I am a neuroimaging specialist in the Emerge Research Program at Yale School of Medicine and the Clinical Neuroscience Division of the National Center for PTSD. My background in MRI/MRS, genetics, biotech device R&D, scale development and latent variable analysis, computer programming, and data science have shaped my interests, which include the neuropathophysiology of chronic stress, applications of neuroimaging and deep learning for precision medicine.
Skills and Expertise
- Neuroimaging Program Manager
- Acquire, process, analyze ,and report findings of sMRI, fMRI, dMRI, pMRI, MRS, NMR, and EEG data. Develop and refine methods for the same. Train and supervise staff in acquisition and processing of data.
Research Items (58)
In soldiers with posttraumatic stress disorder, symptom provocation was found to induce increased connectivity within the salience network, as measured by functional magnetic resonance imaging and global brain connectivity with global signal regression (GBCr). However, it is unknown whether these GBCr disturbances would normalize following effective posttraumatic stress disorder treatment.
Background Better understanding of the neurobiology of posttraumatic stress disorder (PTSD) may be critical to developing novel, effective therapeutics. Here, we conducted a data-driven investigation using a well-established, graph-based topological measure of nodal strength to determine the extent of functional dysconnectivity in a cohort of active duty U.S. Army soldiers with PTSD compared to controls. Methods A total of 102 participants with (n = 50) or without PTSD (n = 52) completed functional magnetic resonance imaging at rest and during symptom provocation using subject-specific script imagery. Vertex/voxel global brain connectivity with global signal regression (GBCr), a measure of nodal strength, was calculated as the average of its functional connectivity with all other vertices/voxels in the brain gray matter. Results In contrast to resting state, where there were no group differences, we found a significantly higher GBCr during symptom provocation, in PTSD participants compared to controls, in areas within the right hemisphere, including anterior insula, caudal-ventrolateral prefrontal, and rostral-ventrolateral parietal cortices. Overall, these clusters overlapped with the ventral and dorsal salience networks. Post hoc analysis showed increased GBCr in these salience clusters during symptom provocation compared to resting state. In addition, resting-state GBCr in the salience clusters predicted GBCr during symptom provocation in PTSD participants but not in controls. Conclusion In PTSD, increased connectivity within the salience network has been previously hypothesized, based primarily on seed-based connectivity findings. The current results strongly support this hypothesis using whole-brain network measure in a fully data-driven approach. It remains to be seen in future studies whether these identified salience disturbances would normalize following treatment.
BACKGROUND: In soldiers with posttraumatic stress disorder (PTSD), symptom provocation was found to induce increased connectivity within the salience network, as measured by functional magnetic resonance imaging (fMRI) and global brain connectivity with global signal regression (GBCr). However, it is unknown whether these GBCr disturbances would normalize following effective PTSD treatment. METHODS: 69 US Army soldiers with (n = 42) and without PTSD (n = 27) completed fMRI at rest and during symptom provocation using subject-specific script imagery. Then, participants with PTSD received 6 weeks (12 sessions) of group cognitive processing therapy (CPT) or present-centered therapy (PCT). At week 8, all participants repeated the fMRI scans. The primary analysis used a region-of-interest approach to determine the effect of treatment on salience GBCr. A secondary analysis was conducted to explore the pattern of GBCr alterations post-treatment in PTSD participants compared to controls. RESULTS: Over the treatment period, PCT significantly reduced salience GBCr (p = .02). Compared to controls, salience GBCr was high pretreatment (PCT, p = .01; CPT, p = .03) and normalized post-PCT (p = .53), but not post-CPT (p = .006). Whole-brain secondary analysis found high GBCr within the central executive network in PTSD participants compared to controls. Post hoc exploratory analyses showed significant increases in executive GBCr following CPT treatment (p = .01). CONCLUSION: The results support previous models relating CPT to central executive network and enhanced cognitive control while unraveling a previously unknown neurobiological mechanism of PCT treatment, demonstrating treatment-specific reduction in salience connectivity during trauma recollection.
BACKGROUND: Better understanding of the neurobiology of posttraumatic stress disorder (PTSD) may be critical to developing novel, effective therapeutics. Here, we conducted a data-driven investigation using a well-established, graph- based topological measure of nodal strength to determine the extent of functional dysconnectivity in a cohort of active duty US Army soldiers with PTSD compared to controls. METHODS: 102 participants with (n=50) or without PTSD (n=52) completed functional magnetic resonance imaging (fMRI) at rest and during symptom provocation using subject-specific script imagery. Vertex/voxel global brain connectivity with global signal regression (GBCr), a measure of nodal strength, was calculated as the average of its functional connectivity with all other vertices/voxels in the brain gray matter. RESULTS: In contrast to during resting-state, where there were no group differences, we found a significantly higher GBCr, in PTSD participants compared to controls, in areas within the right hemisphere, including anterior insula, caudal- ventrolateral prefrontal, and rostral-ventrolateral parietal cortices. Overall, these clusters overlapped with the ventral and dorsal salience networks. Post hoc analysis showed increased GBCr in these salience clusters during symptom provocation compared to resting-state. In addition, resting-state GBCr in the salience clusters predicted GBCr during symptom provocation in PTSD participants but not in controls. CONCLUSION: In PTSD, increased connectivity within the salience network has been previously hypothesized, based primarily on seed-based connectivity findings. The current results strongly support this hypothesis using whole-brain network measure in a fully data-driven approach. It remains to be seen in future studies whether these identified salience disturbances would normalize following treatment.
