Applied Cognitive Neuroscience of Brain Plasticity
Poster #301: Bruna de Souza
Title: Developmental axonal swellings depend on action potential propagation signalling
Abstract: Axonal development is crucial for the proper formation of functional brain circuits. Myelination is an important part of this process ensuring high-fidelity saltatory conduction of action potentials. We have previously demonstrated that axonal swellings appear transiently on cerebellar Purkinje cell during postnatal development in mice and improving action potential propagation fidelity in those axons. Thus, suggesting an enhancement of cerebellar function. Since myelination occurs concurrently with the transient axonal swellings, we wondered whether they were functionally involved with formation and retraction of axonal swellings. Using immunofluorescence, we found that at postnatal day (P)11, when axonal swellings density peaks, over 50% of swellings were myelinated. Interestingly, most swellings were in close contact with immature oligodendrocytes processes. Next, we depleted oligodendrocytes precursor cells with injections of 5-azacytidine (5ug/g) from P6 to P15. Although the number of immature oligodendrocytes was reduced at P11, the total number of axonal swellings was not affected. However, extending the treatment to P15, when the axonal swellings density has decreased, resulted in higher density of axonal swellings and decreased myelin. These results suggest that oligodendrocytes that are myelinating Purkinje cell axons are not involved in the formation of axonal swellings but are required for their pruning. This argues that the presence of axonal swellings may occur during a critical period when axonal propagation is especially vulnerable while axons undergo myelination.
Poster #302: Cathy Chen
Title: Quorum sensing in human social perception: Effects of cognitive load.
Abstract: Following gaze direction from a single individual is often spontaneous, but in groups, the number of consistent gaze cues needed to elicit similar behavior varies with group size. In small groups, a minority of consistent cues, i.e., 1/3 cues can facilitate gaze following while in large groups a majority of consistent cues, i.e., 2/3 cues are needed for the same behavior. One explanation derives from evolutionary biology whereby many animals use the so-called quorum sensing, or act when a relevant proportion of conspecifics from the group performs the same behavior. This is purported to allow for the quick choice of optimal behavior without intensive cognitive involvement. Thus, increases in task’s cognitive load should promote quorum sensing. To examine this, we asked 50 participants (preregistered N=151) to identify a peripheral target which appeared at the location indicated by 0, 1, 2, or 3 consistent gaze or control arrow cues. To increase the cognitive demand, in half the trials, participants also completed a simultaneous working memory task. As expected, preliminary results show that participants responded overall slower under working memory load condition and were overall faster to respond to targets as cues’ spatial consistency increased. For gaze, a minority of cues, i.e., one cue indicating the target was sufficient to elicit gaze following demonstrating quorum sensing; for arrows a majority of consistent cues were needed for the same effect. Thus, so far the data suggest that increased cognitive load does not appear to alter quorum sensing in humans.
Poster #303: Cong Loc Dang
Title: Synaptopodin: A novel therapeutic target for treatment of ASD
Abstract: Autism Spectrum Disorders (ASD) is a heterogeneous group of neurodevelopmental disorders accounting for 1% of the world population and currently has no cure. Evidence shows that ASD-related genes play roles in synaptic function, suggesting that targeting synaptic proteins could potentially be a therapy for ASD. With over 800 genes associated with ASD, developing therapeutics for each is impossible. Therefore, identifying shared molecules in ASD is a promising approach. We propose an actin associated protein Synaptopodin (SP) as a possible novel therapeutic target for treatment of ASD. SP is found in excitatory synapses in limbic brain regions. Our lab has previously reported that SP is required for Hebbian plasticity as well as learning and memory. We recently found that there are changes in the hippocampal SP levels in the Fragile X Syndrome autistic model, Fmr1-/y mice, and Tuberous Sclerosis Complex autistic model, Tsc2+/- mice. Hence, we hypothesize that changes in SP levels during development lead to aberrant synaptic connections and consequently result in autistic traits. To address this hypothesis, we first investigated if the loss of SP is sufficient to induce ASD behaviors. By using mouse behavioral studies, my results indicate that by knocking out SP, these mice display significant autistic traits including repetitive behaviors, higher anxiety and social interaction deficits. Taken all results together, we anticipate that SP could a shared molecule in ASD’s pathology and thus, opens up a novel avenue for potential therapeutic target for multiple forms of autism.
