Browsing by Author "Harris, Ashley D."
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- ItemOpen AccessA Functional Magnetic Resonance Imaging Study to Investigate the Utility of a Picture Imagination Task in Investigating Neural Responses in Patients with Chronic Musculoskeletal Pain to Daily Physical Activity Photographs(Public Library of Science (PLoS), 2015-10-23) Taylor, Ann M.; Harris, Ashley D.; Varnava, Alice; Phillips, Rhiannon; Taylor, Justin O.; Hughes, Owen; Wilkes, Antony R.; Hall, Judith E.; Wise, Richard G.Pain-related anxiety and fear are associated with increased difficulties in attention, increased awareness of pain, impaired disengagement from pain, and can moderate the effects of attentional coping attempts. Accurately assessing the direct impact of pain-related anxiety and fear on pain behavior has proved difficult. Studies have demonstrated no or limited influence of pain-related fear and anxiety on behavior but this may be due to inherent problems with the scales used. Neuroimaging has improved the understanding of neural processes underlying the factors that influence pain perception. This study aimed to establish if a Picture and Imagination Task (PIT), largely developed from the Photographs of Daily Activity (PHODA) assessment tool, could help explore how people living with chronic pain process information about daily activities. Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to compare brain responses in patients with chronic musculoskeletal pain (CMSKP) (n = 15) and healthy controls (n = 15). Subjects were asked to imagine how they would feel mentally and physically if asked to perform daily activities illustrated in PIT. The results found that a number of regions involved in pain processing saw increased BOLD activation in patients compared with controls when undertaking the task and included the insula, anterior cingulate cortex, thalamus and inferior and superior parietal cortices. Similarly, increased BOLD responses in patients compared to controls in the frontal pole, paracingulate and the supplementary motor cortex may be suggestive of a memory component to the responses The amygdala, orbitofrontal cortex, substantia nigra/ventral tegmentum, putamen, thalamus, pallidum, inferior parietal (supramarginal and angular gyrus) and cingulate cortex were also seen to have greater differences in BOLD signal changes in patients compared with controls and many of these regions are also associated with general phobic responses. Therefore, we suggest that PIT is a useful task to explore pain-and movement-related anxiety and fear in fMRI studies. Regions in the Default Mode Network remained active or were less deactivated during the PIT task in patients with CMSKP compared to healthy controls supporting the contention that the DMN is abnormal in patients with CMSKP.
- ItemOpen AccessAdvancing Concussion Assessment in Pediatrics (A-CAP): a prospective, concurrent cohort, longitudinal study of mild traumatic brain injury in children: protocol study(BMJ, 2017-07-01) Yeates, Keith O.; Beauchamp, Miriam; Craig, William; Doan, Quynh; Zemek, Roger; Bjornson, Bruce H.; Gravel, Jocelyn; Mikrogianakis, Angelo; Goodyear, Bradley; Abdeen, Nishard; Beaulieu, Christian; Dehaes, Mathieu; Deschenes, Sylvain; Harris, Ashley D.; Lebel, Catherine; Lamont, Ryan; Williamson, Tyler; Barlow, Karen M.; Bernier, Francois; Brooks, Brian L.; Emery, Carolyn; Freedman, Stephen B.; Kowalski, Kristina; Mrklas, Kelly; Tomfohr-Madsen, Lianne; Schneider, Kathryn J.Introduction Paediatric mild traumatic brain injury (mTBI) is a public health burden. Clinicians urgently need evidence-based guidance to manage mTBI, but gold standards for diagnosing and predicting the outcomes of mTBI are lacking. The objective of the Advancing Concussion Assessment in Pediatrics (A-CAP) study is to assess a broad pool of neurobiological and psychosocial markers to examine associations with postinjury outcomes in a large sample of children with either mTBI or orthopaedic injury (OI), with the goal of improving the diagnosis and prognostication of outcomes of paediatric mTBI. Methods and analysis A-CAP is a prospective, longitudinal cohort study of children aged 8.00-16.99 years with either mTBI or OI, recruited during acute emergency department (ED) visits at five sites from the Pediatric Emergency Research Canada network. Injury information is collected in the ED; follow-up assessments at 10 days and 3 and 6 months postinjury measure a variety of neurobiological and psychosocial markers, covariates/confounders and outcomes. Weekly postconcussive symptom ratings are obtained electronically. Recruitment began in September 2016 and will occur for approximately 24 months. Analyses will test the major hypotheses that neurobiological and psychosocial markers can: (1) differentiate mTBI from OI and (2) predict outcomes of mTBI. Models initially will focus within domains (eg, genes, imaging biomarkers, psychosocial markers), followed by multivariable modelling across domains. The planned sample size (700 mTBI, 300 OI) provides adequate statistical power and allows for internal cross-validation of some analyses. Ethics and dissemination The ethics boards at all participating institutions have approved the study and all participants and their parents will provide informed consent or assent. Dissemination will follow an integrated knowledge translation plan, with study findings presented at scientific conferences and in multiple manuscripts in peer-reviewed journals.
