Story Grammar Analyses Capture Discourse Improvement in the First 2 Years Following a Severe Traumatic Brain Injury.

PURPOSE: Narration within a story grammar framework requires speakers to organize characters and events logically. Despite abundant research characterizing narrative deficits following a traumatic brain injury (TBI), the evolution of narrative story grammar over the first 2 years post-TBI has rarely been explored. This study analyzed story grammar in complex narratives of adults with and without severe TBI to (a) examine between-group differences and (b) investigate longitudinal changes over the first 2 years post-TBI. METHOD: Story grammar analyses of Cinderella narratives from 57 participants with TBI and 57 participants with no brain injury yielded measures of productivity (total number of episodes, total number of story grammar elements), elaboration (total number of elaborated-complete episodes, mean number of episodic elements per episode), and completeness (total number of incomplete episodes). Mann-Whitney U tests compared measures across groups; generalized estimating equation (GEE) models identified predictors of change, including recovery time (3, 6, 9, 12, and 24 months post-TBI) and demographic/injury-related characteristics. RESULTS: Between-group differences were statistically significant for all productivity and elaboration measures at 3, 6, and 9 months post-TBI; one productivity measure and one elaboration measure at 12 months; and none of the measures at 24 months. GEE models showed significant improvements in all productivity and elaboration measures over the first 24 months post-TBI, with educational attainment and duration of posttraumatic amnesia affecting recovery. Incomplete episodes only showed between-group differences at 12 months and did not capture recovery. CONCLUSION: Productivity and elaboration are key story grammar variables that (a) differentiate complex narration in individuals with and without severe TBI and (b) capture narrative improvements over the first 2 years post-TBI. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25148999.

Spoken Discourse Assessment and Analysis in Aphasia: An International Survey of Current Practices.

Purpose Spoken discourse analysis is commonly employed in the assessment and treatment of people living with aphasia, yet there is no standardization in assessment, analysis, or reporting procedures, thereby precluding comparison/meta-analyses of data and hindering replication of findings. An important first step is to identify current practices in collecting and analyzing spoken discourse in aphasia. Thus, this study surveyed current practices, with the goal of working toward standardizing spoken discourse assessment first in research settings with subsequent implementation into clinical settings. Method A mixed-methods (quantitative and qualitative) survey was publicized to researchers and clinicians around the globe who have collected and/or analyzed spoken discourse data in aphasia. The survey data were collected between September and November 2019. Results Of the 201 individuals who consented to participate, 189 completed all mandatory questions in the survey (with fewer completing nonmandatory response questions). The majority of respondents reported barriers to utilizing discourse including transcription, coding, and analysis. The most common barrier was time (e.g., lack of time). Respondents also indicated that there was a lack of, and a need for, psychometric properties and normative data for spoken discourse use in the assessment and treatment of persons with aphasia. Quantitative and qualitative results are described in detail. Conclusions The current survey study evaluated spoken discourse methods in aphasia across research and clinical settings. Findings from this study will be used to guide development of process standardization in spoken discourse and for the creation of a psychometric and normative property database. Supplemental Material https://doi.org/10.23641/asha.166395100.

Cingulo-Opercular and Frontoparietal Network Control of Effort and Fatigue in Mild Traumatic Brain Injury.

Neural substrates of fatigue in traumatic brain injury (TBI) are not well understood despite the considerable burden of fatigue on return to productivity. Fatigue is associated with diminishing performance under conditions of high cognitive demand, sense of effort, or need for motivation, all of which are associated with cognitive control brain network integrity. We hypothesize that the pathophysiology of TBI results in damage to diffuse cognitive control networks, disrupting coordination of moment-to-moment monitoring, prediction, and regulation of behavior. We investigate the cingulo-opercular (CO) and frontoparietal (FP) networks, which are engaged to sustain attention for task and maintain performance. A total of 61 individuals with mild TBI and 42 orthopedic control subjects participated in functional MRI during performance of a constant effort task requiring altering the amount of effort (25, 50, or 75% of maximum effort) utilized to manually squeeze a pneumostatic bulb across six 30-s trials. Network-based statistics assessed within-network organization and fluctuation with task manipulations by group. Results demonstrate small group differences in network organization, but considerable group differences in the evolution of task-related modulation of connectivity. The mild TBI group demonstrated elevated CO connectivity throughout the task with little variation in effort level or time on task (TOT), while CO connectivity diminished over time in controls. Several interregional CO connections were predictive of fatigue in the TBI group. In contrast, FP connectivity fluctuated with task manipulations and predicted fatigue in the controls, but connectivity fluctuations were delayed in the mild traumatic brain injury (mTBI) group and did not relate to fatigue. Thus, the mTBI group's hyper-connectivity of the CO irrespective of task demands, along with hypo-connectivity and delayed peak connectivity of the FP, may allow for attainment of task goals, but also contributes to fatigue. Findings are discussed in relation to performance monitoring of prediction error that relies on internal cues from sensorimotor feedback during task performance. Delay or inability to detect and respond to prediction errors in TBI, particularly evident in bilateral insula-temporal CO connectivity, corresponds to day-to-day fatigue and fatigue during task performance.

