Structural MRI and MRS abnormalities in bipolar disorder

Soares JC. Structural MRI and MRS abnormalities in bipolar disorder. Bipolar Disord 2002: 4(Suppl. 1): 87. © Blackwell Munksgaard, 2002     

Human Cortical Anatomical Networks Assessed by Structural MRI

Mapping the structure and function of the brain with non-invasive brain imaging techniques has become a world-wide enterpise in the last 20 years. The core concept that drives this rapid growth has been the use of a standardized 3D coordinate space for combining data from many subjects and/or time-points. This has allowed geographically-separated laboratories to reproduce experiments in precise detail, to share data or to perform meta-analysis in ways that go far beyond the traditional reviewing of summary results in journal publications. A further corollary of the brain mapping approach is the natural fostering of multi-center collaboration among distant sites. This article describes recent progress in trans-Pacific collaboration between Canadian and Asian laboratories in the study of neuroanatomical networks obtained from MRI data, both in the normal brain and in neurodegenerative disorders.     

Structural brain MRI abnormalities in pediatric patients with migraine

Morphometric MRI studies in adult patients with migraine have consistently demonstrated atrophy of several gray matter (GM) regions involved in pain processing. We explored the regional distribution of GM and white matter (WM) abnormalities in pediatric patients with episodic migraine and their correlations with disease clinical manifestations. Using a 3.0 T scanner, brain T2-weighted and 3D T1-weighted scans were acquired from 12 pediatric migraine patients and 15 age-matched healthy controls. GM and WM volumetric abnormalities were estimated using voxel-based morphometry (p < 0.05, family-wise error corrected). Compared to controls, pediatric migraine patients experienced a significant GM atrophy of several regions of the frontal and temporal lobes which are part of the pain-processing network. They also had an increased volume of the right putamen. The left fusiform gyrus had an increased volume in patients with aura compared to patients without aura and controls, whereas it was significantly atrophied in patients without aura when compared to the other two groups. No abnormalities of WM volume were detected. In migraine patients, regional GM atrophy was not correlated with disease duration and attack frequency, whereas a negative correlation was found between increased volume of the putamen and disease duration (r = ?0.95, p < 0.05). These results show that GM morphometric abnormalities do occur in pediatric patients with migraine. The presence of such abnormalities early in the disease course, and the absence of correlation with patient clinical characteristics suggest that they may represent a phenotypic biomarker of this condition.     

Structural MRI biomarkers for preclinical and mild Alzheimer's disease

Noninvasive MRI biomarkers for Alzheimer's disease (AD) may enable earlier clinical diagnosis and the monitoring of therapeutic effectiveness. To assess potential neuroimaging biomarkers, the Alzheimer's Disease Neuroimaging Initiative is following normal controls (NC) and individuals with mild cognitive impairment (MCI) or AD. We applied high‐throughput image analyses procedures to these data to demonstrate the feasibility of detecting subtle structural changes in prodromal AD. Raw DICOM scans (139 NC, 175 MCI, and 84 AD) were downloaded for analysis. Volumetric segmentation and cortical surface reconstruction produced continuous cortical surface maps and region‐of‐interest (ROI) measures. The MCI cohort was subdivided into single‐ (SMCI) and multiple‐domain MCI (MMCI) based on neuropsychological performance. Repeated measures analyses of covariance were used to examine group and hemispheric effects while controlling for age, sex, and, for volumetric measures, intracranial vault. ROI analyses showed group differences for ventricular, temporal, posterior and rostral anterior cingulate, posterior parietal, and frontal regions. SMCI and NC differed within temporal, rostral posterior cingulate, inferior parietal, precuneus, and caudal midfrontal regions. With MMCI and AD, greater differences were evident in these regions and additional frontal and retrosplenial cortices; evidence for non‐AD pathology in MMCI also was suggested. Mesial temporal right‐dominant asymmetries were evident and did not interact with diagnosis. Our findings demonstrate that high‐throughput methods provide numerous measures to detect subtle effects of prodromal AD, suggesting early and later stages of the preclinical state in this cross‐sectional sample. These methods will enable a more complete longitudinal characterization and allow us to identify changes that are predictive of conversion to AD. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

