Search

Background: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinic-radiological syndrome characterized by neurological deficiencies and reversible magnetic resonance imaging findings in the splenium of the corpus callosum. Usually, it has a good prognosis, and patients recover without any sequelae. A viral infection has caused most MERS cases, and bacterial agents have rarely been reported as a cause of MERS. Case report: A 5-month-old male was admitted to the hospital with fever, poor feeding, decreased activity and groaning. He had focal seizures and required mechanical ventilation. A lumbar puncture was performed, and nucleic acid amplification tests (NAATs) of cerebral spinal fluid was positive for non-typeable serogroup of Neisseria meningitidis. Cranial magnetic resonance imaging (MRI) performed on day 3 of admission showed T2 hyperintensity and diffusion restriction at the splenium of corpus callosum (SCC). Diffusion restriction in the occipital horn of the left ventricular compatible with empyema was also obvious. According to the findings on cranial MRI, this clinical course was diagnosed as MERS associated with meningitis. His fever resolved in one week, cefotaxime was discontinued after 14 days, and the patient completely recovered. A follow-up MRI performed after three weeks of admission showed complete resolution of the signal intensity changes in the SCC and the occipital horn of the left lateral ventricle. Conclusion: To the best of our knowledge, this is the first report of MERS associated with Neisseria meningitidis in children. Bacterial agents as a cause of MERS should be kept in mind, and we should avoid unnecessary treatment strategies due to the good prognosis of MERS in children. (C) 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Background/purpose Increased intra-individual variability (IIV) in reaction time (RT) is a key feature of attention-deficit/hyperactivity disorder (ADHD). However, little is known about neurobiology underpinnings of IIV in ADHD. Methods We assessed 55 youths with ADHD, and 55 individually-matched typically developing control (TDC) with the MRI and Conners' Continuous Performance Test. The ex-Gaussian distribution of RT was estimated to capture IIV with the parameters σ (sigma) and τ (tau). The regional brain volumes, analyzed by voxel-based morphometry, were correlated with IIV parameters. Results We found both distinct and shared correlations among ADHD and TDC. For grey matter, there were significant σ-by-group interactions in the cingulate cortex and thalamus and also a τ-by-group interaction in the right inferior frontal gyrus. There was also shared negative associations between σ and regional volumes of the right posterior cerebellum and a positive association between τ and the right anterior insula. For white matter, there was a significant σ-by-group interaction in the genu of the corpus callosum and significant τ-by-group interactions in the right anterior corona radiata, the left splenium of the corpus callosum, and bilateral posterior cerebellum. There were also shared patterns that increased τ was associated with increased regional volumes of the right anterior corona radiata and decreased regional volumes of the right posterior limb of the internal capsule. Conclusion This study highlights that brain regions responsible for the motor, salience processing and multimodal information integration are associated with increased IIV in youths with ADHD.

In the context of status epilepticus (SE), seizure-induced reversible MRI abnormalities (SRMA) can be difficult to differentiate from epileptogenic pathologies. To identify patterns and characteristics of SRMA, we conducted a systematic review in accordance with the Preferred Items Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included publications describing patients (a) presenting with status epilepticus, (b) exhibiting seizure-induced MRI abnormalities, (c) who demonstrated complete resolution of MRI abnormality at follow-up, and (d) who had availability of descriptive MRI results. A total of 49 cases from 19 publications fulfilled our eligibility criteria. Signal abnormalities were most frequently reported on T2-weighted sequences followed by diffusion-weighted and fluid-attenuated inversion recovery imaging. Both unilateral and bilateral SRMA were reported. Unilateral EEG abnormalities were often associated with ipsilateral SRMA. The signal changes appeared during the ictus itself in some subjects whilst the median time to SRMA appearance and resolution were 24 h and 96.5 days, respectively. Based on the distribution of reversible signal alterations, we identified five 'composite patterns': (1) predominant cortical (with or without subcortical, leptomeningeal or thalamic involvement), (2) hippocampal (with or without cortical, subcortical, leptomeningeal, or thalamic involvement), (3) claustrum, (4) predominant subcortical, and (5) splenium involvement. Amongst treatment-responsive SE patients, the cortical pattern was the most prevalent whereas hippocampal involvement was most frequently reported in refractory SE. Cortical atrophy, hippocampal sclerosis, and cortical laminar necrosis were common long-term sequelae after the resolution of SRMA. In this review, we highlight many limitations of the literature and discuss future directions for research.

Apathy is present at the onset in nearly half the patients with schizophrenia. Current therapies lack the efficiency to improve apathy in patients. The presence of apathy is also associated with poorer outcomes. Despite its clinical importance, the underlying mechanism of apathy in schizophrenia is unclear, but it seems frontostriatal connections play a role. In this study, we investigated whole-brain white matter microstructural properties associated with the severity of apathy-avolition in schizophrenia. We included 80 schizophrenia patients (60 Male, 20 Female) from the Mind Clinical Imaging Consortium database and associated Apathy-Avolition score of "Scale for Assessment of Negative Symptoms" with fiber integrity measures derived from diffusion-weighted imaging using Tract-Based Spatial Statistics (TBSS). We also did tractography on eight tracts, including bilateral superior longitudinal fasciculus, uncinate fasciculus, cingulum, genu and splenium of the corpus callosum. Age, gender, years of education, chlorpromazine equivalent cumulative dose, and acquisition site were inserted as covariates. We showed a widespread association between lower fiber integrity (by measures of increased mean diffusivity and decreased fractional anisotropy) and increased apathy-avolition in TBSS, which we also validated in tractography. Moreover, mean diffusivity, and not fractional anisotropy, was associated with apathy independent of disease severity. In conclusion, we propose diffuse white-matter pathology, within the corpus callosum, limbic system, and the frontostriatal circuit is involved in apathy-avolition in schizophrenia. Also, we suggest that diffuse neuroinflammatory processes may play a part in apathy-avolition, independent of disease severity.

Objective We performed a fine white fiber dissection to demonstrate the extensive connections of the corpus callosum. Material and Methods Three formalin-fixed frozen cadaveric human brain specimens were dissected using Klingler's technique. On one half of each hemisphere, the superior connections of the corpus callosum were dissected and in the other half the inferior connections of the corpus callosum were dissected. Results The mean length of the corpus callosum from the rostrum to the splenium was 7.8 cm. The fibers of the corpus callosum were classified as superior/dorsal radiations, inferior/ventral radiations, anterior radiations, and posterior radiations. The entire transverse length of the dorsal callosal radiation from one hemisphere to the other was 8.1 cm. For anterior interhemispheric approaches, an incision in the anterior part of the body not extending beyond 3.5 cm from the genu was found to be safe with regards to crossing motor fibers. Conclusions The corpus callosum was found to have intricate connections with all the lobes of the cerebral hemispheres, including the insular region and the limbic and paralimbic areas. Based on the course and traverse of the callosal fibers, a transverse incision in the corpus callosum should be preferred when performing a callosotomy to access intraventricular lesions as this splits the callosal fibers instead of transecting them. The analysis of the course of the callosal radiations enhances understanding of the growth pattern of primary corpus callosal gliomas and helps to design a safe surgical strategy.

Background Reversible lesions in the splenium of the corpus callosum (SCC) with viral infections are associated mainly with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). We report a pediatric patient in thyroid crisis with reversible SCC lesions. Case description We diagnosed a 9-year-old girl with thyroid crisis. She had presented with fever, tachycardia, and impaired consciousness. Magnetic resonance imaging revealed hyperintense signals in the splenium and genu of the corpus callosum and a white matter lesion of the left hemisphere in diffusion-weighted imaging. The initial, tentative diagnosis was clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). We initiated intravenous methylprednisolone pulse therapy; thereafter, her level of consciousness rapidly improved. On admission, thyroid function studies revealed elevation of free thyroxine and a low level of thyroid stimulating hormone with thyroid-related autoantibodies. She was begun on thiamazole and was discharged without neurological sequelae. Conclusion Thyroid crisis is similar to acute encephalitis or encephalopathy associated with viral infection, especially with MERS, because the clinical and radiological features resemble those of thyroid crisis; therefore, thyroid diseases should be considered as a possible cause of reversible lesions in the splenium of the corpus callosum.

