Robust hierarchically organized whole-brain patterns of dysconnectivity in schizophrenia spectrum disorders observed after personalized intrinsic network topography.

BACKGROUND: Spatial patterns of brain functional connectivity can vary substantially at the individual level. Applying cortical surface-based approaches with individualized rather than group templates may accelerate the discovery of biological markers related to psychiatric disorders. We investigated cortico-subcortical networks from multi-cohort data in people with schizophrenia spectrum disorders (SSDs) and healthy controls (HC) using individualized connectivity profiles. METHODS: We utilized resting-state and anatomical MRI data from n = 406 participants (n = 203 SSD, n = 203 HC) from four cohorts. Functional timeseries were extracted from previously defined intrinsic network subregions of the striatum, thalamus, and cerebellum as well as 80 cortical regions of interest, representing six intrinsic networks using (1) volume-based approaches, (2) a surface-based group atlas approaches, and (3) Personalized Intrinsic Network Topography (PINT). RESULTS: The correlations between all cortical networks and the expected subregions of the striatum, cerebellum, and thalamus were increased using a surface-based approach (Cohen's D volume vs. surface 0.27-1.00, all p < 10-6 ) and further increased after PINT (Cohen's D surface vs. PINT 0.18-0.96, all p < 10-4 ). In SSD versus HC comparisons, we observed robust patterns of dysconnectivity that were strengthened using a surface-based approach and PINT (Number of differing pairwise-correlations: volume: 404, surface: 570, PINT: 628, FDR corrected). CONCLUSION: Surface-based and individualized approaches can more sensitively delineate cortical network dysconnectivity differences in people with SSDs. These robust patterns of dysconnectivity were visibly organized in accordance with the cortical hierarchy, as predicted by computational models.

Depression Predicts Functional Outcome in Geriatric Inpatient Rehabilitation.

OBJECTIVE: To evaluate the effect of depression on functional recovery in geriatric patients who have completed an inpatient rehabilitation program. DESIGN: Prospective cohort study. SETTING: Inpatient rehabilitation unit of a university-affiliated geriatric hospital. PARTICIPANTS: Convenience sample of patients (N=65; mean age, 81.6y; 25 men) admitted to rehabilitation over a 10-month period. Patients >60 years of age who were proficient in English and capable of providing informed consent were eligible to participate in the study. INTERVENTIONS: Depression was assessed using both the Geriatric Depression Scale-short form (GDS-15) and the Patient Health Questionnaire (9-item screen for depression) (PHQ-9). Measures of well-established predictors of rehabilitation outcome, which may interact with depression, were also obtained, and multiple regression linear modeling was used to evaluate the relation between depression and functional outcome over and above the contribution of these other factors. MAIN OUTCOME MEASURE: FIM (Functional Independence Measure) at discharge from the rehabilitation program. RESULTS: Depression, as assessed by the GDS-15, but not the PHQ-9, was predictive of functional outcome (standardized beta=-.151, P=.030) after controlling for other significant predictors, which included baseline disability, pain, cognition, and educational level. Participation in recreational, but not physio- or occupational, therapy additionally contributed to a small amount of variance in the functional outcome. CONCLUSIONS: Our findings suggest that self-report of depression is an independent predictor of functional outcome in high-tolerance, short-duration geriatric rehabilitation. Routine assessment of depressive symptoms in older adults using an instrument (eg, GDS-15) may help identify those at risk for poorer outcomes in rehabilitation.

Examining the Effect of Age on Visual-Vestibular Self-Motion Perception Using a Driving Paradigm.

Previous psychophysical research has examined how younger adults and non-human primates integrate visual and vestibular cues to perceive self-motion. However, there is much to be learned about how multisensory self-motion perception changes with age, and how these changes affect performance on everyday tasks involving self-motion. Evidence suggests that older adults display heightened multisensory integration compared with younger adults; however, few previous studies have examined this for visual-vestibular integration. To explore age differences in the way that visual and vestibular cues contribute to self-motion perception, we had younger and older participants complete a basic driving task containing visual and vestibular cues. We compared their performance against a previously established control group that experienced visual cues alone. Performance measures included speed, speed variability, and lateral position. Vestibular inputs resulted in more precise speed control among older adults, but not younger adults, when traversing curves. Older adults demonstrated more variability in lateral position when vestibular inputs were available versus when they were absent. These observations align with previous evidence of age-related differences in multisensory integration and demonstrate that they may extend to visual-vestibular integration. These findings may have implications for vehicle and simulator design when considering older users.