Standardizing Assessment of Spoken Discourse in Aphasia: A Working Group With Deliverables.

Purpose The heterogeneous nature of measures, methods, and analyses reported in the aphasia spoken discourse literature precludes comparison of outcomes across studies (e.g., meta-analyses) and inhibits replication. Furthermore, funding and time constraints significantly hinder collecting test-retest data on spoken discourse outcomes. This research note describes the development and structure of a working group, designed to address major gaps in the spoken discourse aphasia literature, including a lack of standardization in methodology, analysis, and reporting, as well as nominal data regarding the psychometric properties of spoken discourse outcomes. Method The initial initiatives for this working group are to (a) propose recommendations regarding standardization of spoken discourse collection, analysis, and reporting in aphasia, based on the results of an international survey and a systematic literature review and (b) create a database of test-retest spoken discourse data from individuals with and without aphasia. The survey of spoken discourse collection, analysis, and interpretation procedures was distributed to clinicians and researchers involved in aphasia assessment and rehabilitation from September to November 2019. We will publish survey results and recommend standards for collecting, analyzing, and reporting spoken discourse in aphasia. A multisite endeavor to collect test-retest spoken discourse data from individuals with and without aphasia will be initiated. This test-retest information will be contributed to a central site for transcription and analysis, and data will be subsequently openly curated. Conclusion The goal of the working group is to create recommendations for field-wide standards in methods, analysis, and reporting of spoken discourse outcomes, as has been done across other related disciplines (e.g., Consolidated Standards of Reporting Trials, Enhancing the Quality and Transparency of Health Research, Committee on Best Practice in Data Analysis and Sharing). Additionally, the creation of a database through our multisite collaboration will allow the identification of psychometrically sound outcome measures and norms that can be used by clinicians and researchers to assess spoken discourse abilities in aphasia.

Potential for Cognitive Communication Impairment in COVID-19 Survivors: A Call to Action for Speech-Language Pathologists.

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.

Macrostructural Analyses of Cinderella Narratives in a Large Nonclinical Sample.

Purpose Macrostructural narrative analyses are important clinical measures, revealing age-related declines and disorder-related impairments in the accuracy, completeness, logical sequencing, and organization of content. The current study aims to provide preliminary data on typical aging and psychometric evidence supporting multilevel Main Concept, Sequencing, and Story Grammar (MSSG) analyses that capture these aspects of narratives. Method Transcripts of Cinderella narratives for 92 healthy control participants stratified across four age brackets from the online database AphasiaBank were coded by Richardson and Dalton (2016) for main concept (MC) analysis. In the current study, MSSG analyses were completed for (a) logical sequencing, independently and in combination with MC accuracy and completeness (MC + sequencing), and (b) story grammar organization (i.e., inclusion of episodic components and complexity of episodes). Interrater agreement (99%-100%) revealed highly reliable scoring. Results Descriptive statistics for the typically aging sample are presented for sequencing, MC + sequencing, total episodic components, and episodic complexity. Scores for participants over 60 years of age were lower (poorer) than scores for those 20-59 years of age, supporting the construct validity of score use for identifying age-related declines in performance. Conclusions This study's novel MSSG analyses of narrative production efficiently assess the logical sequencing and story grammar organization of content in healthy controls. Preliminary reliability and validity evidence support the use of all scores to measure age-related changes in narrative macrostructure. Data from this typically aging sample provide a foundation for future research and clinical assessment aimed at quantifying narrative deficits in adults with communication disorders. Supplemental Material https://doi.org/10.23641/asha.12683495.

Resting-State Functional Magnetic Resonance Imaging Connectivity Between Semantic and Phonological Regions of Interest May Inform Language Targets in Aphasia.