Poster #304: Dasha Vanichkina
Title: Binocular and Monocular Reading in Lazy Eye
Abstract: Introduction: Amblyopia (lazy eye) is a condition where visual information from one eye is improperly processed in the brain, disrupting binocular combination. It has been shown that reading skills are altered in amblyopia with individuals having slower reading speeds and different eye movement patterns. In our experiment, we compared the brain activity of controls and amblyopes using random temporal sampling. Goal: Our goal was to investigate whether there are differences between controls and amblyopes in reading efficiency along the temporal sampling domain. Methods: To quantify reading efficiency, we used random temporal sampling (RTS) at an accuracy level of 50%. RTS is a method of indirectly measuring neural activity. The data was collected using a four-alternative forced-choice task. The target that we used in each trial was one of 800 three-to-six-letter words which were equally divided into four categories. In every trial, participants had to read the presented word as varying levels of noise impeded their reading and sort the word into one of four categories. Results: We found that controls read more efficiently than amblyopes and were most efficient in the binocular condition. Amblyopes were unexpectedly most efficient when reading with their weaker, amblyopic eye. As predicted, amblyopes struggled the most when reading binocularly. Conclusion: In conclusion, our results indicate that the reading patterns of controls and amblyopes differ in meaningful ways, which may be partially explained by differences in neural activity. These results have implications for the development of treatments for amblyopia that specifically target brain activity.
Poster #305: Emmanuel Olarewaju
Title: Beyond the Individual: A Second-Person Neuropsychiatric Approach to Social Dysfunction in Schizophrenia
Abstract: Social dysfunction is a core feature of mental disorders, particularly schizophrenia. This dysfunction arises from disorganized interpersonal interactions that characterize the social behaviour of affected individuals. Traditionally, researchers have studied disorganized verbal and nonverbal communication as the product of hidden cognitive processes (‘private mind’) and attributed dysfunction to the brain afflicted by the illness (‘brain-bound mechanisms’). However, despite extensive research efforts, the prevailing approach to psychiatric disorders, which relies on individual-based methods—such as analyzing biological factors (e.g., brain structure alterations) and subjective assessments (e.g., clinical evaluations)—remains inadequate for measuring or addressing persistent social dysfunction. The emphasis on individual-centric metrics has not yielded clarity or effective treatments because it cannot account for the interpersonal determinants of mental health. This research hypothesizes that disorganization arises from disruptions in bio-behavioural synchronization within the interpersonal space, where shared mental processes (‘social mind’) are co-constructed through interaction. This interpersonal space is dynamically shaped by alignment and timing, enabling precise measurement of bio-behavioural and psychosocial processes within individuals and across interactions. This study employs a multimodal approach, integrating face-to-face imitation tasks, DeepLabCut pose estimation for behavioural coding, NLP for speech analysis, and electroencephalography (EEG) hyperscanning, which captures real-time neural activity from interacting participants. This methodology is applied within a second-person neuropsychiatric framework, positioning disorganization as a problem of interpersonal (attention and inhibitory) processing. This approach offers novel insights into the mechanisms of social dysfunction, with the potential to inform advancements in personalized diagnostic and treatment strategies for schizophrenia and other mental health disorders.
Poster #306: Franziska Mudlaff
Title: Heterogeneity in endocannabinoid-mediated short-term plasticity in the cerebellum is lost in a mouse model of Fragile X syndrome.