Structural MRI correlates of cognitive impairment in patients with multiple sclerosis

In a multicenter setting, we applied voxel‐based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal‐appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing‐remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy, and microstructural WM damage were assessed using voxel‐wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty‐three (38%) MS patients were CI. Compared with cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive‐relevant WM tracts followed by atrophy of cognitive‐relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel‐wise MRI approaches are feasible in a multicenter setting. The combination of different imaging modalities is needed to assess and monitor cognitive impairment in MS. Hum Brain Mapp 37:1627‐1644, 2016. © 2016 Wiley Periodicals, Inc.     

Structural and functional MRI correlates of Stroop control in benign MS

The objective of this study was to assess the functional and structural substrates of cognitive network changes in patients with benign multiple sclerosis (BMS), using an analysis of effective connectivity and MR tractography. Using a 3-Tesla scanner, we acquired dual-echo, diffusion tensor (DT) and functional MRI during the performance of the Stroop task from 15 BMS patients and 19 healthy controls. DT MRI tractography was used to calculate DT derived metrics from several white matter (WM) fiber bundles, thought to be involved in cognitive performance. DT MRI metrics from WM fiber bundles not directly related with cognitive performance were also derived. Effective connectivity analysis was performed using statistical parametric mapping. MS patients had significantly abnormal DT MRI metrics in all the structures analyzed. Compared with controls, MS patients had more significant activations of several areas of the cognitive network involved in Stroop performance, bilaterally. Compared with controls, BMS patients also had increased connectivity strengths between several cortical areas of the sensorimotor network and the right (R) inferior frontal gyrus and the R cerebellum, as well as decreased connectivity strengths with the anterior cingulate cortex. Coefficients of altered connectivity were moderately correlated with structural MRI metrics of tissue damage within intra- and inter-hemispheric cognitive-related WM fiber bundles, while no correlations were found with the remaining fiber bundles studied, suggesting that functional cortical changes in patients with BMS might represent an adaptive response driven by damage of specific WM structures.     

Structural MRI correlates for vulnerability and resilience to major depressive disorder

Background

In major depressive disorder (MDD), it is unclear to what extent structural brain changes are associated with depressive episodes or represent part of the mechanism by which the risk for illness is mediated. The aim of this study was to investigate whether structural abnormalities are related to risk for the development of MDD.

Methods

We compared healthy controls with a positive family history for MDD (HC-FHP), healthy controls with no family history of any psychiatric disease (HC-FHN) and patients with MDD. Groups were age- and sex-matched. We analyzed data from high-resolution magnetic resonance imaging using voxel-based morphometry. We performed small volume corrections for our regions of interest (hippocampus, dorsolateral [DLPFC] and dorsomedial prefrontal cortex [DMPFC], anterior cingulate cortex [ACC] and basal ganglia) using a family-wise error correction (p < 0.05) to control for multiple comparisons.

Results

There were 30 participants in the HC-FHP group, 64 in the HC-FHN group and 33 patients with MDD. The HC-FHP group had smaller right hippocampal and DLPFC grey matter volumes compared with the HC-FHN group, and even smaller right hippocampal volumes compared with patients with MDD. In addition, the HC-FHP group exhibited smaller white matter volumes in the DLPFC and left putamen but also greater volumes in 2 areas of the DMPFC compared with the HC-FHN group. Patients with MDD exhibited smaller volumes in the ACC, DMPFC, DLPFC and the basal ganglia compared with healthy controls.

Limitations

The retrospective identification of family history might result in a bias toward unidentified participants in the control group at risk for MDD, diminishing the effect size.