- ItemOpen AccessCerebral blood flow response to acute hypoxic hypoxia(Wiley, 2013-10-07) Harris, Ashley D.; Murphy, Kevin; Diaz, Claris M.; Saxena, Neeraj; Hall, Judith E.; Liu, Thomas T.; Wise, Richard G.Hypoxic hypoxia (inspiratory hypoxia) stimulates an increase in cerebral blood flow (CBF) maintaining oxygen delivery to the brain. However, this response, particularly at the tissue level, is not well characterised. This study quantifies the CBF response to acute hypoxic hypoxia in healthy subjects. A 20-min hypoxic (mean P(ET)o(2)=52 mmHg) challenge was induced and controlled by dynamic end-tidal forcing whilst CBF was measured using pulsed arterial spin labelling perfusion MRI. The rate constant, temporal delay and magnitude of the CBF response were characterised using an exponential model for whole-brain and regional grey matter. Grey matter CBF increased from 76.1 mL/100 g/min (95% confidence interval (CI) of fitting: 75.5 mL/100 g/min, 76.7 mL/100 g/min) to 87.8 mL/100 g/min (95% CI: 86.7 mL/100 g/min, 89.6 mL/100 g/min) during hypoxia, and the temporal delay and rate constant for the response to hypoxia were 185 s (95% CI: 132 s, 230 s) and 0.0035 s(-1) (95% CI: 0.0019 s(-1), 0.0046 s(-1)), respectively. Recovery from hypoxia was faster with a delay of 20 s (95% CI: -38 s, 38 s) and a rate constant of 0.0069 s(-1) (95% CI: 0.0020 s(-1), 0.0103 s(-1)). R-2*, an index of blood oxygenation obtained simultaneously with the CBF measurement, increased from 30.33 s(-1) (CI: 30.31 s(-1), 30.34 s(-1)) to 31.48 s(-1) (CI: 31.47 s(-1), 31.49 s(-1)) with hypoxia. The delay and rate constant for changes in R-2* were 24 s (95% CI: 21 s, 26 s) and 0.0392 s(-1) (95% CI: 0.0333 s(-1), 0.045 s(-1) ), respectively, for the hypoxic response, and 12 s (95% CI: 10 s, 13 s) and 0.0921 s(-1) (95% CI: 0.0744 s(-1), 0.1098 s(-1)/) during the return to normoxia, confirming rapid changes in blood oxygenation with the end-tidal forcing system. CBF and R-2* reactivity to hypoxia differed between subjects, but only R-2* reactivity to hypoxia differed significantly between brain regions. (c) 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.
