Electroencephalographic evidence of gray matter lesions among multiple sclerosis patients: A case-control study.

ABSTRACT: This study aimed to investigate evidence of gray matter brain lesions in multiple sclerosis (MS) patients by evaluating the resting state alpha rhythm of brain electrical activity.The study included 50 patients diagnosed with MS recruited from the MS clinic with 50 age and gender-matched control participants. The study investigated parameters of posterior dominant rhythm (PDR) in the electroencephalography (EEG) recordings including wave frequency and amplitude. Functional disability among the patients was evaluated according to the expanded disability status scale. Univariate statistical analysis was completed using one-way analysis of variance and t test with a P value of less than .05 to indicate statistical significance.Patients with MS had significantly lower PDR frequency and amplitude values compared to the controls (P value < .01) and 34% of the MS patients had a PDR frequency of less than 8.5 Hz. The PDR frequency was negatively associated with the level of functional disability among the patients (P value <.001) and 4% of the patients had abnormal epileptiform discharges.Background slowing of resting alpha rhythms and epileptiform discharges are suggestive of gray matter degeneration and may help in the prediction and follow-up of cortical damage and functional disabilities among MS patients. Therefore, electroencephalography monitoring of the PDR spectrum may serve as an alternative or complementary tool with other imaging techniques to detect and monitor cerebral cortical lesions.

Brain morphologic abnormalities in migraine patients: an observational study.

BACKGROUND: Migraine is a common neurological disorder characterized by a complex physiopathology. We assessed brain morphologic differences in migraine and the possible pathogenetic mechanism underlying this disease. METHODS: We analyzed brain morphologic images of migraine patients, 14 with aura (MwA) [the mean (SD) age was 42.36 (2.95) years (range, 37-47)] and 14 without aura (MwoA) [the mean (SD) age was 43.5 (3.25) years (range, 39-50)] during episodic attack compared with health subjects balanced (HS) [the mean (SD) age was 42.5 (5.17) years (range, 34-51)]. All subjects underwent a Magnetic Resonance Imaging (MRI) examination with a scanner operating at 3.0 T and voxel based morphometry (VBM) approach was used to examine the gray matter volume (GMV). The statistical analysis to compare clinicl characteristics was performed using unpaired t-test an one-way Anova. RESULTS: Total cerebral GMV showed a significant difference between MwA and HS (p = 0.02), and between MwoA and HS (p = 0.003). In addition, not significative differences were found between MwA and MwoA groups (p = 0.17). We found three clusters of regions which showed significant GMV reduction in MwA compared with MwoA. MwA subjects showed a less of GMV in 4 clusters if compared with HS, and MwoA subjects showed a less of GMV in 3 clusters if compared with HS. We observed that MwA and MwoA patients had a significant reduction of GMV in the frontal and temporal lobe and the cerebellum, if compared to HS. The bilateral fusiform gyrus and the cingulate gyrus were increase in MwoA patients compared with HS. CONCLUSION: Our findings could provide a approach to understand possible differences in the pathogenesis of two type of migraine.

[Neuroanatomical brain profile of juvenile shiftlike schizophrenia: morphometry of grey matter in the prefrontal cortex and subcortical structures]. / Neiroanatomicheskie osobennosti golovnogo mozga pri iunosheskoi pristupoobraznoi shizofrenii: morfometriia serogo veshchestva prefrontal'noi kory i podkorkovykh struktur.

AIM: To determine neuroanatomical peculiarities of grey matter in some regions of the prefrontal cortex and several subcortical structures in patients with juvenile shift like schizophrenia (F20 ICD-10). MATERIAL AND METHODS: Forty-three young male patients and 54 mentally healthy men without family history of mental diseases underwent structural MRI with T1 high resolution images. RESULTS: As compared to mentally healthy subjects, there was a decrease of grey matter thickness in all tested regions of the prefrontal cortex in patients. No between-group differences in subcortical structures volumes were found. No correlations between structural changes and psychopathological symptoms were observed. CONCLUSION: Structural abnormalities of the frontal lobes in juvenile shift like schizophrenia are not associated with severity of psychopathological symptoms.

