Browsing by Author "MacMaster, Frank P."
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Item Open Access A Preliminary Study of the Influence of Age of Onset and Childhood Trauma on Cortical Thickness in Major Depressive Disorder(2014-03-06) Jaworska, Natalia; MacMaster, Frank P.; Gaxiola, Ismael; Cortese, Filomeno; Goodyear, Bradley; Ramasubbu, RajamannarBackground. Major depressive disorder (MDD) neural underpinnings may differ based on onset age and childhood trauma. We assessed cortical thickness in patients who differed in age of MDD onset and examined trauma history influence. Methods. Adults with MDD () and controls (HC; ) underwent magnetic resonance imaging. Twenty patients had MDD onset 24 years of age (pediatric onset) and 16 had onset 25 years of age (adult onset). The MDD group was also subdivided into those with () and without () physical and/or sexual abuse as assessed by the Childhood Trauma Questionnaire (CTQ). Cortical thickness was analyzed with FreeSurfer software. Results. Thicker frontal pole and a tendency for thinner transverse temporal cortices existed in MDD. The former was driven by the pediatric onset group and abuse history (independently), particularly in the right frontal pole. Inverse correlations existed between CTQ scores and frontal pole cortex thickness. A similar inverse relation existed with left inferior and right superior parietal cortex thickness. The superior temporal cortex tended to be thinner in pediatric versus adult onset groups with childhood abuse. Conclusions. This preliminary work suggests neural differences between pediatric and adult MDD onset. Trauma history also contributes to cytoarchitectural modulation. Thickened frontal pole cortices as a compensatory mechanism in MDD warrant evaluation.Item Open Access Cortical thickness in youth with major depressive disorder(BioMed Central, 2014-03-20) Reynolds, Stephanie; Carrey, Normand; Jaworska, Natalia; Langevin, Lisa Marie; Yang, Xiao-Ru; MacMaster, Frank P.Item Open Access Disambiguating the Role of the Retrosplenial Complex in Human Navigation(2018-06-14) Burles, Clayton Ford; Iaria, Giuseppe; Protzner, Andrea B.; MacMaster, Frank P.The role of the human retrosplenial cortex in spatial orientation and navigation has been obscured by a long history of ambiguous localization, beginning as early as Brodmann’s original depiction which intentionally overrepresented it’s extent. While some modern atlases of the brain exclude this region, many include a surprisingly generous delineation; this has resulted in a very large area of the medial parietal cortex implicitly viewed as being equipotentially involved in spatial orientation and navigation. In this thesis, I provide novel evidence of a more precise paradigm by which we can understand the role of the ‘retrosplenial cortex’, i.e. the posterior cingulate, in spatial orientation and navigation. First, from fMRI activity evoked in a novel spatial task, but subsequently from a meta-analysis of the literature more generally, we have identified that ventral portions of the posterior cingulate are relatively more engaged in encoding spatial information, whereas dorsal portions are more involved in recalling and computing spatial information or representations. Not simply descriptive, this delineation proved valuable in characterizing the neural correlates of a lifelong developmental condition in which individuals get lost on a daily basis in very familiar surroundings, a condition known as Developmental Topographical Disorientation (DTD). In fact, we identified that the dorsal posterior cingulate displays far greater differences then the ventral posterior cingulate in functional connectivity between individuals with DTD and healthy controls; these findings would not have been uncovered with traditional delineations of the retrosplenial cortex. Other studies will undoubtedly benefit from appreciating these functional subregions when analyzing or interpreting activity within the posterior cingulate evoked by spatial orientation tasks. A clear understanding of the neural correlates of spatial orientation and navigation in humans will benefit greatly from future research validating this posterior cingulate delineation, as well as extending increasingly meticulous attention to the location of activity evoked in the posterior cingulate and other brain regions.Item Open Access Effects of Transcranial Direct Current Stimulation on GABA and Glx in Children: A pilot study(Public Library of Science (PLoS), 2020-01-07) Nwaroh, Chidera; Giuffre, Adrianna; Cole, Lauran; Bell, Tiffany; Carlson, Helen L.; MacMaster, Frank P.; Kirton, Adam; Harris, Ashley D.Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that safely modulates brain excitability and has therapeutic potential for many conditions. Several studies have shown that anodal tDCS of the primary motor cortex (M1) facilitates motor learning and plasticity, but there is little information about the underlying mechanisms. Using magnetic resonance spectroscopy (MRS), it has been shown that tDCS can affect local levels of gamma-aminobutyric acid (GABA) and Glx (a measure of glutamate and glutamine combined) in adults, both of which are known to be associated with skill acquisition and plasticity; however this has yet to be studied in children and adolescents. This study examined GABA and Glx in response to conventional anodal tDCS (a-tDCS) and high definition tDCS (HD-tDCS) targeting the M1 in a pediatric population. Twenty-four typically developing, right-handed children ages 12-18 years participated in five consecutive days of tDCS intervention (sham, a-tDCS or HD-tDCS) targeting the right M1 while training in a fine motor task (Purdue Pegboard Task) with their left hand. Glx and GABA were measured before and after the protocol (at day 5 and 6 weeks) using a PRESS and GABA-edited MEGA-PRESS MRS sequence in the sensorimotor cortices. Glx measured in the left sensorimotor cortex was higher in the HD-tDCS group compared to a-tDCS and sham at 6 weeks (p = 0.001). No changes in GABA were observed in either sensorimotor cortex at any time. These results suggest that neither a-tDCS or HD-tDCS locally affect GABA and Glx in the developing brain and therefore it may demonstrate different responses in adults.Item Open Access Examining the Relationship Between Obsessive-Compulsive Symptoms, Genetic Risk and Cortical Thickness in Youth(2019-09-04) Corrigan, Kimberly; Arnold, Paul Daniel; MacMaster, Frank P.; Harris, Ashley D.; Dimitropoulos, GinaObsessive-compulsive disorder (OCD) is a disabling neuropsychiatric disorder that affects approximately 1-3% of the population worldwide. One-third to one-half of individuals with OCD have symptom onset before 15 years of age. The heterogeneous clinical expression of OCD has rendered inconsistent findings from structural imaging studies with small sample sizes. Large scale structural imaging studies are needed to better understand the complicated neurobiology of OCD in child and adolescent population. To assess brain structure, magnetic resonance imaging (MRI) was used. FreeSurfer (Version 6.0) recon-all pathway was used to determine cortical thickness. The cingulate cortex, orbitofrontal cortex and insular cortex were selected as regions of interest. A candidate gene analysis of PTPRD SNP rs7856850 was performed using Illumina Multi-Ethnic Global microarray. Obsessive-compulsive symptom severity was determined using the Child Behaviour Checklist Obsessive-Compulsive Scale (CBCL-OCS). A significant relationship was found between the current CBCL-OCS score and the right posterior cingulate. Increase in symptom severity on the current CBCL-OCS predicted an increase in cortical thickness of the right posterior cingulate. Rs7856850 genotype did not significantly modify the relationship between symptom severity and right posterior cingulate thickness. This a unique large scale pediatric imaging study investigating the association between obsessive-compulsive symptoms and cortical thickness with an additional exploration of a PTPRD SNP variant. The results support the concept that the posterior cingulate is involved in the pathophysiology of OCD. The candidate gene analysis was inconclusive but hopefully, this study will encourage more research in the neurobiology of youth OCD.Item Open Access In the Eye Movements of the Beholder: Manipulating Visual Scanpaths During Facial Emotion Perception Modulates Functional Brain Activation in Schizophrenia Patients and Controls(2018-10-20) Spilka, Michael; Bray, Signe L.; Goghari, Vina M.; Achim, Amélie M.; Kopala-Sibley, Daniel C.; MacMaster, Frank P.; Sears, Christopher R.Individuals with schizophrenia exhibit deficits in the ability to perceive and recognize emotions from faces, and these deficits are significant predictors of functional outcome. Research into the origins of facial emotion recognition deficits in schizophrenia has identified abnormalities in visual gaze behaviour and functional brain activation in patients during facial emotion perception; however, these two aspects of facial emotion processing have previously been studied in isolation. Nonetheless, several studies with healthy individuals and other clinical populations suggest a relationship between gaze behaviour and functional activation in regions also implicated in facial emotion