Persistent Brain Connectivity Changes in Healthy Volunteers Following Nitrous Oxide Inhalation.

Background: Nitrous oxide holds promise in the treatment of major depressive disorder. Its psychotropic effects and NMDA receptor antagonism have led to comparisons with ketamine. Despite longstanding use, persistent effects of nitrous oxide on the brain have not been characterized. Methods: Sixteen healthy volunteers were recruited in a double-blind crossover study. In randomized order, individuals underwent a 1-hour inhalation of either 50% nitrous oxide/oxygen or air/oxygen mixtures. At least two 7.5-minute echo-planar resting-state functional magnetic resonance imaging scans were obtained before and at 2 and 24 hours after each inhalation (average 130 min/participant). Using the time series of preprocessed, motion artifact-scrubbed, and nuisance covariate-regressed imaging data, interregional signal correlations were measured and converted to T scores. Hierarchical clustering and linear mixed-effects models were employed. Results: Nitrous oxide inhalation produced changes in global brain connectivity that persisted in the occipital cortex at 2 and 24 hours postinhalation (p < .05, false discovery rate-corrected). Analysis of resting-state networks demonstrated robust strengthening of connectivity between regions of the visual network and those of the dorsal attention network, across 2 and 24 hours after inhalation (p < .05, false discovery rate-corrected). Weaker changes in connectivity were found between the visual cortex and regions of the frontoparietal and default mode networks. Parallel analyses following air/oxygen inhalation yielded no significant changes in functional connectivity. Conclusions: Nitrous oxide inhalation in healthy volunteers revealed persistent increases in global connectivity between regions of primary visual cortex and dorsal attention network. These findings suggest that nitrous oxide inhalation induces neurophysiological cortical changes that persist for at least 24 hours.

Self-compassion and neural activity during self-appraisals in depressed and healthy adolescents.

BACKGROUND: Depression is one of the most concerning mental disorders in youth. Because atypical excessive neural activity during self-referential processing is often implicated in depression, identifying psychological factors that link to lower depression and less excessive neural activity during self-referential processing is critical for treatment development. This study examined the relationship between self-compassion - a protective factor of youth depression - and neural activity during self-appraisals, a well-established experimental paradigm for studying self-referential processing, and their associations with depression severity in depressed and healthy youth. METHODS: The sample consisted of 115 youth (79 met the clinical diagnosis of depression; 36 were matched healthy controls) aged from 11 to 17 years (68 females). Self-compassion and depression severity were measured with self-reported scales. In the scanner, participants were asked to judge whether the phrases they heard described them from four perspectives (self, mother, classmate, and best friend). RESULTS: Higher self-compassion was associated with lower PCC/precuneus activity especially during negatively-valenced self-appraisals and explained its association with reduced depression severity. In depressed youth, higher self-compassion was associated with lower superior temporal gyrus/operculum/postcentral gyrus/insula activity especially during positively-valenced self-appraisals. In healthy youth, higher self-compassion was associated with higher activity in these regions. CONCLUSIONS: Self-compassion was associated with less excessive experiential immersion and/or autobiographical memory retrieval during negative self-appraisals. Neural stimulation interventions targeting PCC/precuneus activity during negative self-appraisals combined with behavioral interventions targeting self-compassion could be a promising approach to youth depression treatment.

Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance.

Background: Recovery after SARS-CoV-2 infection is extremely variable, with some individuals recovering quickly, and others experiencing persistent long-term symptoms or developing new symptoms after the acute phase of infection, including fatigue, poor concentration, impaired attention, or memory deficits. Many existing studies reporting cognitive deficits associated with SARS-CoV-2 infection are limited by the exclusive use of self-reported measures or a lack of adequate comparison groups. Methods: Forty-five participants, ages 18-70, (11 Long-COVID, 14 COVID, and 20 No-COVID) underwent behavioral testing with the NIH Toolbox Neuro-Quality of Life survey and selected psychometric tests, including a flanker interference task and the d2 Test of Attention. Results: We found greater self-reported anxiety, apathy, fatigue, emotional dyscontrol, sleep disturbance and cognitive dysfunction in COVID compared No-COVID groups. After categorizing COVID patients according to self-reported concentration problems, we observed declining performance patterns in multiple attention measures across No-COVID controls, COVID and Long-COVID groups. COVID participants, compared to No-COVID controls, exhibited worse performance on NIH Toolbox assessments, including the Eriksen Flanker, Nine-Hole Pegboard and Auditory Verbal Learning tests. Conclusion: This study provides convergent evidence that previous SARS-CoV-2 infection is associated with impairments in sustained attention, processing speed, self-reported fatigue and concentration. The finding that some patients have cognitive and visuomotor dysfunction in the absence of self-reported problems suggests that SARS-CoV-2 infection can have unexpected and persistent subclinical consequences.