Abstract: The cerebellum is characterized by a uniform cytoarchitecture, while displaying a region-specific functional diversity. This diversity serves to support a range of motor and cognitive behaviors, which require both short- and long-term plasticity. Heterogeneity in long-term plasticity in functionally distinct lobules has previously been described; however, short-term plasticity (STP) has not been investigated yet. STP at parallel fibers to Purkinje cell synapses is mediated by endocannabinoid retrograde signaling and subsequent binding to the presynaptic cannabinoid receptor 1 (CB1R). CB1R displays a heterogeneous expression across anterior and posterior lobules, yet the effect of this heterogeneity on STP remains unknown. In Fragile X Syndrome (FXS), deviations in endocannabinoid-mediated plasticity have been described in forebrain regions. Cerebellar deficits in FXS are prevalent, including enhanced long-term plasticity, however, it remains unknown whether endocannabinoid-mediated STP is affected as well. To assess endocannabinoid-mediated STP at parallel fiber to Purkinje cell synapses in functionally distinct lobules, we combined whole-cell recordings of Purkinje cells from acute cerebellar slices of wildtype and Fmr1 knockout mice of both sexes with biochemical analysis of the endocannabinoid signaling pathway. Whole-cell recordings of wildtype mice suggested a disparity in STP strength across different lobules. This observation is paralleled by heterogeneous expression of key players of the endocannabinoid signaling pathway. In Fmr1 knockout mice, a reduction in overall strength and loss of the lobular heterogeneity was observed. Together, we provide evidence of a previously unelaborated regional heterogeneity of endocannabinoid-mediated STP in the cerebellum, which seems to be compromised in a mouse model of FXS.
Poster #307: Haleigh Bach
Title: Effects of Critical Window Hyperexcitation on Juvenile Rodent Social Behaviour, Cortical Excitability, and Interneuron Formation
Abstract: The neuronal excitation to inhibition ratio (E/I ratio) is crucial in forming and fine-tuning circuitry that dictates behaviour throughout life. This includes the medial prefrontal cortex (mPFC) circuitry involved in modulating social behaviour that is altered in Autism Spectrum Disorder (ASD). Many genetic mouse models of ASD display increased cortical excitability and reduced parvalbumin interneuron (PVIN) density. While altered sociability and E/I balance are well-characterized aspects of ASD, few studies have causally linked them. We address this gap by determining if chemoconvulsant stimuli during a defined critical period of development can alter sociability and the E/I ratio. First, we assayed sociability in mice administered with non-convulsive (30mg/kg) and minimally-convulsive (50mg/kg) doses of the GABAA receptor antagonist pentylenetetrazol (PTZ) from postnatal days 8 to 11. Both groups exhibited impaired social behaviour evaluated 3 weeks after the drug administration, however, only the 50mg/kg treatment led to decreased mPFC sEPSC frequency. Interestingly, the 30mg/kg group displayed increased mPFC PVIN density with the 50mg/kg group currently being quantified. Our data thus far indicates a non-convulsive increase in neuronal activity alters sociability and PVIN formation. Additional work will determine if modulating mPFC excitability during this critical window is sufficient to alter social behaviour through the development of a novel optogenetic model involving transverse sinus injections and transcranial optostimulation.
Poster #308: Hannah Derue
Title: Artificial Intelligence Based Visual Journaling Tools for Chronic Pain
Abstract: Chronic pain conditions influence an estimated 19% of Canadians. Of this significant population, a majority express dissatisfaction with existing treatment options, and only 2% of those impacted access specialized care through a pain clinic. With a rapidly aging demographic, the population of individuals living with chronic pain conditions is projected to grow 17.5% from 2019 to 2030. Due to the increasing demand for solutions to manage the personal, societal, and economic impacts of chronic pain conditions, there has been growing attention towards the potential uses of artificial intelligence (AI) algorithms. This includes machine learning and large language models to predict a patient’s condition trajectory or to streamline diagnosis for those living with chronic pain conditions. However, remarkably little attention has been directed towards the potential use of AI platforms for therapeutic interventions within the context of chronic pain conditions. To address this critical need, we have developed novel AI-supported web-based programs that assist patients in generating and exploring visual representations of their chronic pain to aid in communication with their clinicians and members of their communities. Using the clinical expertise of pain physicians, alongside the machine learning expertise of computer scientists on our team, and the assistance of the HBHL Pre-IGNITE grant, we have created AI-supported imagery-based digital self-expression tools that expand on the existing known benefits of art therapy for chronic pain conditions while overcoming existing barriers to arts-based therapeutics.