processing deficits in schizophrenia (e.g., fusiform gyrus). These findings raise the important question of whether gaze behaviour abnormalities in schizophrenia contribute to reported functional activation abnormalities during facial emotion perception. In this dissertation, I examined whether manipulating visual scanpaths during facial emotion perception would modulate blood-oxygen-level dependent (BOLD) signal change in a sample of schizophrenia patients and community controls. Patients and controls underwent functional magnetic resonance imaging (fMRI) while viewing pictures of emotional faces. During the Typical Viewing condition, a fixation cue directed participants’ gaze primarily to the eyes and mouth, while gaze was directed to peripheral features during the Atypical Viewing condition. Participants additionally completed a practice version of the task outside the scanner and a traditional facial emotion discrimination task, while gaze behaviour was recorded with an eye tracker. Patients had reduced percentage of fixations to salient facial features during facial emotion discrimination, similar to previous findings. During the fMRI task, both viewing conditions elicited BOLD signal change throughout regions of the neural system for face perception. Typical Viewing led to greater activation in visual association cortex including the right “occipital face area”, while Atypical Viewing elicited greater activation in primary visual cortex and regions involved in attentional control, including the intraparietal sulcus and frontal eye fields. There were no group differences in functional activation, in contrast to previous findings. The results of this study indicate that gaze behaviour modulates activation in early face-processing regions, suggesting that abnormal gaze behaviour in schizophrenia may contribute to the documented activation abnormalities in these regions during facial emotion perception.Item Open Access Neural Correlates of Adolescent Mindfulness, Working Memory, and Internalizing Symptoms(2020-08) Stein, Jade Aurelie; Kopala-Sibley, Daniel C.; MacMaster, Frank P.; Bray, Signe L.; Tomfohr-Madsen, LianneThe central aim of this thesis was to investigate behavioural and neural associations between dispositional mindfulness, working memory, and internalizing symptoms in adolescents. One hundred and thirty-one adolescents, aged 11-18 (M = 13.76, SD = 1.65), who had a parent with a history of mood or anxiety disorders completed measures of dispositional mindfulness, internalizing symptoms, and working memory, including a functional Magnetic Resonance Imaging (fMRI) N-Back task. Hierarchal regressions and correlation analyses were performed. The blood oxygen level dependent (BOLD) signal was contrasted between 2-back versus 0-back conditions and a small volume correction was computed in the dorsolateral and ventrolateral prefrontal cortex (dlPFC, vlPFC) and the anterior cingulate cortex (ACC). Controlling for neuroticism, sex, and mindfulness experience, higher adolescent dispositional mindfulness, including higher self-acceptance and the interaction between attention and awareness and nonreactivity, related to fewer internalizing symptoms. Endorsement of attention and awareness was associated with better 2-back efficiency, except when controlling for mindfulness experience. Internalizing symptoms related to slower reaction time, controlling for sex. Significantly less BOLD signal in the right vlPFC was observed in adolescents with higher attention and awareness scores when controlling for mindfulness experience. Self-acceptance and nonreactive observing (attention and awareness x nonreactivity) may be unique components of mindfulness that have implications for adolescent internalizing symptoms. Adolescents with higher attention and awareness may require less cognitive effort when performing working memory tasks. Learning to be mindful on a daily basis may be beneficial for adolescent cognition and emotional well-being.Item Open Access Neuroanatomical Changes Associated with Working Memory Training in Healthy Adults(2018-06-26) Savage, Linette; Goghari, Vina M.; Campbell, Tavis S.; Bodner, Glen E.; Lebel, Catherine A.; MacMaster, Frank P.; Yang, LixiaThe potential for working memory training to enhance cognitive and intellectual abilities is alluring across scientific disciplines and the general public. However, the field has been fraught with inconsistency and controversy. Heterogeneous methodological implementations have led to a divided and contrasting body of literature, which has collectively limited scientific transparency and advancement in the field. However, neuroimaging has the potential to