ABSTRACT
The single-nucleotide polymorphism rs9804190 in the Ankyrin G (ANK3) gene has been reported in genome-wide association studies to be associated with bipolar disorder (BD). However, the neural system effects of rs9804190 in BD are not known. We investigated associations between rs9804190 and gray and white matter (GM and WM, respectively) structure within a frontotemporal neural system implicated in BD. A total of 187 adolescent and adult European Americans were studied: a group homozygous for the C allele (52 individuals with BD and 56 controls) and a T-carrier group, carrying the high-risk T allele (38 BD and 41 controls). Subjects participated in high-resolution structural magnetic resonance imaging and diffusion tensor imaging (DTI) scanning. Frontotemporal region of interest (ROI) and whole-brain exploratory analyses were conducted. DTI ROI-based analysis revealed a significant diagnosis by genotype interaction within the uncinate fasciculus (P⩽0.05), with BD subjects carrying the T (risk) allele showing decreased fractional anisotropy compared with other subgroups, independent of age. Genotype effects were not observed in frontotemporal GM volume. These findings support effects of rs9804190 on frontotemporal WM in adolescents and adults with BD and suggest a mechanism contributing to WM pathology in BD.
Subject(s)
Ankyrins/genetics , Bipolar Disorder/genetics , Bipolar Disorder/pathology , Gray Matter/pathology , White Matter/pathology , Adolescent , Adult , Ankyrins/metabolism , Bipolar Disorder/diagnostic imaging , Bipolar Disorder/metabolism , Brain/diagnostic imaging , Brain/pathology , Diffusion Tensor Imaging , Female , Gene Frequency , Genome-Wide Association Study , Gray Matter/diagnostic imaging , Gray Matter/metabolism , Humans , Magnetic Resonance Imaging/methods , Male , Nerve Net/diagnostic imaging , Nerve Net/pathology , Polymorphism, Single Nucleotide , Risk Factors , White Matter/diagnostic imaging , White Matter/metabolismABSTRACT
BACKGROUND: Convergent studies provide support for abnormalities in the structure and functioning of the prefrontal cortex (PFC) and the amygdala, the key components of the neural system that subserves emotional processing in major depressive disorder (MDD). We used resting-state functional magnetic resonance imaging (fMRI) to examine potential amygdala-PFC functional connectivity abnormalities in treatment-naive subjects with MDD. METHODS: Resting-state fMRI data were acquired from 28 individuals with MDD and 30 healthy control (HC) subjects. Amygdala-PFC functional connectivity was compared between the MDD and HC groups. RESULTS: Decreased functional connectivity to the left ventral PFC (VPFC) from the left and right amygdala was observed in the MDD group, compared with the HC group (p < 0.05, corrected). CONCLUSIONS: The treatment-naive subjects with MDD showed decreased functional connectivity from the amygdala to the VPFC, especially to the left VPFC. This suggests that these connections may play an important role in the neuropathophysiology of MDD at its onset.
Subject(s)
Amygdala/physiopathology , Depressive Disorder, Major/physiopathology , Prefrontal Cortex/physiopathology , Adult , Brain/physiopathology , Female , Functional Neuroimaging , Humans , Magnetic Resonance Imaging , Male , Neural Pathways/physiopathology , Young AdultABSTRACT
BACKGROUND: Patients with major depressive disorder (MDD) show deficits in processing of facial emotions that persist beyond recovery and cessation of treatment. Abnormalities in neural areas supporting attentional control and emotion processing in remitted depressed (rMDD) patients suggests that there may be enduring, trait-like abnormalities in key neural circuits at the interface of cognition and emotion, but this issue has not been studied systematically. METHOD: Nineteen euthymic, medication-free rMDD patients (mean age 33.6 years; mean duration of illness 34 months) and 20 age- and gender-matched healthy controls (HC; mean age 35.8 years) performed the Emotional Face N-Back (EFNBACK) task, a working memory task with emotional distracter stimuli. We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to measure neural activity in the dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC), orbitofrontal cortex (OFC), ventral striatum and amygdala, using a region of interest (ROI) approach in SPM2. RESULTS: rMDD patients exhibited significantly greater activity relative to HC in the left DLPFC [Brodmann area (BA) 9/46] in response to negative emotional distracters during high working memory load. By contrast, rMDD patients exhibited significantly lower activity in the right DLPFC and left VLPFC compared to HC in response to positive emotional distracters during high working memory load. These effects occurred during accurate task performance. CONCLUSIONS: Remitted depressed patients may continue to exhibit attentional biases toward negative emotional information, reflected by greater recruitment of prefrontal regions implicated in attentional control in the context of negative emotional information.