- ItemOpen AccessCharacterizing acute ischemic stroke evolution using magnetic resonance diffusion imaging(2008) Harris, Ashley D.; Frayne, Richard
- ItemOpen AccessContributions of Affective States and Traits to Autistic Features(2024-04) Godfrey, Kate J.; Bray, Signe; Harris, Ashley D.; McMorris, Carly; Protzner, AndreaThis thesis considered the role of affect and reward in autistic features, based on the important role affective brain systems play in emotion and motivated behaviors known to be impacted in autistic individuals. I directly tested multiple affect-based hypotheses in children with and without an autism diagnosis and aimed to inform future clinical work by exploring several methodologies for examining both inter-individual (trait) and intra-individual (state) variation in measures of affect and reward. I first examined multiple behavioral domains (reward sensitivity, anxiety symptoms, and executive function) for associations with interest intensity in early childhood autism. I report that the executive functioning domain of attention shifting associated with interest intensity in early childhood, while there was no relation with general sensitivity to reward and anxiety symptoms. I then considered how to better characterize inter-individuality in reward sensitivity during early childhood, specifically regarding social rewards. I therefore developed and validated the Social Reward Questionnaire–Early Childhood (SRQ-EC) to quantify wanting and liking of distinctly rewarding social situations in young children. I found that autistic-like traits in a community sample associated with reduced wanting and liking of social rewards, particularly for large group interactions, suggesting potential utility of the SRQ-EC for future autism research. I additionally considered a protocol for investigating brain functional connectivity for associations with intra-individual affect variation in a community sample of adults, with relevance for designing future studies to examine neurobiological mechanisms of affective disorders that commonly co-occur in autism. My work replicates recent findings that variance in functional connectivity is largely attributable to individual identity, and that variance attributable to intra-individual affect variation is 7–100x smaller than what can be attributed to viewing condition. This thesis advances methodologies for measuring and modeling both inter- and intra-individual variation in autism, specifically in relation to affective processes which are difficult to measure in a laboratory setting. The methods presented and refined here could be used in future work to better understand state- and trait-like features in autism.
- ItemOpen AccessThe Effect of Transcranial Direct Current Stimulation on GABA and Glx in Children During Motor Learning(2019-06-07) Nwaroh, Chidera; Harris, Ashley D.; Kirton, Adam; Bray, Signe L.; Condliffe, Elizabeth G.; Dunn, Jeffrey F.Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that safely modulates brain activity. 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. Additionally, studies have shown that tDCS can affect local levels of GABA and glutamate both of which are associated with skill acquisition and plasticity. This study aimed to quantify changes in GABA and Glx in response to 5 consecutive days of anodal tDCS or high definition tDCS targeting the M1 in children. Our results suggest HD-tDCS elicits a neurochemical response that is different from anodal tDCS despite resulting in similar motor enhancements. Additionally, we identified a relationship between left sensorimotor cortex GABA and improvements in motor performance. Overall, our results suggest that the developing brain responds differently to tDCS when compared to adult literature.
- ItemOpen AccessEffects 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.
- ItemOpen AccessExamining 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.
- ItemOpen AccessGABA and Glutamate in Children with Primary Complex Motor Stereotypies: An1H-MRS Study at 7T(American Society of Neuroradiology (ASNR), 2015-11-05) Harris, Ashley D.; Singer, H.S.; Horska, A.; Kline, T.; Ryan, M.; Edden, R.A.E; Mahone, E.M.BACKGROUND AND PURPOSE: Complex motor stereotypies are rhythmic, repetitive, fixed, purposeful but purposeless movements that stop with distraction. They can occur in otherwise normal healthy children (primary stereotypies) as well in those with autism spectrum disorders (secondary stereotypies). The underlying neurobiologic basis for these movements is unknown but is thought to involve cortical-striatal-thalamo-cortical pathways. To further clarify potential neurochemical alterations, gamma-aminobutyric acid (GABA), glutamate, glutamine, N-acetylaspartate, and choline levels were measured in 4 frontostriatal regions by using 1H MRS at 7T. MATERIALS AND METHODS: A total of 18 children with primary complex motor stereotypies and 24 typically developing controls, ages 5–10 years, completed MR spectroscopy at 7T. Single voxel STEAM acquisitions from the anterior cingulate cortex, premotor cortex, dorsolateral prefrontal cortex, and striatum were obtained, and metabolites were quantified with respect to Cr by using LCModel. RESULTS: The 7T scan was well tolerated by all the participants. Compared with the controls, children with complex motor stereotypies had lower levels of GABA in the anterior cingulate cortex (GABA/Cr, P = .049; GABA/Glu, P = .051) and striatum (GABA/Cr, P = .028; GABA/Glu, P = .0037) but not the dorsolateral prefrontal cortex or the premotor cortex. Glutamate, glutamine, NAA, and Cho levels did not differ between groups in any of the aforementioned regions. Within the complex motor stereotypies group, reduced GABA to Cr in the anterior cingulate cortex was significantly associated with greater severity of motor stereotypies (r = −0.59, P = .021). CONCLUSIONS: These results indicate possible GABAergic dysfunction within corticostriatal pathways in children with primary complex motor stereotypies.