Self-compassion and dorsolateral prefrontal cortex activity during sad self-face recognition in depressed adolescents.

BACKGROUND: Given the prevalence of adolescent depression and the modest effects of current treatments, research ought to inform development of effective intervention strategies. Self-compassion is inversely associated with depression, and self-compassion interventions have demonstrated promising effects on reducing depression. However, little is known about the neural mechanisms underlying that relationship. Maladaptive self-processing is a characteristic of depression that contributes to the onset and chronicity of depression. Because our own face is an automatic and direct cue for self-processing, this study investigated whether self-compassion was associated with neural responses during sad v. neutral self-face recognition and explore their relationship with depression severity in depressed adolescents and healthy controls (HCs). METHODS: During functional magnetic resonance imaging, 81 depressed youth and 37 HCs were instructed to identify whether morphed self or other faces with sad, happy, or neutral expressions resembled their own. RESULTS: Self-compassion correlated negatively with activity during sad v. neutral self-face recognition in the dorsal anterior cingulate cortex in the total sample, and in the right posterior cingulate cortex/precuneus in HCs, respectively. In depressed adolescents, higher self-compassion correlated with lower activity during sad v. neutral self-face recognition in the right dorsolateral prefrontal cortex (DLPFC), implying that less cognitive effort might be needed to avoid dwelling on sad self-faces and/or regulate negative affect induced by them. Moreover, higher self-compassion mediated the relationship between lower DLPFC activity and reduced depression severity. CONCLUSIONS: Our findings imply that DLPFC activity might be a biological marker of a successful self-compassion intervention as potential treatment for adolescent depression.

Interfering with fear memories by eye movement desensitization and reprocessing.

OBJECTIVE: Pharmacologic and behavioral interventions that block reconsolidation of reactivated fear memory have demonstrated only limited success in modifying stronger and long-standing fear memories. Given the efficacy of Eye Movement Desensitization and Reprocessing (EMDR) in treating PTSD, pursuit eye movements are a promising and novel intervention for studies of human memory reconsolidation. Here, we examined the efficacy of pursuit eye movements in interfering with reconsolidation of conditioned fear memories. METHODS: We conducted a 3-day differential Pavlovian fear conditioning procedure in healthy adults, using videos of biologically prepared stimuli (tarantulas), partly reinforced with electrical shocks while recording skin conductance response (SCR) as a measure of autonomic conditioned responses. Fear conditioning was performed on Day 1. On Day 2, 38 participants were randomized into groups performing pursuit eye movements either immediately after fear memory reactivation, when the fear memory was stable, or 10 min later, when the fear memory was assumed to be more labile. On Day 3, fear memory strength was assessed by SCR to both reactivated and nonreactivated fear memories. RESULTS: Strong differential conditioning to the spider stimuli were observed during both fear acquisition and fear memory reactivation. Reactivated fear memory conditioned responses of participants performing pursuit eye movements after a 10-min delay were significantly smaller in the reinstatement phase (0.16 µS; 95% CI [0.02, 0.31]). CONCLUSIONS: Pursuit eye movements were effective in reducing fear-conditioned SCR in reinstatement. This result supports the theoretical proposition that EMDR can interfere with reactivated fear memory reconsolidation.

Differential Effects of AIDS and Chronic Human Immunodeficiency Virus Infection on Gray Matter Volume.