Background The anatomy of the veins in the pineal region is one of the most complex areas in the brain because all major deep cerebral veins converge there: the internal cerebral veins (ICVs), the great cerebral vein of Galen (GV), the basal veins (BVs), and the internal occipital veins (IOVs). The aim of this study was to comprehensively describe the anatomy of the veins in the pineal region using computed tomography angiography. Methods Head computed tomography angiography scans of 250 adult Polish patients were evaluated. We assessed the location of the junction of 2 ICVs and the presence of a narrowing of the GV and arachnoid granulation at the GV–straight sinus junction. We evaluated the presence, appearance, and termination of the BV, and the presence and termination of the IOV. Results The study showed that 2 ICVs usually converged posterior to the splenium of the corpus callosum (62.4%). Narrowing of the BV was observed in 51.2% of patients, and the arachnoid granulation was found in 25.2%. The 3 segments of the BV were well visualized in 66% of the studied hemispheres. The BV flowed into the GV in 34.8% of the hemispheres. The IOV was present in 90.2% of the hemispheres and terminated medially in 84.5%. Conclusions Because an injury to major deep cerebral veins may result in severe postoperative neurologic deficits, it is essential for neurosurgeons to be familiar with both normal and variant patterns of veins in the pineal region.

Objective The extreme lateral supracerebellar infratentorial (ELSI) approach has the potential to access several distinct anatomical regions that are otherwise difficult to reach. We have illustrated the surgical anatomy through cadaveric dissections and provided an extensive review of the literature to highlight the versatility of this approach, its limits, and comparisons with alternative approaches. Methods The surgical anatomy of the ELSI has been described using 1 adult-injected cadaveric head. Formalized noninjected brain specimens were also dissected to describe the brain parenchymal anatomy of the region. An extensive review of the literature was performed according to each targeted anatomical region. Illustrative cases are also presented. Results The ELSI approach allows for wide exposure of the middle and posterolateral incisural spaces with direct access to centrally located intra-axial structures such as the splenium, pulvinar, brainstem, and mesial temporal lobe. In addition, for skull base extra-axial tumors such as petroclival meningiomas, the ELSI approach represents a rapid and adequate method of access without the use of extensive skull base approaches. Conclusions The ELSI approach represents one of the most versatile approaches with respect to its ability to address several anatomical regions centered at the posterior and middle incisural spaces. For intra-axial pathologies, the approach allows for access to the central core of the brain with several advantages compared with alternate approaches that frequently involve significant brain retraction and cortical incisions. In specific cases of skull base lesions, the ELSI approach is an elegant alternative to traditionally used skull base approaches, thereby avoiding approach-related morbidity.

Background The interhemispheric fissure provides a natural surgical corridor to access tumors of the deep medial surface of the brain. Conventional microscopic approaches to these tumors are limited by the narrow width of the interhemispheric fissure and need for retraction of brain tissue or traversing overlying cortex. Over the last decade, the endoscope has been used to improve visualization of the operative field in neurosurgery, with benefits in terms of surgical ergonomics and extent of tumor resections. In the context of the interhemispheric fissure, an endoscopic approach may improve visualization of some tumors by providing a brighter, more divergent light source at depth and by enabling the operator to inspect around curved structures (e.g., corpus callosum). Case Description In this report, we present a series of 5 cases with tumors at various locations along the anteroposterior extent of the interhemispheric fissure that were resected using an endoscopic ipsilateral interhemispheric approach. Conclusions The endoscopic ipsilateral interhemispheric approach is an effective and versatile approach to resection of selected deep medial brain tumors extending anteriorly from the genu of the corpus callosum to the splenium. It has notable advantages over the microscope and can be considered a useful adjunct in the surgeon's armamentarium.

Since first recognized in July 2019, numerous cases of a lung illness associated with electronic-cigarette use or vaping particularly tetrahydrocannabinol in adolescents and adults have been reported. As of January 2020, the Center for Disease Control has reported over 2500 cases of electronic-cigarette or vaping product use-associated lung injury (EVALI), including 60 deaths. Affected patients most commonly present with respiratory or gastrointestinal complaints although neurological symptoms including headache, confusion and lethargy have been reported. We present a new as yet unpublished finding in the brain of a previously healthy teenage boy with EVALI. Brain imaging may be warranted in this patient population.

Objective To investigate clinical risk factors for acute magnetic resonance imaging (MRI) abnormalities in patients with benign convulsions with mild gastroenteritis or benign infantile epilepsy. Study design We investigated clinical and diffusion-weighted imaging findings in 32 patients with benign convulsions with mild gastroenteritis and 22 patients with benign infantile epilepsy who underwent MRI within seven days of seizure onset between 2010 and 2015. Results Diffusion-weighted imaging showed signal hyperintensity in the splenium of the corpus callosum in seven patients with benign convulsions with mild gastroenteritis, but no abnormalities in patients with benign infantile epilepsy. Patients with benign convulsions with mild gastroenteritis with splenial lesions showed a higher rate of rotavirus detection from feces (P = 0.006), higher serum level of C-reactive protein (P = 0.04), and shorter interval between seizure onset and MRI (P = 0.002) than patients with benign convulsions with mild gastroenteritis without splenial lesions. Multivariate analysis revealed rotavirus infection as a significant risk factor for splenial lesions on diffusion-weighted imaging in patients with benign convulsions with mild gastroenteritis (P = 0.02). Conclusions Splenial lesions are often seen during acute period in patients with benign convulsions with mild gastroenteritis. Rotavirus infection is a risk factor for splenial lesions in patients with benign convulsions with mild gastroenteritis, suggesting the role of rotavirus to cause edema in the corpus callosum. From our observations, benign convulsions with mild gastroenteritis with a splenial lesion on diffusion-weighted imaging suggests good outcomes, and extensive evaluation of these patients may be unnecessary.

Steadily aging populations result in a growing need for research regarding age-related brain alterations and neurodegenerative pathologies. By allowing a good translation of results to humans, nonhuman primates, such as the gray mouse lemur Microcebus murinus, have gained attention in this field. Our aim was to examine correlations between atrophy-induced brain alterations and age, with special focus on sex differences in mouse lemurs. For cerebral volumetric measurements, in vivo magnetic resonance imaging was performed on 59 animals (28♀♀/31♂♂) aged between 1.0 to 11.9 years. Volumes of different brain regions, cortical thicknesses, and ventricular expansions were evaluated. Analyses revealed significant brain atrophies with increasing age, particularly around the caudate nucleus, the thalamus, and frontal, parietal, and temporo-occipital regions. Especially old females showed a strong decline in cingulate cortex thickness and had higher values of ventricular expansion, whereas cortical thickness of the splenium and occipital regions decreased mainly in males. Our study, thus, provides first evidence for sex-specific, age-related brain alterations in a nonhuman primate, suggesting that mouse lemurs can help elucidating the mechanism underlying sex disparities in cerebral aging, for which there is mixed evidence in humans.

Background Childhood aggression has been linked to white matter abnormalities, but research has been inconsistent with regard to both regions of alterations and directionality of the associations. We examined white matter microstructure correlates of aggression using a novel diffusion imaging analysis technique, fixel-based analysis, which leverages connectivity and crossing-fiber information to assess fiber bundle density. Methods The sample included 70 children with aggressive behavior and 25 healthy control children without aggressive behavior. Aggression was measured by the parent-rated Aggressive Behavior scale of the Child Behavior Checklist. Fixel-based analysis was conducted at the whole-brain and region-of-interest levels, including the uncinate fasciculus, inferior longitudinal fasciculus, fornix, cingulum bundle, and genu, body, isthmus, and splenium of the corpus callosum. Results Whole-brain analysis of covariance revealed that children with aggressive behavior, relative to control children, had lower fiber density in a cluster of limbic and cortical pathways, including the inferior fronto-occipital fasciculus, fornix, middle cerebellar peduncle, and superior thalamic radiations (familywise error–corrected p Conclusions Diminished white matter density in pathways connecting limbic and cortical regions is associated with childhood aggression. Abnormal interhemispheric connectivity via corpus callosum may also reflect a potential neural mechanism involved in aggression.

