Structural MRI Studies Research Articles

Regional increases of cortical thickness in untreated, first-episode major depressive disorder

The large majority of structural MRI studies of major depressive disorder (MDD) investigated volumetric changes in chronic medicated patients in whom course of illness and treatment effects may impact anatomic measurements. Further, in few studies, separate measurements of cortical thickness and surface area have been performed that reflect different neurobiological processes regulated by different genetic mechanisms. In the present study, we investigated both cortical thickness and surface area in first-episode, treatment-naïve, mid-life MDD to elucidate the core pathophysiology of this disease and its early impact on the brain. We observed increased cortical thickness in the right hemisphere, including medial orbitofrontal gyrus, pars opercularis, rostral middle frontal gyrus and supramarginal gyrus. Increased thickness of rostral middle frontal gyrus was negatively related with depression severity on the Hamilton Depression Rating Scale. Furthermore, MDD patients showed significantly increased associations in cortical thickness measurements among areas where increased cortical thickness was observed. Analysis of pial area revealed a trend toward increased surface area in the left parahippocampal gyrus in MDD. To permit comparison of our data with those of previous gray matter volume studies, voxel-based morphometry was performed. That analysis revealed significantly increased gray matter volume in left paracentral lobule, left superior frontal gyrus, bilateral cuneus and thalamus which form limbic-cortico–striato–pallido–thalamic loops. These changes in first-episode, treatment-naïve, mid-life MDD patients may reflect an active illness-related cortical change close to illness onset, and thus potentially provide important new insight into the early neurobiology of the disorder.

The Latest Neuroimaging Findings in Borderline Personality Disorder

Borderline personality disorder (BPD) is a severe mental disorder, characterized by pronounced deficits in emotion regulation, cognitive disturbances including dissociation, impulsivity, and interpersonal disturbances. Over the last decades, neuroimaging has become one of the most important methods to investigate neurobiological alterations possibly underlying core features of BPD. The aim of our article is to provide an overview of the latest neuroimaging research in BPD focusing on functional and structural MRI studies published since 2010. Findings of these studies are depicted and discussed referring to central domains of BPD psychopathology. On a neurochemical level, altered function in neurotransmitter systems including the serotonin, glutamate, and GABA systems was observed in patients with BPD. On a neural level, individuals with BPD showed structural and functional abnormalities in a fronto-limbic network including regions involved in emotion processing (e.g., amygdala, insula) and frontal brain regions implicated in regulatory control processes (e.g., anterior cingulate cortex, medial frontal cortex, orbitofrontal cortex, and dorsolateral prefrontal cortex). Limbic hyperreactivity and diminished recruitment of frontal brain regions may yield a link between disturbed emotion processing and other core features of BPD such as impulsivity and interpersonal disturbances. To clarify whether findings are specific to BPD, comparisons with other clinical groups are needed.

The impact of environmental factors in severe psychiatric disorders

During the last decades, schizophrenia has been regarded as a developmental disorder. The neurodevelopmental hypothesis proposes schizophrenia to be related to genetic and environmental factors leading to abnormal brain development during the pre- or postnatal period. First disease symptoms appear in early adulthood during the synaptic pruning and myelination process. Meta-analyses of structural MRI studies revealing hippocampal volume deficits in first-episode patients and in the longitudinal disease course confirm this hypothesis. Apart from the influence of risk genes in severe psychiatric disorders, environmental factors may also impact brain development during the perinatal period. Several environmental factors such as antenatal maternal virus infections, obstetric complications entailing hypoxia as common factor or stress during neurodevelopment have been identified to play a role in schizophrenia and bipolar disorder, possibly contributing to smaller hippocampal volumes. In major depression, psychosocial stress during the perinatal period or in adulthood is an important trigger. In animal studies, chronic stress or repeated administration of glucocorticoids have been shown to induce degeneration of glucocorticoid-sensitive hippocampal neurons and may contribute to the pathophysiology of affective disorders. Epigenetic mechanisms altering the chromatin structure such as histone acetylation and DNA methylation may mediate effects of environmental factors to transcriptional regulation of specific genes and be a prominent factor in gene-environmental interaction. In animal models, gene-environmental interaction should be investigated more intensely to unravel pathophysiological mechanisms. These findings may lead to new therapeutic strategies influencing epigenetic targets in severe psychiatric disorders.

