Alterations in Cortical Morphology after Neonatal Stroke: Compensation in the Contralesional Hemisphere?

Although neonatal arterial ischemic stroke is now well‐studied, its complex consequences on long‐term cortical brain development has not yet been solved. In order to understand the brain development after focal early brain lesion, brain morphometry needs to be evaluated using structural parameters. In this work, our aim was to study and analyze the changes in morphometry of ipsi‐ and contralesional hemispheres in seven‐year‐old children following neonatal stroke. Therefore, we used surface‐based morphometry in order to examine the cortical thickness, surface area, cortical volume, and local gyrification index in two groups of children that suffered from neonatal stroke in the left (n = 19) and right hemispheres (n = 15) and a group of healthy controls (n = 30). Reduced cortical thickness, surface area, and cortical volumes were observed in the ipsilesional hemispheres for both groups in comparison with controls. For the group with left‐sided lesions, higher gyrification of the contralesional hemisphere was observed primarily in the occipital region along with higher surface area and cortical volume. As for the group with right‐sided lesions, higher gyrification was detected in two separate clusters also in the occipital lobe of the contralesional hemisphere, without a significant change in cortical thickness, surface area, or cortical volume. This is the first time that alterations of structural parameters are detected in the “healthy” hemisphere after unilateral neonatal stroke indicative of a compensatory phenomenon. Moreover, findings presented in this work suggest that lesion lateralization might have an influence on brain development and maturation.     

3D FSPGR (fast spoiled gradient echo) magnetic resonance imaging in the diagnosis of focal cortical dysplasia in children

Small dysplastic lesions of the cerebral cortex are often missed by conventional MRI methods. The identification of subtle structural abnormalities by traditional multiplanar rectilinear slices is often limited by the complex convolutional pattern of the brain. We used a method of FSPGR (fast spoiled gradient-echo) of three-dimensional MRI data that improves the anatomical display of the sulcal structure of the hemispheric convexities. It also reduces the asymmetric sampling of gray-white matter that may lead to false-positive results. We present 5 from 12 patients with dysplastic cortical lesions in whom conventional two-dimensional and three-dimensional MRI with multiplanar reformatting was initially considered normal. Subsequent studies using 3D FSPGR identified various types of focal cortical dysplasia in all. These results indicate that an increase in the detection of subtle focal dysplastic lesions may be accomplished when one improves the anatomical display of the brain sulcal structure by performing 3D FSPGR.     

Surface Vulnerability of Cerebral Cortex to Major Depressive Disorder

Major depressive disorder (MDD) is accompanied by atypical brain structure. This study first presents the alterations in the cortical surface of patients with MDD using multidimensional structural patterns that reflect different neurodevelopment. Sixteen first-episode, untreated patients with MDD and 16 matched healthy controls underwent a magnetic resonance imaging (MRI) scan. The cortical maps of thickness, surface area, and gyrification were examined using the surface-based morphometry (SBM) approach. Increase of cortical thickness was observed in the right posterior cingulate region and the parietal cortex involving the bilateral inferior, left superior parietal and right paracentral regions, while decreased thickness was noted in the parietal cortex including bilateral pars opercularis and left precentral region, as well as the left rostral-middle frontal regions in patients with MDD. Likewise, increased or decreased surface area was found in five sub-regions of the cingulate gyrus, parietal and frontal cortices (e.g., bilateral inferior parietal and superior frontal regions). In addition, MDD patients exhibited a significant hypergyrification in the right precentral and supramarginal region. This integrated structural assessment of cortical surface suggests that MDD patients have cortical alterations of the frontal, parietal and cingulate regions, indicating a vulnerability to MDD during earlier neurodevelopmental process.     

