Neuropsychiatric effects of neurodegeneration of the medial versus lateral ventral prefrontal cortex in humans

Edward D Huey; Seonjoo Lee; Adam M Brickman; Masood Manoochehri; Erica Griffith; D P Devanand; Yaakov Stern; Jordan Grafman

doi:10.1016/j.cortex.2015.08.002

Neuropsychiatric effects of neurodegeneration of the medial versus lateral ventral prefrontal cortex in humans

Cortex. 2015 Dec:73:1-9. doi: 10.1016/j.cortex.2015.08.002. Epub 2015 Aug 15.

Authors

Edward D Huey¹, Seonjoo Lee², Adam M Brickman³, Masood Manoochehri⁴, Erica Griffith⁵, D P Devanand⁶, Yaakov Stern³, Jordan Grafman⁷

Affiliations

¹ Taub Institute and Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Division of Geriatric Psychiatry, Department of Psychiatry, Columbia University, College of Physicians and Surgeons and New York State Psychiatric Institute, New York, NY, USA; Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, NY, USA; Department of Psychiatry, Columbia University, College of Physicians and Surgeons and New York State Psychiatric Institute, Columbia University, New York, NY, USA. Electronic address: edh2126@cumc.columbia.edu.
² Department of Psychiatry, Columbia University, College of Physicians and Surgeons and New York State Psychiatric Institute, Columbia University, New York, NY, USA; Department of Biostatistics, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
³ Taub Institute and Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, NY, USA; Cognitive Neuroscience Division, Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
⁴ Taub Institute and Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
⁵ Taub Institute and Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Cognitive Neuroscience Division, Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
⁶ Division of Geriatric Psychiatry, Department of Psychiatry, Columbia University, College of Physicians and Surgeons and New York State Psychiatric Institute, New York, NY, USA; Department of Psychiatry, Columbia University, College of Physicians and Surgeons and New York State Psychiatric Institute, Columbia University, New York, NY, USA.
⁷ Brain Injury Research Program, Rehabilitation Institute of Chicago, Chicago, IL, USA; Northwestern University, Chicago, IL, USA.

Abstract

Animal evidence suggests that a brain network involving the medial and rostral ventral prefrontal cortex (PFC) is central for threat response and arousal and a network involving the lateral and caudal PFC plays an important role in reward learning and behavioral control. In this study, we contrasted the neuropsychiatric effects of degeneration of the medial versus lateral PFC in 43 patients with Frontotemporal dementia (FTD) and 11 patients with Corticobasal Syndrome (CBS) using MRI, the Neuropsychiatric Inventory (NPI), and the Sorting, Tower, Twenty Questions, and Fluency tests of the Delis-Kaplan Executive Function System (D-KEFS). Deviations in MRI grey matter volume from 86 age-matched healthy control subjects were determined for the patients using FreeSurfer. Multivariate regression was used to determine which brain areas were associated with specific neuropsychiatric and cognitive symptoms. Decreased grey matter volume of the right medial ventral PFC was associated with increased anxiety and apathy, decreased volume of the right lateral ventral PFC with apathy and inappropriate repetitive behaviors, and of the left lateral ventral PFC with poor performance on the sorting and Twenty Questions task in patients with FTD and CBS. Similar to in animal studies, damage to the medial OFC appears to be associated with a disruption of arousal, and damage to the lateral OFC appears to be associated with deficits in trial-and-error learning and behavioral dysregulation. Studies of brain dysfunction in humans are valuable to bridge animal and human neuropsychiatric research.

Keywords: Lesion studies; Neurodegeneration; Neuropsychiatry; Prefrontal cortex.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Cognition Disorders / physiopathology*
Executive Function / physiology*
Female
Frontal Lobe / physiology*
Frontal Lobe / physiopathology
Frontotemporal Dementia / physiopathology*
Gray Matter / physiopathology
Humans
Learning / physiology*
Magnetic Resonance Imaging / methods
Male
Middle Aged
Neuropsychological Tests

Abstract

Publication types

MeSH terms

Grants and funding