clarify what, if any, benefit working memory training has on the adult human brain. A recent series of studies used functional neuroimaging to investigate neural activations associated with working memory training. This dissertation uses structural imaging to address another theoretical area: the neuroanatomical correlates of working memory training. Forty-eight healthy community dwelling adults, aged 18 - 40 years, completed a series of cognitive tasks and underwent magnetic resonance imaging (MRI) before and after completing a 6-week trial of working memory training (experimental condition) or processing speed training (active control condition). Group by time repeated measures Analyses of Variance (rm-ANOVAs) were conducted on MRI data to identify changes in surface area, thickness, and volume in theoretically relevant gray matter regions of interest, as well as overall gray and white matter volumes, associated with working memory training. Similar analyses were conducted to investigate changes in cognitive task performance in this sample. Null results were present across all neuroanatomical metrics after correction for multiple comparisons, and findings from cognitive tasks were consistent with the subset of literature suggesting that working memory training does not meaningfully benefit cognitive performance. Albeit limited by low statistical power and the confines of available technology, findings of this study, in consort with recently published investigations, strongly support the idea that working memory training is not an effective method for enhancing cognitive performance or inducing neoplastic changes in brain structure. We suggest that future studies continue attempts to resolve heterogeneity and polarization in this field, or alternatively, concentrate resources on identifying and refining mechanisms of change in populations who may benefit from rehabilitative forms of cognitive training.Item Open Access Neurobiological Correlates of Anxiety and Comorbid Social Phobia in Adolescents with Major Depressive Disorder: A Repetitive Transcranial Magnetic Stimulation Clinical Trial(2018-10-03) Worth, Madelyn Reid; Schwartz, Kelly Dean; MacMaster, Frank P.; Exner-Cortens, Deinera; McMorris, Carly A.; Schwartz, Kelly Dean; MacMaster, Frank P.This study examined repetitive transcranial magnetic stimulation (rTMS) as a treatment for adolescents with major depressive disorder. The study was exploratory, considering the potential influence of comorbid anxiety on treatment response and neurobiological correlates. Adolescents underwent a three-week rTMS clinical trial. Depression and anxiety symptoms were compared pre- and post-treatment to determine treatment response. As well fMRI scans were reviewed, identifying functional connectivity differences based upon comorbid anxiety. Findings indicated a significant relation between depressive symptom response and comorbid social phobia symptoms such that participants without social phobia symptoms were more likely to show a significant reduction in depressive symptoms. Neurobiological differences in terms of functional connectivity were found, based upon anxiety severity, comorbid social phobia symptoms, and anxiety symptom treatment response. These findings indicate that the presence of comorbid anxiety is associated with neurobiological differences that may in turn influence rTMS treatment response. Discussions of these findings are included in this document.Item Open Access Neurochemical Correlates of Executive Functions in Children with Attention-Deficit/Hyperactivity Disorder(2018-09-17) Hai, Tasmia Mobashera; Climie, Emma A.; MacMaster, Frank P.; Wilcox, Gabrielle; Protzner, Andrea B.The current study investigated spectroscopic biomarkers in children with Attention-Deficit/Hyperactivity Disorder (ADHD) and examined neurochemical correlates of Executive Function (EF). Proton Magnetic Resonance Spectroscopy (1H-MRS; TE = 30ms) was conducted in the right prefrontal cortex (RPFC) and left striatum (LS). Twenty-one children with ADHD and 15 control participants took part. Both groups completed performance-based EF tasks. Results indicated lower concentrations of glutamate (p = .009), choline (p = .016), and N-acetyl aspartate (p = .029) in the RPFC in ADHD participants compared to controls. There were no significant differences in the LS. Positive correlations with glutamate concentration and performance in working memory and verbal fluency tasks in the control group were observed. No significant correlations were found in the ADHD group. Findings indicate neurochemical differences between children with ADHD and healthy controls. Additionally, decoupling effects