- ItemOpen AccessGABA Levels in Left and Right Sensorimotor Cortex Correlate across Individuals(MDPI AG, 2018-07-24) Puts, Nicholaas A.J.; Heba, Stefanie; Harris, Ashley D.; Evans, Christopher J.; McGonigle, David J.; Tegenthoff, Martin; Schmidt-Wilcke, Tobias; Edden, Richard A.E.Differences in -aminobutyric acid (GABA) levels measured with Magnetic Resonance Spectroscopy have been shown to correlate with behavioral performance over a number of tasks and cortical regions. These correlations appear to be regionally and functionally specific. In this study, we test the hypothesis that GABA levels will be correlated within individuals for functionally related regionsthe left and right sensorimotor cortex. In addition, we investigate whether this is driven by bulk tissue composition. GABA measurements using edited MRS data were acquired from the left and right sensorimotor cortex in 24 participants. T1-weighted MR images were also acquired and segmented to determine the tissue composition of the voxel. GABA level is shown to correlate significantly between the left and right regions (r = 0.64, p < 0.03). Tissue composition is highly correlated between sides, but does not explain significant variance in the bilateral correlation. In conclusion, individual differences in GABA level, which have previously been described as functionally and regionally specific, are correlated between homologous sensorimotor regions. This correlation is not driven by bulk differences in voxel tissue composition.
- ItemOpen AccessImproving symptom burden in adults with persistent post-concussive symptoms: a randomized aerobic exercise trial protocol(2020-02-05) Mercier, Leah J.; Fung, Tak S.; Harris, Ashley D.; Dukelow, Sean P.; Debert, Chantel T.Abstract Background Persistent post-concussive symptoms (PPCS) affect up to 30% of individuals following mild traumatic brain injury. PPCS frequently includes exercise intolerance. Sub-symptom threshold aerobic exercise has been proposed as a treatment option for symptom burden and exercise intolerance in this population. The primary aim of this study is to evaluate whether a progressive, sub-symptom threshold aerobic exercise program can alleviate symptom burden in adults with PPCS. Methods Fifty-six adults (18–65) with PPCS (>3mos-5 yrs) will be randomized into two groups: an immediate start 12-week aerobic exercise protocol (AEP) or delayed start 6-week placebo-like stretching protocol (SP), followed by AEP. Aerobic or stretching activities will be completed 5x/week for 30 mins during the intervention. Online daily activity logs will be submitted. Exercise prescriptions for the AEP will be 70–80% of heart rate at the point of symptom exacerbation achieved on a treadmill test with heart rate monitoring. Exercise prescription will be updated every 3-weeks with a repeat treadmill test. The Rivermead Post-concussion Symptom Questionnaire will be the primary outcome measure at 6 and 12-weeks of intervention. Secondary outcomes include assessments of specific symptoms (headache, quality of life, mood, anxiety, fatigue, dizziness, sleep parameters, daytime sleepiness) in addition to blood biomarkers and magnetic resonance imaging and spectroscopy data for quantification of brain metabolites including γ-aminobutyric acid (GABA), glutathione, glutamate and N-acetyl aspartate (NAA) all measured at 6 and 12-weeks of intervention. Discussion This trial will evaluate the use of aerobic exercise as an intervention for adults with PPCS, thus expanding our knowledge of this treatment option previously studied predominantly for adolescent sport-related concussion. Trial registration ClinicalTrials.gov - NCT03895450 (registered 2019-Feb-11).
