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Neuropsychiatry

In This Category of CFMM studies, Investigators are exploring different connections and treatments to the following diseases and syndromes:

Schizophrenia and Psychosis

Schizophrenia is a disorder of the brain that often presents with symptoms of disorganized and psychotic thinking. Psychosis is defined as an alteration in the perception of reality.

Mood and Anxiety Disorders (Depression)

Depression is a highly prevalent mental health disorder characterized by a chronic and persistent feeling of sadness or a loss of interest in previously enjoyable activities. One theory is that depression is a brain disorder that may occur because of an imbalance of neurotransmitters.

Post Traumatic Stress Disorders (PTSD)

Post Traumatic Stress Disorder is a mental health disorder that can occur after a traumatic event, such as a threat to life, serious injury, or sexual violence. Some people who experience these types of events may develop PTSD. Sometimes, PTSD can occur in people who hear about trauma that occurs to a close family member or friend.

Addiction

Causes an uncontrollable ( compulsive ) need for a substance. You can be addicted to alcohol, illegal drugs, or prescription medicines, gambling or shopping. You can also become physically dependent on a substance, can change the way your brain works. These changes, getting more of whatever you are addicted to becomes the most important thing to you and feels better than other activities or relationships. Addiction can lead to changes in health, behavior, emotions, relationships, and choices that affect you and everyone around you.

CFREF BrainsCAN Supported Studies

2019


Peer Study
PI: Bodell, Lindsay

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.

Brain MRI of THA patients comparing MoM to MoP
PI: Morton, Bruce

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.

Assessment of (rTMS) in Schizophrenia Subgroup
PI: Palaniyappan, Lena

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.

2018


Pathophysiology of Thought Disorder in Psychosis
PI: Dr. Akshya Vasudev

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.

Preforming Under Pressure
PI: Mitchell, Derek

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.

Impact of violent gaming on the brain as a function of individual differences in trait empathy
PI: Mitchell, Derek

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.

Hippocampus ECT
PI: Kohler, Stefan

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.

2017


Neural responses to social versus non-social threats
PI: Mitchell, Derek

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.

Pathophysiology of Thought Disorder in Psychosis
PI: Palaniyappan, Lena

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.

The Dissociative subtype of PTSD
PI: Lanius, Ruth

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.

Mapping of the somatotopic representations of the superior colliculus in PTSD
PI: Lanius, Ruth

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.

Pathophysiology of Thought Disorder in Psychosis
PI: Dr. Akshya Vasudev

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.

Distinguishing the roles of ventral and dorsal striatum in cognition
PI: Dr. Penny MacDonald

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.