Poster #309: Hossein Jomleh
Title: Role of Sildenafil in Neonatal Brain Metabolite Recovery After Hypoxic-Ischemic Injury
Abstract: Background: Birth asphyxia and hypoxic-ischemic encephalopathy (HIE) are leading causes of mortality and disability. Therapeutic hypothermia (TH), the only treatment in high-income countries, is often ineffective in low- and middle-income countries and does not promote repair. Treatments like enteral sildenafil, are needed to support brain recovery. Objective: Assessing neuronal-health-related brain metabolites in healthy neonates and HIE neonates treated with TH+/-sildenafil during the first month of life. Methods: Prospective neuroimaging study involving healthy neonates and neonates with HIE treated with TH. A subset of HIE neonates with brain injury despite TH received sildenafil from Day 2 to 9. Brain MRS were performed on days of life (DOL) 2, 10 and 30. We compared N-acetyl aspartate (NAA) concentration and NAA/Creatine (Cr) ratio in thalamus in neonates without injury (NoBI), HIE neonates with brain injury treated only with TH (BI+TH), and with brain injury treated with TH and sildenafil (BI+TH/S). Results: 229 MRI scans were obtained from 12 healthy, 54 NoBI+TH, 37 BI+TH, and 19 BI+TH/S neonates. By DOL10, both brain injury groups showed significant reductions in NAA concentration and NAA/Cr ratio. Reductions persisted in the BI+TH group by DOL30, while the BI+TH/S group’s values were no longer significantly different from the NoBI group. By DOL30, the BI+TH/S group also had higher NAA/Cr ratios than the BI+TH group. Conclusion: NAA concentration and NAA/Cr ratio were reduced in HIE neonates despite TH. Sildenafil appeared to promote recovery of both the concentration and the ratios.
Poster #310: Jessica Savoie
Title: The Brain on Gaze: Attending to Social and Symbolic Cues in Groups
Abstract: Gaze following is a spontaneous human behaviour but varies with group size. In small groups of three, a minority of consistent gaze cues facilitates gaze following, while in larger groups of five, a majority of consistent gaze cues is needed for a similar effect. Here, we investigated whether gaze following elicited by minority consistent gaze cues was unique to social gaze stimuli. The participants were presented with a group of three (E1) or five (E2) faces, and visually matched directional arrows which served as non-social control stimuli. They were asked to respond to a target letter indicated by 0, 1, 2 or 3 consistent gaze or arrow cues (E1) or by 0, 1, 2, 3, 4 or 5 consistent gaze or arrow cues (E2). In Experiment 1, we found overall faster response times when gaze served as stimuli. Across both cue types, however, responses were facilitated similarly by increasing cue consistency. In Experiment 2, no overall speeding up of responses occurred for social cues. Interestingly, while responses were reliably facilitated by one, two, and three consistent cues for social gaze, the effect plateaued between 3 and 4 consistent cues. For arrows, response time facilitation followed a linear decreasing trend with increased cue numerosity. These results show that both minority and majority of social and nonsocial consistent cues can facilitate responses, and that evaluation of social information in groups may partially depend on directional information conveyed by these cues rather than their social content alone.
Poster #311: Jhelum Paul
Title: Cortico-kinematic and cortico-muscular plasticity during motor sequence learning
Abstract: Cortico-kinematic Coherence (CKC: cortex-proprioception) and Cortico-muscular Coherence (CMC: cortex-muscle coherence) are used to investigate interactions between the brain, sensory feedback and muscles during voluntary movements. Previous work has primarily focused on simple isometric tasks (grip task) while most movements are continuous, requiring dynamic sensorimotor integration. We investigated how the frequency and magnitude of coherence modulate during the performance of unimanual simple (SMP) and complex (LRN) continuous visuomotor sequences. Fourteen right-handed healthy adults performed five blocks of practice (3 trials/sequence/block) in a single session. Coherence was computed with an optimization technique that maximizes the absolute value of coherence between brain and kinematics (force) and brain and surface muscle activity for each sequence at each frequency. CKC was greater between 1 and 16 Hz during LRN compared to SMP, potentially indicating greater reliance on proprioceptive feedback. Interestingly, CKC decreased across blocks for LRN, suggesting reduced proprioceptive reliance as training progressed. We also detected high CMC in the gamma range (30-45 Hz) for SMP and LRN, indicating that amplitude modulation of dynamic force output occurs for both sequences, with no evidence that sequence complexity modulated CMC. This suggests that during dynamic force the sensorimotor integration shifts towards higher frequencies (gamma) to rapidly integrate cognitive, somatosensory and visual information essential to produce the appropriate motor command. Together, our results provide novel evidence indicating that CKC and CMC provide complementary information and play an important role in orchestrating and optimizing complex continuous movements, potentially serving as a biomarker for motor learning and plasticity.
