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Edison Miyawaki
Harvard Medical School, USATitle: Subjective Time Perception, Dopamine Signaling, and Parkinsonian Slowness
Abstract
The association between
idiopathic Parkinson’s disease, a paradigmatic dopamine-deficiency syndrome,
and problems in the estimation of time has been studied experimentally for
decades. I review that literature, which
raises a question about whether and if dopamine deficiency relates not only to
the motor slowness that is an objective and cardinal parkinsonian sign, but
also to a compromised neural substrate for time perception. Why does a clinically (motorically) significant
deficiency in dopamine play a role in the subjective perception of time’s
passage? After a discussion of a
classical conception of basal ganglionic control of movement under the
influence of dopamine, I describe recent work in healthy mice using
optogenetics; the methodology visualizes dopaminergic neuronal firing in very
short time intervals, then allows for correlation with motor behaviors in
trained tasks. Moment-to-moment neuronal activity is both highly
dynamic and variable, as assessed by photometry of genetically defined
dopaminergic neurons. I use those animal
data as context to review a large experimental experience in humans, spanning
decades, that has examined subjective time perception mainly in Parkinson’s
disease, but also in other movement disorders.
Although the human data are mixed in their
findings, I argue that loss of dynamic variability in dopaminergic neuronal activity over very
short intervals may be a fundamental sensory aspect in the
pathophysiology of parkinsonism. An
important implication is that therapeutic response in Parkinson’s disease needs
to be understood in terms of short-term alterations in dynamic neuronal firing,
as has already been examined in novel ways—for example, in the study of
real-time changes in neuronal network oscillations across very short time
intervals. A finer analysis of a
treatment’s network effects might aid in any effort to augment clinical
response to either medications or functional neurosurgical interventions in
Parkinson’s disease.
Biography
Edison K. Miyawaki, M.D. teaches Neurology
and Psychiatry as an associate neurologist and assistant professor of Neurology
at MassGeneral/Brigham and Harvard Medical School, both in Boston,
Massachusetts USA. In addition to 90
publications (in print and other media) in the fields of movement disorders,
neuroanatomy, and psychopharmacology, he has published ten books: What to Read on Love not Sex, on
Freud’s psychology of love, The Crossed Organization of Brains, The
Frontal Brain and Language, Learning the Brainstem, Teaching
Hippocampal Anatomy, The Visual Cortices, Beneath the Cortical
Surface, Thalamus and its Cortex, and The Autumn Brain Seminars
(in two volumes).