Ekaterina Shatalina, Thomas Whitehurst, Ellis Chika Onwordi, Alexander Whittington, Ayla Mansur, Atheeshaan Arumuham, Tiago Reis Marques, Roger N Gunn, Sridhar Natesan, Matthew M Nour, Eugenii A Rabiner, Matthew B Wall, Oliver D Howes
{"title":"线粒体让你思考：一项[18F]BCPP-EF正电子发射断层扫描研究线粒体复合体I水平和任务转换过程中的大脑激活。","authors":"Ekaterina Shatalina, Thomas Whitehurst, Ellis Chika Onwordi, Alexander Whittington, Ayla Mansur, Atheeshaan Arumuham, Tiago Reis Marques, Roger N Gunn, Sridhar Natesan, Matthew M Nour, Eugenii A Rabiner, Matthew B Wall, Oliver D Howes","doi":"10.1016/j.bpsc.2025.02.007","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial complex I is the largest enzyme complex in the respiratory chain and can be noninvasively measured using [<sup>18</sup>F]BCPP-EF positron emission tomography (PET). Neurological conditions associated with mitochondria complex I pathology are also associated with altered blood oxygen level-dependent (BOLD) response and impairments in cognition. In this study, we aimed to investigate the relationship between mitochondrial complex I levels, cognitive function, and associated neural activity during task switching in healthy humans.</p><p><strong>Methods: </strong>Cognitively healthy adults (N = 23) underwent [<sup>18</sup>F]BCPP-EF PET scans and functional magnetic resonance imaging (fMRI) while performing a task-switching exercise. Task performance metrics included switch cost and switching accuracy. Data were analyzed using linear mixed-effects models and partial least squares regression (PLS-R).</p><p><strong>Results: </strong>We found significant positive associations between [<sup>18</sup>F]BCPP-EF volume of distribution (V<sub>T</sub>) and the task-switching fMRI response (β = 3.351, SE = 1.01, z = 3.249, p = .001). Positive Pearson's correlations between [<sup>18</sup>F]BCPP-EF V<sub>T</sub> and the fMRI response were observed in the dorsolateral prefrontal cortex (r = 0.61, p = .0019), insula (r = 0.46, p = .0264), parietal precuneus (r = 0.51, p = .0139), and anterior cingulate cortex (r = 0.45, p = .0293). [<sup>18</sup>F]BCPP-EF V<sub>T</sub> across task-relevant regions was associated with task switching accuracy (PLS-R, R<sup>2</sup> = 0.48, root mean square error [RMSE] = 0.154, p = .011) and with switch cost (PLS-R, R<sup>2</sup> = 0.38, RMSE = 0.07, p = .048).</p><p><strong>Conclusions: </strong>Higher mitochondrial complex I levels may underlie an individual's ability to exhibit a stronger BOLD response during task switching and are associated with better task-switching performance. This provides the first evidence linking the BOLD response with mitochondrial complex I and suggests a possible biological mechanism for the aberrant BOLD response in conditions associated with mitochondrial complex I dysfunction that should be tested in future studies.</p>","PeriodicalId":93900,"journal":{"name":"Biological psychiatry. Cognitive neuroscience and neuroimaging","volume":" ","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mitochondria and Cognition: An [<sup>18</sup>F]BCPP-EF Positron Emission Tomography Study of Mitochondrial Complex I Levels and Brain Activation During Task Switching.\",\"authors\":\"Ekaterina Shatalina, Thomas Whitehurst, Ellis Chika Onwordi, Alexander Whittington, Ayla Mansur, Atheeshaan Arumuham, Tiago Reis Marques, Roger N Gunn, Sridhar Natesan, Matthew M Nour, Eugenii A Rabiner, Matthew B Wall, Oliver D Howes\",\"doi\":\"10.1016/j.bpsc.2025.02.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Mitochondrial complex I is the largest enzyme complex in the respiratory chain and can be noninvasively measured using [<sup>18</sup>F]BCPP-EF positron emission tomography (PET). Neurological conditions associated with mitochondria complex I pathology are also associated with altered blood oxygen level-dependent (BOLD) response and impairments in cognition. In this study, we aimed to investigate the relationship between mitochondrial complex I levels, cognitive function, and associated neural activity during task switching in healthy humans.</p><p><strong>Methods: </strong>Cognitively healthy adults (N = 23) underwent [<sup>18</sup>F]BCPP-EF PET scans and functional magnetic resonance imaging (fMRI) while performing a task-switching exercise. Task performance metrics included switch cost and switching accuracy. Data were analyzed using linear mixed-effects models and partial least squares regression (PLS-R).