Poster #313: Jiaxuan Deng
Title: Transdiagnostic neurocognitive mechanisms underlying HiTOP spectra dimensions and functioning in youth at risk for mental illness
Abstract: Psychiatry research is shifting towards a transdiagnostic perspective. The Hierarchical Taxonomy of Psychopathology (HiToP) model groups psychiatric symptoms into emotional dysfunction and psychosis spectra. Psychiatric conditions often influence individuals’ cognitive and functioning abilities associated with aberrant brain functional connectivity, specifically within and between the three large-scale functional brain networks (i.e., central executive network [CEN], default mode network [DMN], and salience network [SN]). This research aimed to fill the literature gap on how these brain, cognitive, symptoms, and functioning transdiagnostic dimensions were associated in adolescents at risk for mental illness. Baseline data from the ABCD study was used. Adolescents were considered at risk if their first-degree relatives had a psychiatric hospitalization history (n = 1,059). Pearson r correlations and multivariable logistic regressions were performed, controlling for age and biological sex. Cognition had significant positive correlations with DMN-DMN and DMN-CEN connectivity. Psychosis symptoms showed a significant negative and positive relationship with cognition and emotional dysfunction, respectively. Social functioning was significantly predicted by cognition. Transdiagnostic factors previously identified in patients were also seen in at-risk youth. DMN-DMN and DMN-CEN connectivity were related to at-risk youths’ cognition, which was associated with social functioning. These findings demonstrate a potential transdiagnostic neurocognitive mechanism underlying the psychiatric risk in adolescents from altered DMN connectivity to cognition and social functioning. Future research is needed to examine this possible mechanism longitudinally and identify early transdiagnostic neural and cognitive markers, which may facilitate more accurate early detection and more effective early interventions, given the superior brain plasticity during adolescence.
Poster #314: Maeva Gacoin
Title: Neurodevelopment of the frontoparietal network underlying social interactions in common marmosets
Abstract: Primates navigate complex social environments through cooperative and competitive behaviors. Disruptions in these dynamics may signal neurodevelopmental disorders like autism. The common marmoset, a small primate living in family groups, shares social skills with humans. Its rapid development and reproductive rate make it ideal for studying social cognition. This project examines social cognition in marmosets using advanced imaging (functional and structural MRI) and behavioral tasks. Four marmosets were scanned every three months from 9 months onward, with plans to continue through adulthood. Behavioral assessments using touchscreen and eye-tracking tasks evaluated social categorization and gaze preferences. Preliminary results show increased cortical myelination and strengthened frontoparietal connectivity with maturation. Hierarchical interactions strongly activate the amygdala, while affiliative behaviors elicit minimal response. By adulthood, we expect clearer differentiation in brain activity patterns by relationship type. This research enhances understanding of marmoset social mechanisms and supports their use as a preclinical model for autism.
Poster #315: María José Castro-Gómez
Title: Diffusion Tensor Imaging Detects Early Microstructural Changes Linked to Neurodevelopmental Outcomes in Neonates with Hypoxic-Ischemic Encephalopathy treated with Therapeutic Hypothermia
Abstract: Background: Hypoxic-ischemic encephalopathy (HIE) leads to significant brain injuries and long-term neurodevelopmental impairments. While therapeutic hypothermia (TH) is the standard treatment, up to 29% of treated neonates still experience neurological complications. Diffusion tensor imaging (DTI) provides insights into brain microstructure and its association with neurodevelopmental outcomes in neonates with HIE treated with TH (HIE-TH). This study examined the relationship between DTI metrics and neurodevelopmental outcomes in HIE-TH neonates. Design/Methods: In this prospective study, neurodevelopmental outcomes—cerebral palsy (CP), global developmental delay (GDD), and epilepsy—were assessed at 2 years. Participants were classified into no adverse outcome (noAO) and adverse outcome (AO) groups. MRI scans were performed on days 2, 10, and 30 of life, measuring fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in seven brain regions. Generalized linear models, adjusted for gestational age and MRI timing, compared DTI metrics between groups. Results: Among 81 participants (49 noAO, 32 AO) with 154 MRI scans, FA values were similar between groups on day 2. By days 10 and 30, FA values were significantly lower in AO neonates in the PLIC, thalamus, lentiform nuclei, anterior white matter, and splenium (e.g., PLIC day 10: noAO 0.47±0.03 vs. AO 0.42±0.05, p<0.0001). ADC values showed no significant differences. Conclusion: FA detects early microstructural impairments in HIE-TH neonates developing adverse 2-year neurodevelopmental outcomes, highlighting its potential as an early biomarker for intervention.