Detection of structural abnormalities of cortical and subcortical gray matter in patients with MRI-negative refractory epilepsy using neurite orientation dispersion and density imaging

PurposeNODDI (Neurite Orientation Dispersion and Density Imaging) and DTI (Diffusion tensor imaging) may be useful in identifying abnormal regions in patients with MRI-negative refractory epilepsy. The aim of this study was to determine whether NODDI and DTI maps including neurite density (ND), orientation dispersion index (ODI), mean diffusivity (MD) and fractional anisotropy (FA) can detect structural abnormalities in cortical and subcortical gray matter (GM) in these patients. The correlation between these parameters and clinical characteristics of the disease was also investigated.MethodsNODDI and DTI maps of 17 patients were obtained and checked visually. Region of interest (ROI) was drawn on suspected areas and contralateral regions in cortex. Contrast-to-noise ratio (CNR) was determined for each region. Furthermore volumetric data and mean values of ND, ODI, FA and MD of subcortical GM structures were calculated in both of the patients and controls. Finally, the correlations of these parameters in the subcortical with age of onset and duration of epilepsy were investigated.ResultsCortical abnormalities on ODI images were observed in eight patients qualitatively. CNR of ODI was significantly greater than FA and MD. The subcortical changes including decrease of FA and ND and increase of ODI in left nucleus accumbens and increase of the volume in right amygdala were detected in the patients.ConclusionsThe results revealed that NODDI can improve detection of microstructural changes in cortical and subcortical GM in patients with MRI negative epilepsy.     

Epilepsy due to malformations of cortical development--correlation of clinical, MRI and Tc-99mECD SPECT findings

Malformations of cortical development (MCD) have been increasingly recognized as an important cause of intractable epilepsy. The aim of our study was to define epileptogenicity of MCDs by correlating MRI, EEG and semiology of epileptic attacks, and to determine the effect of MCD on drug resistant epilepsy. We also intended to reveal the utility of interictal single photo emission computed tomography (SPECT) in verification of MCD lesions and relative prevalence of different MCDs. Based on interictal EEG finding, semiology of the epileptic attacks and brain magnetic resonance imaging (MRI) "electroclinical epileptogenicity" of MCD was defined. Brain MRI revealed cortical dysplasia (CD) in nine patients, polymicrogyria in four patients, lissencephaly and schizencephaly in one patient each. Three patients had a combination of malformations. The localization of SPECT hypoperfusion corresponded to MCD lesion in ten (66.67%) patients. Electroclinically confirmed epileptogenicity of MCD overlapped with MR and interictal SPECT findings in fourteen (93.3%) and nine (60.0%) patients, respectively. Our study results demonstrated the MCD lesions to be highly epileptogenic and a frequent cause of intractability.     

Cortical Thickness,Surface Area and Subcortical Volume Differentially Contribute to Cognitive Heterogeneity in Parkinson’s Disease

Parkinson’s disease (PD) is often associated with cognitive deficits, although their severity varies considerably between patients. Recently, we used voxel-based morphometry (VBM) to show that individual differences in gray matter (GM) volume relate to cognitive heterogeneity in PD. VBM does, however, not differentiate between cortical thickness (CTh) and surface area (SA), which might be independently affected in PD. We therefore re-analyzed our cohort using the surface-based method FreeSurfer, and investigated (i) CTh, SA, and (sub)cortical GM volume differences between 93 PD patients and 45 matched controls, and (ii) the relation between these structural measures and cognitive performance on six neuropsychological tasks within the PD group. We found cortical thinning in PD patients in the left pericalcarine gyrus, extending to cuneus, precuneus and lingual areas and left inferior parietal cortex, bilateral rostral middle frontal cortex, and right cuneus, and increased cortical surface area in the left pars triangularis. Within the PD group, we found negative correlations between (i) CTh of occipital areas and performance on a verbal memory task, (ii) SA and volume of the frontal cortex and visuospatial memory performance, and, (iii) volume of the right thalamus and scores on two verbal fluency tasks. Our primary findings illustrate that i) CTh and SA are differentially affected in PD, and ii) VBM and FreeSurfer yield non-overlapping results in an identical dataset. We argue that this discrepancy is due to technical differences and the subtlety of the PD-related structural changes.     

