Reduced cortical plasticity and GABAergic modulation in essential tremor

Abstract

Essential tremor (ET) is the most common movement disorder among adults. Cerebellar dysfunction is thought to be involved in the pathogenesis of ET; however, imaging, electrophysiological studies, and clinical observations have suggested that the cerebral cortex also may participate. We sought to investigate the possible motor cortical contribution to ET by assessing response to continuous theta-burst stimulation (cTBS), a recognized tool that can produce transient plastic changes, in the primary motor and premotor cortex of patients with ET. We compared parameters, including motor-evoked potential amplitude, cortical silent period, and short-interval intracortical inhibition, before and after applying cTBS in healthy controls and patients with ET. We found that, although cTBS applied to either the motor or premotor cortex was capable of producing a suppressive effect on motor cortical excitability in ET patients, the effects lasted for a significantly shorter time compared with the effect produced in healthy individuals. The change seen in measures of intracortical inhibition after motor cortical or premotor cTBS in healthy controls was reduced or absent in the ET patients. Tremor amplitude was decreased significantly after applying cTBS over either the motor or premotor cortex, but the tremor frequency remained unchanged. These findings suggest that inhibitory circuits within the motor cortex are aberrant and less modifiable in ET patients. The reduced plasticity in response to motor and premotor TBS supports the theory of abnormal gamma-aminobutyric acid (GABA) modulation in ET.

Investigation of Motor Cortical Plasticity and Corticospinal Tract Diffusion Tensor Imaging in Patients with Parkinsons Disease and Essential Tremor

“…Therefore, the findings of the previous study [31] do not allow the general conclusion that M1 plasticity is normal in ET. Another study that applied continuous theta-burst stimulation, a protocol that in healthy subjects leads to a long-term depression (LTD)-like decrease in MEP amplitude [34], demonstrated a lack of this type of LTD-like plasticity in ET patients [35]. The current data support the notion that M1 plasticity is impaired in ET patients with intention tremor.…”

Interindividual variability in response to continuous theta-burst stimulation in healthy adults

“…Application of cTBS to M1 and other brain areas has been used to measure abnormalities in cortical plasticity and to assess therapeutic responses to interventions aimed at restoring normal cortical plasticity in several neurological and psychiatric disorders, including Alzheimer’s disease (Freitas et al, 2011a), autism spectrum disorders and fragile X syndrome (Oberman et al, 2010, 2012, 2014, 2016), dementia (Cantone et al, 2014), epilepsy (Carrette et al, 2016), essential tremor (Chuang et al, 2014), hemispatial neglect (Cazzoli et al, 2012; Koch et al, 2012), major depression (Li et al, 2014), multiple sclerosis (Mori et al, 2013), obsessive-compulsive disorders (Wu et al, 2010; Suppa et al, 2014), Parkinson’s disease (Koch et al, 2009), schizophrenia (Poulet et al, 2009; Eberle et al, 2010; McClintock et al, 2011), stroke (Ackerley et al, 2010; Hsu et al, 2012; Di Lazzaro et al, 2013, 2016), tinnitus (Forogh et al, 2014), and Tourette syndrome (Suppa et al, 2014). …”

Recent Advances in Essential Tremor

“…Recent studies focusing on the potential role for primary motor cortex (M1) within the central oscillatory network in ET demonstrated that unilateral continuous theta burst stimulation (cTBS) of M1 cortex improves tremor in ET patients [44]. When compared to DBS, superficial cortical stimulation is less complex to perform and has a lower incidence of cerebral haemorrhage.…”