BACKGROUND: Age, human immunodeficiency virus (HIV) infection, illicit drug use, and central nervous system (CNS) opportunistic infections can affect brain structure, with the striatum being particularly sensitive to HIV effects. Nevertheless, the impact of non-CNS AIDS-defining illness (ADI) on brain structure has been less investigated. We examined ADI and HIV effects on brain volume. METHODS: In a cross-sectional study, including 95 virally suppressed seropositive and 84 demographically matched, seronegative participants, we examined serostatus and ADI effects. Cortical and subcortical gray matter volume (GMV) regions of interest were estimated with computational neuroanatomy techniques applied to high-resolution, T1-weighted magnetic resonance imaging data. Linear regression was used to model HIV serostatus and ADI effects on global and regional GMV, adjusting for age, sex, CD4 nadir, drug use, and total intracranial volume. RESULTS: While HIV serostatus was associated with lower striatal volume (B = -.59 [95% confidence interval {CI}, -1.08 to -.10]), co-occurring ADI was independently associated with lower striatal volume (B = -.73 [95% CI, -1.36 to -.09]). ADI was also associated with lower global (B = -19.35 [95% CI, -32.42 to -6.29]) and regional GMV. CONCLUSIONS: While HIV infection is associated with a localized effect on striatal structure, having a prior ADI is a strong predictor of smaller global and regional GMV. The lack of interaction between HIV serostatus or ADI with age suggests that chronic HIV infection and ADI have independent effects on brain structure, without associated accelerated lower volume with age. ADI history should be incorporated into statistical adjustments in HIV neuroimaging analysis. These findings also lend support to current HIV treatment guidelines urging prompt antiretroviral therapy initiation after HIV diagnosis.

Hunger and BMI modulate neural responses to sweet stimuli: fMRI meta-analysis.

OBJECTIVE: Consuming sweet foods, even when sated, can lead to unwanted weight gain. Contextual factors, such as longer time fasting, subjective hunger, and body mass index (BMI), may increase the likelihood of overeating. Nevertheless, the neural mechanisms underlying these moderating influences on energy intake are poorly understood. METHODS: We conducted both categorical meta-analysis and meta-regression of factors modulating neural responses to sweet stimuli, using data from 30 functional magnetic resonance imaging (fMRI) articles incorporating 39 experiments (N = 995) carried out between 2006 and 2019. RESULTS: Responses to sweet stimuli were associated with increased activity in regions associated with taste, sensory integration, and reward processing. These taste-evoked responses were modulated by context. Longer fasts were associated with higher posterior cerebellar, thalamic, and striatal activity. Greater self-reported hunger was associated with higher medial orbitofrontal cortex (OFC), dorsal striatum, and amygdala activity and lower posterior cerebellar activity. Higher BMI was associated with higher posterior cerebellar and insular activity. CONCLUSIONS: Variations in fasting time, self-reported hunger, and BMI are contexts associated with differential sweet stimulus responses in regions associated with reward processing and homeostatic regulation. These results are broadly consistent with a hierarchical model of taste processing. Hunger, but not fasting or BMI, was associated with sweet stimulus-related OFC activity. Our findings extend existing models of taste processing to include posterior cerebellar regions that are associated with moderating effects of both state (fast length and self-reported hunger) and trait (BMI) variables.

Autologous Mesenchymal Stem Cells Improve Motor Recovery in Subacute Ischemic Stroke: a Randomized Clinical Trial.

While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) promote recovery, few randomized controlled trials (RCT) have assessed cell therapy in humans. In this RCT, we assessed the safety, feasibility, and efficacy of intravenous autologous bone marrow-derived MSCs in subacute stroke. ISIS-HERMES was a single-center, open-label RCT, with a 2-year follow-up. We enrolled patients aged 18-70 years less than 2 weeks following moderate-severe ischemic carotid stroke. Patients were randomized 2:1 to receive intravenous MSCs or not. Primary outcomes assessed feasibility and safety. Secondary outcomes assessed global and motor recovery. Passive wrist movement functional MRI (fMRI) activity in primary motor cortex (MI) was employed as a motor recovery biomarker. We compared "treated" and "control" groups using as-treated analyses. Of 31 enrolled patients, 16 patients received MSCs. Treatment feasibility was 80%, and there were 10 and 16 adverse events in treated patients, and 12 and 24 in controls at 6-month and 2-year follow-up, respectively. Using mixed modeling analyses, we observed no treatment effects on the Barthel Index, NIHSS, and modified-Rankin scores, but significant improvements in motor-NIHSS (p = 0.004), motor-Fugl-Meyer scores (p = 0.028), and task-related fMRI activity in MI-4a (p = 0.031) and MI-4p (p = 0.002). Intravenous autologous MSC treatment following stroke was safe and feasible. Motor performance and task-related MI activity results suggest that MSCs improve motor recovery through sensorimotor neuroplasticity. ClinicalTrials.gov Identifier NCT00875654.