Background: Identifying the neural correlates of ketamine treatment may facilitate and expedite the development of novel, robust, and safe rapid-acting antidepressants. Prefrontal cortex (PFC) global brain connectivity with global signal regression (GBCr) was recently identified as a putative biomarker of major depressive disorder (MDD). Accumulating evidence have repeatedly shown reduced PFC GBCr in MDD, an abnormality which appears to normalize following ketamine treatment. Methods: Fifty-six unmedicated participants with MDD were randomized to intravenous placebo (normal saline; n = 18), ketamine (0.5mg/kg; n = 19) or lanicemine (100mg; n = 19). PFC GBCr was computed using time series from functional magnetic resonance imaging (fMRI) scans that were completed at baseline, during infusion, and 24h post-treatment. Results: Compared to placebo, ketamine significantly increased average PFC GBCr during infusion (p = 0.01) and 24h post-treatment (p = 0.02). Lanicemine had no significant effects on GBCr during infusion (p = 0.45) and 24h post-treatment (p = 0.23), compared to placebo. Average delta PFC GBCr (during minus baseline) showed a pattern of positively predicting depression improvement in participants receiving ketamine (r = 0.44; p = 0.06; d = 1.0) or lanicemine (r = 0.55; p = 0.01; d = 1.3), but not those receiving placebo (r = -0.1; p = 0.69; d = 0.02). Follow-up vertex-wise analyses showed ketamine-induced GBCr increases in the dorsolateral, dorsomedial, and frontomedial PFC during infusion, and in the dorsolateral and dorsomedial PFC 24h post-treatment (corrected p < 0.05). Exploratory vertex-wise analyses examining the relationship with depression improvement showed positive correlation with GBCr in the dorsal PFC during infusion and 24h post-treatment, but negative correlation with GBCr in the ventral PFC during infusion (uncorrected p < 0.01). Conclusions: In a randomized placebo-controlled approach, the results provide the first evidence in MDD of ketamine-induced increases in PFC GBCr during infusion, and suggests that ketamine's rapid-acting antidepressant properties are related to its acute effects on prefrontal connectivity. Overall, the study findings underscore the similarity and differences between ketamine and another N-methyl-D-aspartate receptor (NMDAR) antagonist, while proposing a pharmacoimaging paradigm for optimization of novel rapid-acting antidepressants prior to testing in costly clinical trials.
New approaches to the neurobiology of posttraumatic stress disorder (PTSD) are needed to address the reported crisis in PTSD drug development. These new approaches may require the field to move beyond a narrow fear-based perspective, as fear-based medications have not yet demonstrated compelling efficacy. Antidepressants, particularly recent rapid-acting antidepressants, exert complex effects on brain function and structure that build on novel aspects of the biology of PTSD, including a role for stressrelated synaptic dysconnectivity in the neurobiology and treatment ofPTSD. Here, we integrate this perspective within a broader framework-in other words, a dual pathology model of (a) stress-related synaptic loss arising from amino acid-based pathology and (b) stress-related synaptic gain related to monoamine-based pathology. Then, we summarize the standard and experimental (e.g., ketamine) pharmacotherapeutic options for PTSD and discuss their putative mechanism of action and clinical efficacy. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 59 is January 6, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Here we present functional neuroimaging-based network data (focused on the default mode network) collected from a cohort of US Veterans with history of combat exposure, combined with clinical assessments for PTSD and other psychiatric comorbidities. The data has been processed and analyzed using several network construction methods (signed, thresholded, normalized to phase-randomized and rewired surrogates, functional and multimodal parcellation). An interpretation and discussion of the data can be found in the main NeuroImage article by Akiki et al. 
Question - How to convert .gii files into .nii?
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Walter Roberson posts:
- https://www.artefact.tk/software/matlab/gifti/ to do the reading.
- https://www.mathworks.com/matlabcentral/fileexchange/8797-tools-for-nifti-and-analyze-image to do the writing.
Purpose of the study: Prior studies showed posttraumatic stress disorder (PTSD)-related alterations in white matter integrity, but most of these studies have used region-based approaches. We address this limitation by investigating the relationship between PTSD severity and fractional anisotropy (FA) using a tract-based approach. Procedures: Structural and diffusion magnetic resonance imaging were acquired from 67 combat-exposed US Veterans and processed using FSL/FreeSurfer TRActs Constrained by UnderLying Anatomy. Partial correlations were conducted between PTSD severity and FA of the cingulum and uncinate fasciculi covarying for age, sex, and head motion. Results: Only FA of the left cingulum angular bundle (CAB) was positively correlated with PTSD symptom severity (r = 0.433, p = 0.001, df = 57) and remained significant after Bonferroni correction. Conclusions: This finding may imply greater organization of the CAB with increasing PTSD severity. The CAB connects directly to the cingulate cortex and the hippocampal subiculum, critical nodes of the default mode network, as well as being implicated in neurodegeneration pathology, decision-making, and executive functions, which may help explain previously shown alterations in this network in PTSD. Message of the paper: Further study of white matter tract integrity in PTSD is warranted, particularly to investigate whether the CAB connections with both higher-order cognitive functioning and emotion processing regions contribute to the pathophysiology and comorbidity of PTSD.
