Saul Martínez-Horta1,2,3, Jesús Perez-Perez1,2,3,4,5, Frederic Sampedro1,2, Javier Pagonabarraga1,2,3, Andrea Horta-Barba1, Mar Carceller-Sindreu6, Beatriz Gomez-Anson7,5, Gloria Andrea Lozano-Martinez7, Diego Alfonso Lopez-Mora8, Valle Camacho8, Alejandro Fernández-León8, Ignasi Carrió8, Jaime Kulisevsky1,2,3,9. 1. Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 2. Biomedical Research Institute, Barcelona, Spain. 3. Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. 4. Instituto de Salud Carlos III, Madrid, Spain. 5. Faculty of Medicine, Autonomous University of Barcelona, Barcelona, Spain. 6. Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain. 7. Neuroradiology, Radiology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain. 8. Nuclear Medicine Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain. 9. Health Sciences Department, Universitat Oberta de Catalunya (UOC), Barcelona, Spain.
Abstract
BACKGROUND: Apathy is the most prevalent and characteristic neuropsychiatric feature of Huntington's disease. Congruent with the main early pathological changes, apathy is primarily associated with subcortical damage in frontal-striatal circuits. However, little is known about its precise subserving mechanisms and the contribution of regions other than the basal ganglia. OBJECTIVES: We aimed to define the neural correlates of apathy in Huntington's disease based on gray matter volume and PET/CT of 18 F-fluorodeoxyglucose metabolism. METHODS: We rated the severity of apathy in 40 mild Huntington's disease participants using the Problem Behaviors Assessment for Huntington's disease. Voxelwise regression analysis was performed, controlling for effects of potential confounders, and PET/CT results were corrected for the effects of gray matter atrophy. RESULTS: Apathy was strongly associated with decreased gray matter within a spatially distributed cortico-subcortical network, with major compromise of the bilateral amygdala and temporal cortex. PET metabolism was significantly decreased in frontotemporal and parietal regions. Metabolic uptake and gray matter values in the identified clusters showed significant correlations with multiple clinical measures. CONCLUSIONS: Our findings indicate that apathy in Huntington's disease is not exclusively a consequence of basal ganglia and related frontal-executive alterations. It is subserved by a complex cortico-subcortical network where critical reward and emotional-related prefrontal, temporal, and limbic nodes contribute strongly to its severity. This highlights the contribution of damage in regions other than the basal ganglia to the clinical expression of Huntington's disease.
BACKGROUND: Apathy is the most prevalent and characteristic neuropsychiatric feature of Huntington's disease. Congruent with the main early pathological changes, apathy is primarily associated with subcortical damage in frontal-striatal circuits. However, little is known about its precise subserving mechanisms and the contribution of regions other than the basal ganglia. OBJECTIVES: We aimed to define the neural correlates of apathy in Huntington's disease based on gray matter volume and PET/CT of 18 F-fluorodeoxyglucose metabolism. METHODS: We rated the severity of apathy in 40 mild Huntington's diseaseparticipants using the Problem Behaviors Assessment for Huntington's disease. Voxelwise regression analysis was performed, controlling for effects of potential confounders, and PET/CT results were corrected for the effects of gray matter atrophy. RESULTS: Apathy was strongly associated with decreased gray matter within a spatially distributed cortico-subcortical network, with major compromise of the bilateral amygdala and temporal cortex. PET metabolism was significantly decreased in frontotemporal and parietal regions. Metabolic uptake and gray matter values in the identified clusters showed significant correlations with multiple clinical measures. CONCLUSIONS: Our findings indicate that apathy in Huntington's disease is not exclusively a consequence of basal ganglia and related frontal-executive alterations. It is subserved by a complex cortico-subcortical network where critical reward and emotional-related prefrontal, temporal, and limbic nodes contribute strongly to its severity. This highlights the contribution of damage in regions other than the basal ganglia to the clinical expression of Huntington's disease.
Authors: Christopher D Rowley; Sarah J Tabrizi; Rachael I Scahill; Blair R Leavitt; Raymund A C Roos; Alexandra Durr; Nicholas A Bock Journal: Front Neurosci Date: 2018-11-05 Impact factor: 4.677