Probing the neural mechanisms of adult-onset isolated focal dystonia
Citation:
QUINLIVAN, BRENDAN, Probing the neural mechanisms of adult-onset isolated focal dystonia, Trinity College Dublin.School of Engineering.ELECTRONIC AND ELECTRICAL ENGINEERING, 2018Abstract:
Adult onset isolated focal dystonia (AOIFD) is inherited in an autosomal dominant manner
with a reduced penetrance of 12-15%; cervical dystonia (CD) is the most common phenotype
in northern Europe. It is believed that the different phenotypes of AOIFD are cause by the
same, currently unknown, genetic mutation(s). While the pathogenesis of AOIFD remains a
mystery, recent animal and clinical studies have indicated its probable mechanisms. The
temporal discrimination threshold (TDT) is the shortest interval at which two sequential stimuli
appear to the observer to be asynchronous; a typically developing adult will have a TDT of 30
- 50 ms, although this varies with gender and age. It has been established that an abnormal TDT
is a valid, sensitive and specific mediational endophenotype in several AOIFD phenotypes.
The discovery of this mediational endophenotype has been instrumental in the formation of
novel hypotheses regarding the pathogenesis of AOIFD. The hypothesis examined here states
that both abnormal temporal discrimination and cervical dystonia are the result of a disorder of
the midbrain network involved in covert orientation of attentional, caused by reduced gammaaminobutyric
acid (GABA) inhibition in the superficial layers of the superior colliculus,
resulting from undetermined genetic mutations. Such disinhibition is manifested in two ways:
(1) subclinically, by abnormal temporal discrimination due to prolonged duration firing of the
visual sensory neurons in the superficial laminae of the superior colliculus, (2) clinically by
AOIFD due to disinhibited burst activity of the cephalomotor neurons of the intermediate and
deep laminae of the superior colliculus.
We tested this hypothesis by developing several experiments that involved the midbrain
network for covert orientation of attention, specifically looking at various inputs and outputs
from the superior colliculus in a principled and empirical manner. Three investigations were
carried out to probe this hypothesis.
Sponsor
Grant Number
Health Research Board (HRB)
Author's Homepage:
http://people.tcd.ie/quinlivbDescription:
APPROVED
Author: QUINLIVAN, BRENDAN
Advisor:
Reilly, RichardPublisher:
Trinity College Dublin. School of Engineering. Discipline of Electronic & Elect. EngineeringType of material:
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