Conclusion

Volume reductions in the hippocampus and DLPFC might be associated with a greater risk for MDD. The HC-FHP group had smaller hippocampal volumes compared with patients with MDD, which is suggestive for neuroplastic effects of treatment. The HC-FHP group had not yet experienced a depressive episode and therefore might have been resilient and might have had some protective strategies. Whether resilience is associated with the larger white matter volumes in the DMPFC (e.g., owing to compensatory, neuroplastic remodelling mechanisms) needs to be confirmed in future studies.     

精神分裂症患者脑结构异常的MRI研究

目的　探讨脑结构的改变 (尤其是第Ⅲ脑室 )特点及其与精神分裂症症状产生及疗效的关系。方法　选用我院住院的首发精神分裂症患者 ,共 51例 ,正常对照组为 2 3例健康志愿者。对入组后的患者于治疗前和治疗后 2个月进行PANSS(阳性与阴性症状量表 )评定 ,以PANSS减分率作为疗效指标。磁共振成像扫描采用SiemensMagnetomP8型永磁性磁共振机 ,磁场强度 0 2T。测量包括第Ⅲ脑室横径等在内的 1 7条径线。结果　病例组第Ⅲ脑室横径、双侧外侧裂宽度明显增宽 ,胼胝体厚度明显减少 ,病例组与对照组之间存在显著差异。PANSS阴性分量表、思维解体因子减分率与左侧海马横径均呈负相关。PANSS其他分量表及因子减分率与MRI各参数均无显著相关。结论　精神分裂症患者存在的脑结构异常可能构成了精神分裂症的神经生物学基础。脑结构异常与疗效的关系有待进一步研究     

Structural MRI investigation in schizophrenia with optimised voxel-based morphometry--a pilot study

The quantitative and structural MRI methods have an emergent role in the fields of psychiatric disorders. In our paper we present voxel-based morphometry, which is the most frequently used structural MRI method. We compared eight patients with schizophrenia and eight, age-matched healthy subjects to detect focal tissue differences in gray and white matter, and cerebrospinal fluids between the two groups. As with earlier studies, patients with schizophrenia showed decreased gray matter tissue density in frontotemporal and insular regions bilaterally. Moreover, the left-sided parietal operculum and the calcarina showed focal decrease in tissue density. Density decrease in the frontotemporal and insular white matter was detected bilaterally, which was similar to gray matter changes. The left sided precuneus and lingual gyrus were also involved in reduced white matter density. Increased cerebrospinal fluid spaces were detected in the frontal regions and the ventricles. Our results with the optimised voxel-based morphometry are in line with earlier imaging studies and correspond with neuropsychological detectable frontotemporal deficits in schizophrenia.     

Structural MRI biomarkers of shared pathogenesis in autism spectrum disorder and epilepsy

Etiological factors that contribute to a high comorbidity between autism spectrum disorder (ASD) and epilepsy are the subject of much debate. Does epilepsy cause ASD or are there common underlying brain abnormalities that increase the risk of developing both disorders? This review summarizes evidence from quantitative MRI studies to suggest that abnormalities of brain structure are not necessarily the consequence of ASD and epilepsy but are antecedent to disease expression. Abnormal gray and white matter volumes are present prior to onset of ASD and evident at the time of onset in pediatric epilepsy. Aberrant brain growth trajectories are also common in both disorders, as evidenced by blunted gray matter maturation and white matter maturation. Although the etiological factors that explain these abnormalities are unclear, high heritability estimates for gray matter volume and white matter microstructure demonstrate that genetic factors assert a strong influence on brain structure. In addition, histopathological studies of ASD and epilepsy brain tissue reveal elevated rates of malformations of cortical development (MCDs), such as focal cortical dysplasia and heterotopias, which supports disruption of neuronal migration as a contributing factor. Although MCDs are not always visible on MRI with conventional radiological analysis, quantitative MRI detection methods show high sensitivity to subtle malformations in epilepsy and can be potentially applied to MCD detection in ASD. Such an approach is critical for establishing quantitative neuroanatomic endophenotypes that can be used in genetic research. In the context of emerging drug treatments for seizures and autism symptoms, such as rapamycin and rapalogs, in vivo neuroimaging markers of subtle structural brain abnormalities could improve sample stratification in human clinical trials and potentially extend the range of patients that might benefit from treatment.This article is part of a Special Issue entitled “Autism and Epilepsy”.     

