Augmenting Plasticity Induction in Human Motor Cortex by Disinhibition Stimulation

Abstract

Cellular studies showed that disinhibition, evoked pharmacologically or by a suitably timed priming stimulus, can augment long-term plasticity (LTP) induction. We demonstrated previously that transcranial magnetic stimulation evokes a period of presumably GABA(B)ergic late cortical disinhibition (LCD) in human primary motor cortex (M1). Here, we hypothesized that, in keeping with cellular studies, LCD can augment LTP-like plasticity in humans. In Experiment 1, patterned repetitive TMS was applied to left M1, consisting of 6 trains (intertrain interval, 8 s) of 4 doublets (interpulse interval equal to individual peak I-wave facilitation, 1.3-1.5 ms) spaced by the individual peak LCD (interdoublet interval (IDI), 200-250 ms). This intervention (total of 48 pulses applied over ∼45 s) increased motor-evoked potential amplitude, a marker of corticospinal excitability, in a right hand muscle by 147% ± 4%. Control experiments showed that IDIs shorter or longer than LCD did not result in LTP-like plasticity. Experiment 2 indicated topographic specificity to the M1 hand region stimulated by TMS and duration of the LTP-like plasticity of 60 min. In conclusion, GABA(B)ergic LCD offers a powerful new approach for augmenting LTP-like plasticity induction in human cortex. We refer to this protocol as disinhibition stimulation (DIS).

Transcranial magnetic stimulation follow‐up study in early Parkinson's disease: A decline in compensation with disease progression?

“…Although we acknowledge as a limitation that interhemispheric inhibition was not directly addressed in our study, previous evidence suggests reduced interhemispheric inhibition (mediated also through GABAb receptors) from the more to the less affected hemisphere in early stages of PD . Evidence in humans suggests that GABAb disinhibition within target hemisphere may lead to increased response to experimental plasticity protocol . These changes at, and perhaps before, clinical onset may allow cortical areas to compensate for the underlying deterioration in the BG output and reduce clinical progression.…”

Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions: A position paper

“…This rhythmic input/output gain modulation in turn underlies a series of higher order functional principles of neuronal oscillations, such as communication-through-coherence (Fries, 2005; 2015), hierarchical nesting as indexed by phase-power-coupling (Jensen et al, 2007, Schroeder et al, 2008), phase precession and phase coding (Lisman, 2005, Schyns et al, 2011, Jensen et al, 2014), and gating by pulsed inhibition (Jensen et al, 2010). Moreover, disinhibition, reflected in a transient deflection of the EIB towards relative excitation by release from inhibition, has been proposed as an important mechanism serving plastic processes at the network level (Letzkus et al, 2015, Cash et al, 2016). Together, these principles presumably provide a temporal framework as well as the basic computational building blocks of neuronal network interactions in a variety of sensorimotor and cognitive processes (Varela et al, 2001, VanRullen et al, 2003, Buzsaki et al, 2004, Schroeder et al, 2009).…”

The influence of sensory afferent input on local motor cortical excitatory circuitry in humans

“…More recently such studies have been used as a guide to develop plasticity protocols of increased efficacy (Cash et al . ).…”