Browsing by Author "Brooks, Samantha J"
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- ItemOpen AccessThe BDNF p.Val66Met polymorphism, childhood trauma, and brain volumes in adolescents with alcohol abuse(BioMed Central, 2014-12-16) Dalvie, Shareefa; Stein, Dan J; Koenen, Karestan; Cardenas, Valerie; Cuzen, Natalie L; Ramesar, Raj; Fein, George; Brooks, Samantha JBackground: Previous studies have indicated that early life adversity, genetic factors and alcohol dependence are associated with reduced brain volume in adolescents. However, data on the interactive effects of early life adversity, genetic factors (e.g. p.Met66 allele of BDNF), and alcohol dependence, on brain structure in adolescents is limited. We examined whether the BDNF p.Val66Met polymorphism interacts with childhood trauma to predict alterations in brain volume in adolescents with alcohol use disorders (AUDs). Methods: We examined 160 participants (80 adolescents with DSM-IV AUD and 80 age- and gender-matched controls) who were assessed for trauma using the Childhood Trauma Questionnaire (CTQ). Magnetic resonance images were acquired for a subset of the cohort (58 AUD and 58 controls) and volumes of global and regional structures were estimated using voxel-based morphometry (VBM). Samples were genotyped for the p.Val66Met polymorphism using the TaqMan® Assay. Analysis of covariance (ANCOVA) and post-hoc t-tests were conducted using SPM8 VBM. Results: No significant associations, corrected for multiple comparisons, were found between the BDNF p.Val66Met polymorphism, brain volumes and AUD in adolescents with childhood trauma. Conclusions: These preliminary findings suggest that the BDNF p.Met66 allele and childhood trauma may not be associated with reduced structural volumes in AUD. Other genetic contributors should be investigated in future studies.
- ItemOpen AccessBDNF polymorphisms are linked to poorer working memory performance, reduced cerebellar and hippocampal volumes and differences in prefrontal cortex in a Swedish elderly population(Public Library of Science, 2014) Brooks, Samantha J; Nilsson, Emil K; Jacobsson, Josefin A; Stein, Dan J; Fredriksson, Robert; Lind, Lars; Schiöth, Helgi BBACKGROUND: Brain-derived neurotrophic factor (BDNF) links learning, memory and cognitive decline in elderly, but evidence linking BDNF allele variation, cognition and brain structural differences is lacking. METHODS: 367 elderly Swedish men (n = 181) and women (n = 186) from Prospective Investigation of the Vasculature in Uppsala seniors (PIVUS) were genotyped and the BDNF functional rs6265 SNP was further examined in subjects who completed the Trail Making Task (TMT), verbal fluency task, and had a magnetic resonance imaging (MRI) scan. Voxel-based morphometry (VBM) examined brain structure, cognition and links with BDNF. RESULTS: The functional BDNF SNP (rs6265,) predicted better working memory performance on the TMT with positive association of the Met rs6265, and was linked with greater cerebellar, precuneus, left superior frontal gyrus and bilateral hippocampal volume, and reduced brainstem and bilateral posterior cingulate volumes. CONCLUSIONS: The functional BDNF polymorphism influences brain volume in regions associated with memory and regulation of sensorimotor control, with the Met rs6265 allele potentially being more beneficial to these functions in the elderly.
- ItemOpen AccessBlushing and gaze avoidance in social anxiety disorder : a structural neuroanatomical investigation(2014) Van der Merwe, Nicolina Thandiwe; Stein, Dan J; Malcolm-Smith, Susan; Brooks, Samantha JBackground: Social anxiety disorder (SAD) is a common psychiatric condition characterised by fear and avoidance of social situations. Lifetime prevalence is 5-16% and co-morbidity with other mood and substance abuse disorders is common. Symptoms including cognitive, behavioural and physiological components vary between individuals. Of these, blushing and gaze fear and avoidance are regarded as cardinal symptoms. First line treatment of SAD involves SSRIs and cognitive behavioural therapy, while surgery may also be considered for excessive blushing. Blushing and gaze avoidance are thought to have an evolutionary adaptive advantage, promoting the display of submissive behaviour and appeasement in threatening situations. MRI research has demonstrated differences on functional and structural neuroimaging between patients with SAD and healthy controls (HCs). However, little is known about the neurocircuitry underlying gaze fear and avoidance or increased blushing propensity or how the severity of these traits correlate with the neuroimaging differences found in SAD. In this research, I explored the neuroanatomy of blushing propensity and gaze fear and avoidance in the context of SAD. Methods: 18 SAD patients and 18 HCs underwent structural MRI scans and self-report scales were administered to assess their symptom severity, blushing propensity and gaze fear and avoidance. Structural data was analysed using voxel-based morphometry (VBM). Regression and contrast analyses were used to correlate blushing propensity and gaze anxiety and avoidance symptoms with brain volumes, controlling for total grey matter volume, age and level of education. Results: Anxiety, blushing propensity and gaze fear and avoidance symptoms were all significantly higher in SAD patients (p<0.001). Brainstem volumes were increased for higher blushing scores a (p<0.01), while the volumes of left inferior parietal lobe b (p=0.04) and left occipital cortex a (p<0.01) were decreased. With increased gaze fear and avoidance, there were associated decreases in the right posterior cingulate cortex a (p<0.01), right occipital lobe b (p=0.03) and right fusiform gyrus a (p<0.01). Increased blushing and gaze symptom severity considered together, was associated with increased brainstem volume a (p<0.01) and decreased pons/cerebellum b (p=0.001), right cerebellum b (p=0.009), left cerebellum c (p<0.001) and left inferior parietal lobe a (p<0.1), volumes. Contrast analysis of SAD and HC brain volumes revealed a greater grey matter volume in HCs in the regions of left occipital cortex (p<0.01), left anterior cingulate (p<0.01) and right inferior parietal lobe (p<0.01) when compared to SAD patients. Increased symptom severity in SAD was significantly associated with higher volumes in the left premotor cortex (p<0.01), right hippocampus (p<0.01), left orbitofrontal cortex (p<0.01) and right superior temporal cortex (p<0.01). Possible areas for of interest for volume differences between SAD and HCs include total grey matter volume (d =0.83), left and right anterior cingulate cortex (d =0.68 and d =0.65), and left and right dorsolateral prefrontal cortex (d =0.55 and d =0.54), yet these differences were not significantly different. (a uncorrected peak levels b uncorrected cluster level, c corrected cluster level). Conclusion: Differences in brain volumes pertaining to blushing and gaze fear and avoidance in SAD patients may be a contributing factor or a consequence of these core symptoms, and a potential biomarker for SAD. Future studies could build on this preliminary research with increased sample sizes, and determine the possible effects of reduced symptom severity and treatment options on brain structure and function. Most importantly, an investigation of the genetic underpinnings and functional neural correlates of blushing and gaze avoidance behaviour may enhance our understanding of the complex aetiology of these cardinal SAD symptoms, thereby improving our understanding of SAD as a psychiatric disorder and facilitating better patient care and management.