of glutamate were observed indicating glutamate as a possible spectroscopic biomarker for ADHD and novel treatment target.Item Open Access Novel Functional Magnetic Resonance Imaging Analysis Approaches for Investigations of the Dynamics of Resting-State Functional Connectivity(2018-08-23) Sojoudi, Alireza; Goodyear, Bradley G.; Smith, Michael Richard; Dukelow, Sean P.; MacIntosh, Bradley; MacMaster, Frank P.; Sotero Díaz, RobertoSpontaneous fluctuations of blood-oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) signals are highly synchronous between brain regions that serve similar functions. This provides a means to investigate functional networks of the human brain; however, most data analysis techniques assume functional connections are constant over time. This is problematic when studying brain processes associated with aging or neurological disease, where functional connections may become highly variable. Proposed methods of examining moment-to-moment changes in the strength of functional connections over an imaging session (so called dynamic connectivity) are not well established, and there are several pitfalls in current analysis approaches. In this thesis, novel analysis frameworks are developed to address several issues associated with dynamic resting-state fMRI analysis techniques. These techniques are then used to analyze the dynamics of functional connectivity within long-range and local brain networks. Specifically, a hierarchical observation modeling approach is proposed to permit statistical inference of the presence of dynamic connectivity at any point in time. Also, a sliding-window regional homogeneity approach is developed to examine the dynamics of local functional connectivity, to gain even further insight into the global functional organization of the human brain. Finally, the proposed methods are used in a study to determine resting-state local and long-range connectivity changes related to healthy aging, and further, how these changes demonstrate that age changes the proportion of time the brain occupies certain functional states. The studies in this thesis greatly further our understanding of the functional architecture of the human brain, in terms of how local and long-distance interactions are organized both in space and time. This thesis also helps establish a framework for dynamic resting-state fMRI analysis with consistency and reliability.Item Open Access Predictors of Response to Repetitive Transcranial Magnetic Stimulation Treatment in Adolescent Major Depressive Disorder(2018-04-27) McLellan, Quinn Kenneth; MacMaster, Frank P.; Arnold, Paul Daniel; Bulloch, Andrew G. M.Adolescent major depressive disorder has limited treatment options and response is unpredictable. Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment option while pre-treatment cortical thickness may be an objective biomarker predictive of response. Twenty-three youth (12-21 years; 11 female) with treatment-resistant depression (TRD) underwent 3 weeks of high-frequency rTMS. Baseline left rostral middle frontal gyrus (lRMF) thickness was compared between eventual responders, non-responders and age-matched controls (n=16; 10 female). Symptom-specific treatment response, defined as ≥50% symptom reduction, was evaluated. Demographic and symptom profile differences were explored. Interventional rTMS alleviated both anxious and depressive symptoms. lRMF was thinner in responders than non-responders, and age negatively correlated with lRMF thickness in controls but not TRD subjects. Exploration of demographic and symptom variables showed responders on the depressive measure had greater frequency of past suicide attempts and higher atypical symptom cluster score while social phobia was associated with non-responsiveness.Item Open Access Reducing readmission rates for individuals discharged from acute psychiatric care in Alberta using peer and text message support: Protocol for an innovative supportive program(2022-03-12) Eboreime, Ejemai; Shalaby, Reham; Mao, Wanying; Owusu, Ernest; Vuong, Wesley; Surood, Shireen; Bales, Kerry; MacMaster, Frank P.; McNeil, Diane; Rittenbach, Katherine; Ohinmaa, Arto; Bremault-Phillips, Suzette; Hilario, Carla; Greiner, Russ; Knox, Michelle; Chafe, Janet; Coulombe, Jeff; Xin-Min, Li; McLean, Carla; Rathwell, Rebecca; Snaterse, Mark; Spurvey, Pamela; Taylor, Valerie H.; McLean, Susan; Urichuk, Liana; Tzeggai, Berhe; McCabe, Christopher; Grauwiler, David; Jordan, Sara; Brown, Ed; Fors, Lindy; Savard, Tyla; Grunau, Mara; Kelton, Frank; Stauffer, Sheila; Cao, Bo; Chue, Pierre; Abba-Aji, Adam; Silverstone, Peter; Nwachukwu, Izu; Greenshaw, Andrew; Agyapong, Vincent I. O.Abstract