Poster #316: Megan Sholomiski
Title: Mapping Cerebellar Activation During Motor Learning Based on Immediate Early Gene Expression
Abstract: The cerebellum exhibits functional heterogeneity, yet the specific regions and neuronal populations recruited during distinct behaviours remain largely unknown. This research maps patterns of activation within the cerebellum to better understand how its functional roles are reflected in its non-uniform lobular architecture. Drawing on the framework of immediate early gene (IEG) activation as a molecular marker, we identified the cell populations across specific lobules that underlie the cerebellum’s responsiveness to motor stimuli and learning, providing a foundational analysis of its patterns of activation. First, mice were exposed to the accelerating rotarod task, a form of cerebellum-dependent motor learning, then their cerebella were extracted and immunostained for cell type and lobule-specific analysis of the expression patterns of c-fos, an IEG. Two versions of this task were applied: one following the standard method in which naïve mice were introduced to the task, and one in which the mice were habituated to the apparatus before testing. We then assessed how these activation patterns changed in response to learning. Next, in order to identify changes in IEG expression in the cerebellum over time, TRAP2 mice were exposed to a multi-day motor learning paradigm in which c-fos expression was labeled on day 1, then immunostaining was used on the final day of learning. By mapping cerebellar activation, these experiments bridge the gap between behaviour and cerebellar function, providing a foundation for future studies on how motor learning shapes the properties of neurons while also offering broader insights into the functional organization of the cerebellum.
Poster #317: Melissa Pestemalciyan
Title: Constitutive Targeting to the Autophagosome May Limit Netrin-3 Secretion
Abstract: Although netrin-1 is essential for normal neural development, its close paralogue, netrin-3, has remained largely unstudied. Like netrin-1, netrin-3 is expressed by neurons in the developing and adult CNS. Compared to netrin-1, netrin-3 expression has a more restricted distribution and begins later in embryogenesis. Recent findings have identified de novo single nucleotide mutations in the coding sequence of human netrin-3 in individuals with developmental intellectual disorder and features of autism. We are investigating the hypothesis that these mutations disrupt netrin-3 function, affecting neural development. The literature considers netrin-3 to be a functionally equivalent netrin-1 paralogue. In contrast, my studies identified substantial differences between the two proteins. Secretion of netrin-3 appears to be limited compared to netrin-1. Immunolabeling of cells double-transfected to express ectopic netrin-1 and netrin-3 show the two proteins localized to different subcellular compartments. Furthermore, subcellular fractionation provides evidence that secretion of mutant netrin-3 proteins is severely compromised, consistent with loss-of-function. However, the intracellular trafficking and ultimate destinations of wild-type and mutant netrin-3 proteins remain unclear. Preliminary data suggests netrin-3 may be degraded by the autophagosomal-lysosomal pathway. Ongoing studies are investigating the cellular half-life and secretory processing of netrin-1 and netrin-3 to determine how disruption of its function may contribute to neurodevelopmental disorders like ASD.
Poster #318: Mohammed Noor (Trainee Flash Talks)
Title: A combinatorial strategy targeting multiple microRNA clusters identified in an intraocular inflammation model promotes significant axon regeneration and outgrowth.