Purpose Brain imaging has provided puzzle pieces in the understanding of language. In neurologically healthy populations, the structure of certain brain regions is associated with particular language functions (e.g., semantics, phonology). In studies on focal brain damage, certain brain regions or connections are considered sufficient or necessary for a given language function. However, few of these account for the effects of lesioned tissue on the "functional" dynamics of the brain for language processing. Here, functional connectivity (FC) among semantic-phonological regions of interest (ROIs) is assessed to fill a gap in our understanding about the neural substrates of impaired language and whether connectivity strength can predict language performance on a clinical tool in individuals with aphasia. Method Clinical assessment of language, using the Western Aphasia Battery-Revised, and resting-state functional magnetic resonance imaging data were obtained for 30 individuals with chronic aphasia secondary to left-hemisphere stroke and 18 age-matched healthy controls. FC between bilateral ROIs was contrasted by group and used to predict Western Aphasia Battery-Revised scores. Results Network coherence was observed in healthy controls and participants with stroke. The left-right premotor cortex connection was stronger in healthy controls, as reported by New et al. (2015) in the same data set. FC of (a) connections between temporal regions, in the left hemisphere and bilaterally, predicted lexical-semantic processing for auditory comprehension and (b) ipsilateral connections between temporal and frontal regions in both hemispheres predicted access to semantic-phonological representations and processing for verbal production. Conclusions Network connectivity of brain regions associated with semantic-phonological processing is predictive of language performance in poststroke aphasia. The most predictive connections involved right-hemisphere ROIs-particularly those for which structural adaptions are known to associate with recovered word retrieval performance. Predictions may be made, based on these findings, about which connections have potential as targets for neuroplastic functional changes with intervention in aphasia. Supplemental Material https://doi.org/10.23641/asha.12735785.

A resting-state network comparison of combat-related PTSD with combat-exposed and civilian controls.

Resting-state functional connectivity (rsFC) is an emerging means of understanding the neurobiology of combat-related post-traumatic stress disorder (PTSD). However, most rsFC studies to date have limited focus to cognitively related intrinsic connectivity networks (ICNs), have not applied data-driven methodologies or have disregarded the effect of combat exposure. In this study, we predicted that group independent component analysis (GICA) would reveal group-wise differences in rsFC across 50 active duty service members with PTSD, 28 combat-exposed controls (CEC), and 25 civilian controls without trauma exposure (CC). Intranetwork connectivity differences were identified across 11 ICNs, yet combat-exposed groups were indistinguishable in PTSD vs CEC contrasts. Both PTSD and CEC demonstrated anatomically diffuse differences in the Auditory Vigilance and Sensorimotor networks compared to CC. However, intranetwork connectivity in a subset of three regions was associated with PTSD symptom severity among executive (left insula; ventral anterior cingulate) and right Fronto-Parietal (perigenual cingulate) networks. Furthermore, we found that increased temporal synchronization among visuospatial and sensorimotor networks was associated with worse avoidance symptoms in PTSD. Longitudinal neuroimaging studies in combat-exposed cohorts can further parse PTSD-related, combat stress-related or adaptive rsFC changes ensuing from combat.

Salience Network Disruption in U.S. Army Soldiers With Posttraumatic Stress Disorder.

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 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.

Reduced Salience and Enhanced Central Executive Connectivity Following PTSD 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 posttreatment 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.

Effort and Fatigue-Related Functional Connectivity in Mild Traumatic Brain Injury.

Mental fatigue in healthy individuals is typically observed under conditions of high cognitive demand, particularly when effort is required to perform a task for a long period of time-thus the concepts of fatigue and effort are closely related. In brain injured individuals, mental fatigue can be a persistent and debilitating symptom. Presence of fatigue after brain injury is prognostic for return to work/school and engagement in activities of daily life. As such, it should be a high priority for treatment in this population, but because there is little understanding of its behavioral and neural underpinnings, the target for such treatment is unknown. Here, the neural underpinnings of fatigue and effort are investigated in active duty military service members with mild traumatic brain injury (mTBI) and demographically-matched orthopedic controls. Participants performed a Constant Effort task for which they were to hold a pre-defined effort level constant for long durations during fMRI scanning. The task allowed for investigation of the neural systems underlying fatigue and their relationship with sense of effort. While brain activation associated with effort and fatigue did not differentiate the mTBI and controls, functional connectivity amongst active brain regions did. The mTBI group demonstrated immediate hyper-connectivity that increased with effort level but diminished quickly when there was a need to maintain effort. Controls, in contrast, demonstrated a similar pattern of hyper-connectivity, but only when maintaining effort over time. Connectivity, particularly between the left anterior insula, rostral anterior cingulate cortex, and right-sided inferior frontal regions, correlated with effort-level and state fatigue in mTBI participants. These connections also correlated with effort level in the Control group, but only the connection between the left insula and superior medial frontal gyrus correlated with fatigue, suggesting a differing pattern of connectivity. These findings align, in part, with the dopamine imbalance, and neural efficiency hypotheses that pose key roles for medial frontal connections with insular or striatal regions in motivating or optimizing performance. Sense of effort and fatigue are closely related. As people fatigue, sense of effort increases systematically. The data propose a complex link between sense of effort, fatigue, and mTBI that is centered in what may be an inefficient neural system due to brain trauma that warrants further investigation.

