whether ELS exposure, in the absence of psychiatric illness, also impacts WM-associated brain activity in ways that might improve sensitivity to these ELS effects or provide insights into the mechanisms of these effects. This study evaluated whether ELS affects WM behavioral performance and task-associated activity by acquiring 3T functional images from 27 medication-free healthy adults (14 with ELS) during an N-back WM task that included 0- and 2-back components. Whole brain voxel-wise analysis was performed to evaluate WM activation, followed by region of interest analyses to evaluate relationships between activation and clinical variables. ELS was associated with poorer accuracy during the 2-back (79 % ± 19 vs. 92 % ± 9, p = 0.049); accuracy and response time otherwise did not differ between groups. During the 0-back, ELS participants demonstrated increased activation in the superior temporal gyrus/insula, left inferior parietal lobule (IPL) (both corrected p < 0.001), and middle temporal and parahippocampal gyrus (MTG/PHG)(corrected p < 0.010). During the 2-back, ELS was associated with greater activation in the IPL, MTG/PHG and inferior frontal gyrus (corrected p < 0.001), with a trend towards precuneus activation (p = 0.080). These findings support previous research showing that ELS is associated with impaired neurobehavioral performance and changes in brain activation, suggesting recruitment of additional cognitive resources during WM in ELS. Based on these findings, ELS screening in future WM imaging studies appears warranted.
    Full-text · Article · Mar 2015 · Brain Imaging and Behavior
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    • "PTSD-related dlPFC anomalies observed here may indicate broader cognitive deficits in PTSD. For example, in prior work that used a verbal workingmemory task, individuals with PTSD were found to exhibit less activation of the left dlPFC, even though stimuli were nonthreatening[66](also see[67]). Nevertheless , dlPFC deficits – which may indicate reduced neural support for the verbal manipulation and organization of information – could underlie affective symptomatology in PTSD.[5,68]For instance, reduced verbal representation of working-memory content might play a role in the intrusive nature of traumatic memories in PTSD.[5]However, because PTSD-related neural abnormalities observed here did not co-occur with reduced subjective success at the reappraisal task (i.e., affect ratings ) in the Reappraisal condition, our results come with some caveats. "
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    ABSTRACT: Collectively, functional neuroimaging studies implicate frontal-limbic dysfunction in the pathophysiology of posttraumatic stress disorder (PTSD), as reflected by altered amygdala reactivity and deficient prefrontal responses. These neural patterns are often elicited by social signals of threat (fearful/angry faces) and traumatic reminders (combat sounds, script-driven imagery). Although PTSD can be conceptualized as a disorder of emotion dysregulation, few studies to date have directly investigated the neural correlates of volitional attempts at regulating negative affect in PTSD. Using functional magnetic resonance imaging and a well-validated task involving cognitive regulation of negative affect via reappraisal and known to engage prefrontal cortical regions, the authors compared brain activation in veterans with PTSD (n = 21) and without PTSD (n = 21, combat-exposed controls/CEC), following military combat trauma experience during deployments in Afghanistan or Iraq. The primary outcome measure was brain activation during cognitive reappraisal (i.e., decrease negative affect) as compared to passive viewing (i.e., maintain negative affect) of emotionally evocative content of aversive images RESULTS: The subjects in both groups reported similar successful reduction in negative affect following reappraisal. The PTSD group engaged the dorsolateral prefrontal cortex (dlPFC) during cognitive reappraisal, albeit to a lesser extent than the CEC group. Although the amygdala was engaged in both groups during passive viewing of aversive images, neither group exhibited attenuation of amygdala activation during cognitive reappraisal. Veterans with combat-related PTSD showed less recruitment of the dlPFC involved in cognitive reappraisal, suggesting focal and aberrant neural activation during volitional, self-regulation of negative affective states.
    Full-text · Article · Oct 2014 · Depression and Anxiety
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    • "Contextual cue processing depends on working memory processing (Travis et al, 2013), and working memory processing is known to be affected in PTSD (Vasterling et al, 2002). Additionally, the IPL has previously been implicated in PTSD during working memory updating (Clark et al, 2003; Moores et al, 2008; Shaw et al, 2009). Also, during a working memory task weaker connectivity with the IPL and other areas involved in salience and executive functions was observed in PTSD patients compared with controls (Daniels et al, 2010). "
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    ABSTRACT: Thirty to fifty percent of posttraumatic stress disorder (PTSD) patients do not respond to treatment. Understanding the neural mechanisms underlying treatment response could contribute to improve response rates. PTSD is often associated with decreased inhibition of fear responses in a safe environment. Importantly, the mechanism of effective treatment (psychotherapy) relies on inhibition and so-called contextual cue processing. Therefore, we investigate inhibition and contextual cue processing in the context of treatment. Forty-one male war veterans with PTSD and 22 healthy male war veterans (combat controls) were scanned twice with a six to eight month interval, in which PTSD patients received treatment (psychotherapy). We distinguished treatment responders from non-responders on the base of percentage symptom decrease. Inhibition and contextual cue processing were assessed with the stop-signal anticipation task. Behavioral and functional MRI measures were compared between PTSD patients and combat controls, and between responders and non-responders using repeated measures analyses. PTSD patients showed behavioral and neural deficits in inhibition and contextual cue processing at both time points compared to combat controls. These deficits were unaffected by treatment, therefore, they likely represent vulnerability factors or scar aspects of PTSD. Second, responders showed increased pre-treatment activation of the left inferior parietal lobe (IPL) during contextual cue processing compared to non-responders. Moreover, left IPL activation predicted percentage symptom improvement. The IPL plays an important role in contextual cue processing, and may therefore facilitate the effect of psychotherapy. Hence, increased left IPL activation may represent a potential predictive biomarker for PTSD treatment response.Neuropsychopharmacology accepted article preview online, 26 August 2014. doi:10.1038/npp.2014.220. http://www.nature.com/npp/journal/v40/n3/full/npp2014220a.html
    Full-text · Article · Aug 2014 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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