Neuropsychiatry

Department: LHSC

Award Value: Reduced Scanning Rate, allowing an increased sample size

The proposed study will examine the effect of touch among individuals with post-traumatic stress disorder (PTSD) through fMRI in order to evaluate how neural networks in the brain respond to various types of tactile sensory information, including human touch and inanimate object touch. Touch is critical for developing a healthy attachment system during childhood and for forging neural pathways that elicit a soothing effect to helps calm or heal the body in response to stress, making it highly relevant to the study of early attachment disruption and childhood traumatic experiences. However, the neuroscience underlying the effects of touch in the aftermath of trauma have yet to be fully explored. This study aims to investigate the effects of light versus deep pressure, and self versus other interpersonal human touch during traumatic memory recall. The data collected from this study can aid in discriminating unique neural signatures associated with the sense of touch among individuals with post-traumatic stress disorder. In addition, fMRI data can be correlated with scores from trauma-focused psychological assessments conducted prior to the scan in order to evaluate how touch can be impacted by traumatic experiences, especially those that experience attachment conflict during childhood. Here, the neural correlates identified in response to different types of touch will inform the development of clinically-oriented sensorimotor psychotherapies for PTSD.

The scan will consist of three separate blocks: (1) Resting-State Scan involving an 8-minute mind-wandering task; (2) Experiment that evaluates light versus deep pressure contact on legs using standardized weighted objects (feather and fMRI-compatible weighted sandbags) and (3) Experiment that measures self versus other human touch. The final experimental block will include personalized trauma-related, positive and neutral word stimuli. An experimenter will be in the scanner with the participant during the scan to administer the respective touch protocols for each experimental block. We would also use equipment from Robarts Research Institute to collect heart rate and respiration. Obtaining a reduced scanning rate will allow us to compare results between the two research groups (PTSD and healthy controls) in order to learn more about the sense of touch among traumatized individuals and help inform sensorimotor psychotherapy treatments for PTSD. Taken together, this project involves a novel experimental paradigm that aligns with BrainSCANs goal to reduce the burden of brain disorders and findings from this study can be translated to inform therapeutic targets for emerging clinical treatments for PTSD. The combined use of trauma-focused psychological assessments and fMRI data will significantly help advance our understanding of the brain in the aftermath of trauma.

Department: LHSC

Award Value: Reduced Scanning Rate, allowing an increased sample size

Progress in psychotherapy can be impeded is some trauma clients by the consequences of early attachment disruption or unresolved traumatic experience. Deep Brain Reorienting (DBR) is a clinical method for the treatment of attachment conflicts and traumatic experiences. The approach is based in the observation that the earliest responses in attachment are dependent on the processing of sensory stimuli related to significant others (including those who abuse). The brainstem base for this Innate Connection System is in midbrain structures, specifically the Superior Colliculi (SC) and the Periaqueductal Gray (PAG) which are also at the heart of the brain's Innate Defensive System (i.e., neurocircuitry underlying reflexive defences necessary to survive imminent danger). Therefore the tendency to approach others for connection involves a system which readily engages defensive responses if there is any threat experienced in the interaction. This can lead to conflicted responses held in implicit memories at a very deep brain level. The implications for the body's holding of conflicted attachment tendencies, often made complex at a very early developmental stage when the cortex is not fully mature, can be addressed in DBR. The rationale is as follows: Physiologically, orienting to a stimulus, whether external or in the mind's eye, comes before any affective response to it. That is, there is activity in certain midbrain structures, i.e., SC, and even before that, in the PAG. The deep layers of the SC bring on a brief (orienting) tension in the neck, as well as preparing for eye movements. If we can attend to this tension-even if we have to backtrack from the emotion that follows-we can establish an anchor in the body that precedes the affect, and acts as an anchor against emotional overwhelm. Dr. Corrigan, the developer of DBR, has noticed that sometimes before the affect begins, there is an experience of shock or traumatic realization and he's reasoned that this is because the deep layers of the SC can activate the Innate Alarm System via the locus coeruleus. If people have unresolved "shock" from traumatic experiences, being able to identify this shock or realization, and to sit with it/process it allows it to resolve.

This project aligns with the strategic priorities of BrainsCAN. It involves the use of psychological assessments and imaging to assess patterns of brain functioning and look at important brain areas for attention, executive functioning and higher cognitive processes. The primary task of DBR is to help the participant attend to sensations in the head/neck areas, and to help regulate any sympathetic nervous system arousal. It is believed that this approach will allow the participant to more fully process the distressing memory, changing how it is represented/accessed in the brain's innate defensive system. This study will help advance our understanding of the brain in this condition.

