Locus Coeruleus Integrity Is Linked to Response Inhibition Deficits in Parkinson's Disease and Progressive Supranuclear Palsy

• DOI: 10.1523/jneurosci.0289-22.2023
• Publication Date: 2023-09-05T17:50:54Z
• Authors: Rong Ye; Frank H. Hezemans; Claire O'Callaghan; Kamen A. Tsvetanov; Catarina Rua; P. Simon Jones; Negin Holland; Maura Malpetti; Alexander G. Murley; Roger A. Barker; Caroline H. Willi...; Trevor W. Robbins; Luca Passamonti; James B. Rowe
• Keywords: Locus coeruleus

Parkinson's disease (PD) and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. Inhibitory control deficits vary across individuals are linked with worse prognosis, lack improvement on dopaminergic therapy. Motor cognitive associated noradrenergic innervation of the cortex, arising from locus coeruleus (LC) system. Here we test hypothesis that structural variation LC explains inhibition in PSP PD. Twenty-four people idiopathic PD, 14 PSP-Richardson's syndrome, 24 age- sex-matched controls undertook a stop-signal task ultrahigh field 7T magnetization-transfer-weighted imaging LC. Parameters “race models” go- versus stop-decisions were estimated using hierarchical Bayesian methods to quantify processes inhibition. We tested multivariate relationship between integrity model parameters partial least squares. Both disorders impaired at group level. caused distinct pattern abnormalities inhibitory paradoxically reduced threshold for go responses, but longer nondecision times, more lapses attention. The correlated variability participants clinical groups. Structural LC, coupled behavioral modeling parkinsonian disorders, confirms is degeneration contributes neurobehavioral changes. system therefore promising target treat impulsivity these conditions. optimization treatment likely benefit stratification according integrity. SIGNIFICANCE STATEMENT Response contribute symptoms poor outcomes palsy. used performance identify disease-specific mechanisms abnormal control. patient groups was coeruleus, which measured vivo ultra-high MRI. propose biomarker provides trans-diagnostic tool explain individual differences ability beyond classic nosological borders diagnostic criteria. Our data suggest potential new stratified approach