EPA-1671 – Diagnosing schizophrenia using neuroimaging: a meta-analysis of multivariate pattern recognition studies

Background Numerous studies have applied novel multivariate statistical approaches to the analysis of brain alterations in patients with schizophrenia. However the diagnostic accuracy of the reported predictive models differs largely, making it difficult to evaluate the overall potential of these studies to inform clinical diagnosis. Methods We conducted a comprehensive literature search to identify all studies reporting performance of neuroimaging-based multivariate predictive models for the differentiation of patients with schizophrenia from healthy control subjects. The robustness of the results as well as the effect of potentially confounding continous variables (e.g. age, gender ratio, year of publication) was investigated. Results The final sample consisted of n=37 studies studies including n=1491 patients with schizophrenia and n=1488 healthy controls. Metaanalysis of the complete sample showed a sensitivity of 80.7% (95%-CI: 77.0 to 83.9%) and a specificity of 80.2% (95%-CI: 83.3 to 76.7%). Separate analysis for the different imaging modalities showed similar diagnostic accuracy for the structural MRI studies (sensitivity 77.3%, specificity 78.7%), the fMRI studies (sensitivity 81.4%, specificity 82.4%) and resting-state fMRI studies (sensitivity 86.9%, specificity 80.3%). Moderator analysis showed significant effects of age of patients on sensitivity (p=0.021) and of positive-tonegative symptom ratio on specificity (p=0.028) indicating better diagnostic accuracy in older patients and patients with positive symptoms. Download : Download full-size image Download : Download full-size image Discussion Our analysis indicate an overall sensitivity and overall specificity of around 80 % of neuroimaging-based predictive models for differentiating schizophrenic patients from healthy controls. The results underline the potential applicability of neuroimaging-based predictive models for the diagnosis of schizophrenia.

Alterations in brain structure related to breast cancer and its treatment: chemotherapy and other considerations

Cognitive effects of cancer and its treatment have been a topic of increasing investigation over the past ~30years. Recent studies have focused on better understanding the neural correlates of these effects, with an emphasis on post-chemotherapy effects in breast cancer patients. Structural MRI studies have utilized both automated and manual approaches to quantify gray and white matter characteristics (e.g., regional volume and density) in breast cancer patients treated with chemotherapy relative to patients who did not receive chemotherapy and/or healthy controls. While most work to date has been retrospective, a small number of baseline (pre-systemic therapy) and prospective longitudinal studies have been conducted. Data have consistently shown lower gray and white matter volume and density in patients treated with chemotherapy, particularly in frontal and temporal brain regions. Host factors and/or the cancer disease process and other therapies (e.g., antiestrogen treatment) also seem likely to contribute to the observed differences, though the relative contributions of these effects have not yet been investigated in detail. These structural abnormalities have been shown to relate to subjective and objective cognitive functioning, as well as to biological factors that may help to elucidate the underlying mechanism(s). This review examines the currently available published observations and discusses the major themes and promising directions for future studies.

Structure and function: how to connect?

The majority, but not all, of very preterm-born infants have difficulties with a variety of cognitive functions as children. It is critical to be able to predict as early as possible those who will have difficulties, to be able to direct appropriate interventions. We are conducting multimodal structural and functional MRI studies in very preterm-born infants and following them with behavioural and neuroimaging assessments until 4 years of age. We are also completing structural and more complex functional imaging in school-aged very preterm-born children. A number of MRI measures between preterm and term age correlate with outcome at 2 years of age. Functional and structural differences are also seen at school age; examples from these various studies are presented. Structural and functional studies in preterm-born versus term-born infants and children, particularly if completed longitudinally, provide important information on the evolution of brain-behaviour correlates and can help predict outcome in this high-risk population.

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.

