Case studies in neuroscience: Lack of inhibitory synaptic plasticity in the substantia nigra pars reticulata of a patient with lithium-induced tremor

Abstract

Tremor is a well-known side effect from many psychiatric medications, including lithium and dopamine antagonists. In patients whose psychiatric symptoms are stabilized and only respond to certain medications, deep brain stimulation may offer relief of the consequent motor complications. We report the case of an elderly male with disabling tremor related to lithium therapy for bipolar affective disorder, who was subsequently treated with deep brain stimulation. In this patient, we obtained recordings from the substantia nigra pars reticulata and performed a high-frequency stimulation protocol that robustly elicits long-term potentiation (LTP)-like changes in patients with Parkinson’s disease. We hypothesized that in this patient, who did not have Parkinson’s disease, the levels of inhibitory plasticity would be much greater. However, we found an unanticipated lack of plasticity in the patient with lithium-induced tremor, compared with two de novo control patients with Parkinson’s disease. This patient was successfully treated with deep brain stimulation in the vicinity of the ventral oral posterior nucleus, an area of the thalamus that receives inputs from the basal ganglia. We postulate that the lithium-induced blockade of LTP may bring about motor complications such as tremor while simultaneously contributing to the therapeutic mechanism for treating the symptoms of psychiatric disorders such as bipolar affective disorder. NEW & NOTEWORTHY Use of a dual-microelectrode technique enabled us to compare long-term potentiation (LTP)-like changes in a patient with lithium-induced tremor to that of patients with Parkinson’s disease. This study corroborated the findings in rodent brain slices that chronic lithium treatment may block LTP. Whereas a deficit in LTP may underlie the therapeutic mechanism for treating psychiatric disorders such as bipolar affective disorder, it may simultaneously contribute to consequent appearance of tremor.