Abstract: Axons within the central nervous system (CNS) fail to regenerate following injury, largely due to the developmental loss of intrinsic regenerative capacity. Numerous individual gene knockdown events have yielded modest regenerative outcomes. Although combinatorial strategies tend to be more effective, modulating multiple genes simultaneously within the same cell is difficult. As such, we aimed to identify pro-regenerative microRNA (miRNA) clusters that target overlapping genes, thereby enhancing their inhibitory effects and concurrently regulating large gene programs to facilitate neuronal intrinsic outgrowth and regeneration in the Pam3cys pro-regenerative intraocular inflammation model. We employed a multimodal sequencing approach, incorporating both RNA and miRNA sequencing of fluorescently activated cell-sorted retinal ganglion cells (RGCs) following Pam3cys intraocular inflammation. The integration of our sequencing data revealed that the target genes of miR-96 and let-7 clusters were significantly enriched under regenerative conditions compared to the control. Subsequent functional validation utilizing a multi-miRNA construct, comprising both the miR-96 and Let-7 genomic clusters, resulted in substantial axon regeneration and neurite outgrowth both in vitro and in vivo. These results demonstrate that the targeting of miRNA genomic clusters promotes robust intrinsic regeneration in neurons. Our findings reveal a novel synergistic role for miRNA clusters in facilitating regeneration, representing a previously unrecognized axis of miRNA-mediated neuronal repair and offering promising potential therapeutic targets for CNS injuries.
Poster #319: Prakriti Gupta (Trainee Flash Talks)
Title: Closed-Loop Targeted Memory Stimulation During Sleep Spindles Optimizes Motor Memory Consolidation
Abstract: Sleep plays a critical role in motor memory consolidation by enabling memory trace reactivation during non-rapid eye movement (NREM) sleep spindles. This study provides direct evidence by employing real-time closed-loop auditory stimulation during spindles using the deep learning-based Portiloop EEG device, combined with a Targeted Memory Reactivation (TMR) paradigm. Thirty right-handed young adults completed a modified Motor Sequence Learning (MSL) task involving two distinct 8-element finger sequences, each paired with a specific hand and sound. The sound associated with one sequence was replayed during spindles (TMR condition), while the other sequence served as a control (non-TMR). Participants underwent training, pre- and post-sleep tests in a 3.0T MRI scanner, with overnight auditory stimulation administered in a sleep lab. Behavioral results showed enhanced motor performance post-sleep, with a significantly greater Percentage Change in Duration for Correct Sequences (PCD-CS) in the TMR condition compared to non-TMR. Furthermore, the percentage of stimulated sleep spindles (true positives) positively correlated with the TMR effect (difference in PCD-CS between conditions), indicating that more effective spindle stimulation led to greater performance gains. Notably, stimulation of spindle trains (two or more spindles occurring within 6 seconds) was positively correlated with the TMR effect than isolated (more than 6 seconds apart) spindle stimulation. These findings highlight the critical role of spindle activity in sleep-based memory enhancement and suggest that targeted spindle train stimulation could serve as a non-invasive approach to boost motor memory consolidation, with potential therapeutic applications for age-related or neurodegenerative conditions.
Poster #320: Ruchira Dasgupta
Title: The social brain: How distance between group members influences perception of social groups
Abstract: Human perception is highly attuned to social groups, particularly for groups in facing configurations (i.e., individuals facing toward one another), suggesting high perceptual sensitivity to social interactions. In real life, the distance between group members is also an important determinant of group behaviour, as we engage with others at various interpersonal distances (i.e., intimate, personal, social, and public) for different social reasons. Here, we investigated if our perception was also sensitive to social distances between group members. 163 participants completed an online experiment in which they searched for facing or non-facing groups of two or three individuals, with their members positioned at personal or public distances. Participants were asked to locate the target quickly and accurately by reporting its left or right location on the screen. The results indicated that overall facing groups were found faster than nonfacing groups, and that groups of two were found faster than groups of three. Most importantly, facing groups of two were found the fastest (relative to nonfacing groups of two) when members were positioned at personal relative to public distance, while facing groups of three (relative to nonfacing groups of three) were found equally fast in the two interpersonal distance conditions. These findings show that aside from facing configuration, human perception is also sensitive to the interpersonal distance between group members, highlighting the nuanced perceptual sensitivity of our neurocognitive system to social structures.
