Poster No:
1330
Submission Type:
Abstract Submission
Authors:
Teresa Cheung1, Matt Courtemanche2, Svenja Knappe3, Isabelle Buard4, John Welsh5
Institutions:
1Fraser Health Authority/Simon Fraser University, Vancouver, Canada, 2Simon Fraser University, Burnaby, Canada, 3Univeristy of Colorado, Boulder, USA, 4Anschutz Medical Centre/University of Colorado, Aurora, USA, 5Seattle Children's Research Institute/University of Washington, Seattle, USA
First Author:
Co-Author(s):
John Welsh, PhD
Seattle Children's Research Institute/University of Washington
Seattle, USA
Introduction:
This study hypothesizes that adaptive behavior, cognition, and intellect in humans are supported by rapid, long-range interactions between the cerebellum and the cerebral cortex. A fundamental principle of cerebellar function is that it does not operate in isolation; instead, it interacts with other brain regions through brief, rapid bursts of activity at specific frequencies linked to sensory or motor events. To explore these interactions, we use classical eyeblink conditioning (EBC), a well-established sensory-motor task of associative learning. Performance on trace and delay EBC (Fig 1. A-C) has been shown to distinguish children with Autism Spectrum Disorder (ASD), with and without intellectual disability (ID), and from children with typical development (TD) (Welsh, 2023). Our goal is to investigate the heterogeneity of brain pathophysiology in ASD using EBC. To assess our ability to detect cerebellar activity during EBC, we conducted a pilot study with TD adults using cryo-MEG. Given the potential benefits of wearable optically pumped magnetometer (OPM) MEG for use with children, we also tested EBC using OPMs.
Methods:
The study took place over 2 days. On Day 1, participants underwent trace EBC without MEG, and on Day 2, they performed trace EBC with MEG. EBC was conducted using a 1-kHz tone conditioned stimulus (CS) presented binaurally and a corneal airpuff unconditioned stimulus (US) directed to the right eye. 5 TD adults were measured using cryo-MEG (CTF Systems), 1 adult using OPM MEG (HEDScan, FieldLine Medical) (Alem, 2023), and 1 adult with both systems (Fig. 1D). 90 EBC trials were collected during MEG. Epochs notable for behavioral responses were analyzed to localize cerebellar, thalamic, M1, and prefrontal activations. An event-related beamformer (Jobst, 2018) was used to extract time-dependent activity from CS onset. The resulting network of nodes was examined in relation to conditioned response (CR) parameters (onset, peak latency, amplitude). Coherence trends across epochs were analyzed for correlations with learning, measured by CR acquisition rate.
Results:
Fig. 1E shows performance results for two participants across Day 1 and Day 2. Fig. 1F shows the mean CR topography during trace EBC for 4 participants during MEG, confirming that the CR peaks at US onset. The event-related beamformer results revealed the dynamic interplay between the cerebellum and prefrontal cortex during trace EBC. Notable features (Fig. 2B for one participant) include bilateral auditory components, lateralized responses in the medial and lateral prefrontal cortices, and activation of right cerebellar lobules HVI and HVII. Coherence analysis revealed the frequency dynamics of right HVIIa cerebellar cortex activation in a second TD participant. Discrete bursts of activity in the alpha, beta, and gamma bands were observed in the cerebellar cortex during the CS-US interval, along with coherence between the somatomotor and prefrontal cerebro-cerebellar systems during the CR latency in the alpha and gamma bands. Key findings of the study include: 1) Specific unilateral activations within the posterior lobe cerebellum in cerebellar lobules HVI and HVII; 2) Evidence of cerebello-thalamo-neocortical pathways in wide-band activity; and 3) Distinct activation patterns differentiating the somatomotor cerebro-cerebellar system from the prefrontal cerebro-cerebellar system. These results reveal complex brain activity phenomena that warrant further investigation in individuals with TD vs. those with autism. OPM results for the participant shown in Fig. 2 revealed consistent locations and timing of cerebral cortex activations, and with further analysis expected to identify subcortical activation patterns.
Conclusions:
Preliminary analysis supports the hypothesis that trace EBC in the human brain involves dynamic interactions between the cerebellum and prefrontal cortex. Associative learning in trace EBC appears to be driven by activity coherence between these regions.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism)
Learning and Memory:
Learning and Memory Other 2
Modeling and Analysis Methods:
EEG/MEG Modeling and Analysis 1
Novel Imaging Acquisition Methods:
MEG
Keywords:
Autism
Cerebellum
MEG
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Task-activation
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Healthy subjects
Was this research conducted in the United States?
Yes
Are you Internal Review Board (IRB) certified?
Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.
Yes, I have IRB or AUCC approval
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
Not applicable
Please indicate which methods were used in your research:
MEG
Which processing packages did you use for your study?
Free Surfer
Other, Please list
-
BrainWave
Provide references using APA citation style.
Alem, O. (2023). An integrated full-head OPM-MEG system based on 128 zero-field sensors. Frontiers in Neuroscience. 17(6).
Jobst, C. (2018). BrainWave: A Matlab Toolbox for Beamformer Source Analysis of MEG Data. Frontiers in Neuroscience. 12(8).
Welsh, J. P. (2023). Relationship of impairments in associative learning with intellectual disability and cerebellar hypoplasia in autistic children. Neurology. 100: e639-e650.
No