title: Prodromal Huntington disease as a model for functional compensation of early neurodegeneration.
abstract: Functional compensation demonstrated as mechanism to offset neuronal loss in early Alzheimer disease may also occur in other adult-onset neurodegenerative diseases, particularly Huntington disease (HD) with its genetic determination and gradual changes in structural integrity. In HD, neurodegeneration typically initiates in the dorsal striatum, successively affecting ventral striatal areas. Investigating carriers of the HD mutation with evident dorsal, but only minimal or no ventral striatal atrophy, we expected to find evidence for compensation of ventral striatal functioning. We investigated 14 pre- or early symptomatic carriers of the mutation leading to HD and 18 matched healthy controls. Participants underwent structural T1 magnetic resonance imaging (MRI) and functional MRI during a reward task that probes ventral striatal functioning. Motor functioning and attention were assessed with reaction time (RT) tasks. Structural images confirmed a specific decrease of dorsal striatal but only marginal ventral striatal volume in HD relative to control subjects, paralleling prolonged RT in the motor response tasks. While behavioral performance in the reward task during fMRI scanning was unimpaired, reward-related fMRI signaling in the HD group was differentially enhanced in the bilateral ventral striatum and in bilateral orbitofrontal cortex/anterior insula, as another region sensitive to reward processing. We provide evidence for the concept of functional compensation in premanifest HD which may suggest a defense mechanism in neurodegeneration. Given the so far inevitable course of HD with its genetically determined endpoint, this disease may provide another model to study the different aspects of the concept of functional compensation.
authors.affiliation: Department of Psychiatry, Ulm University, Leimgrubenweg 12-14, 89522, Ulm, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Malejko
authors.affiliation: Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Weydt
authors.affiliation: Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany.
authors.forename: Sigurd D
authors.initials: SD
authors.lastname: Süßmuth
authors.affiliation: Department of Psychiatry, Ulm University, Leimgrubenweg 12-14, 89522, Ulm, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Grön
authors.affiliation: Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany.
authors.forename: Bernhard G
authors.initials: BG
authors.lastname: Landwehrmeyer
authors.affiliation: Department of Psychiatry, Ulm University, Leimgrubenweg 12-14, 89522, Ulm, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Abler
mesh_terms: D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009154:Mutation; D017397:Prefrontal Cortex / Q000473:pathology* / Q000503:physiopathology; D062706:Prodromal Symptoms; D066328:Ventral Striatum / Q000473:pathology / Q000503:physiopathology*