Examining anti-inflammatory therapies in the prevention of cardiovascular events: protocol for a systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: Inflammation is emerging as an important risk factor for atherosclerotic cardiovascular disease and has been a recent target for many novel therapeutic agents. However, comparative evidence regarding efficacy of these anti-inflammatory treatment options is currently lacking. METHODS AND ANALYSIS: This systematic review will include randomised controlled trials evaluating the effect of anti-inflammatory agents on cardiovascular outcomes in patients with known cardiovascular disease. Studies will be retrieved from Medline, Embase, the Cochrane Central Register of Controlled Trials, as well as clinical trial registry websites, Europe PMC and conference abstract handsearching. No publication date or language restrictions will be imposed. Eligible interventions must have some component of anti-inflammatory agent. These include (but are not limited to): non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, prednisone, methotrexate, canakinumab, pexelizumab, anakinra, succinobucol, losmapimod, inclacumab, atreleuton, LP-PLA2 (darapladib) and sPLA2 (varespladib). The primary outcomes will include major adverse cardiac events (MACE), and each individual component of MACE (myocardial infarction, stroke and cardiovascular death). Key secondary outcomes will include unstable angina, heart failure, all-cause mortality, cardiac arrest and revascularisation. Screening, inclusion, data extraction and quality assessment will be performed independently by two reviewers. Network meta-analysis based on the random effects model will be conducted to compare treatment effects both directly and indirectly. The quality of the evidence will be assessed with appropriate tools including the Grading of Recommendations, Assessment, Development and Evaluation profiler or Confidence in Network Meta-Analysis tool. ETHICS AND DISSEMINATION: Ethics approval is not required for this systematic review. The findings will be disseminated through a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022303289.

A dataset of simulated patient-physician medical interviews with a focus on respiratory cases.

Artificial Intelligence (AI) is playing a major role in medical education, diagnosis, and outbreak detection through Natural Language Processing (NLP), machine learning models and deep learning tools. However, in order to train AI to facilitate these medical fields, well-documented and accurate medical conversations are needed. The dataset presented covers a series of medical conversations in the format of Objective Structured Clinical Examinations (OSCE), with a focus on respiratory cases in audio format and corresponding text documents. These cases were simulated, recorded, transcribed, and manually corrected with the underlying aim of providing a comprehensive set of medical conversation data to the academic and industry community. Potential applications include speech recognition detection for speech-to-text errors, training NLP models to extract symptoms, detecting diseases, or for educational purposes, including training an avatar to converse with healthcare professional students as a standardized patient during clinical examinations. The application opportunities for the presented dataset are vast, given that this calibre of data is difficult to access and costly to develop.

Primary Spinal Melanoma: Case Report and Systematic Review.

INTRODUCTION: Primary malignant melanoma of the spinal cord (PSM) is a rare condition with limited evidence regarding its diagnosis (clinical and radiographic), management, and prognosis. Our aim was to report an extremely rare two cases of primary malignant melanoma of the spine one of them is sacral melanoma which represents the second reported case in the literature and to conduct a systematic review of the relevant literature. METHODS: The diagnosis and management of these cases were retrospectively reviewed. Using the PRISMA guideline, we conducted a systematic review of the literature to analyze different management strategies and the prognosis of such pathology. RESULTS: All two patients were operated on, and received gross total removal of their tumors, with extended follow up for tumor recurrences. One of the cases involved a sacral tumor, which was resected without adjuvant therapy. The other one was seen by oncology and received post-operative chemo- and radio- therapy. In addition to the aforementioned cases, we present a comprehensive review of the literature on PSM from 1950 to the present, demonstrating that PSM is a very rare tumor, with a limited counted number of cases reported worldwide. CONCLUSION: In conclusion, we report an exceedingly rare two cases of primary malignant melanoma of the spine. Early surgical intervention is key to the management of these rare and aggressive tumors. GTR should be attempted if possible.

