Poster No:
2127
Submission Type:
Abstract Submission
Authors:
Ke Bo1, Catherine Kelly2, Michio Hirano3, Martin Picard2, Tor Wager4
Institutions:
1Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, 2Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York city, NY, 3Department of Neurology, H. Houston Merritt Center, Columbia University Translational Neuroscience, New York city, NY, 4Department of Psychological and Brain Sciences, Hanover, NH
First Author:
Ke Bo
Department of Psychological and Brain Sciences, Dartmouth College
Hanover, NH
Co-Author(s):
Catherine Kelly
Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center
New York city, NY
Michio Hirano
Department of Neurology, H. Houston Merritt Center, Columbia University Translational Neuroscience
New York city, NY
Martin Picard
Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center
New York city, NY
Tor Wager
Department of Psychological and Brain Sciences
Hanover, NH
Introduction:
Human brain function relies on an extraordinary amount of energy, largely supplied by mitochondria through cellular energy transformation (Picard et al.,2014). Genetic defects in mitochondrial DNA can impair this process, leading to mitochondrial diseases (MitoD) and associated neurological disorders (Picard et al., 2016). Similar to how brain lesion studies illuminate the functional roles of anatomical regions, studying individuals with genetic mitochondrial impairments offers insights into the role of mitochondria in both normal and pathological brain functions. However, the extent to which impaired mitochondrial energy transformation affects brain function across different domains remains poorly understood. This knowledge gap is partly due to the rarity of human studies, as most research on mitochondrial health and brain function has relied on animal models.
Methods:
To address this knowledge gap, we conducted functional magnetic resonance imaging (fMRI) on 29 participants with mitochondrial disease and 62 matched controls during tasks probing brain functions across three domains: cognitive (N-back task), affective (cold pain), and sensory (multisensory visual and auditory perception). All task data were preprocessed using fMRIprep, and task activations were modeled using the canonical HRF response within each block. The estimated beta images were used in the second-level analysis for group contrasts and machine learning analysis. In the machine learning analysis, a paired-SVM classifier was trained to decode brain representations between task and control conditions across participants. The distances to the decision hyperplane from task and control conditions for each participant were extracted as scores to evaluate the participant's effort toward a given task. A higher distance indicates a more differentiated brain pattern between task and control, suggesting greater brain effort for the task. This score was used as a summarized measure of task-related brain engagement for further evaluation.
Results:
Our analysis confirmed robust and significant task-specific activations in relevant brain regions, with whole-brain activation maps achieving classification accuracies exceeding 80% (Cohen's d > 0.9 for all tasks) using support vector machine decoding, validating data quality and analytic methods. Task-specific brain engagement scores, derived from SVM model decoding the whole-brain activation maps, were computed for each participant and compared between groups. While no significant group differences were observed between MitoD and controls overall, significant negative correlations emerged between mitochondrial disease severity and brain engagement in the working memory (R = -0.55, p = 0.002) and multisensory tasks (R = -0.42, p = 0.02) within the MitoD group. Subgroup analyses further revealed a compensatory effect: participants with mild symptoms exhibited higher brain engagement scores than controls (T = 2.00 , p = 0.05 ), while those with severe symptoms showed lower scores (T = -2.43 , p =0.02 ). A similar pattern was observed in the multisensory task but not in the cold pain task.
Behavioral performance in the working memory task also showed a significant negative correlation with mitochondrial disease severity (R = -0.49 , p = 0.01) and was significantly reduced in patients with severe symptoms compared to controls (T = -3.7 , p = 0.0005 ).
Conclusions:
These findings suggest that compensatory mechanisms may sustain brain function in MitoD patients with mild symptoms, as evidenced by heightened brain activation to maintain normal task performance. However, in severe cases, these mechanisms fail, leading to functional impairments. Notably, brain function impairments were evident in working memory and sensory tasks but not in pain processing, suggesting a hierarchy of energy demand or differential energy supply priorities across cognitive, sensory, and affective domains.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems
Cortical Anatomy and Brain Mapping
Physiology, Metabolism and Neurotransmission:
Physiology, Metabolism and Neurotransmission Other 1
Keywords:
Cognition
FUNCTIONAL MRI
Pain
Perception
Other - Mitochondria
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.
Resting state
Task-activation
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
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:
Functional MRI
For human MRI, what field strength scanner do you use?
3.0T
Provide references using APA citation style.
Picard, M., & McEwen, B. S. (2014). Mitochondria impact brain function and cognition. Proceedings of the National Academy of Sciences, 111(1), 7-8.
Picard, M., Wallace, D. C., & Burelle, Y. (2016). The rise of mitochondria in medicine. Mitochondrion, 30, 105-116.
No