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.