Ceramide kinase knockout ameliorates multiple sclerosis-like behaviors and demyelination in cuprizone-treated mice.

Changes in sphingolipid metabolism regulate and/or alter many cellular functions in the brain. Ceramide, a central molecule of sphingolipid metabolism, is phosphorylated to ceramide-1-phosphate (C1P) by ceramide kinase (CerK). CerK and C1P were reported to regulate many cellular responses, but their roles in immune-related diseases in vivo have not been well elucidated. Thus, we investigated the effects of CerK knockout on the onset/progression of multiple sclerosis (MS), which is a chronic neurodegenerative disease accompanied by the loss of myelin sheaths in the brain. MS-model mice were prepared using a diet containing the copper chelator cuprizone (CPZ). Treatment of 8-week-old mice with 0.2% CPZ for 8 weeks resulted in motor dysfunction based on the Rota-rod test, and caused the loss of myelin-related proteins (MRPs) in the brain and demyelination in the corpus callosum without affecting synaptophysin levels. CerK knockout, which did not affect developmental changes in MRPs, ameliorated the motor dysfunction, loss of MRPs, and demyelination in the brain in CPZ-treated mice. Loss of tail tonus, another marker of motor dysfunction, was detected at 1 week without demyelination after CPZ treatment in a CerK knockout-independent manner. CPZ-induced loss of tail tonus progressed, specifically in female mice, to 6-8 weeks, and the loss was ameliorated by CerK knockout. Activities of ceramide metabolic enzymes including CerK in the lysates of the brain were not affected by CPZ treatment. Inhibition of CerK as a candidate for MS treatment was discussed.

Longitudinal thalamic white and grey matter changes associated with visual hallucinations in Parkinson's disease.

OBJECTIVE: Visual hallucinations are common in Parkinson's disease (PD) and associated with worse outcomes. Large-scale network imbalance is seen in PD-associated hallucinations, but mechanisms remain unclear. As the thalamus is critical in controlling cortical networks, structural thalamic changes could underlie network dysfunction in PD hallucinations. METHODS: We used whole-brain fixel-based analysis and cortical thickness measures to examine longitudinal white and grey matter changes in 76 patients with PD (15 hallucinators, 61 non-hallucinators) and 26 controls at baseline, and after 18 months. We compared white matter and cortical thickness, adjusting for age, gender, time-between-scans and intracranial volume. To assess thalamic changes, we extracted volumes for 50 thalamic subnuclei (25 each hemisphere) and mean fibre cross-section (FC) for white matter tracts originating in each subnucleus and examined longitudinal change in PD-hallucinators versus non-hallucinators. RESULTS: PD hallucinators showed white matter changes within the corpus callosum at baseline and extensive posterior tract involvement over time. Less extensive cortical thickness changes were only seen after follow-up. White matter connections from the right medial mediodorsal magnocellular thalamic nucleus showed reduced FC in PD hallucinators at baseline followed by volume reductions longitudinally. After follow-up, almost all thalamic subnuclei showed tract losses in PD hallucinators compared with non-hallucinators. INTERPRETATION: PD hallucinators show white matter loss particularly in posterior connections and in thalamic nuclei, over time with relatively preserved cortical thickness. The right medial mediodorsal thalamic nucleus shows both connectivity and volume loss in PD hallucinations. Our findings provide mechanistic insights into the drivers of network imbalance in PD hallucinations and potential therapeutic targets.

Brain Motor Region Diffusion Tensor Imaging in Patients with Catatonic Schizophrenia: A Case-Control Study.

BACKGROUND: Only a small proportion of schizophrenia patients present with catatonic symptoms. Imaging studies suggest that brain motor circuits are involved in the underlying pathology of catatonia. However, data about diffusivity dysregulation of these circuits in catatonic schizophrenia are scarce. OBJECTIVES: To assess the involvement of brain motor circuits in schizophrenia patients with catatonia. METHODS: Diffusion tensor imaging (DTI) was used to measure white matter signals in selected brain regions linked to motor circuits. Relevant DTI data of seven catatonic schizophrenia patients were compared to those of seven non-catatonic schizophrenia patients, matched for sex, age, and education level. RESULTS: Significantly elevated fractional anisotropy values were found in the splenium of the corpus callosum, the right peduncle of the cerebellum, and the right internal capsule of the schizophrenia patients with catatonia compared to those without catatonia. This finding showed altered diffusivity in selected motor-related brain areas. CONCLUSIONS: Catatonic schizophrenia is associated with dysregulation of the connectivity in specific motoric brain regions and corresponding circuits. Future DTI studies are needed to address the neural correlates of motor abnormalities in schizophrenia-related catatonia during the acute and remitted state of the illness to identify the specific pathophysiology of this disorder.

