The diversity of chronic pain syndromes and the methods employed to study them make integrating experimental findings challenging. This study performed coordinate-based meta-analyses using voxel-based morphometry imaging results to examine gray matter volume (GMV) differences between chronic pain patients and healthy controls. There were 12 clusters where GMV was decreased in patients compared with controls, including many regions thought to be part of the “pain matrix” of regions involved in pain perception, but also including many other regions that are not commonly regarded as pain-processing areas. The right hippocampus and parahippocampal gyrus were the only regions noted to have increased GMV in patients. Functional characterizations were implemented using the BrainMap database to determine which behavioral domains were significantly represented in these regions. The most common behavioral domains associated with these regions were cognitive, affective, and perceptual domains. Because many of these regions are not classically connected with pain and because there was such significance in functionality outside of perception, it is proposed that many of these regions are related to the constellation of comorbidities of chronic pain, such as fatigue and cognitive and emotional impairments. Further research into the mechanisms of GMV changes could provide a perspective on these findings. Perspective Quantitative meta-analyses revealed structural differences between brains of individuals with chronic pain and healthy controls. These differences may be related to comorbidities of chronic pain.

Relationships between structural MRI-based markers of declining cerebral integrity, and regional PET measurements of 18FDG uptake have not been studied well in normal aging. In this manuscript we relate changes in cerebral morphology to regional cerebral glucose uptake for 14 major cortical areas in 19 healthy older individuals (age 59–92 years). Measurements of cerebral integrity included gray matter (GM) thickness, sulcal and intergyral spans, fractional anisotropy (FA) of water diffusion and volume of hyperintense WM (HWM) lesions. 18FDG-PET measurements were converted to standard uptake values and corrected for partial volume artifact. Following this, cortical FDG uptake was significantly correlated with several indices of WM integrity that we previously observed to be sensitive to cognitive decline in executive function, including intergyral span and HWM volumes. Our findings suggest that the age-related decline in white matter integrity, observed as increases in HWM lesions, intergyral spans and reduction in FA, correlated with a decline in the global and regional cerebral glucose uptake. Our findings support the emerging consensus that WM integrity indices are sensitive predictors of declining cerebral health in normal aging. Specifically, age-related WM degradation in the thinly myelinated association tracts appears to track the decreases in global and regional rates of glucose uptake.

Objective Systemic lupus erythematosus (SLE) with central nervous system (CNS) involvement is frequent and can have high morbidity. The primary pathophysiology of SLE in the CNS is thought to be inflammation secondary to autoantibody-mediated vasculitis. Neuroimaging studies have reported hypometabolism (impending cell failure) and atrophy (late-stage pathology), but not inflammation. We used a validated index of SLE-related disease activity as a regressor for positron emission tomographic (PET) images of glucose uptake to detect the presence and regional distribution of inflammation (hypermetabolism) and tissue failure, apoptosis or atrophy (hypometabolism). Methods Eighty-five newly diagnosed SLE patients without focal neurological symptoms were studied. Disease activity was quantified using the SELENA SLE Disease Activity Index (SS). 18Fluoro-deoxy-glucose (FDG) PET images were analyzed by visual inspection and as group statistical parametric images using the SS score as the analysis regressor. Results SS-correlated increases in glucose uptake were found throughout the white matter, most marked in heavily myelinated tracts. SS-correlated decreases were found in frontal and parietal cortex, in a pattern similar to that seen by visual inspection and in prior reports of hypometabolism. Conclusion We interpret the SS-correlated increases in glucose consumption as potential evidence of inflammation, in keeping with prior reports of hypermetabolism in inflammatory disorders. To our knowledge, this is the first imaging evidence of SLE-induced CNS inflammation in an SLE inception cohort. The dissociation between 18FDG uptake characteristics, spatial distribution, and correlation with disease activity argues that glucose hyper- and hypometabolism reflect fundamentally different aspects of the pathophysiology of CNS SLE.