Regional cerebral glucose metabolism differentiates danger- and non-danger-based traumas in post-traumatic stress disorder.

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.

Resting-state regional cerebral blood flow during adolescence: associations with initiation of substance use and prediction of future use disorders.

BACKGROUND: Adolescence is a period of developmental flux when brain systems are vulnerable to influences of early substance use, which in turn relays increased risk for substance use disorders. Our study intent was to assess adolescent regional cerebral blood flow (rCBF) as it relates to current and future alcohol use. The aim was to identify brain-based predictors for initiation of alcohol use and onset of future substance use disorders. METHODS: Quantitative rCBF was assessed in 100 adolescents (age 12-15). Prospective behavioral assessments were conducted annually over a three-year follow-up period to characterize onset of alcohol initiation, future drinking patterns and use disorders. Comparisons amongst use groups (i.e., current-, future-, and non-alcohol using adolescents) identified rCBF associated with initiation of alcohol use. Regression by future drinking patterns identified rCBF predictive of heavier drinking. Survival analysis determined whether or not baseline rCBF predicted later development of use disorders. RESULTS: Baseline rCBF was decreased to the parietal cortex and increased to mesolimbic regions in adolescents currently using alcohol as well as those who would use alcohol in the future. Higher baseline rCBF to the left fusiform gyrus and lower rCBF to the right inferior parietal cortex and left cerebellum was associated with future drinking patterns as well as predicted the onset of alcohol and substance use disorders in this cohort. CONCLUSIONS: Variations in resting rCBF to regions within reward and default mode or control networks appear to represent trait markers of alcohol use initiation and are predictive of future development of use disorders.

Structural brain anomalies and chronic pain: a quantitative meta-analysis of gray matter volume.

UNLABELLED: 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.

A coordinate-based meta-analytic model of trauma processing in posttraumatic stress disorder.

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.

Central sensitization as a component of post-deployment syndrome.

Many service members and veterans report chronic unexplained symptoms such as pain, fatigue and memory complaints, which have most recently been characterized as post-deployment syndrome (PDS). Chronic widespread pain is a component of this syndrome, producing significant disability and considerable health care costs. The similarity between the nature of these complaints and other medically unexplained illnesses such as fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome suggest that they may share a common mechanism. Here, we provide support for PDS as a consequence of pain and sensory amplification secondary to neuroplastic changes within the central nervous system, a phenomenon often termed central sensitization. We also discuss how factors such as stress and genetics may promote chronic widespread pain in veterans and service members who develop PDS.

Neuroimaging evidence of white matter inflammation in newly diagnosed systemic lupus erythematosus.

OBJECTIVE: Central nervous system (CNS) involvement occurs frequently in systemic lupus erythematosus (SLE) and frequently results in morbidity. The primary pathophysiology of CNS involvement in SLE is thought to be inflammation secondary to autoantibody-mediated vasculitis. Neuroimaging studies have shown hypometabolism (representing impending cell failure) and atrophy (representing late-stage pathology), but not inflammation. The purpose of this study was to detect the presence and regional distribution of inflammation (hypermetabolism) and tissue failure, apoptosis, or atrophy (hypometabolism). METHODS: Eighty-five patients with newly diagnosed SLE, who had no focal neurologic symptoms, were studied. Disease activity was quantified using the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI), a validated index of SLE-related disease activity. 18Fluorodeoxyglucose (FDG) positron emission tomography (PET) images of glucose uptake were analyzed by visual inspection and as group statistical parametric images, using the SELENA-SLEDAI score as the analysis regressor. RESULTS: SELENA-SLEDAI-correlated increases in glucose uptake were found throughout the white matter, most markedly in heavily myelinated tracts. SELENA-SLEDAI-correlated decreases were found in the frontal and parietal cortex, in a pattern similar to that seen during visual inspection and presented in previous reports of hypometabolism. CONCLUSION: The SELENA-SLEDAI-correlated increases in glucose consumption are potential evidence of inflammation, consistent with prior reports of hypermetabolism in inflammatory disorders. To our knowledge, this is the first imaging-based evidence of SLE-induced CNS inflammation in an SLE inception cohort. The dissociation among 18FDG uptake characteristics, spatial distribution, and disease activity correlation is in accordance with the notion that glucose hypermetabolism and hypometabolism reflect fundamentally different aspects of the pathophysiology of SLE with CNS involvement.