Inducing neuroplasticity through intracranial θ-burst stimulation in the human sensorimotor cortex

Abstract

The progress of therapeutic neuromodulation greatly depends on improving stimulation parameters to most efficiently induce neuroplasticity effects. Intermittent Theta Burst stimulation (iTBS), a form of electrical stimulation that mimics natural brain activity patterns, has proved to efficiently induce such effects in animal studies and rhythmic Transcranial Magnetic Stimulation studies in humans. However, little is known about the potential neuroplasticity effects of iTBS applied through intracranial electrodes in humans. This study characterizes the physiological effects of intracranial iTBS in humans and compare them with alpha frequency stimulation, another frequently used neuromodulatory pattern. We applied these two stimulation patterns to well-defined regions in the sensorimotor cortex, which elicited contralateral hand muscle contractions during clinical mapping, in epilepsy patients implanted with intracranial electrodes. Treatment effects were evaluated using oscillatory coherence across areas connected to the treatment site, as defined with cortico-cortical evoked potentials. Our results show that iTBS increases coherence in the beta frequency band within the sensorimotor network indicating a potential neuroplasticity effect. The effect is specific to the sensorimotor system, the beta-band and the stimulation pattern, and outlasted the stimulation period by ~3 minutes. The effect occurred in 4/7 subjects depending on the build-up of the effect during iTBS treatment and other patterns of oscillatory activity related to ceiling effects within the beta-band and to pre-existent coherence within the alpha-band. By characterizing the neurophysiological effects of iTBS within well-defined cortical networks, we hope to provide an electrophysiological framework that allows clinicians/researchers to optimize brain stimulation protocols which may have translational value.

Theta-burst direct electrical stimulation remodels human brain networks

“…Understanding how TBS-patterned direct electrical stimulation induces plasticity in humans, remains critical but limited in humans in vivo, particularly in the frontal lobe. Previous studies in epilepsy patients evaluated the effects of TBS in the sensorimotor cortex, revealing modifications in beta-frequency coherence 56 . While other iEEG studies have examined TBS-induced oscillatory changes, notably increasing theta band power 12,100 , the voltage effects of TBS and the dynamics of these neural responses within and across stimulation trains remain unexplored.…”

“…This approach provides anatomically precise information about neuronal populations at a millimeter scale and temporally precise information on neural dynamics at a millisecond scale. Direct electrical TBS-patterned stimulation paired with iEEG measurements have found lasting entrainment of frequency-specific oscillations (in the theta band, 4-8 Hz) after TBS 12 , TBS-specific induced buildup of beta band coherence in the sensorimotor cortex 56 , and improvement in memory within a learning and memory task via TBS microstimulation of medial temporal lobe structures 8 . Crucially, the location of the TBS-specific responses were highly correlated with brain functional connectivity to stimulation 12 .…”

“…Crucially, the location of the TBS-specific responses were highly correlated with brain functional connectivity to stimulation 12 . Hence prior studies have demonstrated that intracranial TBS elicits neural changes persisting beyond mere seconds, shaped by the underlying functional connectivity in the brain 12,56 . However, these studies predominantly focused on oscillatory changes, overlooking potential effects on voltage responses both within and across the TBS train (in the interval between bursts) or across stimulation trains (between rounds of TBS bursts).…”

“…We chose stimulation locations that in prior studies demonstrated stimulation-induced memory or neuropsychiatric improvements in individuals, such as the anterior cingulate cortex (ACC), or temporal lobe cortex, ventrolateral prefrontal cortex (VLPFC), and dorsolateral prefrontal cortex (DLPFC) 1,[61][62][63][64][65][66][67] . Given TBS's purported ability to induce persistent neural changes 39,56,68 , we hypothesized that TBS triggers discernible signatures of changing voltage responses both within and across repeated trains of intracranial TBS. We further posited that these changes are influenced by stimulation intensity, location specificity, and the baseline functional, structural, and effective connectivity of the targeted brain network 13,43,50,[69][70][71][72][73][74][75][76] .…”

Can cerebellar theta-burst stimulation improve balance function and gait in stroke patients? A randomized controlled trial

“… 13 Intermission θ-burst stimulation (iTBS) is a novel stimulation mode of repetitive transcranial magnetic stimulation (TMS). 14 Koch et al 15 reported that cerebellar iTBS can regulate excitability in the posterior parietal cortex. Kim et al 16 used 1-Hz repetitive TMS (rTMS) to stimulate the cerebellum and found that conventional inhibitory rTMS can improve walking and balance function in patients with post-stroke ataxia.…”