Despite neuropsychiatric outcomes of SARS-CoV-2 infection are now under close scrutiny, psychoneuroimmunological characteristics of COVID-19 and precise pathophysiology of neuropsychiatric manifestations of the infection are still obscure. Moreover, there still exists a shortfall in demonstrating specific clinical manifestations of the brain involvement of the virus. Here, we presented a 33-year-old female patient with COVID-19, reporting acute-onset paranoid delusions symptoms, insomnia and irritability. Cranial MRI showed an hyperintense signal in the splenium of the corpus callosum with decreased apparent diffusion coefficient, which might possibly indicate the presence of cytotoxic edema related to the brain involvement of the infection. Following the completion of SARS-CoV-2 treatment, both cytotoxic edema and psychiatric symptoms resolved. In light of this report, we suggest that either heightened immune response and direct viral infection that SARS-CoV-2 may lead to such psychiatric manifestations and neuropsychiatric monitoring should be performed in patients with COVID-19. Prompt recognition of psychiatric consequences of COVID-19 may help clinicians provide guidance for differential diagnosis and manage them accordingly.

Highlights • Mild encephalopathy with reversible splenium lesion (MERS) is a condition characterized by fever, encephalopathy, and a reversible splenium lesion on brain MRI. • MERS has been previously associated with viral infections, such as the influenza virus, and may result from an immune-mediated response to infection. • MERS has not previously been described in conjunction with COVID-19. • We present a case of a patient with MERS and positive SARS-CoV-2 antibodies, the first reported instance of this neurological complication to the virus. • MERS should be considered in a patient with the characteristic clinico-radiological syndrome and COVID-19 infection., Neurological complications of coronavirus 2019 (COVID-19) are common, and novel manifestations are increasingly being recognized. Mild encephalopathy with reversible splenium lesion (MERS) is a syndrome that has been associated with viral infections, but not previously with COVID-19. In this report, we describe the case of a 69 year-old man who presented with fever and encephalopathy in the setting of a diffusion-restricting splenium lesion, initially mimicking an ischemic stroke. A comprehensive infectious workup revealed positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, and a pro-inflammatory laboratory profile characteristic of COVID-19 infection. His symptoms resolved and the brain MRI findings completely normalized on repeat imaging, consistent with MERS. This case suggests that MERS may manifest as an autoimmune response to SARS-CoV-2 infection and should be considered in a patient with evidence of recent COVID-19 infection and the characteristic MERS clinico-radiological syndrome.

Background: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. Its diagnosis is clinical, often confirmed by magnetic resonance imaging. This image modality, however, is not ideal for discrimination of demyelination in grey and white matter regions from inflammatory lesions. Positron Emission Tomography (PET), using specific radiopharmaceuticals, can be a tool to differentiate between these processes. The radiopharmaceutical [C-11]PIB is widely used for detection of beta-amyloid plaques, but has also been suggested for the analysis of myelin content due to its consistent uptake in white matter. The aim of this study was to evaluate [C-11]PIB PET imaging as a tool for detecting demyelinated regions in white and grey matter of non-human primate model of progressive MS.Methods: Experimental autoimmune encephalomyelitis (EAE) was induced in marmosets by injection of re-combinant human myelin oligodendrocyte glycoprotein (rhMOG) emulsified in either Incomplete Freund's Adjuvant (IFA) or Complete Freund's Adjuvant (CFA). [C-11]PIB PET images were acquired prior to immunization (baseline) and after symptoms were present (end of experiment). Brain tissue was isolated for histochemical analysis.Results: All rhMOG/IFA-treated and rhMOG/CFA-treated animals showed clinical signs of EAE. The rhMOG/CFA group presented a significant [C-11]PIB uptake reduction only in the left motor cortex (9%, P = 0.011). For the rhMOG/IFA group, significant decrease in [C-11]PIB uptake was observed in the whole brain (15%, P = 0.015), in the right hemisphere of body of corpus callosum (34%, P = 0.02), splenium of corpus callosum (38%, P = 0.004), hippocampus (19%, P = 0.036), optic tract (13%, P = 0.025), thalamus (14%, P = 0.041), Globus pallidus (23%, P = 0.017), head of caudate nucleus (25%, P = 0.045), tail of caudate nucleus (29%, P = 0.003), putamen (28%, P = 0.047) and left hemisphere of body of corpus callosum (14%, P = 0.037) and head of caudate nucleus (23%, P = 0.023). [C-11]PIB uptake significantly correlated with luxol fast blue histology (myelin marker), both in the rhMOG/IFA (r(2) = 0.32, P Conclusion: [C-11]PIB PET imaging is an efficient tool for detecting demyelination in grey and white matter, in a non-human primate model of progressive MS.

Conduction of action potentials along myelinated axons is affected by their structural features, such as the axonal g-ratio, the ratio between the inner and outer diameters of the myelin sheath surrounding the axon. The effect of g-ratio variance on conduction properties has been quantitatively evaluated using single-axon models. It has recently become possible to estimate a g-ratio weighted measurement in vivo using quantitative MRI. Nevertheless, it is still unclear whether the variance in the g-ratio in the healthy human brain leads to significant differences in conduction velocity. In this work we tested whether the g-ratio MRI measurement can be used to predict conduction delays in the corpus callosum. We present a comprehensive framework in which the structural properties of fibers (i.e. length and g-ratio, measured using MRI), are incorporated in a biophysical model of axon conduction, to model conduction delays of long-range white matter fibers. We applied this framework to the corpus callosum, and found conduction delay estimates that are compatible with previously estimated values of conduction delays. We account for the variance in the velocity given the axon diameter distribution in the splenium, mid-body and genu, to further compare the fibers within the corpus callosum. Conduction delays have been suggested to increase with age. Therefore, we investigated whether there are differences in the g-ratio and the fiber length between young and old adults, and whether this leads to a difference in conduction speed and delays. We found very small differences between the predicted delays of the two groups in the motor fibers of the corpus callosum. We also found that the motor fibers of the corpus callosum have the fastest conduction estimates. Using the axon diameter distributions, we found that the occipital fibers have the slowest estimations, while the frontal and motor fiber tracts have similar estimates. Our study provides a framework for predicting conduction latencies in vivo. The framework could have major implications for future studies of white matter diseases and large range network computations. Our results highlight the need for improving additional in vivo measurements of white matter microstructure.

Background: Lexical tone identification has a unique role in the perceptual processes of Chinese readers. Reduced lexical tone awareness, along with poor word-decoding abilities, is frequently observed in Chinese-speaking children with developmental dyslexia. However, whether this deficit is linked to reduced auditory processing and interrupted structural connectivity in the brain requires further investigation. This study therefore explores the white matter pathways associated with Chinese character recognition and auditory processing of pitch variations, with the objective of to identify the most representative neural correlates for Chinese developmental dyslexia. Methods: Diffusion magnetic resonance imaging and several behavior measures related to reading attainment and phonological awareness were acquired in twenty-four Chinese-speaking children with developmental dyslexia and twenty-two age-matched controls. We used diffusion magnetic resonance imaging connectometry to explore the relationships between behavior performance and specific white matter tracts. Results: The results revealed significant correlations of the left inferior fronto-occipital fasciculus, cerebellar pathways, and thalamopontine tracts with Chinese character recognition (FDR = 0.03235). In addition, the posterior isthmus and anterior splenium of the corpus callosum correlated with auditory processing (FDR = 0.03980). Conclusion: The study provides evidence that the dysconnectivity on white matter pathways correlated with developmental dyslexia in Chinese-speaking children. Furthermore, the impairments of auditory temporal timing processing presented in poor readers with significant phonological deficits are likely to be a result of impoverished myelinization in sub-cortical tracts. Such findings may assist in the clinical identification of Chinese developmental dyslexia. Keywords: auditory frequency-modulation processing, Chinese developmental dyslexia, connectometry, diffusion MRI, lexical tone awareness

