Frontoamygdala hyperconnectivity predicts affective dysregulation in adolescent moderate-severe TBI
In survivors of moderate to severe traumatic brain injury (msTBI), affective disruptions often remain underdetected and undertreated, in part due to poor understanding of the underlying neural mechanisms. We hypothesized that limbic circuits are integral to affective dysregulation in msTBI. To test...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Rehabilitation Sciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fresc.2022.1064215/full |
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| author | Kevin C. Bickart Kevin C. Bickart Alexander Olsen Alexander Olsen Alexander Olsen Emily L. Dennis Talin Babikian Talin Babikian Ann N. Hoffman Aliyah Snyder Aliyah Snyder Christopher A. Sheridan Christopher A. Sheridan Jesse T. Fischer Jesse T. Fischer Christopher C. Giza Christopher C. Giza Meeryo C. Choe Meeryo C. Choe Robert F. Asarnow Robert F. Asarnow |
| author_facet | Kevin C. Bickart Kevin C. Bickart Alexander Olsen Alexander Olsen Alexander Olsen Emily L. Dennis Talin Babikian Talin Babikian Ann N. Hoffman Aliyah Snyder Aliyah Snyder Christopher A. Sheridan Christopher A. Sheridan Jesse T. Fischer Jesse T. Fischer Christopher C. Giza Christopher C. Giza Meeryo C. Choe Meeryo C. Choe Robert F. Asarnow Robert F. Asarnow |
| author_sort | Kevin C. Bickart |
| collection | DOAJ |
| description | In survivors of moderate to severe traumatic brain injury (msTBI), affective disruptions often remain underdetected and undertreated, in part due to poor understanding of the underlying neural mechanisms. We hypothesized that limbic circuits are integral to affective dysregulation in msTBI. To test this, we studied 19 adolescents with msTBI 17 months post-injury (TBI: M age 15.6, 5 females) as well as 44 matched healthy controls (HC: M age 16.4, 21 females). We leveraged two previously identified, large-scale resting-state (rsfMRI) networks of the amygdala to determine whether connectivity strength correlated with affective problems in the adolescents with msTBI. We found that distinct amygdala networks differentially predicted externalizing and internalizing behavioral problems in patients with msTBI. Specifically, patients with the highest medial amygdala connectivity were rated by parents as having greater externalizing behavioral problems measured on the BRIEF and CBCL, but not cognitive problems. The most correlated voxels in that network localize to the rostral anterior cingulate (rACC) and posterior cingulate (PCC) cortices, predicting 48% of the variance in externalizing problems. Alternatively, patients with the highest ventrolateral amygdala connectivity were rated by parents as having greater internalizing behavioral problems measured on the CBCL, but not cognitive problems. The most correlated voxels in that network localize to the ventromedial prefrontal cortex (vmPFC), predicting 57% of the variance in internalizing problems. Both findings were independent of potential confounds including ratings of TBI severity, time since injury, lesion burden based on acute imaging, demographic variables, and other non-amygdalar rsfMRI metrics (e.g., rACC to PCC connectivity), as well as macro- and microstructural measures of limbic circuitry (e.g., amygdala volume and uncinate fasciculus fractional anisotropy). Supporting the clinical significance of these findings, patients with msTBI had significantly greater externalizing problem ratings than healthy control participants and all the brain-behavior findings were specific to the msTBI group in that no similar correlations were found in the healthy control participants. Taken together, frontoamygdala pathways may underlie chronic dysregulation of behavior and mood in patients with msTBI. Future work will focus on neuromodulation techniques to directly affect frontoamygdala pathways with the aim to mitigate such dysregulation problems. |
| first_indexed | 2024-04-11T01:04:05Z |
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| language | English |
| last_indexed | 2024-04-11T01:04:05Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Rehabilitation Sciences |
| spelling | doaj.art-38dcf4d6ed3b4974955c582fa11a9aa02023-01-04T13:48:50ZengFrontiers Media S.A.Frontiers in Rehabilitation Sciences2673-68612023-01-01310.3389/fresc.2022.10642151064215Frontoamygdala hyperconnectivity predicts affective dysregulation in adolescent moderate-severe TBIKevin C. Bickart0Kevin C. Bickart1Alexander Olsen2Alexander Olsen3Alexander Olsen4Emily L. Dennis5Talin Babikian6Talin Babikian7Ann N. Hoffman8Aliyah Snyder9Aliyah Snyder10Christopher A. Sheridan11Christopher A. Sheridan12Jesse T. Fischer13Jesse T. Fischer14Christopher C. Giza15Christopher C. Giza16Meeryo C. Choe17Meeryo C. Choe18Robert F. Asarnow19Robert F. Asarnow20BrainSPORT, Department of Neurosurgery, UCLA, Los Angeles, CA, United StatesDepartment of Neurology, UCLA, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, United StatesDepartment of Psychology, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Physical Medicine and Rehabilitation, St. Olavs Hospital, University Hospital, Trondheim, NorwayTBI and Concussion Center, Department of Neurology, University of Utah, Salt Lake City, UT, United StatesBrainSPORT, Department of Neurosurgery, UCLA, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, United