Surgical intervention for spontaneous intracranial hypotension Type 4 CSF leak: A case report.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is a rare condition that can be very debilitating. SIH is well understood to be due to a CSF leak, however, identifying the source of the leak is still a challenge. We are presenting a case of Type 4 CSF leak and reviewing the related literature. CASE DESCRIPTION: A 46-year-old female presenting with intractable orthostatic headaches was diagnosed with SIH. She was unable to mobilize due to the severity of her symptoms. MRI scans of the brain and spine did not identify a source of the leak. After failing conservative therapy and multiple epidural blood patches, the patient underwent surgery which resulted in significant improvement in symptoms. CONCLUSION: This study has shown that surgical intervention improves symptoms in patients who do not have an identifiable source of CSF leak. Further studies need to be done to fully understand the role of surgery in Type 4 CSF leaks.

Cervical Spine Chondrosarcoma in an Adult with a History of Wilms Tumor.

INTRODUCTION: We report the first case of cervical spine chondrosarcoma in a Wilms tumor survivor. CASE DESCRIPTION: A 52-year-old female patient presented with myelopathic symptoms including poor balance, difficulty walking, and numbness of both feet. A magnetic resonance imaging of the spine showed a mass at the right C7-T1 foramen causing significant cord compression. The patient's symptoms improved after posterior decompression and fusion with excision of the tumor. CONCLUSION: Through our experience with this case, we would like to suggest a possible unknown genetic syndrome predisposing patients with Wilms tumor to chondrosarcoma as secondary neoplasms. We would also like to re-emphasize the need for vigilance when assessing patients with a history of Wilms tumor.

Challenges, Learning Curve, and Safety of Endoscopic Endonasal Surgery of Sellar-Suprasellar Lesions in a Community Hospital.

BACKGROUND AND OBJECTIVE: Endoscopic endonasal surgery (EES) for the management of sellar, suprasellar, and anterior skull base lesions is gaining popularity. Our aim was to analyze and present the clinical outcomes of EES for the management of these lesions in a community hospital setting. METHODS: We retrospectively reviewed the charts of 56 patients with sellar, suprasellar, and anterior skull base lesions who underwent EES between 2010 and 2018. RESULTS: There was male predominance (53.6%) with a mean age of 54.9 ± 13.7 years. Lesions were 45 pituitary adenomas, 5 meningiomas, 3 metastatic, 1 craniopharyngioma, 1 Rathke cyst, and 1 mucocele. Gross total excision was achieved in 57.1%, subtotal excision occurred in 37.5%, and decompression and biopsy were achieved in 5.4% patients. Postoperative vision normalized or improved in 27 patients (86.1%) and was stable in 4 patients (13.9%). Recovery of a preexisting hormonal deficit occurred in 13 (23.2%) patients, and a new hormonal deficit occurred in 9 patients (16.1%). The mean hospital stay was 6.1 ± 4.9 days. Postoperative complications included cerebrospinal fluid leak in 8 patients (14.3%). Four patients (7.1%) had meningitis. Diabetes insipidus was present in 19 patients (33.9%), and postoperative intracranial hematoma requiring evacuation was necessary in 2 patients (3.6%). The mean follow-up duration was 47.5 ± 25.8 months. Lesion progression or recurrence requiring redo surgery occurred in 5 patients (8.9%). Regarding the learning curve, the postoperative cerebrospinal fluid leak, meningitis, new hormonal deficits, and diabetes insipidus decreased in the second half of the patients. CONCLUSIONS: EES provides an effective and safe surgical option with low morbidity and mortality for the treatment of sellar, suprasellar, and anterior skull base lesions in a community hospital setting.

