Retrospective Review of Clinical Effects, Tolerability and Outcomes of Deep Brain Stimulation (DBS) and Vagal Nerve Stimulation (VNS) in Patients Aged 23 and Younger
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Targeted stimulation can be used to modulate the activity of brain networks. Previously we demonstrated that direct electrical stimulation produces predictable poststimulation changes in brain excitability. However, understanding the neural dynamics during stimulation and its relationship to poststimulation effects is limited but critical for treatment optimization. Here, we applied 10 Hz direct electrical stimulation across several cortical regions in 14 human subjects (6 males) implanted with intracranial electrodes for seizure monitoring. The stimulation train was characterized by a consistent increase in high gamma (70–170 Hz) power. Immediately post-train, low-frequency (1–8 Hz) power increased, resulting in an evoked response that was highly correlated with the neural response during stimulation. Using two measures of network connectivity, corticocortical evoked potentials (indexing effective connectivity), and theta coherence (indexing functional connectivity), we found a stronger response to stimulation in regions that were highly connected to the stimulation site. In these regions, repeated cycles of stimulation trains and rest progressively altered the stimulation response. Finally, after just 2 min (∼10%) of repetitive stimulation, we were able to predict poststimulation connectivity changes with high discriminability. Together, this work reveals a relationship between stimulation dynamics and poststimulation connectivity changes in humans. Thus, measuring neural activity during stimulation can inform future plasticity-inducing protocols. SIGNIFICANCE STATEMENT Brain stimulation tools have the potential to revolutionize the treatment of neuropsychiatric disorders. Despite the widespread use of brain stimulation techniques such as transcranial magnetic stimulation, the therapeutic efficacy of these technologies remains suboptimal. This is in part because of a lack of understanding of the dynamic neural changes that occur during stimulation. In this study, we provide the first detailed characterization of neural activity during plasticity induction through intracranial electrode stimulation and recording in 14 medication-resistant epilepsy patients. These results fill a missing gap in our understanding of stimulation-induced plasticity in humans. In the longer-term, these data will also guide our translational efforts toward non-invasive, personalized, closed-loop neuromodulation therapy for neurological and psychiatric disorders in humans.
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Stimulation of the brain for the treatment of epilepsy, indirectly via the vagus nerve and directly through intracranial targets, is feasible and has increased in use and complexity over the past 10 years. Vagus nerve stimulation is widely applied and the present indications and outcomes together with possible ways in which the treatment could be refined are reviewed. The application of stimulation to deep-brain targets is also reviewed along with present practice and results. Possible developments in the use of direct intracranial stimulation are also considered.
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Researchers have used direct electrical brain stimulation to treat a range of neurological and psychiatric disorders. However, for brain stimulation to be maximally effective, clinicians and researchers should optimize stimulation parameters according to desired outcomes.The goal of our large-scale study was to comprehensively evaluate the effects of stimulation at different parameters and locations on neuronal activity across the human brain.To examine how different kinds of stimulation affect human brain activity, we compared the changes in neuronal activity that resulted from stimulation at a range of frequencies, amplitudes, and locations with direct human brain recordings. We recorded human brain activity directly with electrodes that were implanted in widespread regions across 106 neurosurgical epilepsy patients while systematically stimulating across a range of parameters and locations.Overall, stimulation most often had an inhibitory effect on neuronal activity, consistent with earlier work. When stimulation excited neuronal activity, it most often occurred from high-frequency stimulation. These effects were modulated by the location of the stimulating electrode, with stimulation sites near white matter more likely to cause excitation and sites near gray matter more likely to inhibit neuronal activity.By characterizing how different stimulation parameters produced specific neuronal activity patterns on a large scale, our results provide an electrophysiological framework that clinicians and researchers may consider when designing stimulation protocols to cause precisely targeted changes in human brain activity.
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Brain stimulation
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Electrical brain stimulation
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Abstract Researchers have used direct electrical brain stimulation to treat a range of neurological and psychiatric disorders. However, for brain stimulation to be maximally effective, clinicians and researchers should optimize stimulation parameters according to desired outcomes. To examine how different kinds of stimulation affect human brain activity, we compared the changes in neuronal activity that resulted from stimulation at a range of frequencies, amplitudes, and locations with direct human brain recordings. We recorded human brain activity directly with electrodes that were implanted in widespread regions across 106 neurosurgical epilepsy patients while systematically stimulating across a range of parameters and locations. Overall, stimulation most often had an inhibitory effect on neuronal activity, consistent with earlier work. When stimulation excited neuronal activity, it most often occurred from high-frequency stimulation. These effects were modulated by the location of the stimulating electrode, with stimulation sites near white matter more likely to cause excitation and sites near gray matter more likely to inhibit neuronal activity. By characterizing how different stimulation parameters produced specific neuronal activity patterns on a large scale, our results help guide clinicians and researchers when designing stimulation protocols to cause precisely targeted changes in human brain activity.
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Objective.Transcutaneous vagus nerve stimulation (tVNS) is a form of non-invasive brain stimulation that delivers a sequence of electrical pulses to the auricular branch of the vagus nerve and is used increasingly in the treatment of a number of health conditions such as epilepsy and depression. Recent research has focused on the efficacy of tVNS to treat different medical conditions, but there is little conclusive evidence concerning the optimal stimulation parameters. There are relatively few studies that have combined tVNS with a neuroimaging modality, and none that have attempted simultaneous magnetoencephalography (MEG) and tVNS due to the presence of large stimulation artifacts produced by the electrical stimulation which are many orders of magnitude larger than underlying brain activity.Approach.The aim of this study is to investigate the utility of MEG to gain insight into the regions of the brain most strongly influenced by tVNS and how variation of the stimulation parameters can affect this response in healthy participants.Main results.We have successfully demonstrated that MEG can be used to measure brain response to tVNS. We have also shown that varying the stimulation frequency can lead to a difference in brain response, with the brain also responding in different anatomical regions depending on the frequency.Significance.The main contribution of this paper is to demonstrate the feasibility of simultaneous pulsed tVNS and MEG recording, allowing direct investigation of the changes in brain activity that result from different stimulation parameters. This may lead to the development of customised therapeutic approaches for the targeted treatment of different conditions.
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