The seventh round of BrainsCAN’s Accelerator Internal Granting Program results have been announced. Six, one-year projects were funded under this round. 

Detecting fine-grained population codes in human prefrontal cortex
Lead applicant: Marieke Mur
Co-applicants: Julio Martinez-Trujillo, Ravi Menon
Budget: $92,847

Cognitive flexibility is the ability to adapt our thoughts and actions to the demands of the current situation. It allows us to solve problems and adjust quickly to changes in our environment. Impaired cognitive flexibility is a hallmark of many neuropsychiatric disorders, including schizophrenia. Brain research has shown that prefrontal cortex plays an important role in cognitive flexibility. However, we do not understand how neurons in prefrontal cortex work together to support cognitive flexibility.

Progress has been hampered by the difficulty of measuring neural population codes in human prefrontal cortex. Population coding refers to the idea that patterns of activity across a population of neurons reflect the contents of our perceptions, thoughts, and actions. Population codes therefore provide a direct window into brain information processing. Standard techniques for measuring brain activity in humans do not have enough resolution to detect population codes in prefrontal cortex.

In this project, we will develop techniques for improving our measurement resolution so that we can gain access to prefrontal population codes. This is essential for understanding how the brain supports higher order cognition, and ultimately, for treating dysfunctions of cognitive flexibility in the clinic.

Development of a Novel Pharmaceutical to Prevent Hearing Loss and Cognitive Impairment following Loud Noise Exposure
Lead applicant: Brian Allman
Co-applicants: Paul Walton, Shawn Whitehead
Budget: $112,560 

Our team seeks to develop a novel pharmaceutical to prevent the permanent damage caused by loud noise exposure. We will evaluate the efficacy of our designer antioxidant, Catalase-SKL, at (1) protecting the delicate sensory cells of the inner ear from the oxidative stress caused by noise exposure, as well as (2) limiting the neuropathology that underlies the cognitive deficits that persist long after noise exposure. Overall, our transformative approach will combine several methodologies, including exosome-based biochemistry and cell biology, in vivo electrophysiology, cognitive-behavioral testing, as well as inner ear and brain histology, to ultimately determine the effectiveness of our novel pharmaceutical at combating noise trauma.

Multisensory stimuli and virtual navigation tasks during intracranial clinical recordings
Lead applicant: Lyle Muller
Co-applicants: Ana Suller Marti, Laura Batterink, Julio Martinez-Trujillo, David Steven
Budget: $98,500

In recent work, we studied the 11-15 Hz sleep “spindle” oscillation, a brain rhythm specifically and causally implicated in consolidation of long-term memory. We found this rhythm — instead of being perfectly synchronized, where individual cortical areas activate and deactivate at the same time — is organized into a diverse range of spatiotemporal patterns. The functional and computational role for this organization of activity, however, remains unknown. Because local neural networks in each cortical area spike in time with this rhythm, these spatiotemporal patterns can allow spikes to link up across areas that are separated by long distances and axonal conduction delays. We hypothesize these patterns may be useful for modulating plasticity between areas during sleep-dependent memory consolidation. To address this hypothesis, we will use novel computational analysis techniques our group has developed for spatiotemporal data to analyze intracranial recordings from human clinical patients at London Health Sciences Centre (LHSC) during post-learning sleep. This research will identify a key neural mechanism for memory consolidation in sleep, deepen our fundamental understanding of cortical dynamics, and may lead to novel mechanisms for modulating consolidation of newly formed memories.

Neuroplasticity during recovery of attentional function after parietal stroke in NHP
Lead applicant: Corey Baron
Co-applicants: Stefan Everling, Ali Khan, Blake Butler, Dan Miller
Budget: $99,625

Two per cent of Canadians live with the effects of stroke, which include impairments to mobility, speech, and cognition. These symptoms are initially debilitating, but patients with mild or moderate symptoms often show substantial recovery in the following weeks and months. While post-stroke outcomes are broadly considered to be related to the intensity of rehabilitation shortly after injury, how these interventions interact with reorganization of damaged brain networks and the underlying biophysical changes remains poorly understood. In an NHP model of stroke recovery, we will utilize functional MRI to determine brain networks that re-organize during recovery and their relation to behavioural outcomes. We will employ new advances in “microstructural MRI” to, for the first time, uncover the time courses of cellular changes that drive the functional changes. These findings will provide new insight into the neuroplasticity - the mechanisms by which the brain learns, or in this case, adapts in response to injury - and how it changes during recovery.

Temporal interference stimulation in NHP
Lead applicant: Brian Corneil
Co-applicants: Lyle Muller, Sebastian Lehmann
Budget: $95,340

Temporal interference (TI) is an emerging non-invasive brain stimulation technique. During TI, electrical stimulation is applied at two different frequencies (F1 and F2) that are both above the physiological firing rate of neurons but where the difference (F2-F1) is in the physiological range. Theoretical and experimental work in lower animal models has shown that TI has the ability to influence neural activity in both surface and subcortical structures. The goal of this accelerator proposal is to apply TI in a behaving higher animal model, with the eventual goal of combining TI targeting deep structures while recording other nodes of an interconnected network. The immediate deliverables for this project are: i) to develop a computational model of TI stimulation optimized to individual subjects and ii) guided by this model, to establish the physiological feasibility of TI in target cortical and subcortical nodes of the oculomotor network that moves our line of sight. While TI offers the tantalizing potential of non-invasive stimulation of deep brain targets, many questions remain regarding its temporal and spatial precision. Preclinical development in higher animal models is required before TI can be deployed in humans.

Unlocking the roles of aging and disease on white matter and neuroplasticity from development to degeneration using simultaneous PET and 129Xe MRI
Lead applicant: Alexei Ouriadov
Co-applicants: Udunna Anazodo, Jonathan Thiessen, Matthew Fox, Justin Hicks, Shawn Whitehead
Budget: $99,400

The use of laser-polarized Xenon-129 as a novel-contrast-agent for MRI has been shown to be effective for functional and structural imaging of the brain and other organs. The original interest of one of the co-inventors was to use 129Xe to better understand the brain, namely directly imaging the effect of anesthesia on brain function and cognition. As a result of over two decades of research and development within the field, both brain and lung imaging have been made possible in animals and humans, and reliable polarizers are now commercially available. 129Xe-based lung imaging is clinically accepted in the UK, and FDA approval in USA is expected this year.

129Xe-based imaging stands to transform our current imaging methods by improving sensitivity over other MRI methods like ASL and reaching beyond the resolution limitations of PET. Methods include: mapping grey and white matter, perfusion, targeted imaging to detect specific neurotransmitters (biosensors), drugs and cell-tracking-techniques. Our research program focuses on leveraging the use and potential of 129Xe MRI of the brain. This will help further understand the roles of aging and disease on white-matter and neuroplasticity at the microstructural-level, during the full scope of its evolution from developmental stages (infancy) to late-stages of degeneration (late adulthood).

For more information about the Accelerator Internal Granting Program, please visit https://brainscan.uwo.ca/programs/accelerator_program/index.html

For more information about past Accelerator results, please see: https://brainscan.uwo.ca/results/accelerator_program.html