Spatial Network Connectivity and Spatial Reasoning Ability in Children with Nonverbal Learning Disability.

Nonverbal Learning Disability (NVLD) is characterized by deficits in visual-spatial, but not verbal, reasoning. Nevertheless, the functioning of the neural circuits supporting spatial processing have yet to be assessed in children with NVLD. We compared the resting state functional connectivity of a spatial brain network among children with NVLD, children with reading disorder (RD), and typically developing (TD) children. Seventy-five participants (7-15 years old) were included in the study (20 TD, 24 NVLD, and 31 RD). Group differences in global efficiency and functional connectivity among 12 regions comprising a previously defined spatial network were evaluated. Associations with behavior were explored. Global efficiency of the spatial network associated positively with spatial ability and inversely with socioemotional problems. Within the spatial network, associations between left posterior cingulate (PCC) and right retrosplenial cortical activity were reduced in children with NVLD relative to those without spatial deficits (RD and TD). Connectivity between left PCC and right posterior cerebellum (Crus I and II) was reduced in both groups of children with learning disabilities (NVLD and RD) relative to TD children. Functional connectivity of the spatial network was atypically associated with cognitive and socioemotional performance in children with NVLD. Identifying a neurobiological substrate for NVLD provides evidence that it is a discrete clinical entity and suggests targets for treatment.

Meta-analysis of brain metabolite differences in HIV infection.

BACKGROUND: Numerous studies have used magnetic resonance spectroscopy (MRS) neurometabolite measurements to study HIV infection effects. While many have reported differences in total N-Acetylaspartate (tNAA), myo-Inositol (mI), and total Choline (tCho), there have been no meta-analyses performed to evaluate concordance across studies. PURPOSE: To evaluate the consistency of HIV serostatus effects on brain metabolites. STUDY SELECTION: The sample included studies conducted between 1993 and 2019 reporting HIV infection effects measured using proton MRS. tNAA/tCr ratios (21 papers), tCho/tCr ratios (21 papers), mI/tCr ratios (17 papers) and quantitative tCr (9 papers), sampling from basal ganglia (BG), gray matter (GM), and white matter (WM) were included. DATA ANALYSIS: Random effects meta-analysis using inverse variance weighting and bias corrected standardized mean differences (SMDs) was used. Meta-regression examined effects of publication year and data acquisition technique differences. DATA SYNTHESIS: BG SMDs related to positive serostatus were -0.10 [-0.39; 0.18] tNAA/tCr, 0.27 [0.05; 0.49] tCho/tCr, 0.60 [0.31; 0.90] mI/tCr, and -0.26 [-0.59; 0.06] tCr. GM SMDs related to serostatus were -0.29 [-0.49; -0.09] tNAA/tCr, 0.37 [0.19; 0.54] tCho/tCr, 0.41 [0.15; 0.68] mI/tCr, and -0.24 [-0.45; -0.03] tCr. WM SMDs related to serostatus were -0.52 [-0.79; -0.25] tNAA/tCr, 0.41 [0.21; 0.61] tCho/tCr, 0.59 [0.24; 0.94] mI/tCr, and -0.03 [-0.25; 0.19] tCr. WM regions showed larger serostatus effect sizes than BG and GM. I2 ranged from 52 to 88% for the metabolite ratios. Both GM and WM tNAA/tCr SMDs were lower with increasing calendar year. LIMITATIONS: Many studies pooled participants with varying treatment, infection, and comorbidity durations. CONCLUSIONS: HIV neurometabolite studies showed consistently lower tNAA/tCr, higher tCho/tCr and higher mI/tCr ratios associated with chronic HIV infection. Substantial between-study variation may have resulted from measurement technique variations, study population differences and HIV treatment changes over time. Higher WM tCho/tCr and mI/tCr may reflect reactive gliosis or myelin turnover. Neurometabolite measurements can reliably detect chronic HIV infection effects and may be useful in understanding the pathophysiology of cognitive and sensorimotor decline following HIV infection. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence of neurometabolite differences in chronic HIV infection.

