Functional and biochemical alterations of the medial frontal cortex in obsessive-compulsive disorder.
BACKGROUND
The medial frontal cortex (MFC), including the dorsal anterior cingulate and the supplementary motor area, is critical for adaptive and inhibitory control of behavior. Abnormally high MFC activity has been a consistent finding in functional neuroimaging studies of obsessive-compulsive disorder (OCD). However, the precise regions and the neural alterations associated with this abnormality remain unclear.


OBJECTIVE
To examine the functional and biochemical properties of the MFC in patients with OCD.


METHODS
Cross-sectional study combining volume-localized proton magnetic resonance spectroscopy and functional magnetic resonance imaging with a task encompassing inhibitory control processes (the Multi-Source Interference Task) designed to activate the MFC.


METHODS
Healthy control participants and OCD patients recruited from the general community.


METHODS
Nineteen OCD patients (10 males and 9 females) and 19 age-, sex-, education-, and intelligence-matched control participants recruited from the general community.


METHODS
Psychometric measures of symptom severity, Multi-Source Interference Task behavioral performance, blood oxygen level-dependent activation, and proton magnetic resonance spectroscopy brain metabolite concentrations.


RESULTS
Multi-Source Interference Task behavioral performance did not differ between OCD patients and control subjects. Reaction time interference and response errors were correlated with blood oxygen level-dependent activation in the dorsal anterior cingulate region in both groups. Compared with controls, OCD patients had greater relative activation of the supplementary motor area and deactivation of the rostral anterior cingulate during high- vs low-conflict (incongruent > congruent) trials. Patients with OCD also showed reduced levels of neuronal N-acetylaspartate in the dorsal anterior cingulate region, which was negatively correlated with their blood oxygen level-dependent activation of the region.


CONCLUSIONS
Hyperactivation of the MFC during high- vs low-conflict conditions in patients with OCD may be a compensatory response to a neuronal abnormality in the region. This relationship may partly explain the nature of inhibitory control deficits that are frequently seen in this group and may serve as a focus of future treatment studies.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Victoria 3053, Australia. murat@unimelb.edu.au
Murat
M
Yücel
Ben J
BJ
Harrison
Stephen J
SJ
Wood
Alex
A
Fornito
Robert M
RM
Wellard
Jesus
J
Pujol
Kerrie
K
Clarke
Mary L
ML
Phillips
Michael
M
Kyrios
Dennis
D
Velakoulis
Christos
C
Pantelis
D000328:Adult; D001931:Brain Mapping; D003430:Cross-Sectional Studies; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000503:physiopathology*; D007839:Functional Laterality / Q000502:physiology; D006179:Gyrus Cinguli / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D009682:Magnetic Resonance Spectroscopy / Q000706:statistics & numerical data*; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology*; D010100:Oxygen / Q000097:blood; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D012720:Severity of Illness Index; D013647:Task Performance and Analysis
D010100:Oxygen