Structural brain MRI abnormalities in healthy siblings of patients with childhood-onset schizophrenia

OBJECTIVE: Childhood-onset schizophrenia shows progressive brain magnetic resonance imaging (MRI) changes during adolescence, which follow a back-to-front "wave." The authors' goal was to examine whether healthy siblings of patients with childhood-onset schizophrenia show structural brain abnormalities and the age-related pattern of abnormalities seen in patients with childhood-onset schizophrenia. METHOD: Anatomic brain MRI scans were obtained from 15 psychiatrically healthy full siblings of 15 patients with childhood-onset schizophrenia and from 32 matched community volunteers. Automated measures were used to compare total and regional brain volumes of the siblings and volunteers. RESULTS: Siblings of patients with childhood-onset schizophrenia had smaller total cerebral volume and total, frontal, and parietal gray matter volumes than volunteers. When divided into younger and older groups, younger siblings had smaller parietal gray matter volumes and older siblings showed trends for smaller total and frontal gray matter volumes. CONCLUSIONS: Healthy siblings of patients with childhood-onset schizophrenia share brain MRI abnormalities with the patients that may follow a similar pattern of progression. Developmental brain abnormalities in childhood-onset schizophrenia may thus be genetic trait markers.     

A Review of Structural MRI and Diffusion Tensor Imaging in Schizotypal Personality Disorder

Individuals with schizotypal personality disorder (SPD) share genetic, phenomenologic, and cognitive abnormalities with people diagnosed with schizophrenia. To date, 15 structural MRI studies of the brain have examined size, and 3 diffusion tensor imaging studies have examined white matter connectivity in SPD. Overall, both types of structural neuroimaging modalities have shown temporal lobe abnormalities similar to those observed in schizophrenia, while frontal lobe regions appear to show more sparing. This intriguing pattern suggests that frontal lobe sparing may suppress psychosis, which is consistent with the idea of a possible neuroprotective factor. In this paper, we review these 18 studies and discuss whether individuals with SPD who both resemble and differ from schizophrenia patients in their phenomenology, share some or all of the structural brain imaging characteristics of schizophrenia. We attempt to group the MRI abnormalities in SPD into three patterns: 1) a spectrum of severity—abnormalities are similar to those observed in schizophrenia but not so severe; 2) a spectrum of region—abnormalities affecting some, but not all, brain regions affected in schizophrenia; and 3) a spectrum of compensation—abnormalities reflecting greater-than-normal white matter volume, possibly serving as a buffer or compensatory mechanism protecting the individual with SPD from the frank psychosis observed in schizophrenia.     

Structural MRI correlates of the MMSE and pentagon copying test in Parkinson's disease

BackgroundCognitive impairment in Parkinson's disease (PD) is common and recent studies have focused on addressing the most suitable screening tool for its assessment. MMSE is commonly used in clinical practice and longitudinal studies found a relationship between the MMSE pentagon copying item and progression to dementia, but its neuroanatomical correlates have been poorly investigated. The aim of this study is to investigate the MRI structural correlates of the global MMSE and the pentagon item scores in PD patients in the absence of dementia.MethodsWe selected a sample of 92 PD patients and 36 controls. MMSE was used as a global measure of cognitive status, and the pentagon copying test as a measure of visuospatial performance. FreeSurfer software was used to assess intergroup differences in cortical thickness (CTh) and global atrophy measures, as well as their relationship with cognitive performance.ResultsCompared to controls, patients showed significant differences in measures of global atrophy, which correlated with performance on MMSE and the pentagon item. Regional differences in CTh were seen between PD patients and controls bilaterally in the temporo-parietal-occipital region. Patients with impaired performance compared with those of normal performance also showed CTh reductions in these regions.ConclusionOur results suggest MMSE and the pentagon item reflect brain changes which at a regional level involve mainly posterior regions. Correlates of the pentagon item were seen in the same regions where PD patients exhibited significant thinning, and involved more areas and bigger cluster sizes than the correlates of MMSE global scores.     

