PTSD (Brain Imaging) Spring 2015

Editor's Notes

• #7: PHC - parahippocampal cortex/ STS - superior temporal sulcus / VTC - ventral temporal sulcus / STG - superior temporal gyrus / mOFC - medial orbitofrontal cortex rACC - rostral anterior cingulate cortex / / PRC - perirhinal cortex / / / dACC - dorsal anterior cingulate cortex
• #8: 70% of US adults have experienced a traumatic event, 20% of those go on to develop PTSD Women are 2x as likely as men to develop PTSD, or 1 in every 9 women People who are at risk for PTSD are those who have experience abuse in childhood, genetically inherited risk of anxiety depression, and the way their brain regulates chemicals and hormones during stress response
• #11: *in PTSD focus on data collection on limbic system activity -train to executively control emotional response
• #17: -Discordant monozygotic twin paradigm (discordant for trauma exposure) -Images represent four subject groups: (1) combat-exposed (Ex) subjects who developed chronic PTSD (ExP+) (2) their combat-unexposed (Ux) co-twins with no PTSD themselves (UxP+) (3) Ex subjects who never developed PTSD (ExP−) (4) Ux co-twins also with no PTSD (UxP−) Contrast (a) smaller hippocampal volumes in combat veterans with versus without PTSD Contrast (b) identifies the neurotoxicity effect—hippocampal reduction—as environmentally acquired -contrasting hippocampal volumes in combat-exposed PTSD veterans with their unexposed co-twins. Contrast (c) examines pre-existing vulnerability -contrasting hippocampal volumes in the two groups of combat-unexposed co-twins whose combat-exposed brothers did versus did not develop PTSD *both twins with PTSD and their trauma unexposed twin smaller hippocampi relative to trauma exposed non-PTSD twins and their co-twin *These findings offer compelling evidence for reduced hippocampal size serving as a pre-existing and potentially vulnerability or predisposing factor for PTSD. **hippocampal volume measures not a reliable measure of PTSD (severity) **smaller hippocampal volume may be a risk factor for development of disorder
• #18: What is MRS? “Magnetic Resonance Spectroscopy”: in vivo non-invasive and radioactive free used to study metabolic changes in braid due to damage or disease related to MRI -both techniques use signals from hydrogen protons -MRI uses protons to create 2-D image of brain -MRS uses H1 signals to determine relative concentrations of target brain metabolites In this study, used to estimate metabolite NAA What is NAA? 2nd most concentrated molecule in the brain -neuronal health: fluid balance, synthesis in myelin, important in energy production levels in hippocampus related to WM performance So a voxel refers to: a “volume” and “pixel”, a unit of graphic information (computer) that represents a point in 3-Dimensional space (brain) *IMPORTANT WHICH IMAGE YOU CHOSE TO BASE VOXEL OFF OF (CORONAL VS SAGITTAL) TO INCLUDE AS MUCH OF THAT STRUCTURE AS POSS. Results: - sign. decreased NAA concentration in ACC and hippocampus in PTSD subjects -NAA levels of ACC and hippocampus were negatively correlated with re-experience symptom scores in PTSD -mean: as NAA dec. in NAA and hipp., PTSD symptom severity increase [-Absolute NAA, choline, Cr, and myo-inositol metabolite levels were estimated w/ VOIs LCMODEL software and compared against the GE model of metabolite as a base set] [This Study: looked at PTSD in victims who survived a subway fire Purpose: study relationship of NAA levels in brain w/ clinical presentations of PTSD MRI: 3-Tesla whole-body imaging system (GE VH/1, USA) Brian voxels of interest (VOIs)]
• #19: What is VBM? “Voxel-Based Morphometry” -uses statistical parametric mapping VBM registers each brain to a template (this gets rid of most large differences in brain anatomy among people) VBM takes into account the structure’s volume in relation to other brain structures [METHOD: used voxel-based morphometry (VBM) to search for gray matter density reductions in MRI data obtained in a previous study of combat-exposed Vietnam veteran twins with (n = 18) versus without (n = 23) PTSD and their "high-risk" versus "low-risk" (respectively) identical combat-unexposed cotwins.] RESULTS: Compared with the combat-exposed twins without PTSD, the combat-exposed twins with PTSD showed significant gray matter density reductions in four regions: right hippocampus pregenual anterior cingulate cortex (ACC) and left and right insulae CONCLUSIONS: The results point to gray matter volume diminutions in limbic and paralimbic structures in PTSD. The pattern of results obtained for pregenual ACC suggests that gray matter reduction in this region represents an acquired sign of PTSD consistent with stress-induced loss.