The ability of ketamine administration to activate prefrontal glutamate neurotransmission is thought to be a key mechanism contributing to its transient psychotomimetic effects and its delayed and sustained antidepressant effects. Rodent studies employing carbon-13 magnetic resonance spectroscopy (13C MRS) methods have shown ketamine and other N-methyl-D-aspartate (NMDA) receptor antagonists to transiently increase measures reflecting glutamate–glutamine cycling and glutamate neurotransmission in the frontal cortex. However, there are not yet direct measures of glutamate neurotransmission in vivo in humans to support these hypotheses. The current first-level pilot study employed a novel prefrontal 13C MRS approach similar to that used in the rodent studies for direct measurement of ketamine effects on glutamate–glutamine cycling. Twenty-one participants (14 healthy and 7 depressed) completed two 13C MRS scans during infusion of normal saline or subanesthetic doses of ketamine. Compared to placebo, ketamine increased prefrontal glutamate–glutamine cycling, as indicated by a 13% increase in 13C glutamine enrichment (t = 2.4, p = 0.02). We found no evidence of ketamine effects on oxidative energy production, as reflected by 13C glutamate enrichment. During ketamine infusion, the ratio of 13C glutamate/glutamine enrichments, a putative measure of neurotransmission strength, was correlated with the Clinician-Administered Dissociative States Scale (r = −0.54, p = 0.048). These findings provide the most direct evidence in humans to date that ketamine increases glutamate release in the prefrontal cortex, a mechanism previously linked to schizophrenia pathophysiology and implicated in the induction of rapid antidepressant effects.
Manuscript Now Published at Molecular Neuropsychiatry. CITATION: Averill CL, Averill LA, Wrocklage KM, Scott JC, Akiki TJ, Schweinsburg B, Southwick SM, Krystal JH, Abdallah CG. Altered white matter diffusivity of the cingulum angular bundle in posttraumatic stress disorder. Mol Neuropsychiatry 2018;4:75–82. https://doi.org/10.1159/000490464
Disruption in the default mode network (DMN) has been implicated in numerous neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). However, studies have largely been limited to seed-based methods and involved inconsistent definitions of the DMN. Recent advances in neuroimaging and graph theory now permit the systematic exploration of intrinsic brain networks. In this study, we used resting-state functional magnetic resonance imaging (fMRI), diffusion MRI, and graph theoretical analyses to systematically examine the DMN connectivity and its relationship with PTSD symptom severity in a cohort of 65 combat-exposed US Veterans. We employed metrics that index overall connectivity strength, network integration (global efficiency), and network segregation (clustering coefficient). Then, we conducted a modularity and network-based statistical analysis to identify DMN regions of particular importance in PTSD. Finally, structural connectivity analyses were used to probe whether white matter abnormalities are associated with the identified functional DMN changes. We found decreased DMN functional connectivity strength to be associated with increased PTSD symptom severity. Further topological characterization suggests decreased functional integration and increased segregation in subjects with severe PTSD. Modularity analysis suggest a spared connectivity in the posterior DMN community (posterior cingulate, precuneus, angular gyrus) despite overall DMN weakened connections with increasing PTSD severity. Edge-wise network-based statistical analyses revealed a prefrontal dysconnectivity. Analysis of the diffusion networks revealed no alterations in overall strength or prefrontal structural connectivity. DMN abnormalities in patients with severe PTSD symptoms are characterized by decreased overall interconnections. On a finer scale, we found a pattern of prefrontal dysconnectivity, but increased cohesiveness in the posterior DMN community and relative sparing of connectivity in this region. The DMN measures established in this study may serve as a biomarker of disease severity and could have potential utility in developing circuit-based therapeutics.
- Apr 2018
Purpose of review: This review focuses on the relationship between resilience and the ability to effectively modulate the stress response. Neurobiological and behavioral responses to stress are highly variable. Exposure to a similar stressor can lead to heterogeneous outcomes-manifesting psychopathology in one individual, but having minimal effect, or even enhancing resilience, in another. We highlight aspects of stress response modulation related to early life development and epigenetics, selected neurobiological and neurochemical systems, and a number of emotional, cognitive, psychosocial, and behavioral factors important in resilience. We also briefly discuss interventions with potential to build and promote resilience. Recent findings: Throughout this review, we include evidence from recent preclinical and clinical studies relevant to the psychobiology of resilient stress response modulation. Effective modulation of the stress response is an essential component of resilience and is dependent on a complex interplay of neurobiological and behavioral factors.
The Methodological Question: Can fMRI-derived restricted-network biomarkers serve as robust marker of PTSD symptomatology? Can these network-analyses identify abnormalities that can potentially be targeted using circuit-based therapeutics?
The Opioid Abuse Risk Screener was developed to support well-informed decision-making in opioid analgesic prescribing by extending the breadth of psychiatric risk factors evaluated relative to other non–clinician-administered measures. We examined the preliminary predictive validity of the Opioid Abuse Risk Screener relative to the widely used Screener and Opioid Assessment for Patients with Pain–Revised in predicting aberrant urine drug tests and controlled substance database checks. The Opioid Abuse Risk Screener is significantly different from the Screener and Opioid Assessment for Patients with Pain–Revised in predicting aberrant same-day urine drug tests (Z = 2.912, p = 0.0036) and controlled substance database checks within 1 year of assessment (Z = 3.731, p = 0.0002). Promising preliminary analyses using machine learning methods are also discussed.