StatesBrainSPORT, Department of Neurosurgery, UCLA, Los Angeles, CA, United StatesBrainSPORT, Department of Neurosurgery, UCLA, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, United StatesWake Forest School of Medicine, Radiology Informatics and Image Processing Laboratory, Winston-Salem, NC, United StatesWake Forest School of Medicine, Department of Radiology, Section of Neuroradiology, Winston-Salem, NC, United StatesBrainSPORT, Department of Neurosurgery, UCLA, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, United StatesBrainSPORT, Department of Neurosurgery, UCLA, Los Angeles, CA, United StatesUCLA Mattel Children's Hospital, Department of Pediatrics, Division of Neurology, Los Angeles, CA, United StatesBrainSPORT, Department of Neurosurgery, UCLA, Los Angeles, CA, United StatesUCLA Mattel Children's Hospital, Department of Pediatrics, Division of Neurology, Los Angeles, CA, United StatesBrainSPORT, Department of Neurosurgery, UCLA, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, United StatesIn survivors of moderate to severe traumatic brain injury (msTBI), affective disruptions often remain underdetected and undertreated, in part due to poor understanding of the underlying neural mechanisms. We hypothesized that limbic circuits are integral to affective dysregulation in msTBI. To test this, we studied 19 adolescents with msTBI 17 months post-injury (TBI: M age 15.6, 5 females) as well as 44 matched healthy controls (HC: M age 16.4, 21 females). We leveraged two previously identified, large-scale resting-state (rsfMRI) networks of the amygdala to determine whether connectivity strength correlated with affective problems in the adolescents with msTBI. We found that distinct amygdala networks differentially predicted externalizing and internalizing behavioral problems in patients with msTBI. Specifically, patients with the highest medial amygdala connectivity were rated by parents as having greater externalizing behavioral problems measured on the BRIEF and CBCL, but not cognitive problems. The most correlated voxels in that network localize to the rostral anterior cingulate (rACC) and posterior cingulate (PCC) cortices, predicting 48% of the variance in externalizing problems. Alternatively, patients with the highest ventrolateral amygdala connectivity were rated by parents as having greater internalizing behavioral problems measured on the CBCL, but not cognitive problems. The most correlated voxels in that network localize to the ventromedial prefrontal cortex (vmPFC), predicting 57% of the variance in internalizing problems. Both findings were independent of potential confounds including ratings of TBI severity, time since injury, lesion burden based on acute imaging, demographic variables, and other non-amygdalar rsfMRI metrics (e.g., rACC to PCC connectivity), as well as macro- and microstructural measures of limbic circuitry (e.g., amygdala volume and uncinate fasciculus fractional anisotropy). Supporting the clinical significance of these findings, patients with msTBI had significantly greater externalizing problem ratings than healthy control participants and all the brain-behavior findings were specific to the msTBI group in that no similar correlations were found in the healthy control participants. Taken together, frontoamygdala pathways may underlie chronic dysregulation of behavior and mood in patients with msTBI. Future work will focus on neuromodulation techniques to directly affect frontoamygdala pathways with the aim to mitigate such dysregulation problems.https://www.frontiersin.org/articles/10.3389/fresc.2022.1064215/fullamygdalaresting-state fMRImoderate to severe TBIaffective dysregulationfrontoamygdalabehavioral dysregulation |
| spellingShingle | Kevin C. Bickart Kevin C. Bickart Alexander Olsen Alexander Olsen Alexander Olsen Emily L. Dennis Talin Babikian Talin Babikian Ann N. Hoffman Aliyah Snyder Aliyah Snyder Christopher A. Sheridan Christopher A. Sheridan Jesse T. Fischer Jesse T. Fischer Christopher C. Giza Christopher C. Giza Meeryo C. Choe Meeryo C. Choe Robert F. Asarnow Robert F. Asarnow Frontoamygdala hyperconnectivity predicts affective dysregulation in adolescent moderate-severe TBI Frontiers in Rehabilitation Sciences amygdala resting-state fMRI moderate to severe TBI affective dysregulation frontoamygdala behavioral dysregulation |
| title | Frontoamygdala hyperconnectivity predicts affective dysregulation in adolescent moderate-severe TBI |
| title_full | Frontoamygdala hyperconnectivity predicts affective dysregulation in adolescent moderate-severe TBI |
| title_fullStr | Frontoamygdala hyperconnectivity predicts affective dysregulation in adolescent moderate-severe TBI |
| title_full_unstemmed | Frontoamygdala hyperconnectivity predicts affective dysregulation in adolescent moderate-severe TBI |
| title_short | Frontoamygdala hyperconnectivity predicts affective dysregulation in adolescent moderate-severe TBI |
| title_sort | frontoamygdala hyperconnectivity predicts affective dysregulation in adolescent moderate severe tbi |
| topic | amygdala resting-state fMRI moderate to severe TBI affective dysregulation frontoamygdala behavioral dysregulation |
| url | https://www.frontiersin.org/articles/10.3389/fresc.2022.1064215/full |
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