Primary motor cortex LTP/LTD-like plasticity in probable corticobasal syndrome

Abstract

Whether the primary motor cortex (M1) contributes to the pathophysiology of corticobasal syndrome (CBS) remains unclear. In this study in patients with probable CBS, we tested whether M1 plasticity contributes to the pathophysiology of symptoms in the contralateral "less affected" limb, manifesting only parkinsonism, and in the contralateral "more affected" limb, manifesting parkinsonism plus other motor and nonmotor symptoms. In Experiment 1, we applied intermittent/continuous theta-burst stimulation (iTBS/cTBS) over the M1 contralateral to the less affected limb in 17 patients. In Experiment 2, we applied iTBS/cTBS over the M1 contralateral to the more affected limb in 14 of the 17 patients. We measured iTBS/cTBS-induced plasticity as reflected by motor-evoked potential (MEP) changes. Data were compared with those obtained in 17 healthy subjects (HS). In Experiment 1, TBS over the M1 contralateral to the less affected limb disclosed reduced plasticity in patients than in HS. In Experiment 2, in 5 of 14 patients we recorded abnormally low-amplitude MEPs, preventing the evaluation of plasticity in the M1 contralateral to the more affected limb. In the remaining nine patients, TBS disclosed abnormal plasticity characterized by high intersubject variability. In these nine patients, the response to TBS correlated with specific patients' clinical features. In the present study in patients with probable CBS, we have demonstrated heterogeneous abnormalities of M1 that contribute to the pathophysiology of this condition.

The interindividual variability of transcranial magnetic stimulation effects: Implications for diagnostic use in movement disorders

“…Responses to TBS in the most affected hemisphere in CBS have high intersubject variability and can induce response consistent with facilitation of MEP, similar to that seen in PSP. 70,90 The latter would be consistent with a common neuropathology in some patients. We considered cTBS as a "weak" measure for the differential diagnosis of PSP/CBS and other parkinsonism ( Table 2).…”

“…A smaller response to iTBS has been observed in patients with MSA and a smaller response to both iTBS and cTBS in the less affected hemisphere of CBS when compared with controls has also been shown. Responses to TBS in the most affected hemisphere in CBS have high intersubject variability and can induce response consistent with facilitation of MEP, similar to that seen in PSP . The latter would be consistent with a common neuropathology in some patients.…”

The effects of exercise on cognitive function and brain plasticity – a feasibility trial

“…This protocol has been shown to increase MEP amplitude (i.e., facilitate cortico-motor reactivity) for up to 60 minutes in healthy individuals (Wischnewski & Schutter, 2016). Once MEP amplitudes have been altered by iTBS, the time it takes for MEP amplitudes to return to their base-line levels is considered a neurophysiologic index of cortical plasticity (Oberman et al, 2010; Pascual-Leone et al, 2011; Suppa et al, 2016; Wischnewski & Schutter, 2016) (Fig. 2).…”

Corticobasal syndrome: neuroimaging and neurophysiological advances

“…More advanced repetitive TMS techniques, such as theta burst stimulation (TBS), have been used more recently to study mechanisms of synaptic plasticity in M1 in patients with CBS . In humans, synaptic plasticity can be assessed in M1 by measuring long‐term changes in motor evoked potential (MEP) amplitude following repetitive stimulation of M1 with plasticity‐inducing protocols.…”

“…In humans, synaptic plasticity can be assessed in M1 by measuring long‐term changes in motor evoked potential (MEP) amplitude following repetitive stimulation of M1 with plasticity‐inducing protocols. In particular, intermittent‐TBS elicits mechanisms of long‐term potentiation (LTP)‐like plasticity, whereas continuous‐TBS induces mechanisms of long‐term depression (LTD)‐like plasticity . LTP‐like and LTD‐like plasticity are physiological mechanisms that have been widely acknowledged to underlie motor execution and learning.…”