Structural and functional MRI following 4-aminopyridine-induced seizures: a comparative imaging and anatomical study

Structural and functional MRI was used in conjunction with computerized electron microscopy morphometry to study changes 2 h, 24 h and 3 days after 4-aminopyridine-induced seizures lasting 2 h in rats. T2 (relaxation time) values showed changes throughout the cerebral cortex, hippocampus, amygdala and medial thalamus, with a different temporal progression, showing a complete recovery only after 3 days. Two hours after seizures, the apparent diffusion coefficient was decreased throughout the brain compared to control animals, and a further decrease was evident 24 h after seizures. This was followed by a complete recovery at 3 days post-seizures. Functional MRI was performed using regional cerebral blood volume (rCBV) maps. The rCBV was increased shortly after convulsions (2 h) in all structures investigated, with a significant return to baseline values in the parietal cortex and hippocampus, but not in the medial thalamic nuclei, 24 h after seizure onset. No rCBV alterations were detected 3 days after seizures. Electron microscopy of tissue samples of parietal neocortex and hippocampus revealed prominent astrocytic swelling 2 h post-convulsions which decreased thereafter gradually. In conclusion, this experiment reports for the first time structural and functional brain alterations, lasting several hours, in 4-aminopyridine-treated rats after seizure onset. MRI approach combined with histological and ultrastructural analysis provided a clarification of the mechanisms involved in the brain acute response to ictal activity.     

Structural core of the executive control network: A high angular resolution diffusion MRI study

Executive function (EF) is a set of cognitive capabilities considered essential for successful daily living, and is negatively affected by ageing and neurodegenerative conditions. Underpinning EF performance are functional nodes in the executive control network (ECN), while the structural connectivity underlying this network is not well understood. In this paper, we evaluated the structural white matter tracts that interconnect the ECN and investigated their relationship to the EF performance. Using high‐angular resolution diffusion MRI data, we performed tractography analysis of structural connectivity in a cognitively normal cohort (n = 140), specifically targeting the connectivity between ECN nodes. Our data revealed the presence of a strongly‐connected “structural core” of the ECN comprising three components: interhemispheric frontal connections, a fronto‐parietal subnetwork and fronto‐striatal connections between right dorsolateral prefrontal cortex and right caudate. These pathways were strongly correlated with EF performance (p = .003). Post‐hoc analysis of subregions within the significant ECN connections showed that these effects were driven by a highly specific subset of interconnected cortical regions. The structural core subnetwork of the functional ECN may be an important feature crucial to a better future understanding of human cognition and behaviour.     

Structural brain dynamics across reading development: A longitudinal MRI study from kindergarten to grade 5

Primary education is the incubator for learning academic skills that help children to become a literate, communicative, and independent person. Over this learning period, nonlinear and regional changes in the brain occur, but how these changes relate to academic performance, such as reading ability, is still unclear. In the current study, we analyzed longitudinal T1 MRI data of 41 children in order to investigate typical cortical development during the early reading stage (end of kindergarten–end of grade 2) and advanced reading stage (end of grade 2–middle of grade 5), and to detect putative deviant trajectories in children with dyslexia. The structural brain change was quantified with a reliable measure that directly calculates the local morphological differences between brain images of two time points, while considering the global head growth. When applying this measure to investigate typical cortical development, we observed that left temporal and temporoparietal regions belonging to the reading network exhibited an increase during the early reading stage and stabilized during the advanced reading stage. This suggests that the natural plasticity window for reading is within the first years of primary school, hence earlier than the typical period for reading intervention. Concerning neurotrajectories in children with dyslexia compared to typical readers, we observed no differences in gray matter development of the left reading network, but we found different neurotrajectories in right IFG opercularis (during the early reading stage) and in right isthmus cingulate (during the advanced reading stage), which could reflect compensatory neural mechanisms.