Background Two decades of human neuroimaging research have associated volume reductions in the hippocampus with posttraumatic stress disorder. However, little is known about the distribution of volume loss across hippocampal subfields. Recent advances in neuroimaging methods have made it possible to accurately delineate 10 gray matter hippocampal subfields. Here, we apply a volumetric analysis of hippocampal subfields to data from a group of combat-exposed Veterans. Method Veterans (total, n = 68, posttraumatic stress disorder, n = 36; combat control, n = 32) completed high-resolution structural magnetic resonance imaging. Based on previously validated methods, hippocampal subfield volume measurements were conducted using FreeSurfer 6.0. The Clinician-Administered PTSD Scale assessed posttraumatic stress disorder symptom severity; Beck Depression Inventory assessed depressive symptom severity. Controlling for age and intracranial volume, partial correlation analysis examined the relationship between hippocampal subfields and symptom severity. Correction for multiple comparisons was performed using false discovery rate. Gender, intelligence, combat severity, comorbid anxiety, alcohol/substance use disorder, and medication status were investigated as potential confounds. Results In the whole sample, total hippocampal volume negatively correlated with Clinician-Administered PTSD Scale and Beck Depression Inventory scores. Of the 10 hippocampal subfields, Clinician-Administered PTSD Scale symptom severity negatively correlated with the hippocampus–amygdala transition area (HATA). Beck Depression Inventory scores negatively correlated with dentate gyrus, cornu ammonis 4 (CA4), HATA, CA2/3, molecular layer, and CA1. Follow-up analysis limited to the posttraumatic stress disorder group showed a negative correlation between Clinician-Administered PTSD Scale symptom severity and each of HATA, CA2/3, molecular layer, and CA4. Conclusion This study provides the first evidence relating posttraumatic stress disorder and depression symptoms to abnormalities in the HATA, an anterior hippocampal region highly connected to prefrontal-amygdala circuitry. Notably, dentate gyrus abnormalities were associated with depression severity but not posttraumatic stress disorder symptoms. Future confirmatory studies should determine the extent to which dentate gyrus volume can differentiate between posttraumatic stress disorder- and depression-related pathophysiology.
This manuscript (https://goo.gl/ea9UU9) includes an animated 3D video that was created (in Blender) using meshes from one of the combat control (non-PTSD) participants described in the manuscript. It demonstrates the gray matter subfields of the hippocampus, walking through each one to better visualize the more hidden areas. This video is an excellent companion to Table 1 in the manuscript, which briefly summarizes the anatomy and putative function of each gray matter subfield. You can find this video on YouTube, which is the best modality for sharing with your colleagues or students. https://youtu.be/9linXW5qB9Q You can also find the video in the online publication at Chronic Stress: http://journals.sagepub.com/doi/suppl/10.1177/2470547017744538 This video is shared under the same Creative Commons license as the manuscript, and you are welcome to include it in classes, presentations, demonstrations, etc., without seeking express permission.
Background: The discovery of the rapid acting antidepressant effects of ketamine have generated considerable interest in academia and industry about the prospect of targeting NMDA receptors (NMDAR) in the treatment of refractory depression. However, the results from clinical trials failing to reach primary outcomes, combined with recent preclinical evidence proposing NMDAR-independent mechanisms of ketamine, have cast doubts about the potential utility of this line of research. In this study, we investigated the impact of ketamine, and the NMDAR antagonist lanicemine, on prefrontal cortex (PFC) Global Brain Connectivity (GBC), a previously validated biomarker of depression and the rapid acting antidepressant ketamine. Prior studies have repeatedly shown reduced PFC GBC in depression, and open-label trials showed significant increases of PFC GBC 24h post ketamine administration. However, the effects of ketamine on PFC GBC during infusion and placebo-controlled PFC GBC ketamine studies in depressed patients were not previously conducted. Methods: Fifty-six unmedicated participants with major depressive disorder were randomized to intravenous placebo (normal saline; n = 18), ketamine (0.5mg/kg; n = 19), and lanicemine (100mg; n = 19). Functional connectivity magnetic resonance imaging (fc-MRI) scans were completed at baseline, during infusion, and 24h post treatment. The Human Connectome Pipeline was adapted to conduct surface based preprocessing and optimize registration. PFC vertex-wise analyses were corrected for multiple comparisons using permutation testing and threshold-free cluster enhancement. Results: Compared to placebo, ketamine, but not lanicemine, significantly increased GBC in multiple clusters within the PFC during infusion and at 24h post treatment. No reduction in PFC GBC were observed. The GBC increases were found in the dorsolateral, dorsomedial, and frontomedial PFC during infusion, and in the dorsolateral and dorsomedial PFC 24h following treatment. Region-of-interest analysis showed a significant increase in average PFC GBC, compared to placebo, during (mean difference ±SEM = 0.08 ±0.02; p = 0.01) and 24h following ketamine (mean difference ±SEM = 0.13 ±0.04; p = 0.02). Compared to placebo, no significant changes were found during (mean difference ±SEM = 0.03 ±0.03; p = 0.45) or 24h following lanicemine (mean difference ±SEM = 0.07 ±0.04; p = 0.23). In the placebo group, we found no correlation between delta PFC GBC (during minus baseline) and depression improvement at 24h (r = –0.1; p = 0.69). However, delta PFC GBC positively predicted depression improvement regardless whether participants received ketamine or lanicemine (r = 0.47; p = 0.003). Conclusion: The study provides the first evidence of ketamine-induced PFC GBC during infusion in depressed patients. It also replicates, in a placebo-controlled design, previous open label evidence of ketamine-induced PFC GBC 24h post treatment. Lanicemine (100mg) failed to induce significant PFC GBC increases during and 24h post treatment. However, it is evident that numerically the lanicemine-induced PFC GBC changes appear to be in the same direction as ketamine, which raises the question for future studies whether optimization of the lanicemine administration regimen could lead to significant prefrontal connectivity normalization – especially considering the positive relationship between PFC GBC increases and treatment response.
