title: Altered ventral striatal activation during reward and punishment processing in premanifest Huntington's disease: a functional magnetic resonance study.
abstract: Recent research using various neuroimaging methods revealed the crucial role of the striatum concerning the neuropathology of Huntington's disease. Degenerative changes located in the basal ganglia are already observable in premanifest stages of Huntington's disease (pre-HD), i.e., before the onset of manifest motor symptoms. Although the impact of the striatum on reward and punishment processing is well-established in healthy subjects, these processes have not been investigated in manifest and premanifest HD subjects using functional magnetic resonance imaging (fMRI) so far. We used the Monetary Incentive Delay Task to investigate valence discrimination in terms of rewarding and punishing cues in 30 pre-HD and 15 healthy subjects. According to the probability of disease onset within the next 5 years, pre-HD subjects were categorized as either near to motor symptom onset (pre-HD(near); 9.9 [±2.91] years to onset) or far from manifest disease onset (pre-HD(far); 23.49 [±5.99] years to onset). Compared to pre-HD(far) and healthy subjects, pre-HD(near) subjects showed a disturbed neuronal differentiation between reward and control anticipation located in the left ventral striatum. In contrast to pre-HD(far) and healthy subjects, no significant ventral striatal discrimination between punishing and control cues was detected in pre-HD(near) subjects. In the present study, we demonstrated for the first time significant differences in valence discrimination in pre-HD(near) subjects compared to pre-HD(far) subjects and healthy controls. Altered reward and punishment processing could therefore reflect a motivational deficit that may contribute to the pathogenesis of Huntington's disease.
authors.affiliation: Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL-University Hospital Bochum, Ruhr-University Bochum, Bochum, Germany. Bjoern.Enzi@wkp-lwl.org
authors.forename: Björn
authors.initials: B
authors.lastname: Enzi
authors.forename: Marc-Andreas
authors.initials: MA
authors.lastname: Edel
authors.forename: Silke
authors.initials: S
authors.lastname: Lissek
authors.forename: Sören
authors.initials: S
authors.lastname: Peters
authors.forename: Rainer
authors.initials: R
authors.lastname: Hoffmann
authors.forename: Volkmar
authors.initials: V
authors.lastname: Nicolas
authors.forename: Martin
authors.initials: M
authors.lastname: Tegenthoff
authors.forename: Georg
authors.initials: G
authors.lastname: Juckel
authors.forename: Carsten
authors.initials: C
authors.lastname: Saft
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000503:physiopathology*; D001931:Brain Mapping; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011678:Punishment; D012201:Reward