Subcortical heterotopic gray matter brain malformations: Classification study of 107 individuals.

OBJECTIVE: To better evaluate the imaging spectrum of subcortical heterotopic gray matter brain malformations (subcortical heterotopia [SUBH]), we systematically reviewed neuroimaging and clinical data of 107 affected individuals. METHODS: SUBH is defined as heterotopic gray matter, located within the white matter between the cortex and lateral ventricles. Four large brain malformation databases were searched for individuals with these malformations; data on imaging, clinical outcomes, and results of molecular testing were systematically reviewed and integrated with all previously published subtypes to create a single classification system. RESULTS: Review of the databases revealed 107 patients with SUBH, the large majority scanned during childhood (84%), including more than half before 4 years (59%). Although most individuals had cognitive or motor disability, 19% had normal development. Epilepsy was documented in 69%. Additional brain malformations were common and included abnormalities of the corpus callosum (65/102 [64%]), and, often, brainstem or cerebellum (47/106 [44%]). Extent of the heterotopic gray matter brain malformations (unilateral or bilateral) did not influence the presence or age at onset of seizures. Although genetic testing was not systematically performed in this group, the sporadic occurrence and frequent asymmetry suggests either postzygotic mutations or prenatal disruptive events. Several rare, bilateral forms are caused by mutations in genes associated with cell proliferation and polarity (EML1, TUBB, KATNB1, CENPJ, GPSM2). CONCLUSION: This study reveals a broad clinical and imaging spectrum of heterotopic malformations and provides a framework for their classification.

Polygenic risk for neuropsychiatric disease and vulnerability to abnormal deep grey matter development.

Neuropsychiatric disease has polygenic determinants but is often precipitated by environmental pressures, including adverse perinatal events. However, the way in which genetic vulnerability and early-life adversity interact remains obscure. We hypothesised that the extreme environmental stress of prematurity would promote neuroanatomic abnormality in individuals genetically vulnerable to psychiatric disorders. In 194 unrelated infants (104 males, 90 females), born before 33 weeks of gestation (mean gestational age 29.7 weeks), we combined Magnetic Resonance Imaging with a polygenic risk score (PRS) for five psychiatric pathologies to test the prediction that: deep grey matter abnormalities frequently seen in preterm infants are associated with increased polygenic risk for psychiatric illness. The variance explained by the PRS in the relative volumes of four deep grey matter structures (caudate nucleus, thalamus, subthalamic nucleus and lentiform nucleus) was estimated using linear regression both for the full, mixed ancestral, cohort and a subsample of European infants. Psychiatric PRS was negatively associated with lentiform volume in the full cohort (ß = -0.24, p = 8 × 10-4) and a European subsample (ß = -0.24, p = 8 × 10-3). Genetic variants associated with neuropsychiatric disease increase vulnerability to abnormal lentiform development after perinatal stress and are associated with neuroanatomic changes in the perinatal period.

Spared cognitive and behavioral functions prior to epilepsy onset in a rat model of subcortical band heterotopia.

Subcortical band heterotopia (SBH), also known as doublecortex syndrome, is a malformation of cortical development resulting from mutations in the doublecortin gene (DCX). It is characterized by a lack of migration of cortical neurons that accumulate in the white matter forming a heterotopic band. Patients with SBH may present mild to moderate intellectual disability as well as epilepsy. The SBH condition can be modeled in rats by in utero knockdown (KD) of Dcx. The affected cells form an SBH reminiscent of that observed in human patients and the animals develop a chronic epileptic condition in adulthood. Here, we investigated if the presence of a SBH is sufficient to induce cognitive impairment in juvenile Dcx-KD rats, before the onset of epilepsy. Using a wide range of behavioral tests, we found that the presence of SBH did not appear to affect motor control or somatosensory processing. In addition, cognitive abilities such as learning, short-term and long-term memory, were normal in pre-epileptic Dcx-KD rats. We suggest that the SBH presence is not sufficient to impair these behavioral functions.

Youth-Onset Type 2 Diabetes and the Developing Brain.