White matter microstructure can be measured with diffusion tensor imaging (DTI). While increasing age is a predictor of white matter (WM) microstructure changes, roles of other possible modifiers, such as cardiovascular risk factors, APOE e4 allele status and biological sex have not been clarified. We investigated 665 cognitively normal participants from the Baltimore Longitudinal Study of Aging (age 50–95, 56.7% female) with a total of 1384 DTI scans. WM microstructure was assessed by fractional anisotropy (FA) and mean diffusivity (MD). A vascular burden score was defined as the sum of five risk factors (hypertension, obesity, elevated cholesterol, diabetes and smoking status). Linear mixed effects models assessed the association of baseline vascular burden on baseline and on rates of change of FA and MD over a mean follow-up of 3.6 years, while controlling for age, race, and scanner type. We also compared DTI trajectories in APOE e4 carriers vs. non-carriers and men vs. women. At baseline, higher vascular burden was associated with lower FA and higher MD in many WM structures including association, commissural, and projection fibers. Higher baseline vascular burden was also associated with greater longitudinal decline in FA in the hippocampal part of the cingulum and the fornix (crus)/stria terminalis and splenium of the corpus callosum, and with greater increases in MD in the splenium of the corpus callosum. APOE e4 carriers did not differ from non-carriers in baseline DTI metrics but had greater decline in FA in the genu and splenium of the corpus callosum. Men had higher FA and lower MD in multiple WM regions at baseline but showed greater increase in MD in the genu of the corpus callosum. Women showed greater decreases over time in FA in the gyrus part of the cingulum, compared to men. Our findings show that modifiable vascular risk factors (1) have a negative impact on white matter microstructure and (2) are associated with faster microstructural deterioration of temporal WM regions and the splenium of the corpus callosum in cognitively normal adults. Reducing vascular burden in aging could modify the rate of WM deterioration and could decrease age-related cognitive decline and impairment.

Background: A dimensional approach of psychopathology focuses on features and risk factors that are shared across diagnoses. In support for this dimensional approach, studies point to a general psychopathology factor (GPF) associated with risk for multiple psychiatric disorders. It is, however, unknown how GPF relates to white matter integrity (WMI). In the current diffusion tensor imaging (DTI) study, we examined how GPF relates to abnormalities in a skeleton representation of white matter tracts, taking into account a trans-diagnostic risk factor: unresolved-disorganized attachment (Ud) resulting from loss or trauma. Methods: Unique associations between GPF, Ud, and WMI were examined in a combined sample of adolescents (N = 63) with childhood sexual abuse-related posttraumatic stress disorder (N = 18), anxiety and depressive disorders (N = 26) and without psychiatric disorder (N = 19). WMI was measured using DTI. Ud was measured using the Adult Attachment Interview. We controlled for puberty stage, gender, age, and IQ. Results: Controlling for GPF, Ud was associated with reduced fractional anisotropy (FA) in the splenium and inferior fronto-occipital fasciculus (IFOF). Controlling for Ud, GPF was associated with reduced FA in the genu and body of the corpus callosum. Conclusions: Decreasing WMI in the genu and body with increasing psychopathology across diagnoses suggests demyelinization in these areas and may underlie comorbidity and presence of symptoms that transcend psychopathological diagnoses. In contrast, trauma-related WMI reductions in the splenium and IFOF may account for heterogeneity within diagnostic categories as a function of childhood trauma. These findings support the importance of a dimensional approach in addition to traditional diagnostic classifications in clinical research and practice. Keywords: Adversity, Child abuse, Psychopathology, Attachment, Brain imaging

Highlights • Clinical awareness of physicians about neurological complications of COVID-19 decreases the mortality rate among infected people. • Neurological presentation of COVID-19 infection categorized into two groups of symptoms of the central nervous system (CNS) and of the peripheral nervous system (PNS). • Cytokine storm, a well-known immune reaction to this specific viral infection, can cause inflammation and central nervous system (CNS) tissue axonal or demyelinating damage. • Our patient had a central demyelinating brain injury following COVID-19 infection., After the novel coronavirus disease outbreak first began in Wuhan, China, in December 2019, the viral epidemic has quickly spread across the world, and it is now a major public health concern. Here we present a 21-year-old male with encephalomyelitis following intermittent vomiting and malaise for 4 days. He reported upper respiratory signs and symptoms 2 weeks before this presentation. Two cerebrospinal fluid (CSF) analyses were notable for mononuclear pleocytosis, elevated protein (more than 100 mg/dl), and hypoglycorrhachia. Brain Magnetic Resonance Imaging (MRI) showed bilateral posterior internal capsule lesions extending to the ventral portion of the pons and a marbled splenium hyperintensity pattern. Cervical and thoracic MRI showed longitudinally extensive transverse myelitis (LETM), none of which were enhanced with gadolinium. Both the AQP4 and MOG antibodies were negative. Spiral chest computed tomography (CT) scan confirmed to COVID-19 as did the high IgG level against coronavirus, but the oropharyngeal swabs were negative. Neurological manifestations of COVID-19 have not been adequately studied. Some COVID-19 patients, especially those suffering from a severe disease, are highly likely to have central nervous system (CNS) manifestations. Our case is a post-COVID-19 demyelinating event in the CNS.

Chronic musculoskeletal pain is a condition that influences central nervous system structure. In this study, we combined novel structural neuroimaging techniques, using well-validated software packages including FSL, Mrtrix3, and DSI Studio, to characterize brain grey (GM) and white matter (WM) differences in chronic musculoskeletal pain participants (n = 74), compared to age-matched pain-free controls (n = 31). In participants with chronic pain, we identified significantly higher volume in subcortical GM structures using voxel-based morphometry (FSLVBM). These differences were most prominent in the caudate, amygdala, and the hippocampus. At the same time, volume was lower in the dorsolateral prefrontal cortex, as well as the primary motor and sensory regions in patients with chronic pain. To delineate WM microstructural differences of neuronal (e.g., activity-dependent myelin remodeling) and non-neuronal (e.g., neuroinflammation) origins, we utilized Mrtrix3 software pipelines to investigate WM fiber complexity, density, and cross-section. Whole-brain analyses revealed lower WM fiber complexity within the corpus callosum and the anterior limb of the left internal capsule. Whole brain and region of interest analyses revealed fiber complexity differences within the salience and the sensorimotor networks. In contrast, we detected non-neuronal white matter density differences within the dorsal attention network: density was lower in the inferior fronto-occipital fasciculus and the splenium of the corpus callosum in chronic musculoskeletal pain. Consistent with the involvement of the dorsal attention network, WM tractography analysis, conducted with DSI Studio and Network Based Statistics, revealed higher connectivity from the superior parietal lobule to the hippocampus in patients with chronic pain. No differences were detected in measures of fiber cross-section, suggesting the absence of neuronal degeneration in chronic pain. The combination of multiple neuroimaging techniques in this study offers a unique window into the structural differences within the chronic pain brain and provides the first evidence of microstructural variations in fiber complexity and density.

The corpus callosum is the largest white matter tract in the human brain connecting and coordinating homologous regions of the right and left hemispheres and has been strongly implicated in the pathogenesis of psychosis. We investigated corpus callosum morphology in a large community cohort of 917 individuals (aged 8-21), including 267 endorsing subsyndromal or threshold psychotic symptoms (207 on the psychosis spectrum and 60 with limited psychosis based on previously published criteria) and 650 non-psychotic volunteers. We used a highly reliable and previously published algorithm to automatically identify the midsagittal plane and to align the corpus callosum along the anterior and posterior commissures for segmentation, thereby eliminating these sources of error variance in dependent measures, which included perimeter, length, mean thickness and shape (circularity). The parcellation scheme divided the corpus callosum into 7 subregions that consisted of the rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium. Both individuals endorsing psychotic symptoms and those with limited psychosis had significantly (p

Borrowing from findings regarding other problematic behaviors, we posit that excessive social media use (ESMU) can relate to impaired inter-hemispheric connections. These are often reflected in impaired white matter integrity (decreased fractional anisotropy and increased mean diffusivity) of the corpus callosum. We test this idea with diffusion tensor imaging (DTI) data from 20 normal social media users with varying degrees of ESMU. The findings of a Regions of Interest analysis focusing on the corpus callosum indicate that ESMU is associated with increased mean diffusivity in the body and splenium sub-regions of the corpus callosum. Whole-brain Tract Based Spatial Statistics analysis revealed that ESMU is positively associated with mean diffusivity of left superior and inferior longitudinal fasciculi as well as left forceps minor; and that ESMU is positively associated with the fractional anisotropy of the right Corticospinal Tract. It is concluded that inter-hemispheric white matter deficits in the corpus callosum extended to forceps minor, as well as along the ventral semantic path can be associated with ESMU.