Department: University of Guleph

Award Value: Reduced Scanning Rate, allowing an increased sample size

Alcohol use disorder occurs commonly in patients with schizophrenia and dramatically worsens the overall course of this severe psychiatric disorder. Unfortunately, few treatment options are available to limit alcohol use in this population. This study, employing a rat model of schizophrenia and alcohol use disorder, aims to study the neurobiological mechanisms underlying alcohol use disorder in patients with schizophrenia, with an eye toward developing new treatments. First, using MRI methods akin to those used in patients, at 9.4 T, we will assess whether dysfunctions in the brain reward circuit can predict future alcohol intake in this model. Second, employing tools to specifically manipulate communication in the brain reward circuit, we will assess whether this manipulation of the brain reward circuit alters alcohol drinking in the NVHL rat. Lastly, we will use MRI methods assessing communication between brain regions to study the impact of an antipsychotic that is known to reduce alcohol drinking on dysfunctions in brain reward circuit connectivity, with an eye toward developing novel treatments with this information. These studies aligns well with the Scientific philosophy of BrainsCAN, in that through understanding the neural circuitry that drives alcohol drinking in patients with schizophrenia, we improve the diagnosis, classification and treatment of this difficult to treat disorder. This study will also be able to assess the causal consequences of alcohol drinking on the cognitive and positive schizophrenia-like symptoms observed in this model, and the neural correlates of those effects. The brain reward dysfunction has also been observed in other mental illnesses and might serve as a transdiagnostic marker for vulnerability toward substance use in populations beyond schizophrenia. The BrainsCAN MRI rate reduction will also allow us to assess the effects of adolescent alcohol and cannabis on these circuits, and their impact on cognitive and schizophrenia-like behaviours Lastly, this project uses a combinatorial approach reverse-translating findings from patients into rodent models to assess the causal neural circuits underlying alcohol drinking in schizophrenia by combining pre-clinical MRI with cutting-edge chemogenetic and behavioural pharmacology methods.

Department: Psychology

Award Value: Reduced Scanning Rate, allowing an increased sample size

The overall goal of this pilot study is to characterize neural responses to social evaluation in adolescents with or without eating disorders and to examine associations between neural response to social feedback and clinical characteristics of eating disorders. By determining the neural correlates underlying sensitivity to social feedback, we can begin to understand the subtle cognitive markers that may increase eating disorder susceptibility. This information will allow clinicians to shift from syndrome based diagnostics, which are flawed, in part, because of arbitrary clinical thresholds, to pre-clinical based interventions and therapies.

Such pre-clinical interventions could significantly reduce the long-term impact eating disorders have on both mental and brain health. The collection of both task-based and resting state data will allow us to explore multiple scientific avenues related to brain functioning in eating disorders, which is critical to better understanding the pathophysiology of these deadly illnesses.

Department: Psychology

Award Value: Reduced Scanning Rate, allowing an increased sample size

A core feature of the healthy brain is the ability to learn about the circumstances giving rise to conflict in order to adapt attention to goal-relevant and goal-irrelevant information accordingly. This conflict-adaptation ability may be impaired in disorders such as schizophrenia, as demonstrated by impaired performance in interference tasks, that is, tasks that require producing a response in the face of conflict (Becker, Kerns, MacDonald, & Carter, 2008, Neuropsychopharmacology; Abrahamse et al., 2016, Cogn Neuropsychiatry). However, there is currently little consensus among cognitive psychologists on whether interference tasks actually measure conflict-adaptation abilities rather than more general learning abilities, for example, the ability to learn about the response that is typical for a certain event independently from the conflict that event causes.

Clearly however, an accurate understanding of the processes involved in normal performance of interference tasks in the healthy adult population is necessary in order to properly interpret and treat disorders associated with impaired performance of those tasks in clinical populations. By comparing patterns of brain activity during performance of conflicting versus non-conflicting versions of an interference task, this study will help determine whether the healthy brain uses a conflict-adaptation ability, a more general learning ability, or a combination of the two, in dealing with this type of task. The results will provide valuable information for clinical professionals in interpreting patterns of behavior in this class of tasks, now widely used in many diagnostic situations.