Abstract Background The hippocampus and amygdala have been repeatedly implicated in the psychopathology of posttraumatic stress disorder (PTSD). While numerous structural neuroimaging studies examined these two structures in PTSD, these analyses have largely been limited to volumetric measures. Recent advances in vertex-based neuroimaging methods have made it possible to identify specific locations of subtle morphometric changes within a structure of interest. Methods In this cross-sectional study, we used high-resolution magnetic resonance imaging to examine the relationship between PTSD symptomatology, as measured using the Clinician Administered PTSD Scale for the DSM-IV, and structural shape of the hippocampus and amygdala using vertex-wise shape analyses in a group of combat-exposed U.S. Veterans (N = 69). Results Following correction for multiple comparisons and controlling for age and cranial volume, we found that participants with more severe PTSD symptoms showed an indentation in the anterior half of the right hippocampus and an indentation in the dorsal region of the right amygdala (corresponding to the centromedial amygdala). Post hoc analysis using stepwise regression suggest that among PTSD symptom clusters, arousal symptoms explain most of the variance in the hippocampal abnormality, whereas reexperiencing symptoms explain most of the variance in the amygdala abnormality. Conclusion The results provide evidence of localized abnormalities in the anterior hippocampus and centromedial amygdala in combat-exposed U.S. Veterans suffering from PTSD symptoms. This novel finding provides a more fine-grained analysis of structural abnormalities in PTSD and may be informative for understanding the neurobiology of the disorder.
Abstract Background: Two decades of human neuroimaging research have associated volume reductions in the hippocampus with posttraumatic stress disorder. However, little is known about the distribution of volume loss across hippocampal subfields. Recent advances in neuroimaging methods have made it possible to accurately delineate 10 gray matter hippocampal subfields. Here, we apply a volumetric analysis of hippocampal subfields to data from a group of combat-exposed Veterans. Method: Veterans (total, n¼68, posttraumatic stress disorder, n¼36; combat control, n¼32) completed high-resolution structural magnetic resonance imaging. Based on previously validated methods, hippocampal subfield volume measurements were conducted using FreeSurfer 6.0. The Clinician-Administered PTSD Scale assessed posttraumatic stress disorder symptom severity; Beck Depression Inventory assessed depressive symptom severity. Controlling for age and intracranial volume, partial correlation analysis examined the relationship between hippocampal subfields and symptom severity. Correction for multiple comparisons was performed using false discovery rate. Gender, intelligence, combat severity, comorbid anxiety, alcohol/substance use disorder, and medication status were investigated as potential confounds. Results: In the whole sample, total hippocampal volume negatively correlated with Clinician-Administered PTSD Scale and Beck Depression Inventory scores. Of the 10 hippocampal subfields, Clinician-Administered PTSD Scale symptom severity negatively correlated with the hippocampus–amygdala transition area (HATA). Beck Depression Inventory scores negatively correlated with dentate gyrus, cornu ammonis 4 (CA4), HATA, CA2/3, molecular layer, and CA1. Follow-up analysis limited to the posttraumatic stress disorder group showed a negative correlation between Clinician-Administered PTSD Scale symptom severity and each of HATA, CA2/3, molecular layer, and CA4. Conclusion: This study provides the first evidence relating posttraumatic stress disorder and depression symptoms to abnormalities in the HATA, an anterior hippocampal region highly connected to prefrontal-amygdala circuitry. Notably, dentate gyrus abnormalities were associated with depression severity but not posttraumatic stress disorder symptoms. Future confirmatory studies should determine the extent to which dentate gyrus volume can differentiate between posttraumatic stress disorder- and depression-related pathophysiology.
Purpose of review: Although a fine-grained understanding of the neurobiology of posttraumatic stress disorder (PTSD) is yet to be elucidated, the last two decades have seen a rapid growth in the study of PTSD using neuroimaging techniques. The current review summarizes important findings from functional and structural neuroimaging studies of PTSD, by primarily focusing on their relevance towards an emerging network-based neurobiological model of the disorder. Recent findings: PTSD may be characterized by a weakly connected and hypoactive default mode network (DMN) and central executive network (CEN) that are putatively destabilized by an overactive and hyperconnected salience network (SN), which appears to have a low threshold for perceived saliency, and inefficient DMN-CEN modulation. There is considerable evidence for large-scale functional and structural network dysfunction in PTSD. Nevertheless, several limitations and gaps in the literature need to be addressed in future research.
Question - Beyond its syntactical function, do you think that punctuation mark has another social function (especially while texting on social media)?
I think that this highlights one of the beautiful things about language -- it's constantly evolving.
Punctuation has always served a role in helping to shape and refine our written words (increasing clarity, conveying emotion, adding drama, whatever). However, texting and other (usually) short-form communication has created a new syntax that has continued to evolve languages, including the role of punctuation.
When texting, some people interpret sentences differently with and without punctuation (i.e., "I'm busy" might be interpreted as casual/pleasant, while "I'm busy." might be interpreted as being more terse/upsetting). Overuse of punctuation has become common enough (i.e., "AWESOME!!!!!!!") that some people feel like a single exclamation point might be used sarcastically or ironically, or etc.
There's a pervasive concern about whether or not people will read your text message and understand your emotions/intent, and punctuation (along with emoji) have been adopted to help circumvent perceived likelihood of misinterpretation.
The phenomenon is global, I think, because of the way human nature and technology interact with constructs like language. Texting isn't the first technology to change the way we communicate, linguistically. The evolution of writing, and the evolution of language go hand-in-hand :)
Question - Can 0.65 cronbach's Alpha value for five items scales is feasible for 89 respondents, please suggest some citations?
Cronbach's alpha is sensitive to the number of items that you present. Lower numbers of items will often mean lower alpha values, even if the items are very reliable to one another. There are more robust alternatives to measure internal consistency that may be worth exploring.
Question - Importing MR spectroscopy data into the MATLAB?
What formats are you trying to read? Have you checked out any of these?