- ItemOpen AccessThe structural neurobiology of social anxiety disorder : a clinical neuroimaging study(2015) Hattingh, Coenraad Jacobus; Stein, Dan J; Lochner, Christine; Brooks, Samantha JWhile a number of studies have explored the functional neuroanatomy of social anxiety disorder (SAD), comparatively few studies have investigated the structural underpinnings in SAD. 18 psychopharmacologically and psychotherapeutically naïve adult patients with a primary Axis I diagnosis of generalized social anxiety disorder and 18 demographically (age, gender and education) matched healthy controls underwent 3T structural magnetic resonance imaging. A manual tracing protocol was specifically developed to compute the volume of the most prominent subcortical gray matter structures implicated in SAD by previous functional research. Cortical thickness was estimated using an automated algorithm and whole brain analyses of white matter structure were performed using FSL's tract - based spatial statistics comparing fractional anisotropy (FA), mean diffusivity (MD) in individuals with SAD. Manual tracing demonstrated that compared to controls, SAD patients showed an enlarged right globus pallidus. Cortical thickness analyses demonstrated significant cortical thinning in the left isthmus of the cingulate gyrus, the left temporal pole, and the left superior temporal gyrus. Analyses of white matter tractographic data demonstrated reduced FA in in the genu, splenium and tapetum of the corpus callosum. Additionally reduced FA was noticed in the fornix and the right cingulum. Reduced FA was also noted in bilateral corticospinal tracts and the right corona radiata. The results demonstrate structural alterations in limbic circuitry as well as involvement of the basal glanglia and their cortical projections and input pathways.
- ItemOpen AccessSubliminal versus supraliminal stimuli activate neural responses in anterior cingulate cortex, fusiform gyrus and insula: a meta-analysis of fMRI studies(BioMed Central, 2014-12-11) Meneguzzo, Paolo; Tsakiris, Manos; Schioth, Helgi B; Stein, Dan J; Brooks, Samantha JBackground: Non-conscious neural activation may underlie various psychological functions in health and disorder. However, the neural substrates of non-conscious processing have not been entirely elucidated. Examining the differential effects of arousing stimuli that are consciously, versus unconsciously perceived will improve our knowledge of neural circuitry involved in non-conscious perception. Here we conduct preliminary analyses of neural activation in studies that have used both subliminal and supraliminal presentation of the same stimulus. Methods: We use Activation Likelihood Estimation (ALE) to examine functional Magnetic Resonance Imaging (fMRI) studies that uniquely present the same stimuli subliminally and supraliminally to healthy participants during functional magnetic resonance imaging (fMRI). We included a total of 193 foci from 9 studies representing subliminal stimulation and 315 foci from 10 studies representing supraliminal stimulation. Results: The anterior cingulate cortex is significantly activated during both subliminal and supraliminal stimulus presentation. Subliminal stimuli are linked to significantly increased activation in the right fusiform gyrus and right insula. Supraliminal stimuli show significantly increased activation in the left rostral anterior cingulate. Conclusions: Non-conscious processing of arousing stimuli may involve primary visual areas and may also recruit the insula, a brain area involved in eventual interoceptive awareness. The anterior cingulate is perhaps a key brain region for the integration of conscious and non-conscious processing. These preliminary data provide candidate brain regions for further study in to the neural correlates of conscious experience.
- ItemOpen AccessToward a greater understanding of the brain processes underlying handgrip and handgrip fatigue(2016) King, Michael T C; Rauch, Laurie; Stein, Dan J; Brooks, Samantha JHandgrip is a ubiquitous human movement that determines how we interact with our environment. It is involved in almost every aspect of daily life (e.g. opening a door, handling cutlery, using tools) and like all human movement, its application is limited by muscle fatigue. However, the supraspinal mechanisms of handgrip and handgrip fatigue are not fully understood despite the importance of this fundamental movement, numerous publications, and its presence as a longstanding research topic. This thesis investigates the brain mechanisms of handgrip and handgrip fatigue using fMRI. It begins with a review of the literature in Chapter one, which evaluates the theories and evidence for central control of handgrip and muscle fatigue as well as describing the rationale to perform the experiments in this thesis. The methodology and analyses are also reviewed to provide rationale for their use and to facilitate the interpretation of subsequent experimental results. In order to understand the supraspinal mechanisms of handgrip and handgrip fatigue it is logical to first understand the most fundamental grip type (power vs. precision) and pattern (static vs. dynamic) by which handgrip can be performed.