Christine Born

Classifying brain states and determining the discriminating activation patterns: Support Vector Machine on functional MRI data

In the present study, we applied the Support Vector Machine (SVM) algorithm to perform multivariate classification of brain states from whole functional magnetic resonance imaging (fMRI) volumes without prior selection of spatial features. In addition, we did a comparative analysis between the SVM and the Fisher Linear Discriminant (FLD) classifier. We applied the methods to two multisubject attention experiments: a face matching and a location matching task. We demonstrate that SVM outperforms FLD in classification performance as well as in robustness of the spatial maps obtained (i.e. discriminating volumes). In addition, the SVM discrimination maps had greater overlap with the general linear model (GLM) analysis compared to the FLD. The analysis presents two phases: during the training, the classifier algorithm finds the set of regions by which the two brain states can be best distinguished from each other. In the next phase, the test phase, given an fMRI volume from a new subject, the classifier predicts the subjects instantaneous brain state.

Depression-Related Variation in Brain Morphology Over 3 Years: Effects of Stress?

CONTEXT Results of experimental studies suggest that neuroplastic changes may occur during depressive episodes. These effects have not been confirmed in patients with depression, to our knowledge. OBJECTIVE To examine changes in the brains of patients with major depression vs those of healthy control subjects. DESIGN Prospective longitudinal 3-year study. SETTING Inpatients with major depression were recruited from the Department of Psychiatry and Psychotherapy, Ludwig Maximilians University of Munich, Munich, Germany, and controls were recruited from the local community. PARTICIPANTS The study included 38 patients with major depression and 30 healthy controls. MAIN OUTCOME MEASURES High-resolution magnetic resonance imaging was performed at baseline and 3 years later. Voxel-based morphometric measurements were estimated from magnetic resonance images, and psychopathologic findings were assessed at baseline, weekly during the inpatient phase, and then after 1, 2, and 3 years. RESULTS Compared with controls, patients showed significantly more decline in gray matter density of the hippocampus, anterior cingulum, left amygdala, and right dorsomedial prefrontal cortex. Patients who remitted during the 3-year period had less volume decline than nonremitted patients in the left hippocampus, left anterior cingulum, left dorsomedial prefrontal cortex, and bilaterally in the dorsolateral prefrontal cortex. CONCLUSION This study supports findings from animal studies of neuroplastic stress-related processes that occur in the hippocampus, amygdala, dorsomedial prefrontal cortex, dorsolateral prefrontal cortex, and anterior cingulum during depressive episodes.

Enlargement of the amygdala in patients with a first episode of major depression

BACKGROUND The amygdala plays a crucial role in the mediation of affective behavior in humans and is implemented in the limbic-thalamic-cortical network that is supposed to modulate human mood. The aim of the present study was to measure the amygdala volumes in patients with a first episode of major depression. METHODS Thirty inpatients with a first episode of depression were compared with 30 healthy volunteers matched for age, gender, handedness, and education by performing structural magnetic resonance imaging (MRI) measures of the amygdala. RESULTS Patients showed increased amygdala volumes in both hemispheres as compared to healthy control subjects. No significant correlations were found between amygdala volumes and age, age of onset, illness duration, or severity of depression in the patient group. CONCLUSIONS Enlarged amygdala volumes in patients with a first episode of major depression might be due to enhanced blood flow in the amygdala rather than to a neurodevelopmental structural predisposition to major depression.

Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects.

BACKGROUND The aim of our study was to test the hypothesis that amygdala volumes are reduced in patients with recurrent major depression compared with first episode patients. METHODS Using structural magnetic resonance imaging, we compared 30 inpatients with first-episode depression and 27 inpatients with recurrent major depression (DSM-IV) with healthy volunteer subjects from the local community matched for age, gender, and handedness. RESULTS Patients with first-episode depression showed enlarged amygdala volumes compared with patients with recurrent major depression and healthy control subjects. No significant differences were found between patients with recurrent depression and healthy control subjects. No significant correlations were found between amygdala volumes and age of onset, illness duration, or severity of depression. CONCLUSIONS Larger amygdala volumes in patients with first-episode depression may result from higher amygdala metabolism and blood flow. Additionally, disease progression with stress-related excitotoxic processes during recurrent depressive episodes might result in decreased amygdala volumes. Prospective investigations to investigate amygdala changes during the course of depression are needed.