Neurofeedback and neuroplasticity of visual self-processing in depressed and healthy adolescents: A preliminary study.

Adolescence is a neuroplastic period for self-processing and emotion regulation transformations, that if derailed, are linked to persistent depression. Neural mechanisms of adolescent self-processing and emotion regulation ought to be targeted via new treatments, given moderate effectiveness of current interventions. Thus, we implemented a novel neurofeedback protocol in adolescents to test the engagement of circuits sub-serving self-processing and emotion regulation. METHODS: Depressed (n = 34) and healthy (n = 19) adolescents underwent neurofeedback training using a novel task. They saw their happy face as a cue to recall positive memories and increased displayed amygdala and hippocampus activity. The control condition was counting-backwards while viewing another happy face. A self vs. other face recognition task was administered before and after neurofeedback training. RESULTS: Adolescents showed higher frontotemporal activity during neurofeedback and higher amygdala and hippocampus and hippocampi activity in time series and region of interest analyses respectively. Before neurofeedback there was higher saliency network engagement for self-face recognition, but that network engagement was lower after neurofeedback. Depressed youth exhibited higher fusiform, inferior parietal lobule and cuneus activity during neurofeedback, but controls appeared to increase amygdala and hippocampus activity faster compared to depressed adolescents. CONCLUSIONS: Neurofeedback recruited frontotemporal cortices that support social cognition and emotion regulation. Amygdala and hippocampus engagement via neurofeedback appears to change limbic-frontotemporal networks during self-face recognition. A placebo group or condition and contrasting amygdala and hippocampus, hippocampi or right amygdala versus frontal loci of neurofeedback, e.g. dorsal anterior cingulate cortex, with longer duration of neurofeedback training will elucidate dosage and loci of neurofeedback in adolescents.

Is treated HIV infection still toxic to the brain?

Clinically apparent HIV infection, accompanied by CNS opportunistic infections and HIV encephalopathy, was often associated with profound structural and functional brain effects prior to the introduction of anti-retroviral therapy (ART). With treatment, HIV structural and functional brain effects are smaller and have not been as easily detected. With near complete elimination of CNS opportunistic infections, the HIV neuroimaging research community now grapples with the problem of detecting subtler structural and functional changes against a background of persisting confounds, such as comorbidities and clinical features common in the HIV infected population. This situation also raises the question of whether imaging measure changes that are reported as HIV brain effects are purely related to viral infection, rather than originating from confounding effects that might include age, substance use, hepatitis C coinfection, cerebrovascular risk factors, ART, premorbid cognitive skills and illness duration. In addition to cohort characteristics, variation in image acquisition and analysis techniques may also contribute to study outcome heterogeneity. We review the potential effects of these confounds on detection of HIV infection effects and discuss strategies to avoid or mitigate the effects of these confounds. We then present a systematic approach to measurement, design and analysis in HIV neuroimaging studies, combining both experimental and statistical control techniques to determine if HIV infection effects persist, fluctuate or worsen in groups achieving viral suppression from ART.

Why is Clinical fMRI in a Resting State?

While resting state fMRI (rs-fMRI) has gained widespread application in neuroimaging clinical research, its penetration into clinical medicine has been more limited. We surveyed a neuroradiology professional group to ascertain their experience with rs-fMRI, identify perceived barriers to using rs-fMRI clinically and elicit suggestions about ways to facilitate its use in clinical practice. The electronic survey also collected information about demographics and work environment using Likert scales. We found that 90% of the respondents had adequate equipment to conduct rs-fMRI and 82% found rs-fMRI data easy to collect. Fifty-nine percent have used rs-fMRI in their past research and 72% reported plans to use rs-fMRI for research in the next year. Nevertheless, only 40% plan to use rs-fMRI in clinical practice in the next year and 82% agreed that their clinical fMRI use is largely confined to pre-surgical planning applications. To explore the reasons for the persistent low utilization of rs-fMRI in clinical applications, we identified barriers to clinical rs-fMRI use related to the availability of robust denoising procedures, single-subject analysis techniques, demonstration of functional connectivity map reliability, regulatory clearance, reimbursement, and neuroradiologist training opportunities. In conclusion, while rs-fMRI use in clinical neuroradiology practice is limited, enthusiasm appears to be quite high and there are several possible avenues in which further research and development may facilitate its penetration into clinical practice.