Department: Psychology

Award Value: Reduced Scanning Rate, allowing an increased sample size

The goal of this project is to validate MRI and MRS predictors of repetitive transcranial magnetic stimulation (rTMS) treatment response in schizophrenia. This project will assess anatomical (MRI) and metabolic (MRS to measure GABA) measures using the 3T scanner at the CFMM as predictors of rTMS treatment, with positive symptoms, negative symptoms and general functioning as cognitive outcome measures. MRI scans will be performed at baseline and cognitive scores will be collected as measured by clinical assessment within the Prevention and Early Intervention in Psychosis Programme at baseline, day 21 and day 84. rTMS treatment will be delivered between baseline and day 21.

Department: Psychology

Award Value: Reduced Scanning Rate, allowing an increased sample size

Brain injury is sometimes, though not always, accompanied by marked changes in personality, emotion, and decision-making. When such changes do occur, it is thought to be the result of abnormal interactions between prefrontal cortex (particularly medial prefrontal cortex) and other brain areas. However, medial prefrontal cortex dysfunction has been proposed for a diverse range of problems, including disinhibition, depression, mania, anxiety, aggression, impulsivity, and addiction. Currently, we do not fully understand which form of dysregulated behaviour will arise from dysfunction in circumscribed areas of prefrontal cortex. In addition, oftentimes ostensibly similar lesions to prefrontal cortex are unpredictably associated with extremely different symptomatic outcomes (e.g., extreme apathy versus emotional lability).

We will examine emotion and decision making in 70-100 individuals with acquired brain injury while also retrospectively characterizing premorbid emotional styles and decision making through care-giver reports in order to: a) better understand how lesions to particular brain regions map onto specific emotional and cognitive deficits; b) begin to outline the potential interaction between premorbid personality characteristics and these change following brain injury. The study will use voxel-based lesion-symptom mapping, diffusion weighted imaging, and functional connectivity in a sample of brain injury survivors recruited from the London Ontario area, with the support of our community partner, Dale Brain Injury Services.

Department: Psychiatry

Award Value: Reduced Scanning Rate

The present study aims to investigate neurobiological and neurochemical effects of an innovative meditation therapy known as Sahaj Samadhi Meditation (SSM), in late-life depression (LLD) patients. The efficacy of current treatments for depression, such as anti-depressant medication, is limited and novel treatments are urgently required. Non-pharmacological treatments such as meditation have provided promising results in reducing depressive symptoms. A recent study on SSM in LLD patients found a 40% remission rate following SSM treatment. Additionally, response and remission rates were three times more in the SSM arm compared to treatment as usual. Considering SSM's extent of benefit, and the potential to implement it in regular practice, it is imperative to understand the neurobiological basis of its response; hence this study. We will be the first to analyze glutathione (GSH) levels, an indicator of oxidative stress, in LLD and observe changes with SSM in a longitudinal study. The ROI will be the hippocampus and posterior cingulate cortex. A scanning protocol has now been developed in-house to estimate GSH using magnetic resonance spectroscopy (MRS) at 7 Tesla. GSH levels will be correlated with longitudinal changes in brain volume and Resting State Functional Connectivity, before and after SSM, comparted to an active control group. We expect that findings from this study will provide a novel understanding of the molecular mechanisms surrounding late life depression, specifically regarding oxidative stress and neuroinflammation, and moreover, how these mechanisms relate to specific brain regions previously associated with depression. If SSM is found superior to control, and significant neuroimaging correlates are observed, it would further validate SSM as an effective treatment for LLD.

It specifically utilizes novel MRS, coupled with structural and functional imaging techniques to examine how SSM affects critical brain regions previously associated with depression. By being able to correlate these changes with expected improvement in cognition.

Department: Psychology

Award Value: Reduced Scanning Rate, allowing an increased sample size

The purpose of this project is to determine the impact of emotion on 3D stimulus encoding. The impact of 2D versus 3D emotional stimuli on the mind and brain has not yet been directly compared, though we know that neural regions considered critical for emotional encoding rapidly habituate to emotional 2D objects. This rapid habituation poses a problem for affective cognitive neuroscience research where moderate effect sizes are expected because of ethical restrictions concerning the intensity of emotional stimuli that are used. This project will determine if these habituation effects can be allayed by using 3D stimuli. As part of our experiment series, we will use fMRI to measure and compare activation and repetition effects in vision and emotion processing regions in response to repeated presentations of emotional 2D and 3D images. With this information we can determine if there are differences in the neural mechanisms involved in the emotional encoding of the two stimulus types.

This project will use imaging to improve our understanding of emotion processing by delineating the neural mechanisms responsible for the encoding of emotional stimuli. By pursing the improvement of effect sizes in emotion research, this project can strengthen future research on disorders with emotion processing abnormalities.