Multivariate deformation-based analysis of brain atrophy to predict Alzheimer's disease in mild cognitive impairment.

Automated deformation-based analysis of MRI scans can be used to detect specific pattern of brain atrophy in Alzheimers disease (AD), but it still lacks an established model to derive the individual risk of AD in at-risk subjects, such as patients with mild cognitive impairment (MCI). We applied principal component analysis to deformation maps derived from MRI scans of 32 AD patients, 18 elderly healthy controls and 24 MCI patients. Principal component scores were used to discriminate between AD patients and controls and between MCI converters and MCI non-converters. We found a significant regional pattern of atrophy (p<0.001) in medial temporal lobes, neocortical association areas, thalamus and basal ganglia and corresponding widening of cerebrospinal fluid (CSF) spaces (p<0.001) in AD patients compared to controls. Accuracy was 81% for CSF- and 83% for brain-based deformation maps to separate AD patients from controls. Nine out of 24 MCI patients converted to AD during clinical follow-up. Discrimination between MCI converters and non-converters reached 80% accuracy based on CSF maps and 73% accuracy based on brain maps. In a logistic regression model, principal component scores based on CSF maps predicted clinical outcome in MCI patients even after controlling for age, gender, MMSE score and time of follow-up. Our findings indicate that multivariate network analysis of deformation maps detects typical features of AD pathology and provides a powerful tool to predict conversion into AD in non-demented at risk patients.

Structural correlates of psychopathological symptom dimensions in schizophrenia: A voxel-based morphometric study

Structural neuroimaging has substantially advanced the neurobiological research of schizophrenia by describing a range of focal brain alterations as possible neuroanatomical underpinnings of the disease. Despite this progress, a considerable heterogeneity of structural findings persists that may reflect the phenomenological diversity of schizophrenia. It is unclear whether the range of possible clinical disease manifestations relates to a core structural brain deficit or to distinct structural correlates. Therefore, gray matter density (GMD) differences between 175 schizophrenic patients (SZ) and 177 matched healthy control subjects (HC) were examined in a three-step approach using cross-sectional and conjunctional voxel-based morphometry (VBM): (1) analysis of structural alterations irrespective of symptomatology; (2) subdivision of the patient sample according to a three-dimensional factor model of the PANSS and investigation of structural differences between these subsamples and healthy controls; (3) analysis of a common pattern of structural alterations present in all patient subsamples compared to healthy controls. Significant GMD reductions in patients compared to controls were identified within the prefrontal, limbic, paralimbic, temporal and thalamic regions. The disorganized symptom dimension was associated with bilateral alterations in temporal, insular and medial prefrontal cortices. Positive symptoms were associated with left-pronounced alterations in perisylvian regions and extended thalamic GMD losses. Negative symptoms were linked to the most extended alterations within orbitofrontal, medial prefrontal, lateral prefrontal and temporal cortices as well as limbic and subcortical structures. Thus, structural heterogeneity in schizophrenia may relate to specific patterns of GMD reductions that possibly share a common prefrontal-perisylvian pattern of structural brain alterations.

Structural brain alterations in subjects at high-risk of psychosis: a voxel-based morphometric study.

Forty Untreated high-risk (HR) individuals for psychosis and 75 healthy control subjects (HC) matched for age, gender, handedness and educational level were investigated by structural MRI. HR subjects were recruited at the Early Detection and Intervention Centre for Mental Crises (FETZ) of the Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Germany. Measurements of gray matter volumes were performed by voxel-based morphometry using SPM5. The sample of HR subjects showed GM volume reductions in frontal, lateral temporal and medial temporal regions compared to the healthy control group. These regions are compatible with structural findings in the clinically apparent disease of schizophrenia.

Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression

The serotonergic system is involved in the pathophysiology of major depression as well as in the early central nervous system development and adult neuroplasticity. The aim of the study was to examine in 77 patients with major depression and 77 healthy controls the association between the triallelic polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) and gray matter (GM) brain volumes measured with 1.5 T magnetic resonance imaging. Voxel-based morphometry were estimated on magnetic resonance images and genotyping was performed. We found that healthy controls have a strong association between the 5-HTTLPR and GM volumes of the dorsolateral prefrontal cortex, left anterior gyrus cinguli, left amygdala as well as right hippocampus, whereas there is no such association in patients with major depression. Healthy subjects carrying the S- or LG-allele have smaller GM volumes than those with the LA-allele, indicating that 5-HTTLPR contributes to the development of brain structures. Patients with depression show reduced GM volumes, particularly when they are homozygous for the LA-allele, suggesting that these patients are more vulnerable for morphological changes during depressive episodes.

Structural brain alterations at different stages of schizophrenia: A voxel-based morphometric study

Structural alterations in schizophrenia have mainly been regarded as the result of neurodevelopmental processes. However, it remains unresolved whether the pattern of morphological brain changes differs between different stages of disease. We examined structural brain changes in 93 first-episode (FES) and 72 recurrently ill (REZ) patients with schizophrenia (SZ) and 175 matched healthy control subjects (HC) using cross-sectional and conjunctional voxel-based morphometry (VBM) of whole-brain MRI data in a three-step approach. We found significant grey matter density (GMD) reductions in FES compared to HC bilaterally in the temporal and prefrontal areas, including the anterior cingulate gyrus, as well as in both thalami. Hippocampus and amygdala were affected on the left side (P<0.05, corrected). In REZ patients this pattern was spatially extended. The basal ganglia were exclusively reduced in the recurrently ill group compared to controls. Common to both disease groups were reductions in the bilateral perisylvian regions, the opercular region, the insula, prefrontal cortex, left inferior temporal gyrus, limbic system including hippocampus and amygdala, and the thalami. In FES patients there were no regions affected that were not also affected in REZ patients. In contrast, REZ patients showed extended alterations within the frontal and temporal regions, the hippocampus, amygdala and exclusively in the basal ganglia relative to the FES patients. Our findings suggest a system-specific involvement of neuronal networks in schizophrenia. Furthermore, our data suggest that in the advanced stages of schizophrenia additional cortical and subcortical brain areas become involved in the disease process. Longitudinal data will be required to further test this hypothesis.

Comprehensive dissection of the medial temporal lobe in AD: measurement of hippocampus, amygdala, entorhinal, perirhinal and parahippocampal cortices using MRI

BackgroundEarly pathological involvement of specific medial temporal lobe areas is characteristic for Alzheimer’s disease (AD).ObjectiveTo determine the extent of regional medial temporal lobe atrophy, including hippocampus, amygdala, and entorhinal, perirhinal, and parahippocampal cortices in mild AD patients and healthy controls, and to compare diagnostic accuracy across volumetric markers.MethodsWe studied 34 patients with clinically probable AD and 22 healthy elderly control subjects. Regional volumetric measures were obtained from volumetric T1–weighted MRI scans after accounting for global brain atrophy using affine transformation into standard space.ResultsVolumes of medial temporal lobe structures were significantly smaller in AD patients than in controls with exception of the left entorhinal cortex. The degree of atrophy was comparable between all structures. Diagnostic accuracy (number of correctly allocated cases divided by number of all cases) was highest for the right parahippocampal cortex with 85%, but only slightly lower for the right hippocampus and right entorhinal cortex with 82% and 84%. Using a linear combination of markers, the unilateral volumes of the right hippocampus, parahippocampal cortex and perirhinal cortex yielded an accuracy of 93%.ConclusionExtent of atrophy is similar between the different regions of the medial temporal lobe in mild AD.Volume measurements of medial temporal lobe structures in addition to the hippocampus only yield improved diagnostic accuracy if a combination of these structures is used.