Purpose Brain radiation is associated with functional deficits in children. The purpose of this study was to examine white matter integrity as measured by diffusion tensor imaging and associations with region-specific radiation dose and neuropsychological functioning in children treated with cranial irradiation. Methods and Materials A total of 20 patients and 55 age- and sex-matched controls were included in the present study. Diffusion tensor imaging and neuropsychological assessments were conducted at baseline and 6, 15, and 27 months after treatment. The neuropsychological assessment included motor dexterity, working memory, and processing speed. White matter regions were contoured, and the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were recorded for each participant. Linear mixed effects regression models were used to prospectively compare the associations among ADC, FA, radiation dose to contoured structures, and performance on the neuropsychological assessments over time. Results The mean prescription dose was 44 Gy (range 12-54). Across visits, compared with the controls, the patients showed a significantly increased ADC across all selected regions and alterations in FA in the dorsal midbrain and corpus callosum (genu, splenium, body). An increased radiation dose to the genu and body of the corpus callosum was associated with alterations in ADC and FA and reduced neuropsychological performance, most notably motor speed and processing. Conclusions These prospective data suggest that subcortical white matter, especially the genu and body of the corpus callosum, could be regions with increased susceptibility to radiation-induced injury, with implications for cognitive function.

This study aims to determine whether and how diffusion alteration occurs in the earliest stage of multiple sclerosis (MS) and the differences in diffusion metrics between CIS and MS by using the tract-based spatial statistics (TBSS) method based on diffusion tensor imaging (DTI). Thirty-six CIS patients (mean age ± SD: 34.0 years ± 12.6), 36 relapsing-remitting multiple sclerosis (RRMS) patients (mean age ± SD: 35.0 years ± 9.4) and 36 age- and gender-matched normal controls (NCs) were included in this study. Voxel-wise analyses were performed with TBSS using multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1) and radial diffusivity (λ23). In the CIS patients, TBSS analyses revealed diffusion alterations in a few white matter (WM) regions including the anterior thalamic radiation, corticospinal tract, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, body and splenium of the corpus callosum, internal capsule, external capsule, and cerebral peduncle. MS patients showed more widespread diffusion changes (decreased FA, increased λ1, λ23 and MD) than CIS. Exploratory analyses also revealed the possible associations between WM diffusion metrics and clinical variables (Expanded Disability Status Scale and disease duration) in the patients. This study provided imaging evidence for DTI abnormalities in CIS and MS and suggested that DTI can improve our knowledge of the path physiology of CIS and MS and clinical progression.

Case report The case is presented of 42 year-old woman with no significant medical history, with severe headaches, nausea and vomiting, hearing loss, and alteration of mental status with disorientation and confusion. Ophthalmic examination showed optic disc hyperaemia in right eye, and focal areas of arteriolar occlusion in both eyes. Audiometry demonstrated bilateral neurosensory hypoacusis. Magnetic Resonance Imaging showed multiple small round hyperintense lesions located in the splenium, corpus callosum, basal ganglia, and white matter. Discussion Besides branch retinal arteriolar occlusion, the angiopathy in Susac's syndrome may affect the optic disc vessels.

We examined the relationship between white matter microstructure in schizophrenia using diffusion tensor imaging (DTI) and cognitive improvements induced by 70 hours (~16 weeks) of cognitive training. We measured anatomical connectivity in 48 patients with schizophrenia (SZ) and 28 healthy control participants (HC) at baseline, and then examined the relationship between anatomical connectivity at baseline and training-induced cognitive gains in 30 SZ who performed diffusion imaging after completing 70 hours of training. Compared with healthy control participants, individuals with schizophrenia showed reduced white matter integrity at baseline, as indexed by fractional anisotropy metrics, in bilateral posterior corona radiata, bilateral retrolenticular internal capsules, bilateral posterior thalamic radiation, left anterior corona radiata, left superior longitudinal fasciculus, left sagittal stratum, right cerebral peduncle and the genu and splenium of the corpus callosum. After training, schizophrenia participants showed significant gains in attention/vigilance, speed of processing, verbal learning, visual learning and executive functioning. White matter integrity within the right fronto-occipital fasciculus predicted training-induced improvements in attention/vigilance, while white matter integrity within the right corticospinal tract and bilateral medial lemnisci predicted cognitive training-induced improvements in executive functioning, areas that did not show white matter tract deficits at baseline. These findings suggest that preserved white matter integrity connecting long-range prefrontal-thalamic-sensorimotor areas may be an important determinant for training-induced neurocognitive plasticity.

Background Autism spectrum disorder (ASD) is a mental disorder that has long been considered to result from brain underconnectivity. However, volumetric analysis of structural MRI data has failed to find consistent white matter alterations in patients with ASD. The present study aims to examine whether there are consistent focal white matter alterations as measured by diffusion tensor imaging (DTI) in individuals with ASD compared with typically developing (TD) individuals. Method Coordinate-based meta-analysis was performed on 14 studies that reported fractional anisotropy (FA) alterations between individuals with ASD and TD individuals. These studies have in total 297 subjects with ASD and 302 TD subjects. Results Activation likelihood estimation (ALE) analysis identified two clusters of white matter regions that showed consistent reduction of FA in individuals with ASD compared with TD individuals: the left splenium of corpus callosum and the right cerebral peduncle. Conclusions Consistent focal white matter reductions in ASD could be identified by using FA, highlighting the cerebral peduncle which is usually overlooked in studies focusing on major white matter tracts. These focal reductions in the splenium and the cerebral peduncle may be associated with sensorimotor impairments seen in individuals with ASD.

Background The results of recent diffusion tensor imaging (DTI) studies on amyotrophic lateral sclerosis (ALS) are inconclusive and controversial. We performed a voxel-based meta-analysis to identify a statistical consensus among published DTI studies of altered white matter (WM) microarchitecture in ALS. Methods A systematic search was conducted for relevant studies that used voxel-wise analyses of WM microarchitecture in patients with ALS. Anisotropic effect size-signed differential mapping (AES-SDM) was applied to analyze fractional anisotropy (FA) differences between ALS patients and healthy controls. Meta-regression analysis was used to explore the effects of clinical characteristics on WM integrity in patients with ALS. Results A total of 14 studies with 16 datasets that included 396 patients and 360 healthy controls were identified. The pooled meta-analysis revealed that patients with ALS exhibited significant FA reductions in two clusters relative to healthy controls. The largest cluster exhibited a peak coordinate in the left corona radiata, extending to the body and splenium of the corpus callosum, left superior longitudinal fasciculus, posterior limb of the internal capsule, right corona radiata, and bilateral cingulate gyrus. The other cluster exhibited decreased FA in the right corticospinal tract that extended to the right cerebral peduncle. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score was positively correlated with the FA reduction in the left corona radiata. Mean age and illness duration were not linearly correlated with the FA reductions. Conclusions This study provides a thorough profile of WM microarchitecture alterations in patients with ALS and further evidence that the neuronal degeneration is not limited to the corticospinal tract but also includes extra-motor areas, which supports the view that ALS is a multisystem degenerative disorder that involves the white matter., Highlights • To identify statistical consensus between published DTI studies in ALS • Two consistent clusters of FA reductions in patients with ALS. • ALS is a multisystem degenerative disorder involving the WM.