Thicker Temporal Cortex Associates with a Developmental Trajectory for Psychopathic Traits in Adolescents

Psychopathy is a clinical condition characterized by a failure in normal social interaction and morality. Recent studies have begun to reveal brain structural abnormalities associated with psychopathic tendencies in children. However, little is known about whether variations in brain morphology are linked to the developmental trajectory of psychopathic traits over time. In this study, structural magnetic resonance imaging (sMRI) data from 108 14-year-old adolescents with no history of substance abuse (54 males and 54 females) were examined to detect cortical thickness variations associated with psychopathic traits and individual rates of change in psychopathic traits from ages 9 to 18. We found cortical thickness abnormalities to correlate with psychopathic traits both cross-sectionally and longitudinally. Specifically, at age 14, higher psychopathic scores were correlated with thinner cortex in the middle frontal gyrus, particularly in females, and thicker cortex in the superior temporal gyrus, middle temporal gyrus, and parahippocampal gyrus, particularly in males. Longitudinally, individual rates of change in psychopathic tendency over time were correlated with thicker cortex in the superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, parahippocampal gyrus, and posterior cingulate gyrus, particularly in males. Findings suggest that abnormal cortical thickness may reflect a delay in brain maturation, resulting in disturbances in frontal and temporal functioning such as impulsivity, sensation-seeking, and emotional dysregulation in adolescents. Thus, findings provide initial evidence supporting that abnormal cortical thickness may serve as a biomarker for the development of psychopathic propensity in adolescents.     

Clinical and diagnostic approach in unsolved CDG patients with a type 2 transferrin pattern

Dysmorphic features, multisystem disease, and central nervous system involvement are common symptoms in congenital disorders of glycosylation, including several recently discovered Golgi-related glycosylation defects. In search for discriminative features, we assessed eleven children suspected with a Golgi-related inborn error of glycosylation. We evaluated all genetically unsolved patients, diagnosed with a type 2 transferrin isofocusing pattern in the period of 1999-2009. By combining biochemical results with characteristic clinical symptoms, we used a diagnostic flow chart to approach the underlying defect in patients with congenital disorders of glycosylation-IIx. According to specific symptoms and laboratory results, we initiated additional, targeted biochemical and genetic studies. We found a distinctive spectrum of congenital disorders of glycosylation type 2-associated anomalies including sudden hearing loss, brain malformations, wrinkled skin, and epilepsy in combination with skeletal dysplasia, dilated cardiomyopathy, sudden cardiac arrest, abnormal copper and iron metabolism, and endocrine abnormalities in our patients. One patient with severe cortical malformations and mild skin abnormalities was diagnosed with a known genetic syndrome, due to an ATP6V0A2 defect. Here, we present unique congenital disorders of glycosylation type 2-associated anomalies, including both ATPase-related and unrelated cutis laxa and sensorineural hearing loss, a recently recognized symptom of congenital disorders of glycosylation. Based on our findings, we recommend clinicians to consider congenital disorders of glycosylation in patients with cardiac rhythm disorders, spondylodysplasia and biochemical abnormalities of the copper and iron metabolism even in absence of intellectual disability.     

原发全面强直-阵挛型癫痫的体素形态学研究

采用基于体素形态学（voxel- based morphometry,VBM）的方法,分析了全面强直-阵挛型癫痫（epilepsy with generalized tonic clonic seizures,GTCS）患者的大脑结构异常情况。对31例临床诊断为GTCS的患者和31例正常志愿者,采集大脑三维（3-dimensional,3D）T1结构像,进行VBM全脑分析比较。通过GTCS患者组与正常对照组的比较,发现GTCS患者的双侧丘脑、双侧额叶、双侧岛叶、双侧小脑等区域的灰质体积有比较明显的减小,但没发现有意义的灰质体积增高的区域;患者双侧丘脑、左侧中央前回、左侧额内侧回、左侧额中回和其发病频率呈负相关,没有正相关的区域。结果显示,全面强直-阵挛型癫痫患者的大脑结构存在异常,说明大脑灰质体积的异常可能和全面强直-阵挛型癫痫的发病存在一定的关系。     

