Higher Brain Blood Flow at Amygdala and Lower Frontal Cortex Blood Flow in PTSD Patients with Comorbid Cocaine and Alcohol Abuse Compared with Normals

Semple, William E.; Goyer, Peter F.; McCormick, Richard A.; Donovan, Beverly; Muzic, Raymond F.; Rugle, Loreen; Mccutcheon, Kevan; Lewis, Colleen; Liebling, David; Kowaliw, Sean; Vapenik, Ken; Semple, Mary Ann; Flener, Christy R.; Schulz, S. Charles

doi:10.1080/00332747.2000.11024895

Cited by 164 publications

(104 citation statements)

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“…This study provides evidence of a volume reduction of ACC in patients with PTSD. The findings of the present study are consistent with several neuroimaging studies that have suggested dysfunction or neuronal loss in ACC in patients with PTSD (16,17,(42)(43)(44)(45)(46). The results of the present and previous studies support a neuroanatomic model of PTSD that posits a failure of ACC to inhibit a hyperresponsive amygdala (16,43,47,48).…”

Section: Discussionsupporting

confidence: 82%

Voxel-based analysis of MRI reveals anterior cingulate gray-matter volume reduction in posttraumatic stress disorder due to terrorism

Yamasue

Kasai

Iwanami

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

344

198

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MRI studies using the manual tracing method have shown a smaller-than-normal hippocampal volume in patients with posttraumatic stress disorder (PTSD). However, these studies have yielded inconsistent results, and brain structures other than the hippocampus have not been well investigated. A recently developed, fully automated method called voxel-based morphometry enables an exploration of structural changes throughout the brain by applying statistical parametric mapping to high-resolution MRI. Here we first used this technology in patients with PTSD. Participants were 9 victims of the Tokyo subway sarin attack with PTSD and 16 matched victims of the same traumatic event without PTSD. The voxel-based morphometry showed a significant gray-matter volume reduction in the left anterior cingulate cortex (ACC) in trauma survivors with PTSD compared with those without PTSD. The severity of the disorder was negatively correlated with the gray-matter volume of the left ACC in PTSD subjects. There were no significant differences in other gray-matter regions or any of the white-matter regions between two groups. The present study demonstrates evidence for structural abnormalities of ACC in patients with PTSD. Together with previous functional neuroimaging studies showing a dysfunction of this region, the present findings provide further support for the important role of ACC, which is pivotally involved in attention, emotional regulation, and conditioned fear, in the pathology of PTSD.F indings from neuroimaging studies of patients with posttraumatic stress disorder (PTSD) have suggested that some brain pathology plays an important role in the disorder (1, 2). Six structural MRI studies have shown that combat-related or childhood physically and͞or sexually abused subjects with PTSD have a smaller-than-normal hippocampal volume (3-8). However, almost the same number of studies failed to show reduced hippocampal volume in chronically maltreated children (9-11), survivors of acute traumatic events (12), nonalcoholic combat veterans (13), and alcoholic patients (14) with PTSD. In contrast, brain structures other than the hippocampus have received less attention, although a few studies have reported whole-brain volume reduction (9), reduced total white-matter volume (7), smaller corpus callosum (9), larger superior temporal gyrus gray-matter volume (15), and attenuation of frontal lobe asymmetry (11). Therefore, it is unclear whether structural abnormality in brain structures other than the hippocampus exists in patients with PTSD.In contrast to the emphasis on the hippocampus in previous structural MRI studies, symptom-provocation and cognitiveactivation studies using functional neuroimaging have revealed greater activation of the amygdala, anterior paralimbic structures, Broca's region, and other neocortical regions and a failure of activation of anterior cingulate cortex (ACC) in response to trauma-related stimuli in individuals with PTSD (1, 2, 16). Furthermore, one study (17) showed a reduced N-acetylaspartate͞creatine ratio...

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Section: Discussionsupporting

confidence: 82%

Voxel-based analysis of MRI reveals anterior cingulate gray-matter volume reduction in posttraumatic stress disorder due to terrorism

Yamasue

Kasai

Iwanami

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

344

198

View full text Add to dashboard Cite

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“…Functional neuroimaging findings using positron emission topography (PET) and functional magnetic resonance imaging (fMRI) suggest that individuals with PTSD exhibit hyperresponsive amygdala activity to trauma or fear-related stimuli (for review, see Shin and Liberzon, 2010), during emotionally neutral tasks (Bryant et al, 2005;Shin et al, 2004b), and even at rest (Chung et al, 2006;Semple et al, 2000). A hyperresponsive amygdala contributes to the exaggerated fear response characteristic of PTSD (Anderson et al, 2003).…”