Posttraumatic stress disorder (PTSD) has a well-defined set of symptoms that can be elicited during traumatic imagery tasks. For this reason, trauma imagery tasks are often employed in functional neuroimaging studies. Here, coordinate-based meta-analysis (CBM) was used to pool eight studies applying traumatic imagery tasks to identify sites of task-induced activation in 170 PTSD patients and 104 healthy controls. In this way, right anterior cingulate (ACC), right posterior cingulate (PCC) and left precuneus (Pcun) were identified as regions uniquely active in PTSD patients relative to healthy controls. To further characterize these regions, their normal interactions, and their typical functional roles, meta-analytic connectivity modeling (MACM) with behavioral filtering was applied. MACM indicated that the PCC and Pcun regions were frequently co-active and associated with processing of cognitive information, particularly in explicit memory tasks. Emotional processing was particularly associated with co-activity of the ACC and PCC, as mediated by the thalamus. By narrowing the regions of interest to those commonly active across multiple studies (using CBM), and developing a priori hypotheses about directed probabilistic dependencies amongst these regions, this proposed model – when applied in the context of graphical and causal modeling – should improve model fit and thereby increase statistical power for detecting differences between subject groups and between treatments in neuroimaging studies of PTSD.

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Purpose Severe acute respiratory syndrome coronavirus 2 is the virus resulting in COVID-19 infections in nearly 4.3 million Americans with COVID-19 in the United States as of July 29, 2020, with nearly 150,000 deaths and hundreds of thousands of survivors ( https://www.coronavirus.jhu.edu/map.html ). This tutorial reviews (a) what has been reported about neurological insults in cases of COVID-19 infection, (b) what is known from similar conditions in other disorders, and (c) how that combined information can inform clinical decision making. Method PubMed and the Cochrane Central Register of Controlled Trials were searched for COVID-19 or other coronavirus infections, cognitive impairment observed following critical care, and disorders for which intermittent or chronic hypoxia is characteristic. These were combined with searches relating to cognition, brain, and communication. All searches were conducted between April 8 and May 23, 2020. Meta-analyses and randomized clinical trials addressing other critical illnesses were also included to extend findings to potential cognitive communication outcomes following COVID-19. Results COVID-19 infection results in a combination of (a) respiratory infection with mechanical ventilation secondary to inadequate oxygenation, (b) inflammatory system reactivity, and (c) increased blood clotting factors. These affect central nervous system function incurring long-term cognitive communication impairment in a proportion of survivors. Diagnostic and intervention approaches for such impairments are discussed. Conclusions The existing literature on cognitive sequela of COVID-19 infection is small to date, but much can be learned from similar viral infections and disorders. Although COVID-19 is novel, the speech-language pathology approaches to evaluation and intervention of other populations of critical care patients are applicable. However, speech-language pathologists have not routinely been involved in these patients' acute care. As such, this is a call to action to speech-language pathologists to address the unprecedented numbers of patients who will need their services early in the disease process and throughout recovery.

Post-traumatic stress disorder (PTSD) is presumably the result of life threats and conditioned fear. However, the neurobiology of fear fails to explain the impact of traumas that do not entail threats. Neuronal function, assessed as glucose metabolism with (18)fluoro-deoxyglucose positron emission tomography, was contrasted in active duty, treatment-seeking US Army Soldiers with PTSD endorsing either danger- (n = 19) or non-danger-based (n = 26) traumas, and was compared with soldiers without PTSD (Combat Controls, n = 26) and Civilian Controls (n = 24). Prior meta-analyses of regions associated with fear or trauma script imagery in PTSD were used to compare glucose metabolism across groups. Danger-based traumas were associated with higher metabolism in the right amygdala than the control groups, while non-danger-based traumas associated with heightened precuneus metabolism relative to the danger group. In the danger group, PTSD severity was associated with higher metabolism in precuneus and dorsal anterior cingulate and lower metabolism in left amygdala (R(2 )= 0.61). In the non-danger group, PTSD symptom severity was associated with higher precuneus metabolism and lower right amygdala metabolism (R(2 )= 0.64). These findings suggest a biological basis to consider subtyping PTSD according to the nature of the traumatic context.

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 ¼ 50) or without PTSD (n ¼ 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.