Hippocampal signal complexity in mesial temporal lobe epilepsy: a noisy brain is a healthy brain

Patients with mesial temporal lobe epilepsy (mTLE) show structural and functional abnormalities in hippocampus and surrounding mesial temporal structures. Brain signal complexity appears to be a marker of functional integrity or capacity. We examined complexity in 8 patients with intracranial hippocampal electrodes during performance of memory tasks (scene encoding and recognition) known to be sensitive to mesial temporal integrity. Our patients were shown to have right mesial temporal seizure onsets, permitting us to evaluate both epileptogenic (right) and healthy (left) hippocampi. Using multiscale entropy (MSE) as a measure of complexity, we found that iEEG from the epileptogenic hippocampus showed less complexity than iEEG from the healthy hippocampus. This difference was reliable for encoding but not for recognition. Our results indicate that both functional integrity and cognitive demands influence hippocampal signal complexity.     

Detection of structural and numerical chromosome abnormalities in interphase cells using spectral imaging.

Chromosome abnormalities are common causes of congenital malformations and spontaneous abortions. They include structural abnormalities, polyploidy, trisomy, and mosaicism. In in vitro fertilization (IVF) programs, preimplantation genetic diagnosis (PGD) of oocytes and embryos has become the technique of choice to select against abnormal embryos before embryo transfer. For diagnosis of structural abnormalities, we developed case-specific breakpoint-spanning DNA probes. Screening of an in-house yeast artificial chromosome (YAC) library is facilitated by information from publicly available databases and published articles. Most numerical chromosome abnormalities, on the other hand, are detrimental to early embryonic development and increase with maternal age. We therefore developed a multichromosome screening technique based on spectral imaging to simultaneously detect and score as many as 10 different chromosome types. The probe set was chosen to detect more than 70% of all numerical chromosome aberrations responsible for spontaneous abortions. Detecting structural and numerical abnormalities in single interphase cells using spectral imaging is a powerful technique for multilocus genetic screening.     

Computerized tomography of the head in patients with epilepsy

A detection of structural changes in the brain of epileptic patients is of importance to the choice of therapeutical management. Incidence and character of lesions in CT-scans of the skull were analysed in the random group of epileptic patients. Normal areas in CT-scans were prevailing in young patients. Atrophic lesions to the brain increased with the patients' age and duration of the disease. Normal results were obtained in post-traumatic epilepsy and that of unknown etiology similarly to atrophic lesions whereas localized lesions were found in all patients with cerebral tumors. Partial epilepsy, especially of short duration, was characterized by high incidence of localized lesions. Normal EEG records were rare in patients with localized lesions detected with CT-scans whereas normal CT-scans may be related to abnormal EEG record. Presence of the localized lesions in some patients and atrophic areas did not limit clinical results of monitored therapy. CT-scanning of the skull should be performed in case of all patients with epilepsy even if there are no significant changes in EEG records or clinical status.     

Ictal Depth EEG and MRI Structural Evidence for Two Different Epileptogenic Networks in Mesial Temporal Lobe Epilepsy

Hypersynchronous (HYP) and low voltage fast (LVF) activity are two separate ictal depth EEG onsets patterns often recorded in presurgical patients with MTLE. Evidence suggests the mechanisms generating HYP and LVF onset seizures are distinct, including differential involvement of hippocampal and extra-hippocampal sites. Yet the extent of extra-hippocampal structural alterations, which could support these two common seizures, is not known. In the current study, preoperative MRI from 24 patients with HYP or LVF onset seizures were analyzed to determine changes in cortical thickness and relate structural changes to spatiotemporal properties of the ictal EEG. Overall, onset and initial ipsilateral spread of HYP onset seizures involved mesial temporal structures, whereas LVF onset seizures involved mesial and lateral temporal as well as orbitofrontal cortex. MRI analysis found reduced cortical thickness correlated with longer duration of epilepsy. However, in patients with HYP onsets, the most affected areas were on the medial surface of each hemisphere, including parahippocampal regions and cingulate gyrus, whereas in patients with LVF onsets, the lateral surface of the anterior temporal lobe and orbitofrontal cortex showed the greatest effect. Most patients with HYP onset seizures were seizure-free after resective surgery, while a higher proportion of patients with LVF onset seizures had only worthwhile improvement. Our findings confirm the view that recurrent seizures cause progressive changes in cortical thickness, and provide information concerning the structural basis of two different epileptogenic networks responsible for MTLE. One, identified by HYP ictal onsets, chiefly involves hippocampus and is associated with excellent outcome after standardized anteromedial temporal resection, while the other also involves lateral temporal and orbitofrontal cortex and a seizure-free surgical outcome occurs less after this procedure. These results suggest that a more extensive tailored resection may be required for patients with the second type of MTLE.     