PURPOSE OF REVIEW: This review describes the literature evaluating the potential adverse effects of youth-onset type 2 diabetes on the developing brain. A summary of recently published articles and the current state of knowledge are covered succinctly in this manuscript. RECENT FINDINGS: Current literature suggests both cognitive and brain structural differences are found in youth with type 2 diabetes. Studies have shown poorer scores in a number of neurocognitive domains, particularly in areas of executive functioning and memory. Additionally, imaging studies have found differences in brain gray matter volume, white matter volume, and microstructural integrity. These findings are largely consistent with the adult literature. Youth with type 2 diabetes demonstrate lower cognitive scores and structural brain differences. Although causality has not yet been established, these findings are important because these individuals are still undergoing neurodevelopmental maturation.

Brain gray and white matter abnormalities in preterm-born adolescents: A meta-analysis of voxel-based morphometry studies.

INTRODUCTION: Studies using voxel-based morphometry report variable and inconsistent abnormalities of gray matter volume (GMV) and white matter volume (WMV) in brains of preterm-born adolescents (PBA). In such circumstances a meta-analysis can help identify the most prominent and consistent abnormalities. METHOD: We identified 9 eligible studies by systematic search of the literature up to October 2017. We used Seed-based d Mapping to analyze GMV and WMV alterations between PBA and healthy controls. RESULTS: In the GMV meta-analysis, PBA compared to healthy controls showed: increased GMV in left cuneus cortex, left superior frontal gyrus, and right anterior cingulate cortex; decreased GMV in bilateral inferior temporal gyrus (ITG), left superior frontal gyrus, and right caudate nucleus. In the WMV meta-analysis, PBA showed: increased WMV in right fusiform gyrus and precuneus; decreased WMV in bilateral ITG, and right inferior frontal gyrus. In meta-regression analysis, the percentage of male PBA negatively correlated with decreased GMV of bilateral ITG. INTERPRETATION: PBA show widespread GMV and WMV alterations in the default mode network, visual recognition network, and salience network. These changes may be causally relevant to socialization difficulties and cognitive impairments. The meta-regression results perhaps reveal the structural underpinning of the cognition-related sex differences in PBA.

Cerebral gray matter changes in persistent postural perceptual dizziness.

BACKGROUND: Persistent postural perceptual dizziness (PPPD) is the most common vestibular syndrome in middle-aged patients. Multisensory maladjustment involving alterations of sensory response pattern including vestibular, visual and motion stimuli is thought to be a key pathophysiological correlate of this disorder. OBJECTIVE: We aimed to identify regional gray matter changes in PPPD patients that might be involved in the underlying pathophysiology of this disorder. METHODS: 42 PPPD patients and healthy age and gender matched controls were investigated using magnetic resonance imaging-based voxel-based morphometry. All patients fulfilled the current diagnostic criteria for PPPD, established by the Bárány-Society based on previous criteria for chronic subjective dizziness and phobic postural vertigo. RESULTS: PPPD patients showed gray matter volume decrease in the temporal cortex, cingulate cortex, precentral gyrus, hippocampus, dorsolateral prefrontal cortex, caudate nucleus and the cerebellum. A negative correlation of disease duration and gray matter volume was observed in the visual cortex, supplementary motor area and somatosensory processing structures. CONCLUSIONS: In patients with PPPD areas involved in multisensory vestibular processing show gray matter volume decrease. These brain regions resemble those previously described for other vestibular disorders. Longer duration of disease leads to a more pronounced gray matter alteration, which might represent maladaptive mechanisms within the course of disease.

Brain structure abnormalities in young women who presented conduct disorder in childhood/adolescence.