Sex-specific disruption in corticospinal excitability and hemispheric (a)symmetry in multiple sclerosis.

Multiple Sclerosis (MS) is a neurodegenerative disease in which pathophysiology and symptom progression presents differently between the sexes. In a cohort of people with MS (n = 110), we used transcranial magnetic stimulation (TMS) to investigate sex differences in corticospinal excitability (CSE) and sex-specific relationships between CSE and cognitive function. Although demographics and disease characteristics did not differ between sexes, males were more likely to have cognitive impairment as measured by the Montreal Cognitive Assessment (MoCA); 53.3% compared to females at 26.3%. Greater CSE asymmetry was noted in females compared to males. Females demonstrated higher active motor thresholds and longer silent periods in the hemisphere corresponding to the weaker hand which was more typical of hand dominance patterns in healthy individuals. Males, but not females, exhibited asymmetry of nerve conduction latency (delayed MEP latency in the hemisphere corresponding to the weaker hand). In males, there was also a relationship between delayed onset of ipsilateral silent period (measured in the hemisphere corresponding to the weaker hand) and MoCA, suggestive of cross-callosal disruption. Our findings support that a sex-specific disruption in CSE exists in MS, pointing to interhemispheric disruption as a potential biomarker of cognitive impairment and target for neuromodulating therapies.

Cerebral ventriculomegaly in myotonic dystrophy type 1: normal pressure hydrocephalus-like appearances on magnetic resonance imaging.

BACKGROUND: Cerebral ventriculomegaly is an abnormal feature characteristic of myotonic dystrophy type 1 (DM1). This retrospective study investigated the morphologic changes accompanied by ventriculomegaly in DM1 on brain MRI. METHODS: One hundred and twelve adult patients with DM1 and 50 sex- and age-matched controls were assessed. The imaging characteristics for evaluations included the z-Evans Index (ventriculomegaly), callosal angle (CA), enlarged perivascular spaces in the centrum semiovale (CS-EPVS), temporo-polar white matter lesion (WML) on 3D fluid-attenuated inversion recovery (FLAIR), disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and pathological brain atrophy. The "z-Evans Index" was defined as the maximum z-axial length of the frontal horns to the maximum cranial z-axial length. To determine the imaging characteristics and genetic information (CTG repeat numbers) that were associated with the z-Evans Index, we used binominal logistic regression analyses. RESULTS: The z-Evans Index was significantly larger in the patients than in the controls (0.30 ± 0.05 vs. 0.24 ± 0.02; p < 0.01). The z-Evans Index was independently associated with the callosal angle (p < 0.01) and pathological brain atrophy (p < 0.01) but not with age, gender, CTG repeat numbers, or CS-EPVS. Of the 34 patients older than 49 years, 7 (20.6%) were considered to have DESH. CONCLUSIONS: Our MRI study revealed a normal pressure hydrocephalus (NPH)-like appearance as a morphologic finding accompanied by ventriculomegaly in DM1 that tends to occur in elderly patients.

Remote Corticospinal Tract Degeneration After Cortical Stroke in Rats May Not Preclude Spontaneous Sensorimotor Recovery.

