___ Neurological Disorders: Posttraumatic Stress Disorder ___

Posttraumatic Stress Disorder - Brain Regions and their Dysfunctions

Posttraumatic Stress Disorder "Of special interest are four brain areas, the hyperactive amygdala, the hippocampus with volume reduction as well as the cingulate gyrus and orbitofrontal cortical regions, which may not be able to inhibit the hyperactive amygdala to trauma related stimuli." S "Functional activation studies of posttraumatic stress disorder (PTSD) using symptom provocation paradigms have implicated dysfunction in limbic and paralimbic brain regions. Increased or altered cerebral blood flow has been observed in amygdala and insula. Decreased or absent activity has been seen in medial prefrontal and anterior cingulate cortex (ACC)." S "Past trauma experience was associated with decreased amygdala activity (i.e., less activity than healthy control subjects); however, combat control subjects deactivated this region (i.e., greater activity to neutral scripts). All subjects deactivated medial frontal cortex; PTSD patients had greater rostral anterior cingulate (rACC) deactivation compared with control groups, who deactivated ventromedial prefrontal cortex (vmPFC)." S "There is robust evidence of hypothalamic-pituitary-adrenal axis dysfunctions related to posttraumatic stress disorder..." S
Affected Region	Dysfunctions
Insular lobe	Greater activity than matched comparison subjects in the insula during negative emotional processing S Insula activation correlated positively with PTSS severity during a response-inhibition task in youth groups S
Orbitofrontal Cortex	"The OFC, which is thought to be involved in the extinction of fear conditioning and the retrieval of emotional memory, might play an important role in the pathophysiology of PTSD." S "A sub-group of youth with PTSS and a history of self-injurious behaviors demonstrated increased insula and orbitofrontal activation when compared with those PTSS youth with no self-injurious behaviors." S
Medial PFC	"The mPFC plays a role in the "contextualization" of stimuli, and dysregulation of contextualization processes might play a key role in the generation of PTSD symptoms." S "In voxel-wise analyses, the authors found that adrenocorticotropic hormone responses were covaried with regional cerebral blood flow (rCBF) in the dorsal medial prefrontal cortex, rostral anterior cingulate cortex, and right insula, with some differences between PTSD patients and comparison subjects." S
Ventromedial PFC	Hypoactivation in the ventromedial prefrontal cortex-structures linked to the experience and regulation of emotion S Altered neural responses in the ventral MPFC during the processing of emotionally salient but trauma-unrelated stimuli S
Temporal lobe	"In the subgroup (of BPD patients) with additional PTSD, we observed right more than left activation of anterior temporal lobes, mesiotemporal areas, amygdala, posterior cingulate gyrus, occipital areas, and cerebellum (during the recall of traumatic memories)." S
Hippocampus	"On average PTSD patients had a 6.9% smaller left hippocampal volume and a 6.6% smaller right hippocampal volume compared with control subjects." S Hippocampal metabolism is suppressed to a greater extent by pharmacologic stimulation of the noradrenergic system in persons with PTSD S
Dentate gyrus	"Later on (n the stress response), when hormone levels have subsided but gene-mediated effects of corticosteroids start to appear, the excitability is normalized to the pre-stress level, in the CA1 hippocampal area, but possibly less so in the dentate gyrus and amygdala. A disturbed balance between these early and late phases of the stress response as well as a shift toward the relative contribution of the dentate/amygdala pathways may explain why the normal restorative capacity fails in vulnerable people experiencing a life-threatening situation, which could contribute to the development of PTSD." S
Amygdala	Greater activity than matched comparison subjects in the amygdala during negative emotional processing S Altered neural responses in the amygdala during the processing of emotionally salient but trauma-unrelated stimuli S Amygdala is hyperresponsive to fear-related stimuli S Long-term alterations within the amygdala contribute to stress-related mnemonic symptoms S
Anterior Cingulate Cortex	Hypoactivation in the dorsal and rostral anterior cingulate cortices linked to the experience and regulation of emotion S Decreased or absent activity in the anterior cingulate cortex (ACC) during symptom provocation S
HPA Axis	"Pituitary and adrenal hyperreactivity to exogenous corticotropin releasing factor and adrenocorticotropic hormone is demonstrated in premenopausal women with chronic posttraumatic stress disorder." S "Urinary and plasma cortisol levels are considerably lower in PTSD patients than in non-PTSD trauma survivors and normal controls. Furthermore, the circadian pattern of cortisol release from the adrenal glands follows a greater dynamic range in PTSD than in patients with major depression or in normal controls. The reduction in cortisol levels results from an enhanced negative feedback by cortisol, which is secondary to an increased sensitivity of glucocorticoid receptors in target tissues." S
Reticular formation	"Results showed that sensory gating of the P1 potential was significantly decreased at the 250 msec ISI, and that there was a numerical, but not a statistically significant, decrease in sensory gating at the other intervals tested in both male and female PTSD subjects compared to all control groups. Since the P1 potential may be generated, at least in part, by the reticular activating system, dysregulation of sensory processing by elements of this system may be present in PTSD." S "When neurological or psychiatric disorders manifest symptoms related to arousal and sleep-wake control, disturbances of elements of the reticular activating system must be considered responsible." S
Pons	"The PTSD group failed to show differential activation during WM (working memory) 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, and the brainstem pons, key regions that are consistently implicated in the neurobiology of PTSD." S
Locus caeruleus	"Although hypothalamic-pituitary-adrenal axis activation is generally considered to be the hallmark of the stress response, many of the same stimuli that initiate this response also activate the locus coeruleus-norepinephrine system. Given its functional attributes, the parallel engagement of the locus coeruleus-norepinephrine system with the hypothalamic-pituitary-adrenal axis serves to coordinate endocrine and cognitive limbs of the stress response." S

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