Department: Psychiatry

Award Value: Reduced Scanning Rate, allowing an increased sample size

Existing work concerning the impact of violent media remains controversial partly due to methodological concerns and biases. To date, research on violent gaming has failed to consider its impact on subtle cognitive markers of empathy and antisocial behaviour. Instead, there has been an emphasis on correlational studies and observable aggressive behaviour, increasing the potential for experiementer demand effects. The literature also fails to consider how individual differences on key variables assocaited with antisocial outcomes may affect suceptability to the influences of violent gaming. We believe that the limitations of the extant literature may be addressed by applying cognitive neuroscience techniques to target the constituent mediating elements of antisocial behaviour via social cognition. The limitations may also be addressed by cutting across diagnostic boundaries and considering the neurocognitive markers implicated in empathy and social behaviour not only in typically developing individuals, but also across disorders featuring behavioural dysregulation and abnormalities in empathy (e.g., psychopathy, autism).

The current study seeks to determine the acute impact of violent gaming on neurocognitive targets implicated in aggression and antisocial behaviours as a function of individual differences in callous traits (reduced guilt and regard for others' feelings). We predict that BOLD signal reducations in neural regions implicated in emotional empathy and action simulation will be observed in those exposed to violent versus non-violent modes of the same game; further, these effects will be exacerbated by high callous traits.

Department: Psychiatry

Award Value: Reduced Scanning Rate, allowing an increased sample size

The purpose of this project is to assess changes in structural and functional integrity of the hippocampus and associated cognitive functions in individuals undergoing Electroconvulsive Therapy (ECT) for treatment of Depression. One mechanism that has been proposed to play a critical role in the therapeutic effects of ECT and other antidepressant treatments is hippocampal neurogenesis. However, most research that speaks to this proposal has been conducted in animals and research evidence in humans is currently very limited. Furthermore, there are other structural and functional changes that have been proposed. In the current study, we will use ultra-high-resolution T1, T2 images and functional (T2*) images at 7T to comprehensively examine structural and functional components of hippocampal plasticity in relation to ECT treatment (longitudinal design with assessment before and after treatment). The results will provide new insights into the role of hippocampal plasticity in effective treatment of depression with ECT.

we will use high-resolution fMRI methods to assess changes in structural and functional properties of hippocampus after ECT that have not been investigated in previous studies at ultra-high resolution with this combined approach. The project is also clinically significant in understanding the mechanism behind ECT as well as the role of hippocampus integrity in depression and its treatment.

Department: Psychology

Award Value: Reduced Scanning Rate, allowing an increased sample size

The goal of this project is to investigate the neural circuits implicated in regulating distance to social and non-social threats. Keeping an appropriate distance from our surroundings is a defensive mechanism that helps prevent injuries. Prior work from our lab has demonstrated that regions associated with threat processing (e.g., amygdala) respond preferentially to approaching versus receding facial expressions and are associated with regulating the distance from those expressions. However, it is unclear whether this reflects a broader defensive mechanism or is specific to socially relevant information, such as facial expressions. In this study, we will use structural and functional MRI and connectivity analysis to characterize the neural processes implicated in regulating the distance to social versus non-social stimuli.

It involves the combination of brain imaging with novel behavioural paradigms to examine basic defensive processes and their influence on social behavioural. Improving our understanding of these processes will contribute to enhance our knowledge about the pathophysiology and potential treatment of disorders associated with abnormal threat responses.

Department: Psychiatry

Award Value: Reduced Scanning Rate, allowing an increased sample size

This project will study the brain processes that result in thought and language disorder and influence outcomes seen in patients with schizophrenia using a combination of brain scans and clinical assessments. The project will assess patients at various stages of psychosis [first episode and chronic stage (3 years) of illness referred to the Prevention and Early Intervention in Psychosis Programme using Magnetic Resonance Imaging (MRI scans). To track the outcome of this illness, investigators will follow-up patients over 3 years and collect MRI scans over four sessions for each patient. Participants will also complete a clinical assessment examining symptoms and functioning as per the current clinical practice within the PEPP program. In this study, we will use glutamate fMRS, myelin mapping techniques and diffusion imaging along with a perceptual paradigm (auditory interference) to relate auditory signal processing with thought disorder in psychosis and glutamate levels.

It involves collaboration between basic scientists and clinical data from a real-world setting. Improving our understanding of brain processes underlying these symptoms of psychosis will enhance our knowledge about the pathophysiology of thought disorder and provide clinical insights to inform treatment practices. Specifically using functional glutamate MR spectroscopy, we will get insights into the cognitive neurochemistry of stroop test in both health and disease state.