Background. Recovery of motor function after stroke appears to be related to the integrity of axonal connections in the corticospinal tract (CST) and corpus callosum, which may both be affected after cortical stroke. Objective. In the present study, we aimed to elucidate the relationship of changes in measures of the CST and transcallosal tract integrity, with the interhemispheric functional connectivity and sensorimotor performance after experimental cortical stroke. Methods. We conducted in vivo diffusion magnetic resonance imaging (MRI), resting-state functional MRI, and behavior testing in twenty-five male Sprague Dawley rats recovering from unilateral photothrombotic stroke in the sensorimotor cortex. Twenty-three healthy rats served as controls. Results. A reduction in the number of reconstructed fibers, a lower fractional anisotropy, and higher radial diffusivity in the ipsilesional but intact CST, reflected remote white matter degeneration. In contrast, transcallosal tract integrity remained preserved. Functional connectivity between the ipsi- and contralesional forelimb regions of the primary somatosensory cortex significantly reduced at week 8 post-stroke. Comparably, usage of the stroke-affected forelimb was normal at week 28, following significant initial impairment between day 1 and week 8 post-stroke. Conclusions. Our study shows that post-stroke motor recovery is possible despite degeneration in the CST and may be supported by intact neuronal communication between hemispheres.

Clinical Characteristics of H1N1 Influenza A-Associated Mild Encephalopathy with Reversible Splenial Lesion: 4 Pediatric Cases.

OBJECTIVE: Mild encephalopathy with reversible splenial lesion (MERS) is associated with a variety of infections and anti-epileptic drug withdrawal. Here we report the clinical characteristics of H1N1 influenza A-associated MERS based on our experience of four pediatric cases. METHODS: A detailed retrospective analysis of four patients with H1N1 influenza A-associated MERS was performed at Guangzhou Women and Children's Medical Center. RESULTS: All patients exhibited mild influenza-like illness and seizures. Three patients presented with a new-onset seizure with fever after 5 years of age. 75% patients had altered mental status. For all four patients, influenza A (H1N1) viral RNA was detected in throat swab specimens at least twice. Brain magnetic resonance images revealed similar ovoid lesions in the corpus callosum, mainly in the splenium and for one patient in the splenium and genu of the corpus callosum. Only one patient had an abnormal electroencephalogram tracing. Cells and protein in the cerebrospinal fluid were normal in all patients. All patients received oseltamivir and one patient received intravenous immunoglobulin. As a result, all patients fully recovered after 2 months and showed no neurologic sequelae at discharge. CONCLUSION: This case series provides insight towards clinical features of H1N1 influenza A-associated MERS.

Mindfulness and Attention Deficit Hyperactivity Disorder: A Neuropsychological Perspective.

ABSTRACT: Understanding the underlying mechanisms of mindfulness has been a hot topic in recent years, not only in clinical fields but also in neuroscience. Most neuroimaging findings demonstrate that critical brain regions involved in mindfulness are responsible for cognitive functions and mental states. However, the brain is a complex system operating via multiple circuits and networks, rather than isolated brain regions solely responsible for specific functions. Mindfulness-based treatments for attention deficit hyperactivity disorder (ADHD) have emerged as promising adjunctive or alternative intervention approaches. We focus on four key brain circuits associated with mindfulness practices and effects on symptoms of ADHD and its cognitive dysfunction, including executive attention circuit, sustained attention circuit, impulsivity circuit, and hyperactivity circuit. We also expand our discussion to identify three key brain networks associated with mindfulness practices, including central executive network, default mode network, and salience network. We conclude by suggesting that more research efforts need to be devoted into identifying putative neuropsychological mechanisms of mindfulness on how it alleviates ADHD symptoms.

Altered spontaneous brain activity patterns in dysthyroid optic neuropathy: a resting-state fMRI study.

This research investigates the characteristics of spontaneous brain activity in dysthyroid optic neuropathy patients using the regional homogeneity technique. Sixteen patients with dysthyroid optic neuropathy and 16 thyroid-associated ophthalmopathy patients without dysthyroid optic neuropathy were recruited, matched for weight, height, age, sex, and educational level. All participants underwent resting-state functional nuclear resonance imaging, and the characteristics of spontaneous brain activity were evaluated using the regional homogeneity technique. Each participant in the dysthyroid optic neuropathy group also completed the Hospital Anxiety and Depression scale. Receiver operating characteristic curves were used to compare brain activity between the two groups. Pearson correlation analysis evaluated the relationship between regional homogeneity and clinical manifestations in dysthyroid optic neuropathy patients. In addition, we analyzed the correlation between Hospital Anxiety and Depression scale and regional homogeneity. We found that the regional homogeneity values at the corpus callosum/cingulate gyrus and parietal lobe/middle frontal gyrus significantly decreased in dysthyroid optic neuropathy patients. Regional homogeneity values at the corpus callosum/cingulate gyrus and parietal lobe/middle frontal gyrus were negatively correlated with Hospital Anxiety and Depression scale and disease duration. It was found that the regional homogeneity signal values were significantly lower than in thyroid-associated ophthalmopathy without in dysthyroid optic neuropathy, which may indicate a risk of regional brain dysfunction in dysthyroid optic neuropathy. The results show that regional homogeneity has the potential for early diagnosis and prevent dysthyroid optic neuropathy. In addition, the findings suggest possible mechanisms of dysthyroid optic neuropathy optic nerve injury. They may provide a valuable basis for further research on the pathological mechanisms of dysthyroid optic neuropathy.