- ItemOpen AccessIn vivo Assessment of Human Brainstem Cerebrovascular Function: A Multi-Inversion Time Pulsed Arterial Spin Labelling Study(SAGE Publications, 2014-03-05) Warnert, Esther A.H.; Harris, Ashley D.; Murphy, Kevin; Saxena, Neerja; Tailor, Neeta; Jenkins, Nigel S.; Hall, Judith E.; Wise, Richard G.The brainstem (BS) is involved in critical physiologic processes, including control of cardiovascular and respiratory functions. This study implements a multi-inversion time pulsed arterial spin labelling (MTI PASL) imaging sequence that addresses the challenges of BS imaging and aims to measure normal and elevated BS perfusion in healthy volunteers. An initial experiment was performed to obtain the kinetic curve of the label in the BS and consequently to estimate the label arrival times and tissue perfusion in seven participants. A second experiment estimated the BS cerebral vascular reactivity (CVR) to hypercapnia in 10 participants. Images were acquired with a gradient-echo sequence with two spiral interleaves and short echo time (TE=2.7 ms). Data were analyzed with a two-compartment model, including a tissue and arterial component. In both experiments, perfusion in the BS was significantly lower than in cortical gray matter (repeated measures analysis of variance (RM-ANOVA), P<0.05), which is as expected since the BS consists of gray and white matter, the latter typically showing lower perfusion. The BS CVR found here is comparable to previous reports obtained with positron emission tomography (PET) imaging. Multi-inversion time pulsed ASL in combination with a two-compartment signal model can be used to assess BS perfusion and CVR.
- ItemOpen AccessMulti-Regional Investigation of the Relationship between Functional MRI Blood Oxygenation Level Dependent (BOLD) Activation and GABA Concentration(Public Library of Science (PLoS), 2015-02-20) Harris, Ashley D.; Puts, Nicholaas A.J.; Anderson, Brian A.; Yantis, Steven; Pekar, James J.; Barker, Peter B.; Edden, Richard A.E.Several recent studies have reported an inter-individual correlation between regional GABA concentration, as measured by MRS, and the amplitude of the functional blood oxygenation level dependent (BOLD) response in the same region. In this study, we set out to investigate whether this coupling generalizes across cortex. In 18 healthy participants, we performed edited MRS measurements of GABA and BOLD-fMRI experiments using regionally related activation paradigms. Regions and tasks were the: occipital cortex with a visual grating stimulus; auditory cortex with a white noise stimulus; sensorimotor cortex with a finger-tapping task; frontal eye field with a saccade task; and dorsolateral prefrontal cortex with a working memory task. In contrast to the prior literature, no correlation between GABA concentration and BOLD activation was detected in any region. The origin of this discrepancy is not clear. Subtle differences in study design or insufficient power may cause differing results; these and other potential reasons for the discrepant results are discussed. This negative result, although it should be interpreted with caution, has a larger sample size than prior positive results, and suggests that the relationship between GABA and the BOLD response may be more complex than previously thought.
- ItemOpen AccessNeural responses to a modified Stroop paradigm in patients with complex chronic musculoskeletal pain compared to matched controls: an experimental functional magnetic resonance imaging study(Springer Science and Business Media LLC, 2016-02-01) Taylor, Ann M.; Harris, Ashley D.; Varnava, Alice; Phillips, Rhiannon; Hughes, Owen; Wilkes, Antony R.; Hall, Judith E.; Wise, Richard G.Chronic musculoskeletal pain (CMSKP) is attentionally demanding, complex and multi-factorial; neuroimaging research in the population seen in pain clinics is sparse. A better understanding of the neural activity underlying attentional processes to pain related information compared to healthy controls may help inform diagnosis and management in the future.
- ItemOpen AccessOpposite Dynamics of GABA and Glutamate Levels in the Occipital Cortex during Visual Processing(Society for Neuroscience, 2018-10-03) Kurcyus, Katarzyna; Annac, Efsun; Hanning, Nina M.; Harris, Ashley D.; Oeltzschner, George; Edden, Richard; Riedl, ValentinMagnetic resonance spectroscopy (MRS) measures the two most common inhibitory and excitatory neurotransmitters, GABA and glutamate, in the human brain. However, the role of MRS-derived GABA and glutamate signals in relation to system-level neural signaling and behavior is not fully understood. In this study, we investigated levels of GABA and glutamate in the visual cortex of healthy human participants (both genders) in three functional states with increasing visual input. Compared with a baseline state of eyes closed, GABA levels decreased after opening the eyes in darkness and Glx levels remained stable during eyes open but increased with visual stimulation. In relevant states, GABA and Glx correlated with amplitude of fMRI signal fluctuations. Furthermore, visual discriminatory performance correlated with the level of GABA, but not Glx. Our study suggests that differences in brain states can be detected through the contrasting dynamics of GABA and Glx, which has implications in interpreting MRS measurements.
