Saccadic latency distributions in Parkinson's disease and the effects of L-dopa.
Parkinson's disease (PD) is associated with a loss of central dopaminergic pathways in the brain leading to an abnormality of movement, including saccades. In PD, analysis of saccadic latency distributions, rather than mean latencies, can provide much more information about how the neural decision process that precedes movement is affected by disease or medication. Subject to the constraints of intersubject variation and reproducibility, latency distribution may represent an attractive potential biomarker of PD. Here we report two studies that provide information about these parameters, and demonstrate a novel effect of dopamine on saccadic latency, implying that it influences the neural decision process itself. We performed a detailed cross-sectional study of saccadic latency distributions during a simple step task in 22 medicated patients and 27 age-matched controls. This revealed high intersubject variability and an overlap of PD and control distributions. A second study was undertaken on a different population specifically to investigate the effects of dopamine on saccadic latency distributions in 15 PD patients. L-dopa was found to prolong latency, although the magnitude of the effect varied between subjects. The implications of these observations for the use of saccadic latency distributions as a potential biomarker of PD are discussed, as are the effects of L-dopa on neural decision making, where it is postulated to increase the criterion level of evidence required before the decision to move is made.
Cambridge Centre for Brain Repair, Forvie Site, Robinson Way, CB2 2PY, Cambridge, UK. awm13@cam.ac.uk
A W
AW
Michell
Z
Z
Xu
D
D
Fritz
S J G
SJ
Lewis
T
T
Foltynie
C H
CH
Williams-Gray
T W
TW
Robbins
R H S
RH
Carpenter
R A
RA
Barker
D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D003657:Decision Making / Q000187:drug effects; D005260:Female; D006801:Humans; D007206:Individuality; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects; D015203:Reproducibility of Results; D012438:Saccades / Q000187:drug effects / Q000502:physiology*
D000978:Antiparkinson Agents; D007980:Levodopa