Intracortical and Intercortical Motor Disinhibition to Transcranial Magnetic Stimulation in Newly Diagnosed Celiac Disease Patients.

BACKGROUND: Celiac disease (CD) may present or be complicated by neurological and neuropsychiatric manifestations. Transcranial magnetic stimulation (TMS) probes brain excitability non-invasively, also preclinically. We previously demonstrated an intracortical motor disinhibition and hyperfacilitation in de novo CD patients, which revert back after a long-term gluten-free diet (GFD). In this cross-sectional study, we explored the interhemispheric excitability by transcallosal inhibition, which has never been investigated in CD. METHODS: A total of 15 right-handed de novo, neurologically asymptomatic, CD patients and 15 age-matched healthy controls were screened for cognitive and depressive symptoms to the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively. TMS consisted of resting motor threshold, amplitude, latency, and duration of the motor evoked potentials, duration and latency of the contralateral silent period (cSP). Transcallosal inhibition was evaluated as duration and latency of the ipsilateral silent period (iSP). RESULTS: MoCA and HDRS scored significantly worse in patients. The iSP and cSP were significantly shorter in duration in patients, with a positive correlation between the MoCA and iSP. CONCLUSIONS: An intracortical and interhemispheric motor disinhibition was observed in CD, suggesting the involvement of GABA-mediated cortical and callosal circuitries. Further studies correlating clinical, TMS, and neuroimaging data are needed.

Structural Connectivity Remote From Lesions Correlates With Somatosensory Outcome Poststroke.

Background and Purpose: Changes in connectivity of white matter fibers remote to a stroke lesion, suggestive of structural connectional diaschisis, may impact on clinical impairment and recovery after stroke. However, until recently, we have not had tract-specific techniques to map changes in white matter tracts in vivo in humans to enable investigation of potential mechanisms and clinical impact of such remote changes. Our aim was to identify and quantify white matter tracts that are affected remote from a stroke lesion and to investigate the associations between reductions in tract-specific connectivity and impaired touch discrimination function after stroke. Methods: We applied fixel-based analysis to diffusion magnetic resonance imaging data from 37 patients with stroke (right lesion =16; left lesion =21) and 26 age-matched healthy adults. Three quantitative metrics were compared between groups: fiber density; fiber-bundle cross-section; and a combined measure of both (fiber-bundle cross-section) that reflects axonal structural connectivity. Results: Compared with healthy adults, patients with stroke showed significant common fiber-bundle cross-section and fiber density reductions in 4 regions remote from focal lesions that play roles in somatosensory and spatial information processing. Structural connectivity along the somatosensory fibers of the lesioned hemisphere was correlated with contralesional hand touch function. Touch function of the ipsilesional hand was associated with connectivity of the superior longitudinal fasciculus, and, for the right-lesion group, the corpus callosum. Conclusions: Remote tract-specific reductions in axonal connectivity indicated by diffusion imaging measures are observed in the somatosensory network after stroke. These remote white matter connectivity reductions, indicative of structural connectional diaschisis, are associated with touch impairment in patients with stroke.

Minocycline attenuation of rat corpus callosum abnormality mediated by low-dose lipopolysaccharide-induced microglia activation.