Impaired illness awareness in schizophrenia and posterior corpus callosal white matter tract integrity.

Impaired illness awareness (Imp-IA) in schizophrenia is associated with interhemispheric imbalance, resulting in left hemisphere dominance, primarily within the posterior parietal area (PPA). This may represent an interhemispheric "disconnection syndrome" between PPAs. To test this hypothesis, we aimed to determine if diffusion-based measures of white matter integrity were disrupted in the corpus callosal tracts linking PPAs (i.e., splenium) in patients with Imp-IA in schizophrenia. T1-weighted and diffusion-weighted scans were acquired on a 1.5T GE scanner for 100 participants with a DSM-IV-TR diagnosis of schizophrenia and 134 healthy controls aged 18 to 79 years. The corpus callosal white matter tracts were compared among patients with Imp-IA (n = 40), intact illness awareness (n = 60), and healthy controls. White matter disruption was measured with fractional anisotropy (FA) and mean diffusivity (MD). Group differences in FA were found in the splenium, with patients with Imp-IA having the lowest FA, which remained significant after controlling for sex, age, global cognition, and premorbid intelligence. No group differences in MD were observed. Splenial white matter tracts of the corpus callosum appear compromised in patients with Imp-IA. Transcallosal interhemispheric PPA white matter disruption may represent a "disconnection syndrome", manifesting as Imp-IA in schizophrenia. Future studies are required to investigate the effects of noninvasive brain stimulation interventions, such as transcranial direct current or magnetic stimulation, on Imp-IA in association with white matter changes in patients with schizophrenia.

Brain structure, cognition, and brain age in schizophrenia, bipolar disorder, and healthy controls.

Schizophrenia and bipolar disorder (BD) may be disorders of accelerated aging. Direct comparison of healthy aging populations with schizophrenia and BD patients across the adult lifespan may help inform this theory. In total, 225 individuals (91 healthy controls, 81 schizophrenia, 53 euthymic BD) underwent 3T T1-weighted magnetic resonance imaging, diffusion tensor imaging, and cognitive testing. We analyzed associations among age, diagnosis, and cognition with cortical thickness and fractional anisotropy (FA) using general linear models. We then assessed "brain age" using a random forest algorithm, which was also assessed in an independent sample (n = 147). Participants with schizophrenia had lower cortical thickness and FA compared with the other two groups, most prominently in fronto-temporal circuitry. These brain changes were more evident in younger participants than in older ones, yet were associated with cognitive performance independent of diagnosis. Predicted age was 8 years greater than chronological age in individuals with schizophrenia in the first sample and 6 years greater in the second sample. Predicted and chronological age were not different in BD. Differences in brain circuitry are present from illness onset most prominently in schizophrenia and to a lesser extent in BD. These results support a non-progressive "early hit" hypothesis/etiology of illness in the major psychoses. Brain age differences support the hypothesized early aging mechanism in schizophrenia but not in BD.

Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a major sequela of traumatic brain injury (TBI) in youths. The objective of this study was to examine whether ADHD symptoms are differentially associated with genetic risk and brain structure in youths with and without a history of TBI. METHODS: Medical history, ADHD symptoms, genetic data, and neuroimaging data were obtained from a community sample of youths. ADHD symptom severity was compared between those with and without TBI (TBI n = 418, no TBI n = 3193). The relationship of TBI history, genetic vulnerability, brain structure, and ADHD symptoms was examined by assessing 1) ADHD polygenic score (discovery sample ADHD n = 19,099, control sample n = 34,194), 2) basal ganglia volumes, and 3) fractional anisotropy in the corpus callosum and corona radiata. RESULTS: Youths with TBI reported greater ADHD symptom severity compared with those without TBI. Polygenic score was positively associated with ADHD symptoms in youths without TBI but not in youths with TBI. The negative association between the caudate volume and ADHD symptoms was not moderated by a history of TBI. However, the relationship between ADHD symptoms and structure of the genu of the corpus callosum was negative in youths with TBI and positive in youths without TBI. CONCLUSIONS: The identification of distinct ADHD etiology in youths with TBI provides neurobiological insight into the clinical heterogeneity in the disorder. Results indicate that genetic predisposition to ADHD does not increase the risk for ADHD symptoms associated with TBI. ADHD symptoms associated with TBI may be a result of a mechanical insult rather than neurodevelopmental factors.