Department: Neuropsychiatry

Award Value: Reduced Scanning Rate, allowing a more diverse population size

This study is to investigate how the brain might function differently and be structured differently in people experiencing different subtypes of Post-Traumatic Stress Disorder (PTSD). The dissociative subtype of PTSD is characterized primarily by symptoms of derealization (i.e., feeling as if the world is not real) and depersonalization (i.e., feeling as if oneself is not real) and the dissociative subtype of PTSD contrasts with the majority of cases of PTSD where re-experiencing and hyperarousal symptoms predominate. To date, no work has sought to identify specifically the underlying neural, cognitive and physiological changes that may mediate the increased treatment resistance and heightened functional impairment observed among this newly identified population. Identifying the underlying mechanisms that decrease treatment response and contribute to continued illness in the dissociative subtype of PTSD will be very important in developing effective treatment interventions for this newly identified patient group.

It involves the use of imaging and psychological assessments to assess patterns of brain functioning and cognition and look at important brain areas used for attention, executive functioing and higher cognitive processes.

Department: Neuropsychiatry

Award Value: Reduced Scanning Rate, allowing an increased sample size

The current project aims to provide initial empirical evidence to substantiate the neural mechanistic underpinning of an innovative model of Post-traumatic stress disorder (PTSD) and its recently described dissociative sub-type. This model posits the basic role of anomalous bodily experiences such as feelings of misrepresentation of body parts and out-of-body experiences, in underpinning impairment of high-cognitive processes characterising PTSD and its dissociative subtype, such as traumatic memory retrieval and self-identity.

The specific aim of the current project is to define for the first time in humans the spatiotopic organization of the representation of the human body in one powerful subcortical structure engaged in sensorimotor transformations, the superior colliculus. Animal studies robustly demonstrated that the superior colliculus plays an essential role in the representation of the animal's body, relating it to a multisensory representation of the external world, enabling in this way the computation of a motor program integrating the represented body and the external world.This study will employ the most novel methods of image acquisition in ultra-high field 7T MRI to determine the spatiotopic maps of the human body in the superior colliculus in healthy individuals, PTSD patients, and PTSD sub-type dissociative patients. Moreover, the acquired structural images will allow the implementation of a morphometry study in agreement with the most updated methods of morphometric studies of the brainstem, aiming to determine the existence of differences in superior colliculus' volume between the three participants' groups.

Department: Psychiatry

Award Value: Reduced Scanning Rate

Late-life depression (LLD) affects 2-8% of adults 60 years of age or older. It has high health and economic costs including increased mortality caused by cardiovascular episodes and the leading cause of suicide. A critical barrier to the effective treatment of LLD is an inadequate understanding of the biological mechanisms underpinning this disease. Evidence suggests a role for oxidative/nitrosative stress in psychiatric disorders; the resulting reactive oxygen/nitrogen species can damage healthy cells and tissues particularly when antioxidant defense mechanisms are impaired. MDD has been associated with reduced antioxidant capacity and it has been suggested that this may be a state marker for depression. Because aging is associated with inflammation, these pathways may be particularly relevant for LLD.

However, the aetiology of LLD, and the role of inflammation and associated oxidative damage in this disease, remains poorly understood. Glutathione (GSH) is a key antioxidant important for protecting cells against oxidative stress, particularly in the brain; a limited, though growing, body of evidence suggests that GSH dysfunction may play a role in depression.

Department: CNS

Award Value: Reduced Scanning Rate

Recent studies including our own suggest that different cognitive functions are mediated by ventral and dorsal striatum. Our aim is to identify the unique role that ventral and dorsal striatum perform in cognition, independent of those mediated by their structural and functional cortical partners, using fMRI and in healthy volunteers as well as in our patients. We also aim to understand how striatal dysfunction of various forms (i.e., biochemical in PD and structural in lesion patients) and dopaminergic therapy affect activity in the different brain circuits that implicate ventral and dorsal striatum respectively.

Measuring resting brain activity and activity correlated with certain tasks and conditions using fMRI, we will investigate the cognitive functions mediated by ventral and dorsal striatum by contrasting performance of patients with a) ventral and dorsal striatal lesions, b) neurological and psychiatric disorders that might implicate the striatum (e.g., multiple sclerosis, epilepsy, migraine, OCD/anxiety, depression, schizophrenia, ADHD and addiction), and c) Parkinson's disease at early (i.e., < 5 years) and late disease stages (i.e., > 5 years) on and off dopamine-replacement medication, relative to healthy age-matched controls.