HIV infection and age effects on striatal structure are additive.

The age of the HIV-infected population is increasing. Although many studies document gray matter volume (GMV) changes following HIV infection, GMV also declines with age. Findings have been inconsistent concerning interactions between HIV infection and age on brain structure. Effects of age, substance use, and inadequate viral suppression may confound identification of GMV serostatus effects using quantitative structural measures. In a cross-sectional study of HIV infection, including 97 seropositive and 84 seronegative, demographically matched participants, ages 30-70, we examined serostatus and age effects on GMV and neuropsychological measures. Ninety-eight percent of seropositive participants were currently treated with anti-retroviral therapies and all were virally suppressed. Gray, white, and CSF volumes were estimated using high-resolution T1-weighted MRI. Linear regression modeled effects of serostatus, age, education, comorbidities, and magnetic field strength on brain structure, using both a priori regions and voxel-based morphometry. Although seropositive participants exhibited significant bilateral decreases in striatal GMV, no serostatus effects were detected in the thalamus, hippocampus, or cerebellum. Age was associated with cortical, striatal, thalamic, hippocampal, and cerebellar GMV reductions. Effects of age and serostatus on striatal GMV were additive. Although no main effects of serostatus on neuropsychological performance were observed, serostatus moderated the relationship between pegboard performance and striatal volume. Both HIV infection and age were associated with reduced striatal volume. The lack of interaction of these two predictors suggests that HIV infection is associated with premature, but not accelerated, brain age. In serostatus groups matched on demographic and clinical variables, there were no observed differences in neuropsychological performance. Striatal GMV measures may be promising biomarker for use in studies of treated HIV infection.

Psychiatric Symptom Profiles Predict Functional Impairment.

Objective: Mental illness often interferes with daily functioning and an individual's pattern of psychiatric signs and symptoms may predict risk of future disability. Understanding the linkage between psychiatric symptoms and impaired functioning is critical for accurate rehabilitation planning and legal assessment. Here, we investigated the stability of functional impairment measures over 18 months and their association with psychiatric symptoms. Moreover, we developed a clinical self-report measure that allows estimation of functional impairment levels over 18 month observation periods. Methods: Consecutively treated outpatients and daycare patients (N = 155) from several psychiatric units in Switzerland completed the Dissociative Experiences Scale, Somatoform Dissociation Questionnaire, Multidimensional Inventory for Dissociation, Beck Depression Inventory, Brief Symptom Inventory, and WHO Disability Assessment Schedule at baseline, 6, 12, and 18 month follow-up examinations. The association between symptoms functional impairment over time was investigated using longitudinal linear mixed models. Penalized regression was used to identify questionnaire items that best predicted functional impairment. Results: We found high stability in the extent of functional impairment over 18 months. Fear of negative evaluation, fatigue, concentration problems, negative alterations in mood, and dissociative symptoms showed the strongest association with functional impairment measures. The empirically derived scale for functional impairment prediction explained between 0.62 and 0.77 of the variance in disability across various life domains. Conclusion: Given the capability for somatic and mental symptoms associated with social anxiety, depression, and dissociation to predict future disability, these symptoms have strong potential for guiding rehabilitation planning and prognostic evaluation in insurance medicine. The Functional Impairment Prediction Scale may serve as a valuable, empirical-based extension in legal assessments of how work capacity is affected by psychological factors.

Gender Trends in Academic Radiology Publication in the United States Revisited.