The phenotype and genotype of antisocial behavior among females are different from those among males. Previous studies have documented structural brain alterations in males with antisocial behavior, yet little is known about the neural correlates of female antisocial behavior. The present study examined young women who had presented conduct disorder (CDW) prior to age 15 to determine whether brain abnormalities are present in adulthood and whether the observed abnormalities are associated with comorbid disorders or maltreatment that typically characterize this population. Using magnetic resonance imaging and voxel-based morphometry, we compared gray matter volumes (GMV) of 31 women who presented CD by midadolescence and 25 healthy women (HW), age, on average, 23 years. Participants completed structured, validated interviews to diagnose mental disorders, and validated questionnaires to document physical and sexual abuse. Relative to HW, CDW presented increased GMV in the left superior temporal gyrus that was associated with past alcohol and drug dependence, current use of alcohol and drugs, and current anxiety and depression symptoms and maltreatment. Additionally, CDW displayed reduced GMV in lingual gyrus, hippocampus, and anterior cingulate cortex that was associated with past comorbid disorders, current alcohol and drugs use, current anxiety and depression symptoms, and maltreatment. The CDW also presented reduced total GMV that was associated with past comorbid disorders and current anxiety/depression symptoms. Alterations of brain structure were observed among young adult females with prior CD, relative to HW, all of which were associated with internalizing and externalizing disorders and maltreatment that typically accompany CD.

Gray matter abnormalities in pediatric autism spectrum disorder: a meta-analysis with signed differential mapping.

The gray matter abnormalities revealed by magnetic resonance imaging are inconsistent, especially in pediatric individuals with autism spectrum disorder (ASD) (age < 18 years old), a phenomenon possibly related to the core pathophysiology of ASD. The purpose of our meta-analysis was to identify and map the specific gray matter abnormalities in pediatric ASD individuals thereby exploring the potential effects of clinical and demographic characteristics of these gray matter changes. A systematic search was conducted to identify voxel-based morphometry studies in pediatric individuals with ASD. The effect-size signed differential mapping method was used to quantitatively estimate the regional gray matter abnormalities in pediatric ASD individuals. Meta-regression was used to examine the associations among age, gender, intelligence quotient, symptom severity and gray matter changes. Fifteen studies including 364 pediatric individuals with ASD (male = 282, age = 10.3 ± 4.4 years) and 377 healthy controls (male = 289, age = 10.5 ± 4.2 years) were included. Pediatric ASD individuals showed significant gray matter increases in the right angular gyrus, left superior and middle frontal gyrus, left precuneus, left inferior occipital gyrus and right inferior temporal gyrus, most of which involving the default mode network, and decreases in the left cerebellum and left postcentral gyrus. The meta-regression analysis showed that the repetitive behavior scores of the Autism Diagnostic Interview-Revised were positively associated with increased gray matter volumes in the right angular gyrus. Increased rather than decreased gray matter volume, especially involving the angular gyrus and prefrontal cortex may be the core pathophysiology in the early course of ASD.

Alterations of gray and white matter morphology in obsessive compulsive disorder / Las alteraciones de morfología de la sustancia blanca y gris en el trastorno obsesivo compulsivo

BACKGROUND: While the ethio-pathogenesis of Obsessive-Compulsive disorder (OCD) remains unknown, there is increased evidence of widespread structural alterations in both white and gray matter in OCD patients that include, but are not restricted, to abnormalities in corticostriatal-thalamo-cortical (CSTC) regions. The objective of this study was to test the existence of structural alterations in both white and gray matter in a sample of OCD patients when compared with a group of non-clinical matched controls (NCC), using voxel-based morphometry (VBM). METHOD: Fifteen patients with OCD and 15 NCC underwent MRI structural scanning. RESULTS: Frontal (increased gray matter in the middle frontal gyrus) and subcortical regions (increased white matter in the pallidum) were found to be affected in patients. Additionally, temporalparietal regions were also found to be affected and highly correlated with OCD symptom severity (decrease of gray matter in the superior parietal lobe and white matter in the angular and superior temporal gyri). CONCLUSIONS: These alterations may be associated with prominent OCD symptoms, such as diffi culties with inhibitory control (pallidum, angular gyrus), executive functioning (middle frontal gyris), compulsive checking (superior temporal gyrus) and visual-spatial defi cits (superior parietal lobe)