• #20: -identify altered functions of regions associated with pathophysiology PTSD -studies utilizing personal trauma narrative or other arousing stimuli first employed and most common studies of PTSD function -give relatively stable and replicable findings -cognitive activation studies test processing impairments using neurocognitive tasks -activates a circuit without activating symptoms -great advantage for understanding general or nonspecific trauma-related responses
• #21: Positron Emission Tomography METHOD: 22 women with a history of childhood sexual abuse -injected with [15O]H2O -underwent PET scan while listen to neutral and traumatic (personalized childhood sexual abuse events) scripts -compared brain blood flow during traumatic and neutral scripts for sexually abused women w/ and w/o PTSD Greater increases in blood flow were seen in superior and middle frontal gyrus, posterior cingulate, and motor cortex in women with PTSD than in women without PTSD.
• #22: Greater decreases in blood flow in medial prefrontal cortex in women with PTSD than in women without PTSD. Decreases in blood flow were also seen in visual association cortex, right insula/inferior frontal gyrus, fusiform gyrus, and right hippocampus region. CONCLUSIONS: -Dysfunction in these brain areas may underlie PTSD symptoms provoked by traumatic reminders in subjects with PTSD. -Dysfunction of medial prefrontal cortex (subcallosal gyrus and anterior cingulate), hippocampus, and visual association cortex in pathological memories of childhood abuse in women with PTSD -Increased activation in posterior cingulate and motor cortex was seen in women with PTSD.
• #23: Study where use both MRI (structure) and PET (function) to look at PTSD *Women with abuse and PTSD differed significantly from women w/ abuse w/o PTSD and women w/o abuse or PTSD in hippocampal volume (measure by MRI) *PET imaging that used [15O]H2O (half-life 110 seconds) -subjects scanned during verbal declarative memory and control tasks -paragraph was read during first 60 seconds after peak of tracer in the brain, subjects count # times heard letter “d”while try to recall paragraph -statistical parametric map overlaid on MRI template -yellow=areas of activation -blood flow increased in left hippocampus in sexually abused women w/o PTSD but not in sexually abused women w/ PTSD *failure of activation of left hippocampus in sex abused women w/ PTSD *however, no significant diff b/n abused women w/ and w/o PTSD
• #24: -mu-opiod implicates alterations of endogenous opiods involved in inhibiting and modualting emotional responses in PTSD
• #25: -model does not explain avoidance, emotional numbing, etc. -mPFC hypofrontality may be connected to issues with “contextualization” of stimuli and may lead to PTSD symptoms -perception of threat (triggers) Knowledge gained from imaging: There is dysregulation in threat-related processing in PTSD. However, this explains only some aspects of PTSD.
• #26: Hippocampus learning and memory known target for stress hormones PTSD PTSD perform poorly on memory tasks Show decreased volume Failure/decreased activation Declarative memory* Declarative memory is important in identifying signal of potential threat in stress situations
• #27: Anterior Cingulate Cortex (ACC) Involved in cognitive-emotion interactions rACC associated with assessing emotional info and regulating emotional responses. PTSD Decreased volume/reduction grey matter Failure/reduced activation (cBRF) Amygdala Generation and maintenance of emotional responses Rapidly assess emotional and threatening stimuli Important in conditioned fear responses PTSD Decreased volume Increased responsivity Influence activity: visual cortex, subcallosal gyrus, anterior cingulate Mediates symptoms of hyperarousal and vigilance in PTSD* Insula Emotional processing *Anterior Insula: consciousness of feelings & autobiographical memory Large cortical structure with many subdivisions of major afferent and efferent projections PTSD Lower gray matter density Abnormal functioning associated with anxiety (hyperactivation) Increased activation (cBRF) Medial Prefrontal Cortex Stress and emotion Sympathetic response Extinction of fear PTSD Deactivation/decreased cBRF Inhibitory connections to amygdala Mediates symptom of PTSD Other Structures Cerebellum Visual Cortex* Posterior Cingulate Cortex Motor Cortex Remembrance Middle/Inferior frontal gyrus Parietal Cortex Parietal Lobe