Abnormal Striatal Dopaminergic Neurotransmission during Rest and Task Production in Spasmodic Dysphonia

Abstract

Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal gangliathalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [ 11 C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D 2 /D 3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ⌬BP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ⌬BP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ⌬BP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ⌬BP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D 2 /D 3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder.

Neural correlates of dystonic tremor: a multimodal study of voice tremor in spasmodic dysphonia

“…The putamen has been historically known to play an important role in the pathophysiology of dystonia (Berardelli et al 1985; Marsden 1984), and its functional, structural and dopaminergic abnormalities have been previously reported in SD (Haslinger et al 2005; Simonyan et al 2013; Simonyan and Ludlow 2010, 2012; Simonyan et al 2008). The putamen receives heavy projections from the laryngeal motor cortex (Simonyan et al 2009), and its lesioning has been associated with SD symptom manifestation (Lee et al 1996).…”

Alcohol responsiveness in laryngeal dystonia: a survey study

“…Taking into account that brain abnormalities in LD are not limited to the basal ganglia but include, in addition, the sensorimotor cortex and cerebellum [2, 19, 40, 42–44], effects of alcohol on GABAergic transmission may also be exerted at multiple levels. Indeed, alcohol has been shown to potentiate GABA-mediated neurotransmission in the cortex of healthy subjects and patients with myoclonus-dystonia [35, 48], decrease cerebellar hyperactivity in patients with essential tremor [8], and directly elevate the dopamine level in the nucleus accumbens in the rat [28].…”

Phenotype‐ and genotype‐specific structural alterations in spasmodic dysphonia

“…These recordings were anonymized, randomized, and blindly rated by an experienced speech‐language pathologist. SD symptoms were assessed by counting the number of SD‐characteristic voice breaks in each sentence . Information on SD onset and duration was obtained from the medical history.…”