Background Individuals discharged from inpatient psychiatry units have the highest readmission rates of all hospitalized patients. These readmissions are often due to unmet need for mental health care compounded by limited human resources. Reducing the need for hospital admissions by providing alternative effective care will mitigate the strain on the healthcare system and for people with mental illnesses and their relatives. We propose implementation and evaluation of an innovative program which augments Mental Health Peer Support with an evidence-based supportive text messaging program developed using the principles of cognitive behavioral therapy. Methods A pragmatic stepped-wedge cluster-randomized trial, where daily supportive text messages (Text4Support) and mental health peer support are the interventions, will be employed. We anticipate recruiting 10,000 participants at the point of their discharge from 9 acute care psychiatry sites and day hospitals across four cities in Alberta. The primary outcome measure will be the number of psychiatric readmissions within 30 days of discharge. We will also evaluate implementation outcomes such as reach, acceptability, fidelity, and sustainability. Our study will be guided by the Consolidated Framework for Implementation Research, and the Reach-Effectiveness-Adoption-Implementation-Maintenance framework. Data will be extracted from administrative data, surveys, and qualitative methods. Quantitative data will be analysed using machine learning. Qualitative interviews will be transcribed and analyzed thematically using both inductive and deductive approaches. Conclusions To our knowledge, this will be the first large-scale clinical trial to assess the impact of a daily supportive text message program with and without mental health peer support for individuals discharged from acute psychiatric care. We anticipate that the interventions will generate significant cost-savings by reducing readmissions, while improving access to quality community mental healthcare and reducing demand for acute care. It is envisaged that the results will shed light on the effectiveness, as well as contextual barriers and facilitators to implementation of automated supportive text message and mental health peer support interventions to reduce the psychological treatment and support gap for patients who have been discharged from acute psychiatric care. Trial registration clinicaltrials.gov, NCT05133726 . Registered 24 November 2021Item Open Access Using Machine Learning for Prognostication of Diagnosis and Identifying Neural Correlates of Impulse Dyscontrol in Preclinical and Prodromal Dementia(2019-08-22) Gill, Sascha Charlene; Ismail, Zahinoor; Smith, Eric Edward; Forkert, Nils Daniel; MacMaster, Frank P.Introduction: Mild Behavioural impairment (MBI) is a validated syndrome that describes neuropsychiatric symptoms (NPS) in preclinical and prodromal dementia. This thesis uses machine learning (ML) and traditional statistical models to: 1) Explore the utility of NPS for predicting diagnostic status 2) Identify the neural correlates of MBI impulse dyscontrol (ID) domain. Methods: Data from the Alzheimer’s Disease Neuroimaging (ADNI) database were extracted. All subjects enrolled in ADNI were between the age of 55-90 years, English or Spanish speakers, and accompanied by study partners who completed the NPI-Q 1) To address the first objective, the logistic model tree classifier combined with an information gain feature selection was trained to predict follow-up diagnosis (normal cognition [NC], MCI, or AD-dementia) using baseline neuroimaging, neuropsychiatric, and demographic data. 2) To address the second objective, ID was identified as behavioural symptoms of agitation/aggression, irritability, and aberrant motor behaviour. Linear mixed effect models were used to assess if ID was related to regional diffusion tensor imaging (DTI) and volumetric parameters. Additionally, ML modeling used a rule-based classification algorithm combined with an information gain feature selector to predict ID using neuroimaging variables. Results: 1) MBI total scores and volume of the left hippocampus were identified as the most important features to predict follow-up diagnostic status. 2) Cingulum, fornix, inferior/superior fronto-occipital fasciculus, superior cerebellar peduncle, and corpus callosum, were the white matter tracts associated with ID. Grey matter regions associated with ID included the parahippocampal gyrus supramarginal gyrus, superior frontal regions, and hippocampus. Conclusion: NPS are early indicators of neurodegenerative disease and can be used predict cognitive decline and dementia.