Sex and Diffusion Tensor Imaging of White Matter in Schizophrenia: A Systematic Review Plus Meta-analysis of the Corpus Callosum.

Sex is considered an understudied variable in health research. Schizophrenia is a brain disorder with known sex differences in epidemiology and clinical presentation. We systematically reviewed the literature for sex-based differences of diffusion properties of white matter tracts in schizophrenia. We then conducted a meta-analysis examining sex-based differences in the genu and splenium of the corpus callosum in schizophrenia. Medline and Embase were searched to identify relevant papers. Studies fulfilling the following criteria were included: (1) included individuals with a diagnosis of schizophrenia, (2) included a control group of healthy individuals, (3) included both sexes in the patient and the control groups, (4) used diffusion tensor imaging, and (5) involved analyzing metrics of white matter microstructural integrity. Fractional anisotropy (FA) was used as the measure of interest in the meta-analysis. Of 730 studies reviewed, 75 met the inclusion criteria. Most showed no effect of sex, however, those that did found either that females have lower FA than males, or that the effect of disease in females is larger than that in males. The findings of the meta-analysis in the corpus callosum supported this result. There is a recognized need for studies on schizophrenia with a sufficient sample of female patients. Lack of power undermines the ability to detect sex-based differences. Understanding the sex-specific impact of illness on neural circuits may help inform development of new treatments, and improvement of existing interventions.

Personalized Intrinsic Network Topography Mapping and Functional Connectivity Deficits in Autism Spectrum Disorder.

BACKGROUND: Recent advances in techniques using functional magnetic resonance imaging data demonstrate individually specific variation in brain architecture in healthy individuals. To our knowledge, the effects of individually specific variation in complex brain disorders have not been previously reported. METHODS: We developed a novel approach (Personalized Intrinsic Network Topography, PINT) for localizing individually specific resting-state networks using conventional resting-state functional magnetic resonance imaging scans. Using cross-sectional data from participants with autism spectrum disorder (ASD; n = 393) and typically developing (TD) control participants (n = 496) across 15 sites, we tested: 1) effect of diagnosis and age on the variability of intrinsic network locations and 2) whether prior findings of functional connectivity differences in persons with ASD compared with TD persons remain after PINT application. RESULTS: We found greater variability in the spatial locations of resting-state networks within individuals with ASD compared with those in TD individuals. For TD persons, variability decreased from childhood into adulthood and increased in late life, following a U-shaped pattern that was not present in those with ASD. Comparison of intrinsic connectivity between groups revealed that the application of PINT decreased the number of hypoconnected regions in ASD. CONCLUSIONS: Our results provide a new framework for measuring altered brain functioning in neurodevelopmental disorders that may have implications for tracking developmental course, phenotypic heterogeneity, and ultimately treatment response. We underscore the importance of accounting for individual variation in the study of complex brain disorders.

Gray Matter Neuritic Microstructure Deficits in Schizophrenia and Bipolar Disorder.