RATIONALE AND OBJECTIVES: Although substantial increases in publications by female academic radiologists have appeared over the last several decades, it is possible that the rate of increase is decreasing. We examined temporal trends in gender composition for full-time radiology faculty, radiology residents, and medical students over a 46-year period. METHODS: We examined authorship gender trends to determine if the increases in female authorship seen since 1970 have been sustained in recent years and whether female radiologists continue to publish in proportion to their numbers in academic departments. Original articles for selected years in Radiology and in the American Journal of Roentgenology between 1970 and 2016 were examined to determine the gender of first, corresponding, and last authors. Generalized linear models evaluated (1) changes in proportions of female authorship over time and (2) associations between proportions of female authorship and female radiology faculty representation. RESULTS: While linear increases in first, corresponding, and senior authorships were observed for female radiologists from 1970 to 2000, the rate of increase in female first and corresponding authorships then changed, with the slope of the first author relationship decreasing from 0.81 to 0.34, corresponding to 47% fewer female first authors added per year. In contrast, the proportion of female last authorship continued to increase at the same rate. The proportion of female first authorship was linearly related to the proportion of female radiology faculty from 1970 to 2016. CONCLUSIONS: Annual increases in first author academic productivity of female radiologists have lessened in the past 16 years, possibly related to reductions in the growth of female radiology faculty and trainees. As mixed, compared to homogeneous gender, authorship teams are associated with more citations, efforts to encourage more women to pursue careers in academic radiology could benefit the radiology research community.

Locus Coeruleus Activity Mediates Hyperresponsiveness in Posttraumatic Stress Disorder.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) are hyperresponsive to unexpected or potentially threatening environmental stimuli. Research in lower animals and humans suggests that sensitization of the locus coeruleus-norepinephrine system may underlie behavioral and autonomic hyperresponsiveness in PTSD. However, direct evidence linking locus coeruleus system hyperactivity to PTSD hyperresponsiveness is sparse. METHODS: Psychophysiological recording and functional magnetic resonance imaging were used during passive listening to brief, 95-dB sound pressure level, white noise bursts presented intermittently to determine whether behavioral and autonomic hyperresponsiveness to sudden sounds in PTSD is associated with locus coeruleus hyperresponsiveness. RESULTS: Participants with PTSD (n = 28) showed more eye-blink reflexes and larger heart rate, skin conductance, and pupil area responses to loud sounds (multivariate p = .007) compared with trauma-exposed participants without PTSD (n = 26). PTSD participants exhibited larger responses in locus coeruleus (t = 2.60, region of interest familywise error corrected), intraparietal sulcus, caudal dorsal premotor cortex, and cerebellar lobule VI (t ≥ 4.18, whole-brain familywise error corrected). Caudal dorsal premotor cortex activity was associated with both psychophysiological response magnitude and levels of exaggerated startle responses in daily life in PTSD participants (t ≥ 4.39, whole-brain familywise error corrected). CONCLUSIONS: Behavioral and autonomic hyperresponsiveness in PTSD may arise from a hyperactive alerting/orienting system in which processes related to attention and motor preparation localized to lateral premotor cortex, intraparietal sulcus, and posterior superior cerebellar cortex are modulated by atypically high phasic noradrenergic influences originating in the locus coeruleus.

Brain Structural Changes following HIV Infection: Meta-Analysis.

BACKGROUND: Numerous studies have used structural neuroimaging to measure HIV effects on brain macroarchitecture. While many have reported changes in total brain volume, gray matter volume, white matter volume, CSF volume, and basal ganglia volume following HIV infection, quantitative inconsistencies observed across studies are large. PURPOSE: Our aim was to evaluate the consistency and temporal stability of serostatus effects on a range of structural neuroimaging measures. DATA SOURCES: PubMed, reference lists, and corresponding authors. STUDY SELECTION: The meta-analysis included 19 cross-sectional studies reporting HIV effects on cortical and subcortical volume from 1993 to 2016. DATA ANALYSIS: Random-effects meta-analysis was used to estimate individual study standardized mean differences and study heterogeneity. Meta-regression was used to examine the effects of the study publication year. DATA SYNTHESIS: Meta-analysis revealed standardized mean differences related to the serostatus of -0.65 (P = .002) for total brain volume, -0.28 for gray matter volume (P = .008), -0.24 (P = .076) for white matter volume, and 0.56 (P = .001) for CSF volume. Basal ganglia volume differences related to serostatus were not significant. Nevertheless, estimates of between-study heterogeneity suggested that much of the observed variance was between studies. Publication year was associated with recent reductions in many neurostructural effects. LIMITATIONS: Many studies pooled participants with varying durations of treatment, disease, and comorbidities. Image-acquisition methods changed with time. CONCLUSIONS: While published studies of HIV effects on brain structure had substantial variations that are likely to result from changes in HIV treatment practice during the study period, quantitative neurostructural measures can reliably detect the effects of HIV infection during treatment, serving as reliable biomarkers.