Adaptive Modulation of Adult Brain Gray and White Matter to High Altitude: Structural MRI Studies

The aim of this study was to investigate brain structural alterations in adult immigrants who adapted to high altitude (HA). Voxel-based morphometry analysis of gray matter (GM) volumes, surface-based analysis of cortical thickness, and Tract-Based Spatial Statistics analysis of white matter fractional anisotropy (FA) based on MRI images were conducted on 16 adults (20–22 years) who immigrated to the Qinghai-Tibet Plateau (2300–4400 m) for 2 years. They had no chronic mountain sickness. Control group consisted of 16 matched sea level subjects. A battery of neuropsychological tests was also conducted. HA immigrants showed significantly decreased GM volumes in the right postcentral gyrus and right superior frontal gyrus, and increased GM volumes in the right middle frontal gyrus, right parahippocampal gyrus, right inferior and middle temporal gyri, bilateral inferior ventral pons, and right cerebellum crus1. While there was some divergence in the left hemisphere, surface-based patterns of GM changes in the right hemisphere resembled those seen for VBM analysis. FA changes were observed in multiple WM tracts. HA immigrants showed significant impairment in pulmonary function, increase in reaction time, and deficit in mental rotation. Parahippocampal and middle frontal GM volumes correlated with vital capacity. Superior frontal GM volume correlated with mental rotation and postcentral GM correlated with reaction time. Paracentral lobule and frontal FA correlated with mental rotation reaction time. There might be structural modifications occurred in the adult immigrants during adaptation to HA. The changes in GM may be related to impaired respiratory function and psychological deficits.     

Hemispherically-Unified Surface Maps of Human Cerebral Cortex: Reliability and Hemispheric Asymmetries

Understanding the anatomical and structural organization of the cerebral cortex is facilitated by surface-based analysis enabled by FreeSurfer, Caret, and related tools. Here, we examine the precision of FreeSurfer parcellation of the cortex and introduce a method to align FreeSurfer-registered left and right hemispheres onto a common template in order to characterize hemispheric asymmetries. The results are visualized using Mollweide projections, an area-preserving map. The regional distribution, inter-hemispheric asymmetries and intersubject variability in cortical curvature, sulcal depth, cortical thickness, and cortical surface area of 138 young, right handed subjects were analyzed on the Mollweide projection map of the common spherical space. The results show that gyral and sulcal structures are aligned with high but variable accuracy in different cortical regions and show consistent hemispheric asymmetries that are maximal in posterior temporal regions.     

Genetic basis in epilepsies caused by malformations of cortical development and in those with structurally normal brain

Epilepsy is the most common neurological disorder affecting young people. The etiologies are multiple and most cases are sporadic. However, some rare families with Mendelian inheritance have provided evidence of genes’ important role in epilepsy. Two important but apparently different groups of disorders have been extensively studied: epilepsies associated with malformations of cortical development (MCDs) and epilepsies associated with a structurally normal brain (or with minimal abnormalities only). This review is focused on clinical and molecular aspects of focal cortical dysplasia, polymicrogyria, periventricular nodular heterotopia, subcortical band heterotopia, lissencephaly and schizencephaly as examples of MCDs. Juvenile myoclonic epilepsy, childhood absence epilepsy, some familial forms of focal epilepsy and epilepsies associated with febrile seizures are discussed as examples of epileptic conditions in (apparently) structurally normal brains.     