Neuroanatomical Correlates of Childhood Sexual Abuse: Identifying Biological Substrates for Environmental Effects on Clinical Phenotypes

Neuroanatomical Correlates of Childhood Sexual Abuse: Identifying Biological Substrates for Environmental Effects on Clinical Phenotypes

Relapse Duration, Treatment Intensity, and Brain Tissue Loss in Schizophrenia: A Prospective Longitudinal MRI Study

Longitudinal structural MRI studies have shown that patients with schizophrenia have progressive brain tissue loss after onset. Recurrent relapses are believed to play a role in this loss, but the relationship between relapse and structural MRI measures has not been rigorously assessed. The authors analyzed longitudinal data to examine this question. The authors studied data from 202 patients drawn from the Iowa Longitudinal Study of first-episode schizophrenia for whom adequate structural MRI data were available (N=659 scans) from scans obtained at regular intervals over an average of 7 years. Because clinical follow-up data were obtained at 6-month intervals, the authors were able to compute measures of relapse number and duration and relate them to structural MRI measures. Because higher treatment intensity has been associated with smaller brain tissue volumes, the authors also examined this countereffect in terms of dose-years. Relapse duration was related to significant decreases in both general (e.g., total cerebral volume) and regional (e.g., frontal) brain measures. Number of relapses was unrelated to brain measures. Significant effects were also observed for treatment intensity. Extended periods of relapse may have a negative effect on brain integrity in schizophrenia, suggesting the importance of implementing proactive measures that may prevent relapse and improve treatment adherence. By examining the relative balance of effects, that is, relapse duration versus antipsychotic treatment intensity, this study sheds light on a troublesome dilemma that clinicians face. Relapse prevention is important, but it should be sustained using the lowest possible medication dosages that will control symptoms.

Brain imaging of mild cognitive impairment and Alzheimer's disease.

The rapidly increasing prevalence of cognitive impairment and Alzheimer's disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer's disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and Alzheimer's disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer's disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer's disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed.

Schizofreni – hva viser strukturell MR?

Schizophrenia is a serious mental disorder that affects several brain functions. MRI technology has enabled in vivo studies of brain anatomy in patients with schizophrenia aimed at understanding more about the disorder. This article is based on a search in PubMed on «schizophrenia MRI» and on the authors' own research and experience. We included structural MRI studies, carried out on humans, written in English. Here we present a selection of studies that we believe are representative of the field. In patients with schizophrenia, MR imaging shows a smaller total brain volume and enlarged ventricles. Specific subcortical regions are affected, with reduced hippocampal and thalamic volumes, and an increase in the volume of the globus pallidus. In the cortex can be seen changes in folding patterns and a reduction in cortical volume and thickness, most pronounced in the frontal and temporal lobes. These findings are at group level--there is a high degree of overlap between sick and healthy individuals, and the effect sizes are medium to small. Several of the changes are present at onset of the disorder; this supports the theory that schizophrenia may be related to abnormal neurodevelopment. Longitudinal anatomical changes are reported, but it is uncertain what these changes represent. The research literature shows that schizophrenia has neuroanatomical correlates that can be seen at group level by studying MR images. Structural MRI cannot currently be used to identify schizophrenia at the level of the individual.

Comment on “Hierarchical genetic organization of human cortical surface area” by Chen et al. [Science 335 (2012) 1634–1636 (supporting information)

Grey matter pathology in MS is known to be extensive (Kutzelnigg et al., 2005) and clinically relevant, even in the early phase of the disease (Chard et al., 2002). Grey matter imaging studies in MS have contributed greatly to improving our understanding of the disease mechanisms (Hulst and Geurts, 2011). These studies generally refer to the Brodmann’s scheme for human cortex, which identifies separate cortical areas on the basis of the cellular structure and organisation. Functional MRI studies in MS commonly describe increased or decreased activation associated with specific tasks in specific cortical areas (Pantano et al., 2002); structural MRI studies in MS often report cortical atrophy and thinning of cortical regions (Calabrese et al., 2010). In addition to cortical volume and thickness, cortical region surface area can be estimated from brain imaging. However, little is known about changes in cortical surface area in MS. One study has reported a reduction in the cortical surface area of each hemisphere in MS patients when compared with controls (Hier and Wang, 2007); a more recent study has reported a smaller surface area of the precentral gyrus in MS patients than controls (Gorgoraptis et al., 2010). Although changes in the functional and structural organisation of the cortex have been the focus of imaging papers in MS for a long time, the factors that are responsible for variation in cortical volume and surface area in humans, independently of disease status, are only now becoming clearer. Genetic factors are emerging as important