BACKGROUND: Microglia are resident innate immune cells in the brain, and activation of these myeloid cells results in secretion of a variety of pro-inflammatory molecules, leading to the development of neurodegenerative disorders. Lipopolysaccharide (LPS) is a widely used experimental stimulant in microglia activation. We have previously shown that LPS produced microglia activation and evoked detectable functional abnormalities in rat corpus callosum (CC) in vitro. Here, we further validated the effects of low-dose LPS-induced microglia activation and resultant white matter abnormality in the CC in an animal model and examined its attenuation by an anti-inflammatory agent minocycline. METHODS: Twenty-four SD rats were divided randomly into three groups and intra-peritoneally injected daily with saline, LPS, and LPS + minocycline, respectively. All animals were subject to MRI tests 6 days post-injection. The animals were then sacrificed to harvest the CC tissues for electrophysiology, western blotting, and immunocytochemistry. One-way ANOVA with Tukey's post-test of all pair of columns was employed statistical analyses. RESULTS: Systemic administration of LPS produced microglial activation in the CC as illustrated by Iba-1 immunofluorescent staining. We observed that a large number of Iba-1-positive microglial cells were hyper-ramified with hypertrophic somata or even amoeba like in the LPS-treated animals, and such changes were significantly reduced by co-administration of minocycline. Electrophysiological recordings of axonal compound action potential (CAP) in the brain slices contained the CC revealed an impairment on the CC functionality as detected by a reduction in CAP magnitude. Such an impairment was supported by a reduction of fast axonal transportation evidenced by ß-amyloid precursor protein accumulation. These alterations were attenuated by minocycline, demonstrating minocycline reduction of microglia-mediated interruption of white matter integrity and function in the CC. CONCLUSIONS: Systemic administration of LPS produced microglia activation in the CC and resultant functional abnormalities that were attenuated by an anti-inflammatory agent minocycline.

Investigating the white matter correlates of reading performance: Evidence from Chinese children with reading difficulties.

PURPOSE: Reading comprehension is closely associated with word recognition, particularly at the early stage of reading development. This association is reflected in children with reading difficulties (RD) who demonstrate poor reading comprehension along with delayed word recognition or reduced recognition accuracy. Although the neural mechanisms underlying reading comprehension and word recognition are well studied, few has investigated the white matter (WM) structures that the two processes potentially share. METHODS: To explore the issue, behavioral scores (word recognition & reading comprehension) and diffusion spectrum imaging (DSI) were acquired from Chinese-speaking children with RD and their age-matched typically developing children. WM structures were measured with generalized fractional anisotropy and normalized quantitative anisotropy to optimize fiber tracking precision. RESULTS: The children with RD performed significantly poorer than the typically developing children in both behavioral tasks. Between group differences of WM structure were found in the right superior temporal gyrus, the left medial frontal gyrus, the left medial frontal gyrus, and the left caudate body. A significant association between reading comprehension and Chinese character recognition and the DSI indices were found in the corpus callosum. The findings demonstrated the microstructural difference between children with and without reading difficulties go beyond the well-established reading network. Further, the association between the WM integrity of the corpus callosum and the behavioral scores reveals the involvement of the WM structure in both tasks. CONCLUSION: It suggests the two reading-related skills have partially overlapped neural mechanism. Associating the corpus callosum with the reading skills leads to the reconsideration of the right hemisphere role in the typical reading process and, potentially, how it compensates for children with reading difficulties.

Mapping and anatomo-surgical techniques for SMA-cingulum-corpus callosum gliomas; how I do it.

BACKGROUND: Awake brain mapping paradigms are variable, particularly in SMA, and not personalised to each patient. In addition, subpial resections do not offer full protection to vascular injury, as the pia can be easily violated. METHODS: Mapping paradigms developed by a multidisciplinary brain mapping team. During resection, a combined subpial/interhemispheric approach allowed early identification and arterial skeletonization. Precise anatomo-surgical dissection of the affected cingulum and corpus callosum was achieved. CONCLUSIONS: In SMA-cingulum-CC tumours, a combined subpial/interhemispheric approach reduces risk of vascular injury allowing precise anatomo-surgical dissections. Knowledge of cognitive functions of affected parcels is likely to offer best outcomes.

Clinical Significance of Cytotoxic Lesions of the Corpus Callosum in Subarachnoid Hemorrhage Patients: A Retrospective Analysis.