- ItemOpen AccessResting-State Functional Connectivity Differences in Pediatric Migraine(2019-11-17) Khaira, Akashroop; Bell, Tiffany; Noel, Melanie; Amoozegar, Farnaz; Harris, Ashley D.Pediatric migraines are highly prevalent but not well-understood. Neuroimaging can provide great insight to brain physiology, but few studies have applied imaging to study pediatric migraines. Previous adult literature has shown differences in resting-state functional connectivity (rsFC) in migraine patients compared to controls; however, adult migraine findings may not be directly transferable to children. This study’s aim was to investigate rsFC differences between children with migraine and controls to better understand pediatric migraines. Resting-state functional magnetic resonance imaging (rsfMRI) data from 26 participants (10 controls and 16 migraines), between the ages of 7-16 years. Data was preprocessed and analyzed using FSL. An independent component analysis constrained to 30 components was used to identify resting-state networks across all subjects. Group average spatial maps were regressed into each subject’s dataset for a time course, which was then regressed into the subject-specific spatial maps. Permutation testing compared rsFC differences in the groups while controlling for age. Initial analysis indicated significant rsFC differences (p < 0.05) in two networks. In the frontoparietal network, there is decreased rsFC in the right motor cortex in the migraine group compared to controls. In the hippocampal/amygdala network, there is decreased rsFC in migraine patients in the right amygdala and right hippocampus. The frontoparietal and hippocampal/amygdala networks are relevant to migraine with roles in pain perception and processing, learning, emotion, and memory. Detecting differences in these networks in children with migraine compared to controls shows that even between migraines, there is intrinsically altered rsFC in pediatric migraine patients.
- ItemOpen AccessThe effect of movie-watching on electroencephalographic responses to tactile stimulation(Elsevier BV, 2020-10-01) Espenhahn, Svenja; Yan, Tingting; Beltrano, Winnica; Kaur, Sakshi; Godfrey, Kate; Cortese, Filomeno; Bray, Signe; Harris, Ashley D.Movie-watching is becoming a popular acquisition method to increase compliance and enable neuroimaging data collection in challenging populations such as children, with potential to facilitate studying the somatosensory system. However, relatively little is known about the possible crossmodal (audiovisual) influence of movies on cortical somatosensory processing. In this study, we examined the impact of dynamic audiovisual movies on concurrent cortical somatosensory processing using electroencephalography (EEG). Forty healthy young adults (18–25 years) received passive tactile fingertip stimulation while watching an “entertaining” movie and a novel “low-demand” movie called ‘Inscapes’ compared to eyes-open rest. Watching a movie did not modulate properties of early or late somatosensory-evoked potentials (SEPs). Similarly, no crossmodal influence on somatosensory adaptation, denoted by a reduction in SEP amplitude with repetitive tactile stimulation, was found. The prominent oscillatory responses in the alpha and beta frequency bands following tactile stimulation differed as a function of viewing condition, with stronger alpha/beta event-related desynchronization (ERD) during movie-watching compared to rest. These findings highlight that movie-watching is a valid acquisition method during which SEPs can be measured in basic research and clinical studies, but that the attentional demands of movies need to be taken into account when performing oscillatory analyses.
