Thalamic deep brain stimulation improves eyeblink conditioning deficits in essential tremor.
Several lines of evidence point to a disturbance of olivo-cerebellar pathways in essential tremor (ET). For example, subjects with ET exhibit deficits in eyeblink conditioning, a form of associative learning which is known to depend on the integrity of olivo-cerebellar circuits. Deep brain stimulation (DBS) of the ventrolateral thalamus is an established therapy for ET. If tremor in ET is related to the same pathology of the olivo-cerebellar system as impaired eyeblink conditioning, one may expect modulation of eyeblink conditioning by DBS. Delay eyeblink conditioning was assessed in 11 ET subjects treated with DBS (ET-DBS subjects) who were studied on two consecutive days with DBS switched off (day 1) and on (day 2). For comparison, 11 age-matched ET subjects without DBS (ET subjects) and 11 age-matched healthy controls were studied. On day 1, eyeblink conditioning was diminished in ET-DBS subjects and in ET subjects compared with controls. When DBS was switched on ET-DBS subjects exhibited conditioning rates within the range of controls on day 2, while ET subjects improved only minimally. Improved eyeblink conditioning in ET-DBS subjects suggests that thalamic DBS counteracts a functional disturbance of olivo-cerebellar circuits which is thought to be responsible for eyeblink conditioning deficits in ET. Modulation of cerebello-thalamic and/or thalamo-cortico-cerebellar pathways by DBS may play a role.
Kronenbuerger
M
M
Department of Neurology, University Hospital Aachen, RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Tronnier
V M
VM
Gerwig
M
M
Fromm
C
C
Coenen
V A
VA
Reinacher
P
P
Kiening
K L
KL
Noth
J
J
Timmann
D
D
D000368:Aged; D003215:Conditioning, Eyelid / Q000502:physiology*; D046690:Deep Brain Stimulation / Q000379:methods*; D020329:Essential Tremor / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013788:Thalamus / Q000502:physiology*