INTRODUCTION: Cytotoxic lesions of the corpus callosum are secondary lesions induced by significant increases in cytokine levels in the brain and are associated with subarachnoid hemorrhage (SAH). However, their clinical significance in SAH patients remains unclear. METHODS: We retrospectively analyzed SAH patients who were treated in our hospital and evaluated between-group differences in the backgrounds, clinical findings, and outcomes between SAH patients who developed cytotoxic lesions of the corpus callosum and those who did not. We further compared patients who achieved good outcomes with those who had poor outcomes. Multivariate logistic regression analysis was used to identify risk factors for poor clinical outcomes. RESULTS: We analyzed 159 SAH patients; 17 patients (10.7%) had cytotoxic lesions of the corpus callosum. Patients with cytotoxic lesions of the corpus callosum were more likely to be in a severe condition (World Federation of Neurosurgical Societies grading IV-V: odds ratio [OR], 4.53; 95% confidence interval [95% CI]: 1.60-12.84; p = 0.0042) and have an intraventricular (OR, 5.98; 95% CI: 1.32-27.13; p = 0.0054) or an intraparenchymal hematoma (OR, 3.62; 95% CI: 1.25-10.45; p = 0.023). Patients with cytotoxic lesions of the corpus callosum had a greater propensity of a poor outcome 3 months after onset (modified Rankin Scale score 0-2: OR, 0.22; 95% CI: 0.07-0.66; p = 0.0043). Multivariate analysis confirmed that cytotoxic lesions of the corpus callosum increased the risk of a poor outcome (OR, 4.39; 95% CI: 1.06-18.1; p = 0.037). DISCUSSION/CONCLUSIONS: The development of cytotoxic lesions of the corpus callosum may be related to the extent of hematomas in SAH patients. Although they are usually reversible lesions, the development of cytotoxic lesions of the corpus callosum may be a predictor of poor outcomes in SAH patients.

Four-dimensional tractography animates propagations of neural activation via distinct interhemispheric pathways.

OBJECTIVE: To visualize and validate the dynamics of interhemispheric neural propagations induced by single-pulse electrical stimulation (SPES). METHODS: This methodological study included three patients with drug-resistant focal epilepsy who underwent measurement of cortico-cortical spectral responses (CCSRs) during bilateral stereo-electroencephalography recording. We delivered SPES to 83 electrode pairs and analyzed CCSRs recorded at 268 nonepileptic electrode sites. Diffusion-weighted imaging (DWI) tractography localized the interhemispheric white matter pathways as streamlines directly connecting two electrode sites. We localized and visualized the putative SPES-related fiber activation, at each 1-ms time window, based on the propagation velocity defined as the DWI-based streamline length divided by the early CCSR peak latency. RESULTS: The resulting movie, herein referred to as four-dimensional tractography, delineated the spatiotemporal dynamics of fiber activation via the corpus callosum and anterior commissure. Longer streamline length was associated with delayed peak latency and smaller amplitude of CCSRs. The cortical regions adjacent to each fiber activation site indeed exhibited CCSRs at the same time window. CONCLUSIONS: Our four-dimensional tractography successfully animated neural propagations via distinct interhemispheric pathways. SIGNIFICANCE: Our novel animation method has the potential to help investigators in addressing the mechanistic significance of the interhemispheric network dynamics supporting physiological function.

White matter abnormalities in fetal alcohol spectrum disorders: Focus on axon growth and guidance.

Fetal Alcohol Spectrum Disorders (FASDs) describe a range of deficits, affecting physical, mental, cognitive, and behavioral function, arising from prenatal alcohol exposure. FASD causes widespread white matter abnormalities, with significant alterations of tracts in the cerebral cortex, cerebellum, and hippocampus. These brain regions present with white-matter volume reductions, particularly at the midline. Neural pathways herein are guided primarily by three guidance cue families: Semaphorin/Neuropilin, Netrin/DCC, and Slit/Robo. These guidance cue/receptor pairs attract and repulse axons and ensure that they reach the proper target to make functional connections. In several cases, these signals cooperate with each other and/or additional molecular partners. Effects of alcohol on guidance cue mechanisms and their associated effectors include inhibition of growth cone response to repellant cues as well as changes in gene expression. Relevant to the corpus callosum, specifically, developmental alcohol exposure alters GABAergic and glutamatergic cell populations and glial cells that serve as guidepost cells for callosal axons. In many cases, deficits seen in FASD mirror aberrancies in guidance cue/receptor signaling. We present evidence for the need for further study on how prenatal alcohol exposure affects the formation of neural connections which may underlie disrupted functional connectivity in FASD.