- ItemOpen AccessThe neurobiology of wellness: 1H-MRS correlates of agency, flexibility and neuroaffective reserves in healthy young adults(Elsevier BV, 2020-10-27) White, Tara L.; Gonsalves, Meghan A.; Cohen, Ronald A.; Harris, Ashley D.; Monning, Mollie A.; Walsh, Edward G.; Nitenson, Adam Z.; Porges, Eric C.; Lamb, Damon G.; Woods, Adam J.; Borja, Cara B.Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive imaging technique that measures the concentration of metabolites in defined areas of the human brain in vivo. The underlying structure of natural metabolism-emotion relationships is unknown. Further, there is a wide range of between-person differences in metabolite concentration in healthy individuals, but the significance of this variation for understanding emotion in healthy humans is unclear. Here we investigated the relationship of two emotional constructs, agency and flexibility, with the metabolites glutamate and glutamine (Glx), N-acetylaspartate (tNAA), choline (Cho), creatine (tCr), and myo-inositol (Ins) in the right dorsal anterior cingulate cortex (dACC) in medically and psychiatrically healthy volunteers (N = 20, 9 female; mean age = 22.8 years, SD = 3.40). The dACC was selected because this region is an integrative hub involved in multiple brain networks of emotion, cognition and behavior. Emotional traits were assessed using the Multidimensional Personality Questionnaire Brief Form (MPQ-BF), an empirically derived self-report instrument with an orthogonal factor structure. Phenotypes evaluated were positive and negative agency (MPQ-BF Social Potency, Aggression), emotional and behavioral flexibility (MPQ-BF Absorption, Control-reversed), and positive and negative affect (MPQ-BF Social Closeness; Stress Reaction, Alienation). The resting concentration of tNAA in the dACC was robustly positively correlated with Absorption (r = +0.56, unadjusted p = .005), moderately positively correlated with Social Potency (r = +0.42, unadjusted p = .03), and robustly negatively correlated with Aggression (r = -0.59, unadjusted p = .003). Absorption and Aggression accounted for substantial variance in tNAA (R2 = 0.31, 0.35; combined R2 = 0.50), and survived correction for multiple comparisons (Holm-Bonferroni adjusted p = .032, 0.021, respectively). dACC Glx and Cho had modest relationships with behavioral flexibility and social affiliation that did not survive this multiple correction, providing effect sizes for future work. Principal Component Analysis (PCA) revealed a three-factor orthogonal solution indicating specific relationships between: 1) Glx and behavioral engagement; 2) Cho and affiliative bonding; and 3) tNAA and a novel dimension that we term neuroaffective reserves. Our results inform the neurobiology of agency and flexibility and lay the groundwork for understanding mechanisms of natural emotion using 1H-MRS.
- ItemOpen AccessUnboxing the "Black Box": Learning Interpretable Deep Learning Features of Brain Aging(2019-11) Souto Maior Neto, Luis; Frayne, Richard; Pichardo, Samuel; Smith, Eric Edward; Harris, Ashley D.; Beg, Mirza FaisalDeep learning (DL) algorithms are state-of-the-art techniques for automatic inference tasks like classification and regression in medical imaging and many other fields. Despite growing interest, DL models have had restricted implementation in practical settings as they are often considered to be “black boxes”. Their inner workings are not easily interpretable by humans, which in medicine has limited wider use. In this work, I apply DL models to predict subject age based on brain magnetic resonance (MR) data. While accurate predictions (< 2 years) are made, the purpose of this work is not to establish prediction accuracy but to better understand brain aging by studying the learned representations of the trained models. I use autoencoder-based models that enable translation between the domain of the model’s internal representations of the data, about which we have little understanding, and the domain of MR images, about which we have expert knowledge. The goal of this research is to investigate whether such DL models are capable of learning representations of age-related features similar to what is already known in literature. I show that such DL models, when trained to predict brain age, are capable of learning known features of brain aging, such as brain atrophy. In addition, this approach may potentially identify new features of aging on brain images.
- ItemOpen AccessVoxel Placement Precision for GABA-Edited Magnetic Resonance Spectroscopy(Scientific Research Publishing, Inc., 2017-01-01) Bai, Xu; Harris, Ashley D.; Gong, Tao; Puts, Nicolaas A.J.; Wang, Guangbin; Schär, Michael; Barker, Peter B.; Edden, Richard A.E.The purpose of the present study was to assess the reproducibility of voxel placement for GABA-edited MRS. GABA-edited MRS data were acquired in 13 healthy volunteers from (3 cm)3 voxel; and within the same session a second acquisition was independently prescribed. A three-dimensional voxel mask image was reconstructed in T1-image-space using the SVMask tool (in house software). Reproducibility of voxel placement was assessed using the Dice overlap coefficient, both within-subject and between-subject following co-registration of T1 images and transformation of voxel mask images to standard space. Within-subject overlap coefficients were 86% ± 5%. Between-subject overlap coefficients were 75% ± 10%. For the two voxel locations considered (occipital and sensorimotor), voxel overlap was very similar. Between-subject values are higher due to between-session effects, anatomical variability and volume mismatch in standard space. While surprisingly low in terms of volume overlap, the overlap coefficients correspond to acceptable linear displacements.