Question - How to fix the Error During Packaging issue in MATLAB stand-alone application building?
Would you post the contents of the log/error? The screenshot alone wasn't informative enough for me.
Background: Chronic stress and related physiological responses are known to have deleterious effects on neural integrity. Combat exposure is a notoriously pathogenic stressor and with over 2 million U.S. troops deployed to active combat zones since 2001, there is an urgent need to advance our understanding of its potential neural impact. Previous evidence suggests structural alterations in PTSD and more recent studies have explored cortical thinning specifically. This preliminary study investigates the impact of combat exposure on cortical thickness, controlling for history of early life stress and age. Methods: Twenty-one combat-exposed Veterans with PTSD and 20 non-PTSD combat-exposed controls (mean age 32.7) completed the Combat Exposure Scale, Childhood Trauma Questionnaire and structural magnetic resonance imaging in a Siemens 3T TIM trio system. GLM was used to examine the effect of combat exposure on cortical thickness, controlling for early life trauma exposure and age using cluster-wise correction (p<0.05). Results: This preliminary study found a negative correlation between combat exposure severity (CES) and cortical thickness in the left superior temporal and left rostral middle frontal regions, as well as an interaction between PTSD diagnosis status and CES, in the superior temporal/insular region showing a stronger negative correlation between CES and cortical thickness in the non-PTSD group. Conclusions: Though caution should be taken with interpretation given the preliminary nature of the findings, the results indicate combat exposure may affect cortical structure beyond possible alterations due to early life stress exposure or PTSD psychopathology. Though replication in larger samples is required, these results provide useful information regarding possible neural biomarkers and treatment targets for combat-related psychopathology as well as highlighting the pathogenic effects of combat.
Background: The hippocampus and amygdala have been repeatedly implicated in the psychopathology of posttraumatic stress disorder (PTSD). While numerous structural neuroimaging studies examined these two structures in PTSD, these analyses have largely been limited to volumetric measures. Recent advances in vertex-based neuroimaging methods have made it possible to identify specific locations of subtle morphometric changes within a structure of interest. Methods: In this cross-sectional study, we used high-resolution magnetic resonance imaging to examine the relationship between PTSD symptomatology, as measured using the Clinician Administered PTSD Scale for the DSM-IV (CAPS), and structural shape of the hippocampus and amygdala using vertex-wise shape analyses in a group of combat-exposed US Veterans (N = 69). Results: Following correction for multiple comparisons and controlling for age and cranial volume, we found that participants with more severe PTSD symptoms showed an indentation in the anterior half of the right hippocampus and an indentation in the dorsal region of the right amygdala (corresponding to the centromedial amygdala). Post hoc analysis using stepwise regression suggest that among PTSD symptom clusters, arousal symptoms explain most of the variance in the hippocampal abnormality, whereas re-experiencing symptoms explain most of the variance in the amygdala abnormality. Conclusion: The results provide evidence of localized abnormalities in the anterior hippocampus and centromedial amygdala in combat-exposed US Veterans suffering from PTSD symptoms. This novel finding provides a more fine-grained analysis of structural abnormalities in PTSD and may be informative for understanding the neurobiology of the disorder.
Background: Prefrontal global brain connectivity with global signal regression (GBCr) was proposed as a robust biomarker of depression, and was associated with ketamine’s mechanism of action. Here, we investigated prefrontal GBCr in treatment-resistant depression (TRD) at baseline and following treatment. Then, we conducted a set of pharmacological challenges in healthy subjects to investigate the glutamate neurotransmission correlates of GBCr. Methods: In study A, we used functional magnetic resonance imaging (fMRI) to compare GBCr between 22 TRD and 29 healthy control. Then, we examined the effects of ketamine and midazolam on GBCr in TRD patients 24h post-treatment. In study B, we acquired repeated fMRI in 18 healthy subjects to determine the effects of lamotrigine (a glutamate release inhibitor), ketamine, and lamotrigine-by-ketamine interaction. Results: In study A, TRD patients showed significant reduction in dorsomedial and dorsolateral prefrontal GBCr compared to healthy control. In TRD patients, GBCr in the altered clusters significantly increased 24h following ketamine (effect size = 1.0 [0.3 1.8]), but not midazolam (effect size = 0.5 [-0.6 1.3]). In study B, oral lamotrigine reduced GBCr 2h post-administration, while ketamine increased medial prefrontal GBCr during infusion. Lamotrigine significantly reduced the ketamine-induced GBCr surge. Exploratory analyses showed elevated ventral prefrontal GBCr in TRD and significant reduction of ventral prefrontal GBCr during ketamine infusion in healthy subjects. Conclusions: This study provides first replication of the ability of ketamine to normalize depression-related prefrontal dysconnectivity. It also provides indirect evidence that these effects may be triggered by the capacity of ketamine to enhance glutamate neurotransmission.
We investigated the extent of cortical thinning in U.S. Veterans exposed to combat who varied in the severity of their posttraumatic stress disorder (PTSD) symptoms. In addition, we explored the neural correlates of PTSD symptom dimensions and the interactive effects of combat exposure and PTSD upon cortical thickness. Sixty-nine combat exposed Veterans completed high-resolution magnetic resonance imaging (MRI) scans to estimate cortical thickness. The Clinician Administered PTSD Scale (CAPS) and Combat Exposure Scale (CES) assessments were completed to measure current PTSD and historical combat severity, respectively. PTSD symptom dimensions (numbing, avoidance, reexperiencing, anxious arousal, and dysphoric arousal) were studied. Vertex-wise whole cerebrum analyses were conducted. We found widespread negative correlations between CAPS severity and cortical thickness, particularly within the prefrontal cortex. This prefrontal correlation remained significant after controlling for depression severity, medication status, and other potential confounds. PTSD dimensions, except anxious arousal, negatively correlated with cortical thickness in various unique brain regions. CES negatively correlated with cortical thickness in the left lateral prefrontal, regardless of PTSD diagnosis. A significant interaction between CES and PTSD diagnosis was found, such that CES negatively correlated with cortical thickness in the non-PTSD, but not in the PTSD, participants. The results underscore the severity of cortical thinning in U.S. Veterans suffering from high level of PTSD symptoms, as well as in Veterans with no PTSD diagnosis but severe combat exposure. The latter finding raises considerable concerns about a concealed injury potentially related to combat exposure in the post-9/11 era.