Age-Related Decline of Wrist Position Sense and its Relationship to Specific Physical Training.

Perception of limb and body positions is known as proprioception. Sensory feedback, especially from proprioceptive receptors, is essential for motor control. Aging is associated with a decline in position sense at proximal joints, but there is inconclusive evidence of distal joints being equally affected by aging. In addition, there is initial evidence that physical activity attenuates age-related decline in proprioception. Our objectives were, first, to establish wrist proprioceptive acuity in a large group of seniors and compare their perception to young adults, and second, to determine if specific types of training or regular physical activity are associated with preserved wrist proprioception. We recruited community-dwelling seniors (n = 107, mean age, 70 ± 5 years, range, 65-84 years) without cognitive decline (Mini Mental State Examination-brief version ≥13/16) and young adult students (n = 51, mean age, 20 ± 1 years, range, 19-26 years). Participants performed contralateral and ipsilateral wrist position sense matching tasks with a bimanual wrist manipulandum to a 15° flexion reference position. Systematic error or proprioceptive bias was computed as the mean difference between matched and reference position. The respective standard deviation over five trials constituted a measure of random error or proprioceptive precision. Current levels of physical activity and previous sport, musical, or dance training were obtained through a questionnaire. We employed longitudinal mixed effects linear models to calculate the effects of trial number, sex, type of matching task and age on wrist proprioceptive bias and precision. The main results were that relative proprioceptive bias was greater in older when compared to young adults (mean difference: 36% ipsilateral, 88% contralateral, p < 0.01). Proprioceptive precision for contralateral but not for ipsilateral matching was smaller in older than in young adults (mean difference: 38% contralateral, p < 0.01). Longer years of dance training were associated with smaller bias during ipsilateral matching (p < 0.01). Other types of training or physical activity levels did not affect bias or precision. Our findings demonstrate that aging is associated with a decline in proprioceptive bias in distal arm joints, but age does not negatively affect proprioceptive precision. Further, specific types of long-term dance related training may attenuate age-related decline in proprioceptive bias.

Visual and Motor Recovery After "Cognitive Therapeutic Exercises" in Cortical Blindness: A Case Study.

BACKGROUND AND PURPOSE: Spontaneous visual recovery is rare after cortical blindness. While visual rehabilitation may improve performance, no visual therapy has been widely adopted, as clinical outcomes are variable and rarely translate into improvements in activities of daily living (ADLs). We explored the potential value of a novel rehabilitation approach "cognitive therapeutic exercises" for cortical blindness. CASE DESCRIPTION: The subject of this case study was 48-year-old woman with cortical blindness and tetraplegia after cardiac arrest. Prior to the intervention, she was dependent in ADLs and poorly distinguished shapes and colors after 19 months of standard visual and motor rehabilitation. Computed tomographic images soon after symptom onset demonstrated acute infarcts in both occipital cortices. INTERVENTION: The subject underwent 8 months of intensive rehabilitation with "cognitive therapeutic exercises" consisting of discrimination exercises correlating sensory and visual information. OUTCOMES: Visual fields increased; object recognition improved; it became possible to watch television; voluntary arm movements improved in accuracy and smoothness; walking improved; and ADL independence and self-reliance increased. Subtraction of neuroimaging acquired before and after rehabilitation showed that focal glucose metabolism increases bilaterally in the occipital poles. DISCUSSION: This study demonstrates feasibility of "cognitive therapeutic exercises" in an individual with cortical blindness, who experienced impressive visual and sensorimotor recovery, with marked ADL improvement, more than 2 years after ischemic cortical damage.Video Abstract available for additional insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A173).