PURPOSE/OBJECTIVE(S) To characterize the association between neurocognitive outcomes and radiation dose to the corpus callosum and the hippocampus in children with medulloblastoma treated on a phase III study. MATERIALS/METHODS Patients aged 3 to 21 years with medulloblastoma were treated at a single institution on a phase III risk-adapted study. Craniospinal radiation dose was 23.4 Gy for average-risk patients (M0 and GTR/NTR) and 36-39.6 Gy for high-risk patients (M+ or STR). All patients were treated with photons and received 55.8 Gy to the tumor bed using a 1cm clinical target volume margin. Metastasis > 0.5 cm received 50.4-54 Gy. Patients underwent age-appropriate cognitive testing at baseline (prior to completion of radiation) and yearly for 5 years. Neurocognitive scores were reported as standard deviations (SD) derived from age-standardized normative samples. Mixed effects models were used to estimate the longitudinal trends in neurocognitive scores. Reliable change index was used to identify patients whose scores declined significantly from baseline to last follow-up. Logistic regression was used to identify variables associated with a significant decline in neurocognitive outcomes. RESULTS One hundred and twenty-four patients were eligible for analysis. The median neurocognitive follow-up was 59.4 months. Decline in processing speed was associated with mean dose to the corpus callosum genu (slope: -.166 points/year/Gy, P < .001), body (slope: -.176 points/year/Gy, P < .001) and splenium (slope: -.115 points/year/Gy, P < .001), after adjusting for age and sex. Of the 90 patients with baseline processing speed scores, 21 (19%) demonstrated significant decline at last follow up. Patients with a mean corpus callosum genu and body dose of ≥40 Gy were at a four to seven-fold increased odds of experiencing significant decline compared to those with a mean dose of < 40 Gy (genu: OR: 7.47, 95% CI: 2.64 - 21.12, P < .001; body: OR: 4.47, 95% CI: 1.65 - 12.11, P = .003). Decline in associative memory was associated with mean right hippocampal dose (slope: -.11 points/year/Gy, P = .013) and left hippocampal dose (slope: -.109 points/year/Gy, P = .019), after adjusting for age and sex. Of 98 patients with baseline memory scores, 11 (11%) demonstrated significant decline at last follow up. Patients with a mean hippocampal dose of ≥50 Gy were at a five to seven-fold increased odds of experiencing significant decline compared to those with mean dose < 50 Gy (right hippocampus: Odds Ratio [OR]: 7.21, 95% Confidence Interval [CI]: 1.98 - 27.46, P = .004; left hippocampus: OR: 5.17, 95% CI: 1.38 - 19.36, P = .015). CONCLUSION For children with medulloblastoma, increasing radiation dose to the corpus callosum and hippocampus is associated with decreased performance on tests of processing speed and memory, respectively. During radiation plan optimization, careful consideration should be given to minimizing dose to these structures while achieving appropriate tumor bed coverage.

Objective to report an unusual pattern of brain petechial hemorrhages in 2 patients after veno-arterial extracorporeal membrane oxygenation support (VA-ECMO) Case 1 a 28-year-old man (Marfan disease) presented in the early post-operative period a multi-organ failure associated with a disseminated intravascular coagulation (DIC). He was placed on continuous veno-venous hemofiltration and VA-ECMO. He was weaned from ECMO 4 days later. He then developed bacterial pneumoniae leading to respiratory failure and requiring mechanical ventilation. MRI 30 days later showed widespread petechial hemorrhages in the subcortical and deep white matter (WM) (optic radiations, corpus callosum, predominantly in the splenium, internal and external capsules), caudate nuclei, basal ganglia, frontal and parietal cortex and in infratentorial structures. These hemorrhages were bilateral and almost symmetric and marked at the border zones of the carotid arteries territories. Case 2 a 60-year-old man presented an out-of-hospital refractory hypothermic cardiac arrest. At arrival, cardiopulmonary resuscitation was continued; he presented bleeding at the puncture sites related to DIC and associated with multi-organ failure. VA-ECMO was implanted. After ECMO removal (day 7) he presented a severe spatial orientation deficit. MRI showed petechial hemorrhages in both hippocampi and microbleeds at the cerebral cortex and the juxta-cortical WM. Both patients had good functional outcome. Conclusion Two unusual presentations of brain hemorrhages in patients who underwent VA-ECMO are reported. If their specific cause remains unclear, there seems to be a relationship in time between DIC and microhemorrhages in these cases, even if in case 1 brain hemorrhages seem to have a multifactorial cause.

Recent neurodevelopmental research supports the contribution of pubertal stage to local and global grey and white matter remodelling. Little is known, however, about white matter microstructural alterations at pubertal onset. This study investigated differences in white matter properties between pre-pubertal and pubertal children using whole brain fixel-based analysis (FBA) of the microscopic density and macroscopic cross-section of fibre bundles. Diffusion-weighted imaging data were acquired for 74 typically developing children (M=10.4, SD=0.43 years, 31 female) at 3.0T (60 diffusion gradient directions, b-value=2800 s/mm 2 ). Group comparisons of fibre density (FD) and fibre cross-section (FC) were made between age-matched pre-pubertal and pubertal groups, and post-hoc analyses were performed on regions of interest (ROIs) defined in the splenium, body and genu of the corpus callosum. Significant fixel-wise differences in FD were observed between the pubertal groups, where the pubertal group had significantly higher FD compared with age-matched pre-pubertal children, localised to the posterior corpus callosum. Post-hoc analyses on mean FD in the corpus callosum ROIs revealed group differences between the pubertal groups in the splenium, but not body or genu. The observed higher apparent fibre density in the splenium suggests that pubertal onset coincides with white matter differences explained by increasing axon diameter. This may be an important effect to account for over pubertal development, particularly for group studies where age-matched clinical and typical populations may be at various stages of puberty.

A number of structural properties of white matter can be assessed in vivo using multimodal magnetic resonance imaging (MRI). We measured profiles of R1 and R2 relaxation rates, myelin water fraction (MWF) and diffusion tensor measures (fractional anisotropy [FA], mean diffusivity [MD]) across the mid-sagittal section of the corpus callosum in two samples of young individuals. In Part 1, we compared histology-derived axon diameter (Aboitiz et al., 1992) to MRI measures obtained in 402 young men (19.55 ± 0.84 years) recruited from the Avon Longitudinal Study on Parents and Children. In Part 2, we examined sex differences in FA, MD and magnetization transfer ratio (MTR) across the corpus callosum in 433 young (26.50 ± 0.51 years) men and women recruited from the Northern Finland Birth Cohort 1986. We found that R1, R2, and MWF follow the anterior-to-posterior profile of small-axon density. Sex differences in mean MTR were similar across the corpus callosum (males > females) while these in FA differed by the callosal segment (Body: M>F; Splenium: F>M). We suggest that the values of R1, R2 and MWF are driven by high surface area of myelin in regions with high density of “small axons”.

Background Prenatal cocaine exposure (PCE) is associated with risk-taking behaviors, including increased initiation of substance use in adolescence. The neurobiological underpinnings of these behaviors in adolescents with PCE are not well understood. The goal of this study was to compare diffusion-weighted imaging data between adolescents with and without PCE using crossing-fiber models, which may provide more comprehensive estimates of white-matter microstructure within regions of multiple (e.g., primary and secondary) fiber orientations. Methods Thirty-nine PCE individuals and 17 comparably aged prenatally non-drug-exposed (NDE) youths were recruited from a longitudinal cohort followed since birth. White matter was examined using tensor-derived and crossing-fiber models. Whole-brain investigations were performed, as were analyses on seven white-matter regions, which included the splenium, body and genu of the corpus callosum, bilateral cingulum, and the right and left superior longitudinal fasciculus (SLF). Results Whole-brain analyses revealed no group differences. However, ROI analyses for anisotropy estimates derived from the crossing-fiber model revealed significant group differences for secondary fibers, with reduced anisotropy among PCE adolescents compared to prenatally non-exposed youth in the right cingulum and the left SLF, and increased anisotropy in the genu. Conclusions Our findings suggest that white-matter differences in PCE adolescents are subtle and localized primarily within secondary fiber orientations, perhaps arising from altered white-matter development.