Brain Magnetic Resonance Imaging Volumetric Measures of Functional Outcome after Severe Traumatic Brain Injury in Adolescents.

Adolescent traumatic brain injury (TBI) is a major public health concern, resulting in >35,000 hospitalizations in the United States each year. Although neuroimaging is a primary diagnostic tool in the clinical assessment of TBI, our understanding of how specific neuroimaging findings relate to outcome remains limited. Our study aims to identify imaging biomarkers of long-term neurocognitive outcome after severe adolescent TBI. Twenty-four adolescents with severe TBI (Glasgow Coma Scale ≤8) enrolled in the ADAPT (Approaches and Decisions after Pediatric TBI) study were recruited for magnetic resonance imaging (MRI) scanning 1-2 years post-injury at 13 participating sites. Subjects underwent outcome assessments ∼1-year post-injury, including the Wechsler Abbreviated Scale of Intelligence (IQ) and the Pediatric Glasgow Outcome Scale-Extended (GOSE-Peds). A typically developing control cohort of 38 age-matched adolescents also underwent scanning and neurocognitive assessment. Brain-image segmentation was performed on T1-weighted images using Freesurfer. Brain and ventricular cerebrospinal fluid volumes were used to compute a ventricle-to-brain ratio (VBR) for each subject, and the corpus callosum cross-sectional area was determined in the midline for each subject. The TBI group demonstrated higher VBR and lower corpus callosum area compared to the control cohort. After adjusting for age and sex, VBR was significantly related with GOSE-Peds score in the TBI group (n = 24, p = 0.01, cumulative odds ratio = 2.18). After adjusting for age, sex, intracranial volume, and brain volume, corpus callosum cross-sectional area correlated significantly with IQ score in the TBI group (partial cor = 0.68, n = 18, p = 0.007) and with PSI (partial cor = 0.33, p = 0.02). No association was found between VBR and IQ or between corpus callosum and GOSE-Peds. After severe adolescent TBI, quantitative MRI measures of VBR and corpus callosum cross-sectional area are associated with global functional outcome and neurocognitive outcomes, respectively.

Single Mild Traumatic Brain Injury Deteriorates Progressive Interhemispheric Functional and Structural Connectivity.

The present study examined dynamic interhemispheric structural and functional connectivity in mild traumatic brain injury (mTBI) patients with longitudinal observations from early subacute to chronic stages within 1 year of injury. Forty-two mTBI patients and 42 matched healthy controls underwent clinical and neuropsychological evaluations, diffusion tensor imaging, and resting-state functional magnetic resonance imaging. All mTBI patients were initially evaluated within 14 d post-injury (T-1) and at 3 months (T-2) and 6-12 months (T-3) follow-ups. Separate transcallosal fiber tracts in the corpus callosum (CC) with respect to their specific interhemispheric cortical projections were derived with fiber tracking and voxel-mirrored homotopic connectivity analyses. With diffusion tensor imaging-based tractography, five vertical segments of the CC (I-V) were distinguished. Correlation analyses were performed to evaluate relationships between structural and functional imaging measures as well as imaging indices and neuropsychological measures. The loss of integrity in the CC demonstrated saliently persistent and time-dependent regional specificity after mTBI. The impairment spanned multiple segments from CC II at T-1 and CC I, II, VI, and V at T-2 to all subregions at T-3. Moreover, loss of interhemispheric structural connectivity through the CC corresponded well to regions presenting altered interhemispheric functional connectivity. Decreased functional connectivity in the dorsolateral prefrontal cortex thereafter contributed to poor executive function in mTBI patients. The current study provides further evidence that the CC is a sign to interhemispheric highways underpinning the widespread cerebral pathology typifying mTBI syndrome.