Asymmetry of the Dorsal Anterior Cingulate Cortex: Evidences from Multiple Modalities of MRI

The dorsal anterior cingulate cortex (dACC) has been consistently implicated in cognitive control processes. Many studies have found higher fractional anisotropy (FA) in the left anterior cingulum bundle (aCB) than in the right. However, the asymmetry of gray matter density (GMD) is not clear. Using multiple modalities of MRI, we investigated both FA and GMD in the dACC in two independent groups of healthy participants (50 per group, 18-24years old, half males and half females). Consistent with previous findings, the mean FA of the left aCB was significantly higher than that of the right. Males showed higher FA in the bilateral aCB than females. Voxel-based analysis of GMD in the dACC presented a region-specific significant asymmetry: right > left in the lower part (around callosal sulcus) but left > right in the upper part (around cingulate sulcus). No significant sex effect was found for GMD in the dACC. All these results were almost the same across the two independent groups. The complex pattern of asymmetry in GMD may imply highly differentiated functions of the dACC. Future fine-scale structural and diffusion MRI studies and a battery of cognitive behavioral measurements are needed to fully elucidate the asymmetry of the dACC.

Structural brain changes in first episode Schizophrenia compared with Fronto-Temporal Lobar Degeneration: a meta-analysis

BackgroundThe authors sought to compare gray matter changes in First Episode Schizophrenia (FES) compared with Fronto-Temporal Lobar Degeneration (FTLD) using meta-analytic methods applied to neuro-imaging studies.MethodsA systematic search was conducted for published, structural voxel-based morphometric MRI studies in patients with FES or FTLD. Data were combined using anatomical likelihood estimation (ALE) to determine the extent of gray matter decreases and analysed to ascertain the degree of overlap in the spatial distribution of brain changes in both diseases.ResultsData were extracted from 18 FES studies (including a total of 555 patients and 621 comparison subjects) and 20 studies of FTLD or related disorders (including a total of 311 patients and 431 comparison subjects). The similarity in spatial overlap of brain changes in the two disorders was significant (p = 0.001). Gray matter deficits common to both disorders included bilateral caudate, left insula and bilateral uncus regions.ConclusionsThere is a significant overlap in the distribution of structural brain changes in First Episode Schizophrenia and Fronto-Temporal Lobar Degeneration. This may reflect overlapping aetiologies, or a common vulnerability of these regions to the distinct aetio-pathological processes in the two disorders.

Hippocampal Atrophy in Alzheimer’s Disease

SUMMARY New research criteria for Alzheimer’s disease (AD) and mild cognitive impairment (MCI) emphasize the use of imaging biomarkers in clinical diagnosis of these disorders. The volume loss of medial temporal lobe structures, especially hippocampal atrophy, is the best validated marker of AD. Manual tracing on MRI is the present gold standard for evaluating hippocampal volume; however, it is laborious and tracer-dependent. We categorized the most recent full- or semi-automated methods by the nature of the output of the method: size and shape of subcortical structures, cortical thickness, atrophy-rate and voxel- and region-based characteristics. The features of each method are introduced. The findings in structural MRI studies, especially in those studies utilizing the most recent methods, and the accuracies of those new methods in differentiating AD from healthy controls and stable MCI from progressive MCI are reviewed.

Development of the social brain in adolescence

The brain has evolved to understand and interact with other people. We are increasingly learning more about the neurophysiological basis of social cognition and what is known as the social brain, that is the network of brain regions involved in understanding others. This paper focuses on how the social brain develops during adolescence. Adolescence is a time characterized by change - hormonally, physically, psychologically and socially. Yet until recently this period of life was neglected by cognitive neuroscience. In the past decade, research has shown that the brain develops both structurally and functionally during adolescence. Large-scale structural MRI studies have demonstrated development during adolescence in white matter and grey matter volumes in regions within the social brain. Activity in some of these regions, as measured using fMRI, also shows changes between adolescence and adulthood during social cognition tasks. I will also present evidence that theory of mind usage is still developing late in adolescence. Finally, I will speculate on potential implications of this research for society.