ANTECEDENTES: mientras que la etiopatogenia del trastorno obsesivo-compulsivo (TOC) sigue siendo desconocida, hay una mayor evidencia en las personas que sufren este trastorno de alteraciones estructurales que incluyen, pero no se limitan, a anormalidades en regiones cortico-estriado-tálamo-corticales (CSTC). El objetivo de este estudio fue comprobar la existencia de alteraciones estructurales tanto en la materia blanca como en la materia gris en una muestra de pacientes con TOC en comparación con un grupo de controles no clínicos (NCC), utilizándose para ello análisis morfométricos basados en «voxel» (VBM). MÉTODO: quince pacientes con TOC y quince NCC fueron estudiados mediante resonancia magnética estructural. RESULTADOS: se encontraron alteraciones en los pacientes en regiones frontales (aumento de la materia gris en la circunvolución frontal media) y subcorticales (aumento de la materia blanca en el pallidum). Además, también se encontraron afectadas regiones témporo-parietales con una alta correlación con la gravedad de los síntomas del TOC (disminución de la materia gris en el lóbulo parietal superior y de la materia blanca en las circunvoluciones temporales angular y superior). CONCLUSIONES: las alteraciones encontradas pueden estar asociados con síntomas predominantes en el TOC, como dificultades en el control inhibitorio (pallidum, giro angular), función ejecutiva (circunvolución frontal media), verificaciones compulsivas (circunvolución temporal superior) y déficit visual-espacial (lóbulo parietal superior)

Common and Specific Abnormalities in Cortical Thickness in Patients with Major Depressive and Bipolar Disorders.

Major depressive disorder (MDD) and bipolar disorder (BD) are severe psychiatric diseases with overlapping symptomatology. Although previous studies reported abnormal brain structures in MDD or BD patients, the disorder-specific underlying neural mechanisms remain poorly understood. The purpose of this study was to investigate the whole-brain gray matter morphological patterns in unmedicated patients with MDD or BD and to identify the shared and disease-specific brain morphological alterations in these two disorders. We acquired high-resolution brain structural MRI data from a sample of 36 MDD patients, 32 BD patients, and 30 healthy controls. Using FreeSurfer, we estimated their brain cortical thickness (CT) and compared between-group difference in multiple locations across the continuous cortical surface. Compared to the healthy controls, both the MDD and BD patient groups showed significantly reduced CT in the left inferior temporal cortex (ITC). However, compared to the MDD patients, the BD patients showed a significantly thinner CT in the left rostral middle frontal region. In addition, compared to the healthy controls, the BD patients displayed thinner CT in the left ITC, left frontal pole (FPO), left superior frontal, right lateral occipital, right pars triangularis (PTRI) and right lateral orbitofrontal regions. Further analysis revealed a significantly positive correlation between the mean CT in the left FPO and the onset age, but a negative correlation between the mean CT in the right PTRI and the number of episodes, in the BD patients. Our findings revealed that the BD and MDD patients had variations in CT that were in common, but many more that were distinct, suggesting potential differences in their neural mechanisms.

Structural brain abnormalities in patients with vestibular migraine.

New advances in understanding the pathophysiology of vestibular migraine (VM) have suggested a large overlap between migraine and vestibular pathways. We explored the regional distribution of gray (GM) and white matter (WM) abnormalities in VM patients in comparison to migraine patients with (MWA) and without aura (MWoA) and their correlations with patients' clinical manifestations. Using a 3.0 Tesla scanner, brain T2-weighted and 3D T1-weighted MRI scans were acquired from 19 VM, 19 MWA, 19 MWoA and 20 age-matched controls. GM and WM volumetric abnormalities were estimated using voxel-based morphometry (SPM12). Compared to controls, migraine patients had decreased GM volume of the left cerebellum and an increased GM volume of the left temporal lobe. VM patients had a selective GM volume increase of frontal and occipital regions compared to controls and the other two groups of migraineurs and no regions with decreased GM volume. Compared to MWoA and MWA, VM had increased GM volume of the left thalamus. Regional GM abnormalities did not correlate with disease duration and attack frequency. No WM volumetric differences were detected between migraine patients and controls. These results show that GM volume abnormalities of nociceptive and multisensory vestibular brain areas occur in VM patients. Overall, our findings suggest that an abnormal brain sensitization might lead to a dismodulation of multimodal sensory integration and processing cortical areas in VM patients.

Delayed cortical gray matter development in neonates with severe congenital heart disease.

