Electrical brain stimulation (EBS) has been studied as a tool to improve speech perception. Available EBS methods compromise between precision and power and rarely consider temporal dynamics. Noninvasive EBS delivers currents to wide areas but may lack regional specificity and is susceptible to current shunting through the skin. We introduce a novel minimally-invasive electrical brain stimulation approach using clinically implanted epicranial electrodes and cranial bolts, circumventing the current shunting limitations of traditional transcranial stimulation. Two types of contacts were used in five epilepsy patients (one female) over six experimental sessions undergoing intracranial monitoring: epicranial electrodes (served as reference electrodes for clinical recordings) and cranial bolts (holding fixtures for depth electrodes). Participants monaurally listened to pseudo-randomly presented sentences from matrix sentence speech-in-noise task in 3 conditions: no-stimulation, 50 ms, or 200 ms stimulation lag relative to sentence onset. EBS parameters were 100 Hz, biphasic, amplitude-balanced, square-wave pulses where the amplitude (1-6 mA) was modulated by the ongoing speech envelope. Accuracy in the task improved in 5 of 6 sessions while not reaching significance across sessions possibly limited due to the limited number of sessions and trials (p = 0.087 and 0.068 for 50 ms and 200 ms delay, linear mixed-effects model). In 5/6 sessions, there was increased accuracy with 50 ms delay, and in 3 of those, there was further improvement with 200 ms delay. We successfully demonstrated the dynamic EBS patterns delivered through minimally-invasive electrodes during speech perception with 83% responder rate for improvement in speech perception with short latency (50 ms) and 50% with longer latency (200 ms) stimulation.
Alcohol use disorder (AUD) is a chronic relapsing brain disorder characterized by an impaired ability to stop or control alcohol consumption despite adverse social, occupational, or health consequences. AUD affects nearly one-third of adults at some point during their lives, with an associated cost of approximately $249 billion annually in the U.S. alone. The effects of alcohol consumption are expected to increase significantly during the COVID-19 pandemic, with alcohol sales increasing by approximately 54%, potentially exacerbating health concerns and risk-taking behaviors. Unfortunately, existing pharmacological and behavioral therapies for AUD are associated with poor success rates, with approximately 40% of individuals relapsing within three years of treatment.Pre-clinical studies have shown that chronic alcohol consumption leads to significant changes in synaptic function within the dorsal medial striatum (DMS), one of the brain regions associated with AUD and responsible for mediating goal-directed behavior. Specifically, chronic alcohol consumption has been associated with hyperactivity of dopamine receptor 1 (D1) medium spiny neurons (MSN) and hypoactivity of dopamine receptor 2 (D1) MSNs within the DMS. Optogenetic, chemogenetic, and transgenic approaches have demonstrated that reducing the D1/D2 MSN signaling imbalance decreases alcohol self-administration in rodent models of AUD.Here, we present an electrical stimulation approach that uses ultra-low (≤ 1 Hz) frequency (ULF) spike-timing-dependent plasticity (STDP) in mouse models of AUD to reduce DMS D1/D2 MSN signaling imbalances by stimulating D1-MSN afferents into the GPi and ACC glutamatergic projections to the DMS in a time-locked stimulation sequence. Our data suggest that GPi/ACC ULF-STDP selectively decreases DMS D1-MSN hyperactivity leading to reduced alcohol consumption without evoking undesired affective behaviors using electrical stimulation rather than approaches requiring genetic modification. This work represents a step towards fulfilling the unmet need for a reliable method of treating severe AUD through cell-type-specific control with clinically available neuromodulation tools.
θ-Burst stimulation (TBS) protocols in transcranial magnetic stimulation studies have shown improved treatment efficacy in a variety of neuropsychiatric disorders. The optimal protocol to induce neuroplasticity in invasive direct electrical stimulation approaches is not known. We report that intracranial TBS applied in human sensorimotor cortex increases local coherence of preexistent β rhythms. The effect is specific to the stimulation frequency and the stimulated network and outlasts the stimulation period by ∼3 min.
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 the natural brain activity patterns, has shown efficacy in inducing such effects in animal studies and rhythmic Transcranial Magnetic Stimulation (rTMS) studies in humans. However, little is known about the potential neuroplasticity effects of iTBS applied through intracranial electrodes in humans which could have implications for deep brain stimulation therapies. This study characterizes the physiological effects of cortical iTBS in the human cortex and compare them with single pulse alpha stimulation, another frequently used paradigm in rTMS research. We applied these stimulation paradigms to well-defined regions in the sensorimotor cortex which elicited contralateral hand or arm muscle contractions during electrical stimulation mapping in epilepsy patients implanted with intracranial electrodes. Treatment effects were evaluated using effective connectivity and beta oscillations coherence measures in areas connected to the treatment site as defined with cortico-cortical evoked potentials. Our results show that iTBS increases beta band synchronization within the sensorimotor network indicating a potential neuroplasticity effect. The effect is specific to the sensorimotor system, the beta frequency band and the stimulation pattern (no effect was found with single-pulse alpha stimulation). The effects outlasted the stimulation by three minutes. By characterizing the neurophysiological effects of iTBS within well-defined cortical networks, we hope to provide an electrophysiological framework that allows clinicians and researchers to optimize brain stimulation protocols which may have translational value.
Neural implants that deliver multi-site electrical stimulation to the nervous systems are no longer the last resort but routine treatment options for various neurological disorders. Multi-site electrical stimulation is also widely used to study nervous system function and neural circuit transformations. These technologies increasingly demand dynamic electrical stimulation and closed-loop feedback control for real-time assessment of neural function, which is technically challenging since stimulus-evoked artifacts overwhelm the small neural signals of interest. We report a novel and versatile artifact removal method that can be applied in a variety of settings, from single- to multi-site stimulation and recording and for current waveforms of arbitrary shape and size. The method capitalizes on linear electrical coupling between stimulating currents and recording artifacts, which allows us to estimate a multi-channel linear Wiener filter to predict and subsequently remove artifacts via subtraction. We confirm and verify the linearity assumption and demonstrate feasibility in a variety of recording modalities, including in vitro sciatic nerve stimulation, bilateral cochlear implant stimulation, and multi-channel stimulation and recording between the auditory midbrain and cortex. We demonstrate a vast enhancement in the recording quality with a typical artifact reduction of 25-40 dB. The method is efficient and can be scaled to arbitrary number of stimulus and recording sites, making it ideal for applications in large-scale arrays, closed-loop implants, and high-resolution multi-channel brain-machine interfaces.