The anterior hippocampus (aHPC) has a central role in the regulation of anxiety-related behavior, stress response, emotional memory and fear. However, little is known about the presence and extent of aHPC abnormalities in posttraumatic stress disorder (PTSD). In this study, we used a multimodal approach, along with graph-based measures of global brain connectivity (GBC) termed functional GBC with global signal regression (f-GBCr) and diffusion GBC (d-GBC), in combat-exposed US Veterans with and without PTSD. Seed-based aHPC anatomical connectivity analyses were also performed. A whole-brain voxel-wise data-driven investigation revealed a significant association between elevated PTSD symptoms and reduced medial temporal f-GBCr, particularly in the aHPC. Similarly, aHPC d-GBC negatively correlated with PTSD severity. Both functional and anatomical aHPC dysconnectivity measures remained significant after controlling for hippocampal volume, age, gender, intelligence, education, combat severity, depression, anxiety, medication status, traumatic brain injury and alcohol/substance comorbidities. Depression-like PTSD dimensions were associated with reduced connectivity in the ventromedial and dorsolateral prefrontal cortex. In contrast, hyperarousal symptoms were positively correlated with ventromedial and dorsolateral prefrontal connectivity. We believe the findings provide first evidence of functional and anatomical dysconnectivity in the aHPC of veterans with high PTSD symptomatology. The data support the putative utility of aHPC connectivity as a measure of overall PTSD severity. Moreover, prefrontal global connectivity may be of clinical value as a brain biomarker to potentially distinguish between PTSD subgroups.
Posttraumatic stress disorder (PTSD) is a chronic and debilitating psychiatric disorder afflicting millions of individuals across the world. While the availability of robust pharmacologic interventions is quite lacking, our understanding of the putative neurobiological underpinnings of PTSD has significantly increased over the past two decades. Accumulating evidence demonstrates aberrant glutamatergic function in mood, anxiety, and trauma-related disorders and dysfunction in glutamate neurotransmission is increasingly considered a cardinal feature of stress-related psychiatric disorders including PTSD. As part of a PTSD Special Issue, this mini-review provides a concise discussion of (1) evidence of glutamatergic abnormalities in PTSD, with emphasis on human subjects data; (2) glutamate-modulating agents as potential alternative pharmacologic treatments for PTSD; and (3) selected gaps in the literature and related future directions.
Capitalizing on recent advances in resting state functional connectivity magnetic resonance imaging (rs-fcMRI) and the distinctive paradigm of rapid mood normalization following ketamine treatment, the current study investigated intrinsic brain networks in major depressive disorder (MDD) during a depressive episode and following treatment with ketamine. Medication-free patients with MDD and healthy control subjects (HC) completed baseline rs-fcMRI. MDD patients received a single infusion of ketamine and underwent repeated rs-fcMRI at 24 h post-treatment. Global brain connectivity with global signal regression (GBCr) values were computed as the average of correlations of each voxel with all other gray matter voxels in the brain. MDD group showed reduced GBCr in the prefrontal cortex (PFC), but increased GBCr in the posterior cingulate, precuneus, lingual gyrus, and cerebellum. Ketamine significantly increased GBCr in the PFC and reduced GBCr in the cerebellum. At baseline, 2174 voxels of altered GBCr were identified, but only 310 voxels significantly differed relative to controls following treatment (corrected α<0.05). Responders to ketamine showed increased GBCr in the lateral PFC, caudate, and insula. Followup seed-based analyses illustrated a pattern of dysconnectivity between the PFC/subcortex and the rest of the brain in MDD, which appeared to normalize post-ketamine. The extent of the functional dysconnectivity identified in MDD and the swift and robust normalization following treatment, suggest that GBCr may serve as a treatment response biomarker for the development of rapid acting antidepressants. The data also identified unique prefrontal and striatal circuitry as putative marker of successful treatment and target for antidepressants development.Neuropsychopharmacology accepted article preview online, 08 September 2016. doi:10.1038/npp.2016.186.
Prescription opioid drug abuse has reached epidemic proportions. Individuals with chronic pain represent a large population at considerable risk of abusing opioids. The Opioid Abuse Risk Screener was developed as a comprehensive self-administered measure of potential risk that includes a wide range of critical elements noted in the literature to be relevant to opioid risk. The creation, refinement, and preliminary modeling of the item pool, establishment of preliminary concurrent validity, and the determination of the factor structure are presented. The initial development and validation of the Opioid Abuse Risk Screener shows promise for effective risk stratification.