Poster #321: Shima Yaghoubian
Title: Decreased Functional Dynamics with fMRI as a Biomarker of Aging
Abstract: Aging is hypothesized to reshape brain activity through disruptions in coordinated temporal dynamics. These disruptions are reflected in changes to the long-range temporal stability in resting EEG and fMRI (i.e., their functional dynamics). The Hurst Exponent (HE) assesses temporal stability by quantifying the degree of temporal self-similarity in time series, with higher values indicating more predictable/structured activity, and lower values indicating increased randomness (i.e., structured vs noisy functional activity). To understand normative changes in the brain’s functional dynamics over the course of aging, we used detrended fluctuation analysis to quantify HE across the brain in resting state fMRI data from 750 healthy adults aged 36- 100yrs. Aging was significantly correlated with decreased HE both globally and (most strongly) in regions critical for executive function (including inferior and middle frontal gyri, insula, precuneus) (fwe-p <0.05). Atlas-based analyses confirmed these results, even after controlling for potential cognitive and educational confounds. Our findings suggest that diminished temporal regularity in functional dynamics is a potential biomarker of aging, particularly within regions linked to executive function, aligning well with prior work in fractal dynamics and connectivity. Decreased HE may reflect accumulated neural noise or synaptic inefficiency, though mechanistic interpretation requires further work. Our findings illustrate HE’s sensitivity to aging-related changes and highlights its potential as an aging-related biomarker for monitoring normative and disease-related alterations in brain function.
Poster #322: Siyu Long
Title: Age-Related Changes in Beta Burst Onset Timing and Spatial Dynamics During Motor Task
Abstract: Introduction: Beta-band power recorded using magnetoencephalography (MEG) originates from beta-band bursts, which are known to be associated with motor inhibitory control and voluntary movements (Little & Brown, 2014). Importantly, burst onset timing relative to movement execution impacts motor performance (Diesburg et al., 2021). With aging, these bursts exhibit altered spatial distribution across cortical regions, particularly the frontal ones (Power & Bardouille, 2021). Examining the timing variations of bursts throughout aging may elucidate mechanisms underlying age-related motor function changes. Methods: The dataset comes from the Cam-CAN repository, comprising MEG signals from 608 participants aged 18-88 years performing a finger-tapping task. MEG signals were segmented into epochs 1.4 seconds before/after movement onset. Source localization was applied to project the MEG activity onto the cortical surface. Beta bursts were extracted using the 75th percentile threshold in each epoch. For each segment, burst onset time was defined as the first timepoint of burst occurrence. Results: With advancing age, beta burst onset timing occurred significantly earlier during the pre-movement (p<0.001), while post-movement onset timing was significantly delayed (p<0.001). Across all age groups, beta bursts emerged earlier during the pre-movement phase in motor regions, followed by visual areas, and lastly in frontal regions. This spatiotemporal pattern was reversed during the post-movement phase, with beta bursts appearing first in frontal regions, followed by visual and motor ones. Conclusion: Our findings demonstrate that aging is associated with prolonged temporal dynamics for motor initiation and post-movement processes. Additionally, this motor modulation demonstrates spatial specificity across different cortical regions.
Poster #323: Vasvi Dhir
Title: Gender-Sensitive Facilitators and Barriers to Participation in Observational Neurocognitive Aging Research in Older Adults: A Fuzzy Cognitive Mapping Approach
Abstract: Gender selection bias erroneously regards research participants with different gender identities as similar/different. Neurocognitive aging research is largely subject to this bias given that study samples often overrepresent White, well-educated, women living in less socioeconomically deprived areas. This biased representation raises cardinal concerns about health equity and discrimination in neuroscientific endeavours. Objective: To identify gender-sensitive barriers and facilitators older adults perceive when considering participation in observational neurocognitive aging research. Methods: We employed a participatory research methodology, called fuzzy cognitive mapping. We discussed with participants from diverse groups on what they perceived as factors hindering or encouraging their involvement in research. We standardized the factors across participants and organized them in a causal network. The factors were aggregated into categories through inductive analysis. We computed measures of centrality to determine categories perceived as causes and those as outcomes in the causal network. Analyses were operated in a gender-segregated manner. Results: We co-created 24 maps with participants (12 women, 12 men). Our results indicate the shared and distinct factors older women and men perceive when considering participation in brain health research. Both women and men perceived personal traits, quality of communications, logistic considerations, and research-specific practices as influential. Personal experiences was facilitating research engagement for women exclusively, whereas willingness to return benefits to the general population was encouraging for men. This study addressed the lack of diversity and poor representativeness, particularly of older men in neurocognitive aging research samples. Our results suggest gender-sensitive evidence-based recruitment recommendations, supporting equitable and inclusive neuroscience.
HBHL Symposium 