Limbic system structure volumes and associated neurocognitive functioning in former NFL players

Christian Lepage^{1

2}, Marc Muehlmann^{1

3}, Yorghos Tripodis^{4

5}, Jakob Hufschmidt^{1

6}, Julie Stamm^{1

4

7}, Katie Green¹, Pawel Wrobel^{1

6}, Vivian Schultz^{1

6}, Isabelle Weir⁵, Michael L Alosco^{4

8}, Christine M Baugh^{4

9}, Nathan G Fritts⁴, Brett M Martin¹⁰, Christine Chaisson^{4

10}, Michael J Coleman¹, Alexander P Lin^{1

11}, Ofer Pasternak^{1

12}, Nikos Makris^{1

13

12

14}, Robert A Stern^{4

7

15}, Martha E Shenton^{1

12

16}, Inga K Koerte^{17

18}

Affiliations

¹ Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
² Department of Psychology, University of Ottawa, Ottawa, ON, Canada.
³ Department of Radiology, University Hospital, LMU Munich, Munich, Germany.
⁴ BU Alzheimer's Disease and CTE Center, Boston University, Boston, MA, USA.
⁵ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁶ Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilian University, Munich, Germany.
⁷ Department of Kinesiology, University of Wisconsin - Madison, Madison, WI, USA.
⁸ Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
⁹ Interfaculty Initiative in Health Policy, Harvard University, Cambridge, MA, USA.
¹⁰ Data Coordinating Center, Boston University School of Public Health, Boston, MA, USA.
¹¹ Center for Clinical Spectroscopy, Brigham and Women's Hospital, Boston, MA, USA.
¹² Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹³ Center for Morphometric Analysis, Massachusetts General Hospital, Boston, MA, USA.
¹⁴ Center for Neural Systems Investigations, Massachusetts General Hospital, Boston, MA, USA.
¹⁵ Departments of Neurosurgery, and Anatomy & Neurobiology, Boston University School of Medicine, Boston, MA, USA.
¹⁶ VA Boston Healthcare System, Brockton Division, Brockton, MA, USA.
¹⁷ Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ikoerte@bwh.harvard.edu.
¹⁸ Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilian University, Munich, Germany. ikoerte@bwh.harvard.edu.

PMID: 29779184
PMCID: PMC6854905
DOI: 10.1007/s11682-018-9895-z

Limbic system structure volumes and associated neurocognitive functioning in former NFL players

Christian Lepage et al. Brain Imaging Behav. 2019 Jun.

. 2019 Jun;13(3):725-734.

doi: 10.1007/s11682-018-9895-z.

Authors

Affiliations

¹ Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
² Department of Psychology, University of Ottawa, Ottawa, ON, Canada.
³ Department of Radiology, University Hospital, LMU Munich, Munich, Germany.
⁴ BU Alzheimer's Disease and CTE Center, Boston University, Boston, MA, USA.
⁵ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁶ Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilian University, Munich, Germany.
⁷ Department of Kinesiology, University of Wisconsin - Madison, Madison, WI, USA.
⁸ Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
⁹ Interfaculty Initiative in Health Policy, Harvard University, Cambridge, MA, USA.
¹⁰ Data Coordinating Center, Boston University School of Public Health, Boston, MA, USA.
¹¹ Center for Clinical Spectroscopy, Brigham and Women's Hospital, Boston, MA, USA.
¹² Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹³ Center for Morphometric Analysis, Massachusetts General Hospital, Boston, MA, USA.
¹⁴ Center for Neural Systems Investigations, Massachusetts General Hospital, Boston, MA, USA.
¹⁵ Departments of Neurosurgery, and Anatomy & Neurobiology, Boston University School of Medicine, Boston, MA, USA.
¹⁶ VA Boston Healthcare System, Brockton Division, Brockton, MA, USA.
¹⁷ Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ikoerte@bwh.harvard.edu.
¹⁸ Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilian University, Munich, Germany. ikoerte@bwh.harvard.edu.

PMID: 29779184
PMCID: PMC6854905
DOI: 10.1007/s11682-018-9895-z

Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts. CTE has been linked to disruptions in cognition, mood, and behavior. Unfortunately, the diagnosis of CTE can only be made post-mortem. Neuropathological evidence suggests limbic structures may provide an opportunity to characterize CTE in the living. Using 3 T magnetic resonance imaging, we compared select limbic brain regional volumes - the amygdala, hippocampus, and cingulate gyrus - between symptomatic former National Football League (NFL) players (n = 86) and controls (n = 22). Moreover, within the group of former NFL players, we examined the relationship between those limbic structures and neurobehavioral functioning (n = 75). The former NFL group comprised eighty-six men (mean age = 55.2 ± 8.0 years) with at least 12 years of organized football experience, at least 2 years of active participation in the NFL, and self-reported declines in cognition, mood, and behavior within the last 6 months. The control group consisted of men (mean age = 57.0 ± 6.6 years) with no history of contact-sport involvement or traumatic brain injury. All control participants provided neurobehavioral data. Compared to controls, former NFL players exhibited reduced volumes of the amygdala, hippocampus, and cingulate gyrus. Within the NFL group, reduced bilateral cingulate gyrus volume was associated with worse attention and psychomotor speed (r = 0.4 (right), r = 0.42 (left); both p < 0.001), while decreased right hippocampal volume was associated with worse visual memory (r = 0.25, p = 0.027). Reduced volumes of limbic system structures in former NFL players are associated with neurocognitive features of CTE. Volume reductions in the amygdala, hippocampus, and cingulate gyrus may be potential biomarkers of neurodegeneration in those at risk for CTE.

Keywords: Chronic Traumatic Encephalopathy; Hippocampus; Limbic System; Repetitive Head Impacts; Volumetric MRI.

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Conflict of interest statement

Conflict of interest: Dr. Robert Stern is a paid consultant to Avanir Pharmaceuticals, Inc. (Aliso Viejo, CA), Biogen (Cambridge, MA), and Eli Lilly (Indianapolis, IN). He receives royalties for published neuropsychological tests from Psychological Assessment Resources, Inc. (Lutz, FL, USA). CMB receives research funding through the Harvard Football Players Health Study, which is funded by the NFL Players’ Association.

Figures

**Fig. 1**
A three-dimensional reconstruction of left hemisphere regions of interest. The model was created from one randomly selected dataset using the model maker module of Slicer 4.1. Yellow = cingulate gyrus (CG), blue = hippocampus (H), terracotta = amygdala (A) The model is shown on a paramidsagittal slice and is superimposed on the individual T1-weighted images.

**Fig. 2**
Significant associations between neurobehavioral factors and cingulate gyrus and hippocampus in the NFL group. A displays the association between volume in the right cingulate and Factor 2 (attention and psychomotor speed). B displays the association between the volume of the left cingulate gyrus and Factor 2. C displays the association between the right hippocampus and Factor 4 (visual memory). All analyses are based on partial correlations, adjusting for age, body-mass index, estimated total intracranial volume, and years of education.

See this image and copyright information in PMC

References

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Limbic system structure volumes and associated neurocognitive functioning in former NFL players

Affiliations

Limbic system structure volumes and associated neurocognitive functioning in former NFL players

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

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