Brain Stimulation最新文献

Background: Single-pulse electrical stimulation (SPES) can help guide neuromodulation therapy in an iterative process to reveal ideal circuits and degrees of engagement. Understanding the relationship between parameter input and neural output will be necessary both to build informative models of the brain's functional connectivity and to improve responses to stimulation-based neuromodulation therapies. Modulating pulse width alters the total charge delivered to neural tissue and is thought to selectively activate fibers with different diameters, potentially shifting therapeutic thresholds. The anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) are of great clinical relevance to the pathophysiology and treatment of neuropsychiatric disorders.

Objective: To provide empirical evidence for the impact of pulse width on pulse-evoked responses and promote the ability to modify specific circuits.

Methods: We measured evoked response robustness, peak amplitude, and latency to peak amplitude from depth electrode contacts in 20 epilepsy patients undergoing intracranial monitoring for treatment-refractory epilepsy.

Results: A nonlinear relationship between pulse width with evoked potential robustness was determined. Pulse width modulation is further shown to be distance-dependent, with distant connections responding maximally to a shorter pulse width.

Conclusion: These results emphasize the importance of input stimulation parameters on CCEP response magnitude and consistency and are a step towards guiding selective engagement of specific fiber populations for both research and clinical settings.

Background: In Parkinson's disease, motor network electrophysiology frequently exhibits excessive beta oscillations. The cornerstone of therapeutic efficacy lies in the ability to modulate these pathological oscillations. Transcranial alternating current stimulation (tACS), a non-invasive method that applies oscillating electric fields to modulate ongoing brain activity, offers a promising approach.

Objective: The objective of the manuscript is to investigate the dose-dependent effects of tACS on motor network cortical neurons in a Parkinson's disease model.

Methods: We recorded neuronal spike activity in the motor cortex in parkinsonian non-human primates during tACS to determine how stimulation-induced electric fields affect spike timing.

Results: Strong electric fields entrained neural activity at the stimulation frequency but altered the preferred spiking phase. Conversely, weak fields disrupted beta-band synchronization by modulating spike timing and phase preference. Frequency-matched stimulation significantly enhanced entrainment when aligned with endogenous oscillatory activity.

Conclusion: Thus, with appropriately chosen stimulation parameters, tACS exhibits significant potential for controlling and modulating pathological oscillatory patterns that are characteristic of many neurological disorders.

Stimulation of sensory vagal pathways is typically delivered via invasive, cervical vagus nerve stimulation (cVNS) or noninvasive, trans-auricular nerve stimulation (taNS). While both methods are investigated therapeutically, their effects on brain physiology remain poorly understood, hindering mechanistic insights and stimulus optimization. In 6 awake nonhuman primates, we recorded cortical vagal-evoked potentials (VEPs) from subdural electrodes placed in prefrontal, sensorimotor and parietal cortical areas, in response to cVNS or taNS. Across 478 different taNS and cVNS protocols, we varied stimulation side, intensity, frequency, pulse count, and pulse width and assessed independent effects on amplitude and latency of early (EC; 30-100 ms), intermediate (IC; 101-200 ms) and late components (LC; 201-500 ms) of VEPs. Fixed and random effects of stimulation parameters and subjects, respectively, on VEPs were assessed using a linear mixed-effects model. Overall, cVNS elicits more robust VEPs than taNS, with larger EC, IC and LC amplitudes, in both hemispheres. cVNS-elicited ECs and LCs are largest in PFC and PC areas, whereas ICs are largest in SM areas. On the other hand, taNS generally does not elicit area-specific responses. cVNS-elicited ECs have slower latency than ta-NS elicited ECs. Higher stimulation frequencies and intensities and a longer pulse width elicit larger ECs and ICs for cVNS, and to some extent for taNS. Both short and long cVNS trains elicit stronger ECs, and long trains elicit slower ICs. Earlobe stimulation elicits VEPs that partially overlap with those from taNS. In conclusion, cVNS and taNS elicit cortical VEPs in a manner consistent with distinct engagement of ascending vagal pathways, with both similarities and differences in the effects of stimulation parameters on evoked responses.

Theta and gamma oscillations are prominent features of cortical local field potentials (LFPs) and stimulation of the motor cortex at these frequencies can enhance motor learning. Phase-targeted closed-loop stimulation could provide a more precise and effective method to modulate these oscillations, particularly if stimulation parameters could harness the dynamics of the specific circuit mechanisms underpinning the generation of these activities. To investigate this, we defined the response of theta- and gamma-frequency oscillations in the motor cortex to closed-loop optogenetic stimulation of excitatory pyramidal neurons and inhibitory interneurons transfected with Channelrhodopsin-2 in awake, head-fixed RBP4-Cre (retinol-binding-protein-4) and PV-Cre (parvalbumin) mice, respectively. Phase-targeted blue-light pulses were delivered using the OscillTrack algorithm to track theta phase in the cortical LFP in real time and trigger stimulation at one of four target theta phases. Stimulation was delivered over a quarter of the target theta cycle, either as a single continuous pulse ("continuous" protocol) or three short pulses at gamma (75Hz) frequency ("gamma" protocol). Stimulation of both neuron types, using either stimulation protocol, modulated theta power in a phase-dependent manner, with continuous stimulation of excitatory neurons leading to stronger modulation. Phase-dependent amplification during stimulation of excitatory vs inhibitory neurons was offset by 90°, in line with predictions from computational models. Replay of previously recorded closed-loop stimulation patterns in an open-loop configuration failed to reproduce the same phase-specific effects, highlighting the necessity of real-time closed-loop interaction to achieve precise modulation. Additionally, stimulation of pyramidal neurons using the gamma protocol selectively amplified gamma power, independently of the target theta phase. These findings demonstrate that phase-dependent amplification of cortical theta power can be induced through targeted stimulation of local excitatory or inhibitory neurons, with the observed phase offset likely reflecting underlying circuit dynamics. This approach provides a framework for developing more effective brain stimulation strategies aimed at modulating oscillatory activity in humans.