Section: Clinicalmentioning

confidence: 99%

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

Huang

Risling

Baker

2016

Psychoneuroendocrinology

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SummaryBackground: Pervasive use of improvised explosive devices (IEDs), rocket-propelled grenades, and land mines in the recent conflicts in Iraq and Afghanistan has brought traumatic brain injury (TBI) and its impact on health outcomes into public awareness. Blast injuries have been deemed signature wounds of these wars. War-related TBI is not new, having become prevalent during WWI and remaining medically relevant in WWII and beyond. Medicine's past attempts to accurately diagnose and disentangle the pathophysiology of war-related TBI parallels current lines of inquiry and highlights limitations in methodology and attribution of symptom etiology, be it organic, psychological, or behavioral. New approaches and biomarkers are needed. Preclinical: Serological biomarkers and biomarkers of injury obtained with imaging techniques represent cornerstones in the translation between experimental data and clinical observations. Experimental models for blast related TBI and PTSD can generate critical data on injury threshold, for example for white matter injury from acceleration. Carefully verified and validated models can be evaluated with gene expression arrays and proteomics to identify new candidates for serological biomarkers. Such models can also be analyzed with diffusion MRI and microscopy in order to identify criteria for detection of diffuse white matter injuries, such as DAI (diffuse axonal injury). The experimental models can also be analyzed with focus on injury outcome in brain stem regions, such as locus coeruleus or nucleus raphe magnus that can be involved in response to anxiety changes. * Corresponding author at: UCSD Radiology Imaging Laboratory, San Diego, CA 92121, USA. Tel.: +1 858 534 1254; fax: +1 8585346046. E-mail address: mxhuang@ucsd.edu (M. Huang). Clinical: Mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. There is accumulating evidence that injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). MEG imaging detects TBI abnormalities at the rates of 87% for the mild TBI, group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities are 96% and 77% for the blast and non-blast TBI groups, respectively. There is emerging evidence based on fMRI and MEG studies showing hyper-activity in the amygdala and hypo-activity in prefrontal cortex in individuals with PTSD. MEG signal may serve as a sensitive imaging marker for mTBI, distinguishable from abnormalities generated in association with PTSD. More work is needed to fully describe physiological mechanisms of post-concussive symptoms.Published by Elsevier Ltd. BackgroundBlast injuries are deemed the signature wounds of the first wars (Afghanistan and Iraq) of the 21st century (Lancet, 2007;Galarneau et al., 2008). According to a recent U.S. Department Veterans Affairs (DVA) ...

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“…Previous findings for the amygdala are discordant. Most studies report greater amygdalar activation associated with PTSD (Shin et al, 1997;Rauch et al, 2000;Semple et al, 2000;Hendler et al, 2003;Shin et al, 2004;Shin et al, 2005;Williams et al, 2006), but there are contradictory reports of greater activation in controls (Britton et al, 2005;Phan et al, 2006), and numerous studies lack amygdalar findings entirely (Bremner et al, 1999a;Bremner et al, 1999b;Lanius et al, 2001;Shin et al, 2001;Lanius et al, 2002;Lanius et al, 2003b;Sakamoto et al, 2005). Quantitative analysis of signal-to-noise in this region showed poor signal quality using our standard echoplanar imaging sequence at 3T.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

“…A subsequent study confirmed lower ACC activation in the PTSD group for the emotional Stroop condition, and lower activation in inferior parietal lobule, visual association cortex, and precuneus for the classic Stroop condition (Bremner et al, 2004). An auditory continuous performance task study of patients with comorbid cocaine and alcohol abuse also found lower activity in rostral ACC (Semple et al, 2000). Converging support across symptom provocation studies combined with neuropsychological assessment, posit an inability of the PFC to inhibit a hyperresponsive limbic system in PTSD (Bremner et al, 1999b;Rauch et al, 2000;Shin et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Neural systems for executive and emotional processing are modulated by symptoms of posttraumatic stress disorder in Iraq War veterans

Morey

Petty

Cooper

et al. 2008

Psychiatry Research: Neuroimaging

113

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The symptom provocation paradigms generally used in neuroimaging studies of posttraumatic stress disorder (PTSD) have placed high demands on emotion processing but lacked cognitive processing, thereby limiting the ability to assess alterations in neural systems that subserve executive functions and their interactions with emotion processing. Thirty-nine veterans from Iraq and Afghanistan underwent functional MR imaging while exposed to emotional combat-related and neutral civilian scenes interleaved with an executive processing task. Contrast activation maps were regressed against PTSD symptoms as measured by the Davidson Trauma Scale. Activation for emotional compared to neutral stimuli was highly positively correlated with level of PTSD symptoms in ventral frontolimbic regions, notably the ventromedial prefrontal cortex, inferior frontal gyrus, and ventral anterior cingulate gyrus. Conversely, activation for the executive task was negatively correlated with PTSD symptoms in the dorsal executive network, notably the middle frontal gyrus, dorsal anterior cingulate gyrus, and inferior parietal lobule. Thus, there is a strong link between the subjectivelyassessed behavioral phenomenology of PTSD and objective neurobiological markers. These findings extend the largely symptom provocation-based functional neuroanatomy to provide evidence that interrelated executive and emotional processing systems of the brain are differentially affected by PTSD symptomatology in recently deployed war veterans.

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Higher Brain Blood Flow at Amygdala and Lower Frontal Cortex Blood Flow in PTSD Patients with Comorbid Cocaine and Alcohol Abuse Compared with Normals

Cited by 164 publications

References 0 publications

Voxel-based analysis of MRI reveals anterior cingulate gray-matter volume reduction in posttraumatic stress disorder due to terrorism

Voxel-based analysis of MRI reveals anterior cingulate gray-matter volume reduction in posttraumatic stress disorder due to terrorism

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

Neural systems for executive and emotional processing are modulated by symptoms of posttraumatic stress disorder in Iraq War veterans

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