</p><p><strong>Results: </strong>We found significant positive associations between [<sup>18</sup>F]BCPP-EF volume of distribution (V<sub>T</sub>) and the task-switching fMRI response (β = 3.351, SE = 1.01, z = 3.249, p = .001). Positive Pearson's correlations between [<sup>18</sup>F]BCPP-EF V<sub>T</sub> and the fMRI response were observed in the dorsolateral prefrontal cortex (r = 0.61, p = .0019), insula (r = 0.46, p = .0264), parietal precuneus (r = 0.51, p = .0139), and anterior cingulate cortex (r = 0.45, p = .0293). [<sup>18</sup>F]BCPP-EF V<sub>T</sub> across task-relevant regions was associated with task switching accuracy (PLS-R, R<sup>2</sup> = 0.48, root mean square error [RMSE] = 0.154, p = .011) and with switch cost (PLS-R, R<sup>2</sup> = 0.38, RMSE = 0.07, p = .048).</p><p><strong>Conclusions: </strong>Higher mitochondrial complex I levels may underlie an individual's ability to exhibit a stronger BOLD response during task switching and are associated with better task-switching performance. This provides the first evidence linking the BOLD response with mitochondrial complex I and suggests a possible biological mechanism for the aberrant BOLD response in conditions associated with mitochondrial complex I dysfunction that should be tested in future studies.</p>\",\"PeriodicalId\":93900,\"journal\":{\"name\":\"Biological psychiatry. Cognitive neuroscience and neuroimaging\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-02-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological psychiatry. Cognitive neuroscience and neuroimaging\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.bpsc.2025.02.007\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological psychiatry. Cognitive neuroscience and neuroimaging","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.bpsc.2025.02.007","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Mitochondria and Cognition: An [18F]BCPP-EF Positron Emission Tomography Study of Mitochondrial Complex I Levels and Brain Activation During Task Switching.
Background: Mitochondrial complex I is the largest enzyme complex in the respiratory chain and can be noninvasively measured using [18F]BCPP-EF positron emission tomography (PET). Neurological conditions associated with mitochondria complex I pathology are also associated with altered blood oxygen level-dependent (BOLD) response and impairments in cognition. In this study, we aimed to investigate the relationship between mitochondrial complex I levels, cognitive function, and associated neural activity during task switching in healthy humans.
Methods: Cognitively healthy adults (N = 23) underwent [18F]BCPP-EF PET scans and functional magnetic resonance imaging (fMRI) while performing a task-switching exercise. Task performance metrics included switch cost and switching accuracy. Data were analyzed using linear mixed-effects models and partial least squares regression (PLS-R).
Results: We found significant positive associations between [18F]BCPP-EF volume of distribution (VT) and the task-switching fMRI response (β = 3.351, SE = 1.01, z = 3.249, p = .001). Positive Pearson's correlations between [18F]BCPP-EF VT and the fMRI response were observed in the dorsolateral prefrontal cortex (r = 0.61, p = .0019), insula (r = 0.46, p = .0264), parietal precuneus (r = 0.51, p = .0139), and anterior cingulate cortex (r = 0.45, p = .0293). [18F]BCPP-EF VT across task-relevant regions was associated with task switching accuracy (PLS-R, R2 = 0.48, root mean square error [RMSE] = 0.154, p = .011) and with switch cost (PLS-R, R2 = 0.38, RMSE = 0.07, p = .048).
Conclusions: Higher mitochondrial complex I levels may underlie an individual's ability to exhibit a stronger BOLD response during task switching and are associated with better task-switching performance. This provides the first evidence linking the BOLD response with mitochondrial complex I and suggests a possible biological mechanism for the aberrant BOLD response in conditions associated with mitochondrial complex I dysfunction that should be tested in future studies.
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