Cortical thinning in patients with recent onset post-traumatic stress disorder after a single prolonged trauma exposure

Most of magnetic resonance imaging (MRI) studies about post-traumatic stress disorder (PTSD) focused primarily on measuring of small brain structure volume or regional brain volume changes. There were rare reports investigating cortical thickness alterations in recent onset PTSD. Recent advances in computational analysis made it possible to measure cortical thickness in a fully automatic way, along with voxel-based morphometry (VBM) that enables an exploration of global structural changes throughout the brain by applying statistical parametric mapping (SPM) to high-resolution MRI. In this paper, Laplacian method was utilized to estimate cortical thickness after automatic segmentation of gray matter from MR images under SPM. Then thickness maps were analyzed by SPM8. Comparison between 10 survivors from a mining disaster with recent onset PTSD and 10 survivors without PTSD from the same trauma indicates cortical thinning in the left parietal lobe, right inferior frontal gyrus, and right parahippocampal gyrus. The regional cortical thickness of the right inferior frontal gyrus showed a significant negative correlation with the CAPS score in the patients with PTSD. Our study suggests that shape-related cortical thickness analysis may be more sensitive than volumetric analysis to subtle alteration at early stage of PTSD.     

Altered Topological Organization of Cortical Network in Adolescent Girls with Idiopathic Scoliosis

Adolescent idiopathic scoliosis (AIS) is a multifactorial disease affecting approximately 1–4% of teenagers especially girls at the age of 10–16, but its etiopathogenesis remains uncertain. Previous study has revealed that the cortical thickness in AIS patients is different from that in normal controls. Cortical thickness measurements are known to be strongly correlated between regions that are axonally connected. Hence, a hypothesis is proposed to study the possibility to demonstrate abnormal structural network revealed by cortical thickness in AIS patients. The aim of the study is to investigate abnormalities in the organization of the brain cortical network in AIS patients. This study included 42 girls with severe idiopathic scoliosis (14.7±1.3 years old) and 41 age-matched normal controls (NC, 14.6±1.4 years old). The brain cortex was partitioned into 154 cortical regions based on gyral and sulcal structure. The interregional connectivity was measured as the statistical correlations between the regional mean thicknesses across the subjects. We employed the graph theoretic analysis to examine the alteration in interregional correlation, small-world efficiency, hub distribution, and regional nodal characteristics in AIS patients. We demonstrated that the cortical network of AIS patients fully preserved the small-world architecture and organization, and further verified the hemispheric asymmetry of AIS brain. Our results indicated increased central role of temporal and occipital cortex and decreased central role of limbic cortex in AIS patients compared with controls. Furthermore, decreased structural connectivity between hemispheres and increased connectivity in several cortical regions were observed. The findings of the study reveal the pattern of structural network alteration in AIS brain, and would help in understanding the mechanism and etiopathogenesis of AIS.     

The Structural Correlates of Statistical Information Processing during Speech Perception

The processing of continuous and complex auditory signals such as speech relies on the ability to use statistical cues (e.g. transitional probabilities). In this study, participants heard short auditory sequences composed either of Italian syllables or bird songs and completed a regularity-rating task. Behaviorally, participants were better at differentiating between levels of regularity in the syllable sequences than in the bird song sequences. Inter-individual differences in sensitivity to regularity for speech stimuli were correlated with variations in surface-based cortical thickness (CT). These correlations were found in several cortical areas including regions previously associated with statistical structure processing (e.g. bilateral superior temporal sulcus, left precentral sulcus and inferior frontal gyrus), as well other regions (e.g. left insula, bilateral superior frontal gyrus/sulcus and supramarginal gyrus). In all regions, this correlation was positive suggesting that thicker cortex is related to higher sensitivity to variations in the statistical structure of auditory sequences. Overall, these results suggest that inter-individual differences in CT within a distributed network of cortical regions involved in statistical structure processing, attention and memory is predictive of the ability to detect structural structure in auditory speech sequences.