Preterm birth is associated with an increased risk for lasting changes in both the cortico-thalamic system and attention; however, the link between cortico-thalamic and attention changes is as yet little understood. In preterm newborns, cortico-cortical and cortico-thalamic structural connectivity are distinctively altered, with increased local clustering for cortico-cortical and decreased integrity for cortico-thalamic connectivity. In preterm-born adults, among the various attention functions, visual short-term memory (vSTM) capacity is selectively impaired. We hypothesized distinct associations between vSTM capacity and the structural integrity of cortico-thalamic and cortico-cortical connections, respectively, in preterm-born adults.\ud \ud A whole-report paradigm of briefly presented letter arrays based on the computationally formalized Theory of Visual Attention (TVA) was used to quantify parameter vSTM capacity in 26 preterm- and 21 full-term-born adults. Fractional anisotropy (FA) of posterior thalamic radiations and the splenium of the corpus callosum obtained by diffusion tensor imaging were analyzed by tract-based spatial statistics and used as proxies for cortico-thalamic and cortico-cortical structural connectivity.\ud \ud The relationship between vSTM capacity and cortico-thalamic and cortico-cortical connectivity, respectively, was significantly modified by prematurity. In full-term-born adults, the higher FA in the right posterior thalamic radiation the higher vSTM capacity; in preterm-born adults this FA-vSTM-relationship was inversed. In the splenium, higher FA was correlated with higher vSTM capacity in preterm-born adults, whereas no significant relationship was evident in full-term-born adults.\ud \ud These results indicate distinct associations between cortico-thalamic and cortico-cortical integrity and vSTM capacity in preterm-and full-term-born adults. Data suggest compensatory cortico-cortical fiber re-organization for attention deficits after preterm delivery.

Background Previous diffusion tensor imaging (DTI) studies have consistently shown that subjects with cocaine use disorder (CocUD) had altered white matter microstructure in the corpus callosum. It is believed that these alterations are due to preexisting factors, chronic cocaine use, or both. However, there is no published longitudinal DTI study on human cocaine users yet which could shed light on the relationship between cocaine use and DTI findings. Methods This study used a longitudinal design and DTI to test if the white matter microstructure shows quicker alteration in CocUD subjects than controls. DTI data were acquired from eleven CocUD subjects who participated a treatment study and eleven non-drug-using controls at baseline (Scan 1) and after ten weeks (Scan 2). The baseline fractional anisotropy (FA), a general measure of white matter microstucture, and the change in FA (ΔFA, equals Scan 1 FA minus Scan 2 FA) were both compared between groups. Results The two groups did not show a difference in FA at baseline. The CocUD subjects had significantly greater ΔFA than the controls in the left splenium of the corpus callosum. In CocUD subjects, greater ΔFA in this region was associated with shorter lifetime cocaine use and greater number of positive cocaine urine samples collected during the treatment. Conclusion The finding in the left splenium is consistent with previous animal studies and provide indirect evidence about the effects of chronic cocaine use on white matter alterations. The subject sample size is small, therefore the results should be treated as preliminary.

Cytotoxic lesions of the corpus callosum will be present in a wide range of clinical conditions. The term “cytotoxic lesions of the corpus callosum” reflects our current understanding of the underlying pathophysiology of these lesions and does not necessarily imply confinement to the splenium. Because the symptoms vary and are not specific, the clinical diagnosis can be difficult. Brain magnetic resonance imaging will be of pivotal value in the investigation. We report the case of a patient with obsessive-compulsive disorder who underwent bilateral deep brain stimulation of the nucleus accumbens and developed infection along the surgical path of both electrodes associated with a cytotoxic lesion in the splenium of corpus callosum.

Despite the development of empirically supported treatments for posttraumatic stress disorder (PTSD), many individuals remain symptomatic following therapy or dropout prematurely. Neuroimaging studies examining PTSD treatment outcome may offer valuable insights into possible mechanisms that may impact treatment efficacy. To date, few studies of PTSD have used neuroimaging to examine symptom change following completed treatment, and most have focused on gray matter. Studies of white matter are equally important, as changes in white matter integrity (WMI) are connected to a host of detrimental outcomes. The current study examined symptom change of 21 women with PTSD as a result of interpersonal violence who received baseline diffusion tensor imaging (DTI) scans and completed 12 weeks of Cognitive Processing Therapy (CPT). After controlling for baseline PTSD severity, fractional anisotropy (FA) in the left internal capsule, posterior limb of the internal capsule, left cingulate gyrus, superior longitudinal fasciculus, and splenium of the corpus callosum was predicted by PTSD symptom change. Results contribute to understanding neural changes within therapy and may assist in predicting individual treatment response. Namely, by identifying areas potentially impacted by PTSD treatment, future studies may be able to connect the function of these white matter areas to better predict patient PTSD treatment outcome.

Backgrounds Optic radiation protection is crucial in the basal temporal approach to the mesial temporal lobe. Clear description of the optic radiation in the basal brain surface is lacking. Our aim is to describe the anatomy of optic radiation in the basal cerebral surface and define safety zone of basal temporal approach avoiding of optic radiation injury. Methods Five brain specimens (10 hemispheres) were dissected using Klingler method to observe the course of the optic radiation. Diffusion tensor imaging data of 25 volunteers were used to verify the fiber dissection results. The relationship of the optic radiation to nearby structures were illustrated and measured. Results The optic radiation bends from the lateral wall of the lateral ventricle to its bottom at a basal turning point of optic radiation (bTPOR). The bTPOR is at the plane crossing the center point of the splenium of corpus callosum. MRI measurements showed no significant difference in the distance from the center of the splenium of corpus callosum and the bTPOR to the occipital pole (59.46 ± 4.338 mm vs 59.54 ± 3.805 mm, p = 0.95). Anterior to bTPOR, no optic radiation fibers were found at the basal brain surface. Conclusions The bTPOR was found as a landmark of the optic radiation in the cerebral basal surface. With neuronavigation, the splenium of corpus callosum can be a landmark of the bTPOR. By approaching mesial temporal lesions using the basal temporal approach anterior to bTPOR, optic radiation injury can be prevented.

BACKGROUND Although the changes of diffusion tensor imaging (DTI) in corpus callosum (CC) in patients with relapsing-remitting multiple sclerosis (RRMS) has been reported, the results are controversial. We aimed to determine the damage to the CC in patients with RRMS using DTI. MATERIAL AND METHODS A systematic search of English databases (PubMed, Embase, Cochrane Library, and Scopus) was performed. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) values of DTI were compared between RRMS patients and healthy controls (HC) using Stata 12.0. RESULTS A total of 461 patients and 365 HC from 15 studies were included. Compared with HC, the FA values of the whole CC (SMD -1.894, P < 0.001), genu (SMD -0.830, P < 0.001) and splenium (SMD -1.431, P < 0.001) of CC were significantly reduced in patients with RRMS. Moreover, the MD values of the whole CC (SMD 1.213, P < 0.001), genu (SMD 0.657, P < 0.001) and splenium (SMD 0.830, P < 0.001) of CC were significantly increased in patients with RRMS. Additionally, the AD values (SMD 0.635, P < 0.001) and RD values (SMD 1.480, P < 0.001) were significantly increased in the whole CC in patients with RRMS. The meta-regression analysis revealed that the male ratio showed a significant effect on the FA reduction in the splenium CC in RRMS patients. CONCLUSIONS These results indicated that DTI parameters were potential biomarkers with increased sensitivity for detecting pathological damage in the CC in patients with RRMS.

