Untersuchung der neuronalen Korrelate des Belohnungssystems mit der funktionellen Magnetresonanztomographie (fMRT) bei prä- bzw. frühsymptomatischen Huntington-Genträgern und gesunden Kontrollprobanden
Functional hypercompensation demonstrated as mechanism to offset neuronal loss in early Alzheimer"s 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 hypercompensation of ventral striatal functioning. We investigated 14 pre- or early symptomatic mutation carriers (MC) and 18 matched control subjects. 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 MC 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 MC 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 hypercompensation 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 an ideal model to study the different aspects of the concept of functional compensation.
Erstellung / Fertigstellung
Normierte SchlagwörterBelohnung [GND]
Funktionelle Kernspintomographie [GND]
Huntington protein, human [MeSH]
Tomography, X-ray computed [MeSH]