Subject(s)
Attention/physiology , Depressive Disorder, Major/physiopathology , Emotions/physiology , Memory, Short-Term/physiology , Prefrontal Cortex/physiopathology , Adult , Analysis of Variance , Basal Ganglia/physiopathology , Brain Mapping , Case-Control Studies , Depressive Disorder, Major/psychology , Facial Expression , Female , Functional Laterality , Humans , Magnetic Resonance Imaging/methods , Male , Oxygen/blood , Photic Stimulation/methods , Reaction Time , Regression AnalysisSubject(s)
Brain/anatomy & histology , Exons/genetics , Nerve Fibers, Myelinated , Nerve Tissue Proteins/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Anisotropy , Cysteine/genetics , Diffusion Magnetic Resonance Imaging , Female , Genome-Wide Association Study , Genotype , Humans , Male , Serine/genetics , Young AdultABSTRACT
Shape comparison is a key scenario in morphometric study, where registration is often involved and found to be unreliable: different registrations can lead to different shape differences. This paper proposes a generic scheme applicable to most registration methods, to reduce this unreliability. It perturbs the registration processes by feeding them with resampled shape groups, and then aggregates the results to yield the final result. This scheme can be simplified for pair-wise registration methods to reduce the computation. Experiments are conducted on both synthetic and biomedical shapes using different registration methods, which demonstrate its effectiveness.
ABSTRACT
BACKGROUND: Executive control of cognition, emotion, and behavior are disrupted in the manic state of bipolar disorder. Whereas frontal systems are implicated in such dysfunction, the localization of functional brain abnormalities in the manic state is not well understood. METHODS: We utilized a high-sensitivity H(2)(15)0 positron emission tomography technique to investigate regions of increased brain activity in mania, compared to euthymia, in bipolar disorder. RESULTS: The principal findings were manic state-related increased activity in left dorsal anterior cingulate, and left head of caudate. CONCLUSIONS: The findings suggest that the manic state of bipolar disorder may be associated with heightened activity in a frontal cortical-subcortical neural system that includes the anterior cingulate and caudate.
Subject(s)
Bipolar Disorder/diagnostic imaging , Bipolar Disorder/physiopathology , Caudate Nucleus/physiopathology , Cerebrovascular Circulation , Dominance, Cerebral , Gyrus Cinguli/physiopathology , Adult , Brain/blood supply , Brain/diagnostic imaging , Brain/physiopathology , Case-Control Studies , Caudate Nucleus/blood supply , Caudate Nucleus/diagnostic imaging , Cognition , Confounding Factors, Epidemiologic , Female , Gyrus Cinguli/blood supply , Gyrus Cinguli/diagnostic imaging , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Tomography, Emission-ComputedABSTRACT
OBJECTIVE: This study investigated prefrontal cortex function in the manic state of bipolar disorder. METHOD: High-sensitivity [15O]H2O positron emission tomography and a word generation activation paradigm were used to study regional cerebral blood flow in five manic and six euthymic individuals with bipolar disorder and in five healthy individuals. RESULTS: Decreased right rostral and orbital prefrontal cortex activation during word generation and decreased orbitofrontal activity during rest were associated with mania. CONCLUSIONS: The data support the presence of rostral and orbital prefrontal dysfunction in primary mania. These findings, when seen in the context of the human brain lesion and the behavioral neuroanatomic literatures, may help to explain some of the neurobehavioral abnormalities characteristic of the manic state.
Subject(s)
Bipolar Disorder/physiopathology , Neuropsychological Tests , Prefrontal Cortex/physiopathology , Tomography, Emission-Computed , Adult , Bipolar Disorder/diagnostic imaging , Female , Humans , Male , Oxygen Radioisotopes , Prefrontal Cortex/blood supply , Prefrontal Cortex/diagnostic imaging , Regional Blood Flow , WaterABSTRACT
This case highlights the complexities of evaluating and treating psychiatric symptoms that are concurrent with a seizure disorder. Interictal and postictal psychoses, affective disorders, personality changes, and cognitive deficits are common problems that require modified psychiatric treatments.