Background: Major depressive disorder is a disabling neuropsychiatric condition that is associated with disrupted functional connectivity across brain networks. The precise nature of altered connectivity, however, remains incompletely understood. The current study was designed to examine the coherence of large-scale connectivity in depression using a recently developed technique termed global brain connectivity. Methods: A total of 82 subjects, including medication-free patients with major depression (n = 57) and healthy volunteers (n = 25) underwent functional magnetic resonance imaging with resting data acquisition for functional connectivity analysis. Global brain connectivity was computed as the mean of each voxel's time series correlation with every other voxel and compared between study groups. Relationships between global connectivity and depressive symptom severity measured using the Montgomery-Åsberg Depression Rating Scale were examined by means of linear correlation. Results: Relative to the healthy group, patients with depression evidenced reduced global connectivity bilaterally within multiple regions of medial and lateral prefrontal cortex. The largest between-group difference was observed within the right subgenual anterior cingulate cortex, extending into ventromedial prefrontal cortex bilaterally (Hedges' g = -1.48, P < 0.000001). Within the depressed group, patients with the lowest connectivity evidenced the highest symptom severity within ventromedial prefrontal cortex (r = -0.47, P = 0.0005). Conclusions: Patients with major depressive evidenced abnormal large-scale functional coherence in the brain that was centered within the subgenual cingulate cortex, and medial prefrontal cortex more broadly. These data extend prior studies of connectivity in depression and demonstrate that functional disconnection of the medial prefrontal cortex is a key pathological feature of the disorder. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.
Reduced cortical thickness in combat-exposed veterans with and without a history of early life abuse and neglect
Background: Global brain connectivity (GBC) is a recently developed graph-based measure of nodal strength in functional connectivity networks. Using fully data-driven approaches, GBC has been shown to identify major intrinsic brain networks (e.g. default mode network), to correlate with normal brain functions (e.g. intelligence), and to be disrupted in major depressive disorder (MDD), bipolar disorder, schizophrenia, and obsessive-compulsive disorder (OCD). In treatment-resistant MDD, our group has demonstrated prefrontal GBC abnormalities, which rapidly normalized 24 hours post ketamine treatment. These prior data highlight the potential utility of GBC as a replicable measure for data-driven identification of brain functional connectivity biomarkers. Here we investigated whether GBC is altered in US veterans with severe symptoms of posttraumatic stress disorder (PTSD). Methods: Sixty-eight combat-exposed US veterans (age mean±SEM ¼ 34.5±1.6, 8 females) completed the Clinician-Administered PTSD Scale (CAPS) and restingstate functional connectivity magnetic resonance imaging (rs-fcMRI) scans. Whole brain GBC analyses were conducted. The GBC value of each voxel is the average of its time series correlation with all other voxels, providing a measure of nodal strength in a graph-based network. Voxelwise correlations between GBC values and CAPS scores were performed, along with cluster-level type I error correction (p < 0.05). Results: We found negative correlations between CAPS scores and GBC in the left superior temporal cortex (Brodmann’s Area [BA]22; an area involved in complex sounds processing) and bilateral medial temporal regions, including primarily the anterior bilateral hippocampi and the right amygdala such that participants with severe PTSD symptomatology showed reduced amygdala and anterior hippocampal GBC. Two small clusters of positive correlations between CAPS scores and GBC were found in left visual cortex (BA 17 & 18) and left precuneus (BA 7; a hub in the default mode network). Conclusions: In contrast to findings by our group, and others, showing that GBC abnormalities in depression are predominantly in the prefrontal cortex, GBC alterations in PTSD were primarily found in mediotemporal structures, highlighting the potential disease specificity of the derived GBC measure. GBC dysconnectivity in the anterior hippocampus and amygdala may contribute to previously reported alterations in limbic system functioning in PTSD. In addition, it is believed that the posterior hippocampus is involved in spatial navigation and memory, while the anterior hippocampus mediates fear, reward, and motivation. Thus, the localization of the dysconnectivity to the anterior, but not posterior, hippocampus may have essential theoretical, clinical and therapeutic implications. Keywords: PTSD, fMRI Functional Connectivity, ventral hippocampus
- Apr 2014
- 35th Annual Meeting & Scientific Sessions of the Society of Behavioral Medicine
The ability to accurately identify individuals at-risk for opioid abuse is critical given the often catastrophic consequences of opioid misuse. The Opioid Abuse Risk Screener (OARS) was developed as a brief, comprehensive, evidence-based, risk stratification assessment tool. The OARS is a 46-item inventory that includes two factor-analytically derived subscales: Emotional Lability (e.g., issues related to depression, anxiety, & trauma response) and Aberrant Behavior (e.g., history of medical non-compliance, smoking, and history of medication or illicit substance abuse). Scores from each of these subscales are subjected to a statistically and clinically-informed algorithm to compute overall opiate abuse potential (low, medium, and high risk). The present purpose was to examine the ability of the OARS to differentiate abuse risk in three types of individuals sampled from clinics across Utah: Healthy (H; n = 88; denying substance use disorders, chronic pain, or significant psychiatric concerns); Pain Treatment (PT; n = 144; actively receiving pain management services at a pain clinic); and Substance Abuse Treatment (SAT; n = 152; currently involved in outpatient substance abuse treatment). It was hypothesized that individuals within the SAT group would reflect higher risk on the OARS versus the H or PT groups. Results of a chi-square test demonstrated statistically significantly differences (p = .000) among risk stratifications across the groups. Among the SAT group, 86% of the sample was categorized as either moderate or high risk. Among the H group, 85% of the sample fell in either the low or moderate risk categories. The PT group was relatively evenly distributed across risk assessment categories. The potential value of the OARS to quantify opiate abuse risk is discussed. Plans for future predictive validity studies of the OARS are elucidated. CORRESPONDING AUTHOR: Michael S. DeBerard, PhD, Psychology, Utah State University, Logan, UT, 84322-2810; email@example.com Volume 47, Issue 1 Supplement, April 2014; pp S289. DOI: 10.1007/s12160-014-9596-9.
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