BACKGROUND: Postmortem studies have demonstrated considerable dendritic pathologies among persons with schizophrenia and to some extent among those with bipolar I disorder. Modeling gray matter (GM) microstructural properties is now possible with a recently proposed diffusion-weighted magnetic resonance imaging modeling technique: neurite orientation dispersion and density imaging. This technique may bridge the gap between neuroimaging and histopathological findings. METHODS: We performed an extended series of multishell diffusion-weighted imaging and other structural imaging series using 3T magnetic resonance imaging. Participants scanned included individuals with schizophrenia (n = 36), bipolar I disorder (n = 29), and healthy controls (n = 35). GM-based spatial statistics was used to compare neurite orientation dispersion and density imaging-driven microstructural measures (orientation dispersion index and neurite density index [NDI]) among groups and to assess their relationship with neurocognitive performance. We also investigated the accuracy of these measures in the prediction of group membership, and whether combining them with cortical thickness and white matter fractional anisotropy further improved accuracy. RESULTS: The GM-NDI was significantly lower in temporal pole, anterior parahippocampal gyrus, and hippocampus of the schizophrenia patients than the healthy controls. The GM-NDI of patients with bipolar I disorder did not differ significantly from either schizophrenia patients or healthy controls, and it was intermediate between the two groups in the post hoc analysis. Regardless of diagnosis, higher performance in spatial working memory was significantly associated with higher GM-NDI mainly in the frontotemporal areas. The addition of GM-NDI to cortical thickness resulted in higher accuracy to predict group membership. CONCLUSIONS: GM-NDI captures brain differences in the major psychoses that are not accessible with other structural magnetic resonance imaging methods. Given the strong association of GM-NDI with disease state and neurocognitive performance, its potential utility for biological subtyping should be further explored.

Age Differences in Visual-Auditory Self-Motion Perception during a Simulated Driving Task.

Recent evidence suggests that visual-auditory cue integration may change as a function of age such that integration is heightened among older adults. Our goal was to determine whether these changes in multisensory integration are also observed in the context of self-motion perception under realistic task constraints. Thus, we developed a simulated driving paradigm in which we provided older and younger adults with visual motion cues (i.e., optic flow) and systematically manipulated the presence or absence of congruent auditory cues to self-motion (i.e., engine, tire, and wind sounds). Results demonstrated that the presence or absence of congruent auditory input had different effects on older and younger adults. Both age groups demonstrated a reduction in speed variability when auditory cues were present compared to when they were absent, but older adults demonstrated a proportionally greater reduction in speed variability under combined sensory conditions. These results are consistent with evidence indicating that multisensory integration is heightened in older adults. Importantly, this study is the first to provide evidence to suggest that age differences in multisensory integration may generalize from simple stimulus detection tasks to the integration of the more complex and dynamic visual and auditory cues that are experienced during self-motion.

rTMS of the dorsomedial prefrontal cortex for major depression: safety, tolerability, effectiveness, and outcome predictors for 10 Hz versus intermittent theta-burst stimulation.

BACKGROUND: Conventional rTMS protocols for major depression commonly employ stimulation sessions lasting >30 min. However, recent studies have sought to improve costs, capacities, and outcomes by employing briefer protocols such as theta burst stimulation (iTBS). OBJECTIVE: To compare safety, effectiveness, and outcome predictors for DMPFC-rTMS with 10 Hz (30 min) versus iTBS (6 min) protocols, in a large, naturalistic, retrospective case series. METHODS: A chart review identified 185 patients with a medication-resistant major depressive episode who underwent 20-30 sessions of DMPFC-rTMS (10 Hz, n = 98; iTBS, n = 87) at a single Canadian clinic from 2011 to 2014. RESULTS: Clinical characteristics of 10 Hz and iTBS patients did not differ prior to treatment, aside from significantly higher age in iTBS patients. A total 7912 runs of DMPFC-rTMS (10 Hz, 4274; iTBS, 3638) were administered, without any seizures or other serious adverse events, and no significant differences in rates of premature discontinuation between groups. Dichotomous outcomes did not differ significantly between groups (Response/remission rates: Beck Depression Inventory-II: 10 Hz, 40.6%/29.2%; iTBS, 43.0%/31.0%. 17-item Hamilton Rating Scale for Depression: 10 Hz, 50.6%/38.5%; iTBS, 48.5%/27.9%). On continuous outcomes, there was no significant difference between groups in pre-treatment or post-treatment scores, or percent improvement on either measure. Mixed-effects modeling revealed no significant group-by-time interaction on either measure. CONCLUSIONS: Both 10 Hz and iTBS DMPFC-rTMS appear safe and tolerable at 120% resting motor threshold. The effectiveness of 6 min iTBS and 30 min 10 Hz protocols appears comparable. Randomized trials comparing 10 Hz to iTBS may be warranted.