Highlights • Maturation of specific WM tracts in preterm individuals differs from those of term controls. • The elastic net logistic regression model was used to identify altered white matter tracts in the preterm brain. • The alteration of the cingulum in the preterm at near-term correlate with neurodevelopmental scores at 18–22 months of age., Background Relative to full-term infants, very preterm infants exhibit disrupted white matter (WM) maturation and problems related to development, including motor, cognitive, social-emotional, and receptive and expressive language processing. Objective The present study aimed to determine whether regional abnormalities in the WM microstructure of very preterm infants, as defined relative to those of full-term infants at a near-term age, are associated with neurodevelopmental outcomes at the age of 18–22 months. Methods We prospectively enrolled 89 very preterm infants (birth weight

It is well established that the posterior region of the corpus callosum, known as the splenium, is relatively preserved during the course of normal ageing. However, the effect of age on its distinct interhemispheric tract bundles that project to bilateral occipital, parietal and temporal areas of the cortex, is largely unknown. In the present study, diffusion tensor imaging was used to directly examine the integrity of these distinct segregations and their diffusion metrics were compared between groups of young adults (n = 20, mean age = 30.75) and older adults (n = 19, mean age = 80.21). Results revealed that while occipital tracts were preserved in older adults, parietal and temporal segments were particularly impaired. These findings are the first to indicate the existence of selective alterations in the posterior region of the corpus callosum in older age.

Previous studies demonstrate profound sex-specific patterns of white matter microstructural neurodevelopment (i.e. fractional anisotropy; FA, and mean diffusivity; MD) during adolescence. While alcohol use has been associated with alterations in FA and MD, no studies have addressed the potential for sex-specific, alcohol-dose-dependent effects, during development. This prospective longitudinal study (2-4 visits, 310 total scans) used voxel-wise multilevel modeling, in 132 (68 female) adolescents (ages 12-21), to assess the sex-specific effects of lifetime alcohol use on FA and MD, during development. Follow-up analyses tested the role of sex hormones, testosterone and estradiol, in explaining the effects of alcohol use on FA and MD. In the splenium of the corpus callosum and posterior thalamic radiation, male adolescents demonstrated lower FA and greater MD as a function of more lifetime alcohol use, while female adolescents demonstrated the opposite. Further, significant associations between sex hormones and FA/MD partially explained the effect of alcohol use on FA and MD in male adolescents. These results provide evidence for sex-specific and dose-related effects of alcohol use on white matter microstructure, which are partially explained by sex hormones, and highlight the importance of studying sex and hormones when investigating the effects of alcohol use on the adolescent brain.

Background Some MRI studies have noted alterations in the corpus callosum (CC) white matter integrity of individuals with mood disorders and also in patients with suicidal behavior. We investigated the specific impact of suicidal behavior on CC integrity in mood disorders. Methods CC structural changes were assessed by diffusion tensor imaging (DTI) in 121 women 18-50-year-old): 41 with bipolar disorder (BD), 50 with major depressive disorder (MDD) and 30 healthy controls (HC). Fractional anisotropy (FA) and DTI metrics were calculated for the genu, body and splenium of CC and compared in the three groups by MANCOVA. Then, they were re-analyzed relative to the suicide attempt history within the MDD and BD groups and to the suicide number/severity. Results FA values for the CC genu and body were lower in non-suicide attempters with BD than with MDD and in HC. Conversely, FA values for all CC regions were significantly lower in suicide attempters with BD than in HC. Finally, higher number of suicide attempts (>2) and elevated Suicidal Intent Scale score were associated with significant splenium alterations. Limitations Limitations include the cross-sectional design (non-causal study), the potential influence of medications and concerns about the generalizability to men. Conclusion Genu and body are altered in non-suicide attempters with BD, while splenium is specifically altered in suicide attempters, independently from their psychiatric status. History of suicide attempts may be a source of heterogeneity in the association between CC alterations and BD and may partially explain the variable results of previous studies.

Background The corpus callosum has been implicated in the pathogenesis of schizophrenia and bipolar disorder. However, it is unclear whether corpus callosum alterations are related to the underlying familial diathesis for psychotic disorders. We examined the corpus callosum and its subregion volumes and their relationship to cognition, psychotic symptoms, and age in probands with schizophrenia (SZ), psychotic bipolar disorder (PBD), and schizoaffective disorder; their first-degree relatives; and healthy control subjects. Methods We present findings from morphometric and neurocognitive analyses of 1381 subjects (SZ probands, n = 224; PBD probands, n = 190; schizoaffective disorder probands, n = 142; unaffected relatives, n = 483 [SZ relatives, n = 195; PBD relatives, n = 175; schizoaffective disorder relatives, n = 113]; control subjects, n = 342). Magnetization prepared rapid acquisition gradient-echo T1 scans across five sites were obtained using 3-tesla magnets. Image processing was done using FreeSurfer Version 5.1. Neurocognitive function was measured using the Brief Assessment of Cognition in Schizophrenia scale. Results Anterior and posterior splenial volumes were significantly reduced across the groups. The SZ and PBD probands showed robust and significant reductions, whereas relatives showed significant reductions of intermediate severity. The splenial volumes were positively but differentially correlated with aspects of cognition in the probands and their relatives. Proband groups showed a significant age-related decrease in the volume of the anterior splenium compared with control subjects. Among the psychosis groups, the anterior splenium in probands with PBD showed a stronger correlation with psychotic symptoms, as shown by the Positive and Negative Syndrome Scale. All five subregions showed significantly high familiality. Conclusions The splenial volumes were significantly reduced across the psychosis dimension. However, this volume reduction impacts cognition and clinical manifestation of the illnesses differentially.

Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have revealed deviations of the corpus callosum in children and adolescents. However, little is known about the link between callosal morphology and symptoms of inattention or hyperactivity in adulthood, especially later in life. Here, we investigated in a large population-based sample of 280 adults (150 males, 130 females) in their late sixties and early seventies whether ADHD symptoms correlate with callosal thickness. In addition, we tested for significant sex interactions, which were followed by correlation analyses stratified by sex. Within males, there were significant negative correlations with respect to inattention and hyperactivity in various callosal regions, including the anterior third, anterior and posterior midbody, isthmus, and splenium. A thinner corpus callosum may be associated with fewer fibers or less myelination of fibers. Thus, the observed negative correlations suggest impaired inter-hemispheric communication channels necessary to sustain motor control and attention, which may contribute to symptoms of hyperactivity, impulsivity and/or inattention. Interestingly, within females, callosal thickness was positively related to hyperactivity in a small area within the rostral body, suggesting a sexually dimorphic neurobiology of ADHD symptoms. Altogether, the present results may reflect a lasting relationship between callosal morphology and ADHD symptoms throughout life.

The magnetic resonance imaging findings of reversible isolated lesions with transiently reduced diffusion in the splenium of corpus callosum of patients with a wide spectrum of pathological conditions are referred to as reversible splenial lesion syndrome (RESLES). Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is probably included within the spectrum of RESLES; however, its exact pathophysiology is not known. Here, we describe three patients with MERS and one patient with RESLES, all of whom showed elevated urinary β2-microglobulin regardless of diagnosis and presence of pathogens. Elevated urinary β2-microglobulin suggested that an excessive immune response might play a role in the pathophysiology of reversible splenial lesions.

Microstructural damage to white matter and resultant abnormal structural connectivity are a potential underlying pathophysiological mechanism of mild traumatic brain injury (mTBI). Many Tract-Based Spatial Statics studies have investigated the pathophysiology of mTBI, but they yielded inconsistent results potentially due to insufficient statistical power in spite of methodological homogeneity. We used anisotropic effect size signed differential mapping (AES-SDM) to integrate previous studies that recruited patients without a psychiatric history. AES-SDM revealed that fractional anisotropy values were significantly lower in mTBI patients than in control in three clusters. The peak of the largest cluster was in the left thalamus and the cluster extended to the splenium of the corpus callosum and to the anterior thalamic radiation. The second largest cluster was situated in the left forceps minor, and the third largest cluster was in the right superior longitudinal fasciculus III. These results suggest that the pathophysiology of mTBI includes abnormal structural connectivity between the thalamus and the prefrontal cortex, and abnormal intra- and inter-hemispheric structural connectivity involving the prefrontal cortex.

Knowledge regarding the association between functional connectivity and white-matter (WM) maturation of motor and visual networks in preterm infants at term equivalent age (TEA) and their association with behavioral outcome is currently limited. Thirty-two preterm infants born