Cortical thickness, neuron density and size in the inferior parietal lobe in schizophrenia

The inferior parietal lobe (IPL) is a center of multisensory integration, and both functional and structural MRI studies have found evidence that pathology in this region may contribute to disrupted sensory perception in schizophrenia. To further define this pathology, we used postmortem samples from the left and right IPL, to compare the thickness and volume of the upper (I–III) and lower (IV–VI) cortical layers. The samples were divided into supramarginal and angular gyri, and neuron density and size were measured in the supramarginal gyrus. The laminar thickness and volume measurements did not demonstrate significant changes in schizophrenia, but did show that the angular gyrus was thinner than the supramarginal gyrus, due to a difference mainly in the lower layers. Measurements of cortical thickness, neuron size and neuron density all showed some evidence of previously reported normal hemispheric differences. These asymmetries were reduced in schizophrenia, but the small changes were at the threshold of detection, and are discussed in the context of the sensitivity of the methods applied.

Long-Term Neuropsychological, Neuroanatomical, and Life Outcome in Hippocampal Amnesia

Focal bilateral hippocampal damage typically causes severe and selective amnesia for new declarative information (facts and events), a cognitive deficit that greatly impacts the ability to live a normal, fully independent life. We describe the case of 1846, a 48-year-old woman with profound hippocampal amnesia following status epilepticus and an associated anoxic episode at age 30. Patient 1846 has undergone extensive neuropsychological testing on many occasions over the 18 years since her injury, and we present data indicating that her memory impairment has remained severe and stable during that time. New, high-resolution, structural MRI studies of 1846's brain reveal substantial bilateral hippocampal atrophy resembling that of other well-known amnesic patients. In spite of severe amnesia 1846 lives a full and mostly independent adult life, facilitated by an extensive social support network of family and friends. Her case provides an example of a rare and unlikely positive outcome in the face of severe memory problems.

P-1247 - Cognition and schizophrenia-the role of cognitive assessment for diagnosis and treatment

Cognitive problems have long been considered a core component of schizophrenia but have only recently been considered as possible diagnostic features of the illness or as potential treatment targets. The cognitive impairment tends to be more independent of the typical clinical symptoms of schizophrenia than similar problems in the affective disorders. Recently it has become apparent that there are some aspects of impaired neurocognition that are consistently found in schizophrenia and may have both prognostic and treatment implications for clinical practice. Neurocognitive impairment symptoms are present prior to the initiation of antipsychotic treatment. Schizophrenia was mostly considered as neurocognitive disorder. Schizophrenic patients in recent studies perform an average of 1.5 to 2 standard deviations below healthy controls on many neurocognitive tests and this impairment is greatest in the domains of memory, attention, working memory, problem solving, processing speed, and social cognition. Specific aspects of cognitive dysfunction are different from hallucinations, delusions, and paranoia and they are largely unrelated according to CATIE study. Functional magnetic resonance imaging (fMRI), positron emission tomography (PET), electroencephalogram (EEG) and even structural MRI studies all show relations between neuroanatomical measures and cognitive deficits in schizophrenia. These relations are strongest in frontal regions, temporal cortex, and hippocampus. Clinical assessment of cognitive functioning in schizophrenia and proposal for including of cognitive dysfunction as diagnostic criteria in DSM-IV. The treatment of cognitive deficits, the most beneficial method for patients.

Meta‐analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects

About 50-80% of ADHD cases have been found to persist into adulthood, but ADHD symptoms change with age. The aim of this study was to perform a meta-analysis of MRI voxel-based morphometry (VBM) and manual tracing studies to identify the differences between adults and children with ADHD as well as between treated and untreated individuals. Several databases were searched using keywords 'attention-deficit and MRI', 'ADHD and MRI'. Gray matter volumes from VBM studies and caudate volumes from tracing studies of patients and controls were analyzed using signed differential mapping. Meta-analyses detected reduced right globus pallidus and putamen volumes in VBM studies as well as decreased caudate volumes in manual tracing studies in children with ADHD. Adult patients with ADHD showed volume reduction in the anterior cingulate cortex (ACC). A higher percentage of treated participants were associated with less changes. Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure.