Cortisol Reactivity to Stress and Its Association With White Matter Integrity in Adults With Schizophrenia

While acute hypothalamic-pituitary-adrenal axis response to stress is often adaptive, prolonged responses may have detrimental effects. Many components of white matter structures are sensitive to prolonged cortisol exposure. We aimed to identify a behavioral laboratory assay for which cortisol response related to brain pathophysiology in schizophrenia. We hypothesized that an abnormally prolonged cortisol response to stress may be linked to abnormal white matter integrity in patients with schizophrenia

Automated ventricular measurements using Gabor wavelets

Magnetic Resonance Imaging (MRI) is one of the widely used medical technologies for diagnosis of various degenerative diseases like Alzheimer\u27s disease. In degenerative diseases the brain atrophies resulting in enlarged ventricles. The segmentation of the ventricle and the total ventricle volume measurement can be important in the analysis of the neurological disease severity and in studies of animal models of disease used to advance treatments for people. This thesis is focused on using Gabor wavelets for ventricular measurements in a rabbit model of Alzheimer\u27s disease.;Standard intensity-based tools like Statistical Parametric Mapping (SPM) used for human brain segmentation requires a priori knowledge of the data. As there is no available rabbit brain atlas incorporated into the algorithm, SPM failed for rabbit brain segmentation. Hence, texture-based segmentation was used to solve the problem. Gabor wavelet decomposition of the textures in an image provides a powerful mathematical tool for feature extraction. The features contain important frequency information that can be estimated from biological parameters to choose the wavelet set. Our goal is to develop an automated method for extracting ventricular structures from whole-head rabbit MRI.;Rabbit brain segmentation is a complex process in low contrast MRI images. Hence the Gabor wavelets were first studied on the high resolution digital histological rabbit brain images. With the success of ventricle segmentation in the histology images, the Gabor parameters were modified for the rabbit brain MR images. Initially, manually guided segmentation results were obtained using Gabor wavelets. This work continued further to automate the process of brain region of interest (ROI) selection to automate the ventricle extraction process

Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia

Background Altered brain connectivity is implicated in the development and clinical burden of schizophrenia. Relative to matched controls, schizophrenia patients show (1) a global and regional reduction in the integrity of the brain\u27s white matter (WM), assessed using diffusion tensor imaging (DTI) fractional anisotropy (FA), and (2) accelerated age‐related decline in FA values. In the largest mega‐analysis to date, we tested if differences in the trajectories of WM tract development influenced patient–control differences in FA. We also assessed if specific tracts showed exacerbated decline with aging. Methods Three cohorts of schizophrenia patients (total n = 177) and controls (total n = 249; age = 18‐61 years) were ascertained with three 3T Siemens MRI scanners. Whole‐brain and regional FA values were extracted using ENIGMA‐DTI protocols. Statistics were evaluated using mega‐ and meta‐analyses to detect effects of diagnosis and age‐by‐diagnosis interactions. Results In mega‐analysis of whole‐brain averaged FA, schizophrenia patients had lower FA (P = 10−11) and faster age‐related decline in FA (P = 0.02) compared with controls. Tract‐specific heterochronicity measures, that is, abnormal rates of adolescent maturation and aging explained approximately 50% of the regional variance effects of diagnosis and age‐by‐diagnosis interaction in patients. Interactive, three‐dimensional visualization of the results is available at http://www.enigma-viewer.org. Conclusion WM tracts that mature later in life appeared more sensitive to the pathophysiology of schizophrenia and were more susceptible to faster age‐related decline in FA values

The common genetic influence over processing speed and white matter microstructure: Evidence from the Old Order Amish and Human Connectome Projects.

Speed with which brain performs information processing influences overall cognition and is dependent on the white matter fibers. To understand genetic influences on processing speed and white matter FA, we assessed processing speed and diffusion imaging fractional anisotropy (FA) in related individuals from two populations. Discovery analyses were performed in 146 individuals from large Old Order Amish (OOA) families and findings were replicated in 485 twins and siblings of the Human Connectome Project (HCP). The heritability of processing speed was h(2)=43% and 49% (both p<0.005), while the heritability of whole brain FA was h(2)=87% and 88% (both p<0.001), in the OOA and HCP, respectively. Whole brain FA was significantly correlated with processing speed in the two cohorts. Quantitative genetic analysis demonstrated a significant degree to which common genes influenced joint variation in FA and brain processing speed. These estimates suggested common sets of genes influencing variation in both phenotypes, consistent with the idea that common genetic variations contributing to white matter may also support their associated cognitive behavior

Hippocampal volume change in the alzheimer disease cholesterol-lowering treatment trial

Numerous clinical studies suggest a link between elevated cholesterol and increased risk of Alzheimer disease (AD), and the preponderance of data suggests that statin therapy may reduce the risk of AD later in life. The first clinical investigation of statin therapy in patients with AD, the AD Cholesterol-Lowering Treatment (ADCLT) trial, found that atorvastatin 80 mg/day was associated with improvements relative to placebo on some, but not all, cognitive measures after 6 months and 1 year of therapy.We report here findings from a pilot ADCLT substudy showing a nonsignificant reduction in total hippocampal volume with 1 year of atorvastatin therapy compared with placebo, driven by a highly significant reduction in right hippocampal volume with atorvastatin therapy

Cortical connectomic mediations on gamma band synchronization in schizophrenia

Abstract Aberrant gamma frequency neural oscillations in schizophrenia have been well demonstrated using auditory steady-state responses (ASSR). However, the neural circuits underlying 40 Hz ASSR deficits in schizophrenia remain poorly understood. Sixty-six patients with schizophrenia spectrum disorders and 85 age- and gender-matched healthy controls completed one electroencephalography session measuring 40 Hz ASSR and one imaging session for resting-state functional connectivity (rsFC) assessments. The associations between the normalized power of 40 Hz ASSR and rsFC were assessed via linear regression and mediation models. We found that rsFC among auditory, precentral, postcentral, and prefrontal cortices were positively associated with 40 Hz ASSR in patients and controls separately and in the combined sample. The mediation analysis further confirmed that the deficit of gamma band ASSR in schizophrenia was nearly fully mediated by three of the rsFC circuits between right superior temporal gyrus—left medial prefrontal cortex (MPFC), left MPFC—left postcentral gyrus (PoG), and left precentral gyrus—right PoG. Gamma-band ASSR deficits in schizophrenia may be associated with deficient circuitry level connectivity to support gamma frequency synchronization. Correcting gamma band deficits in schizophrenia may require corrective interventions to normalize these aberrant networks

Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia.

BACKGROUND: Altered brain connectivity is implicated in the development and clinical burden of schizophrenia. Relative to matched controls, schizophrenia patients show (1) a global and regional reduction in the integrity of the brain's white matter (WM), assessed using diffusion tensor imaging (DTI) fractional anisotropy (FA), and (2) accelerated age-related decline in FA values. In the largest mega-analysis to date, we tested if differences in the trajectories of WM tract development influenced patient-control differences in FA. We also assessed if specific tracts showed exacerbated decline with aging. METHODS: Three cohorts of schizophrenia patients (total n = 177) and controls (total n = 249; age = 18-61 years) were ascertained with three 3T Siemens MRI scanners. Whole-brain and regional FA values were extracted using ENIGMA-DTI protocols. Statistics were evaluated using mega- and meta-analyses to detect effects of diagnosis and age-by-diagnosis interactions. RESULTS: In mega-analysis of whole-brain averaged FA, schizophrenia patients had lower FA (P = 10-11 ) and faster age-related decline in FA (P = 0.02) compared with controls. Tract-specific heterochronicity measures, that is, abnormal rates of adolescent maturation and aging explained approximately 50% of the regional variance effects of diagnosis and age-by-diagnosis interaction in patients. Interactive, three-dimensional visualization of the results is available at www.enigma-viewer.org. CONCLUSION: WM tracts that mature later in life appeared more sensitive to the pathophysiology of schizophrenia and were more susceptible to faster age-related decline in FA values. Hum Brain Mapp 37:4673-4688, 2016. (c) 2016 Wiley Periodicals, Inc