BACKGROUND: This study aimed to assess cortical gray matter growth and maturation in neonates with congenital heart disease (CHD). METHODS: Thirty-one (near) term neonates with severe CHD (8 univentricular heart malformation (UVH), 21 d-transposition of great arteries (d-TGA) and 2 aortic coarctation) underwent cerebral MRI before (postnatal-day 7) and after (postnatal-day 24) surgery. Eighteen controls with similar gestational age had one MRI (postnatal-day 23). Cortical gray matter volume (CGM), inner cortical surface (iCS), and median cortical thickness were extracted as measures of volumetric growth, and gyrification index (GI) as measure of maturation. RESULTS: Over a median of 18 d, CGM increased by 21%, iCS by 17%, thickness and GI both by 9%. Decreased postoperative CGM and iCS were seen for CHD compared to controls (P values < 0.01), however with similar thickness and GI. UVH showed lower postoperative iCS, thickness (P values < 0.05) and GI (P value < 0.01) than d-TGA and controls. Infants requiring preoperative balloon-atrioseptostomy (BAS, 61%) had reduced postoperative CGM, iCS, and GI (P values < 0.05). CONCLUSION: Infants with severe CHD show reduced cortical volumes compared to controls with gyrification being delayed in UVH, but not in d-TGA. Infants requiring BAS show higher risk of impaired cortical volume and gyrification.

Gray Matter Abnormalities in Temporal Lobe Epilepsy: Relationships with Resting-State Functional Connectivity and Episodic Memory Performance.

Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, and compared between groups. Finally, we investigated the relation between EM, GM and FC findings. Patients with and without temporal pathology were analyzed separately. The results revealed reduced GM volume in multiple regions in the patients relative to the controls. Using FC, we found the abnormal GM regions did not display abnormal functional connectivity. Lastly, we found in left TLE patients, verbal episodic memory was associated with abnormal left posterior hippocampus volume, while in right TLE, non-verbal episodic memory was better predicted by resting-state FC measures. This study investigated TLE abnormalities using a multi-modal approach combining GM, FC and neurocognitive measures. We did not find that the GM abnormalities were functionally or abnormally connected during an inter-ictal resting state, which may reflect a weak sensitivity of functional connectivity to the epileptic network. We provided evidence that verbal and non-verbal episodic memory in left and right TLE patients may have distinct relationships with structural and functional measures. Lastly, we provide data suggesting that in the setting of occult, non-lesional right TLE pathology, a coupling of structural and functional abnormalities in extra-temporal/non-ictal regions is necessary to produce reductions in episodic memory recall. The latter, in particular, demonstrates the complex structure/function interactions at work when trying to understand cognition in TLE, suggesting that subtle network effects can emerge bearing specific relationships to hemisphere and the type of pathology.

Cerebellar Bottom-of-Fissure Dysplasia-a Novel Cerebellar Gray Matter Neuroimaging Pattern.

We report on seven patients with a novel neuroimaging finding that involves exclusively the cerebellar gray matter at the bottom of several fissures of both hemispheres but spares the vermis. The abnormal fissures were predominantly located in the lower and lateral parts of the cerebellar hemispheres. The affected cerebellar cortex was hypointense on T1-weighted and hyperintense on T2-weighted and fluid attenuation inversion recovery sequences. In some patients, the involved cerebellar gray matter was mildly thickened and the affected fissures slightly widened. In three of seven patients, the neuroimaging findings were unchanged on follow-up studies up to 6 years. The seven patients had various indications for the brain magnetic resonance imaging studies, and none of them had cerebellar dysfunction. Based on the similarity of the neuroimaging pattern with the cerebral "bottom-of-sulcus dysplasia," we coined the term "cerebellar bottom-of-fissure dysplasia" to refer to this novel neuroimaging finding. The neuroimaging characteristic as well as the unchanged findings on follow-up favors a stable "developmental" (malformative) nature. The lack of cerebellar dysfunction in the affected patients suggests that cerebellar bottom-of-fissure dysplasia represents most likely an incidental finding that does not require specific diagnostic investigation but allows a reassuring attitude.