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Time and frequency-dependent modulation of local field potential synchronization by deep brain stimulation.

ABSTRACT: High-frequency electrical stimulation of specific brain structures, known as deep brain stimulation (DBS), is an effective treatment for movement disorders, but mechanisms of action remain unclear. We examined the time-dependent effects of DBS applied to the entopeduncular nucleus (EP), the rat homolog of the internal globus pallidus, a target used for treatment of both dystonia and Parkinson's disease (PD). We performed simultaneous multi-site local field potential (LFP) recordings in urethane-anesthetized rats to assess the effects of high-frequency (HF, 130 Hz; clinically effective), low-frequency (LF, 15 Hz; ineffective) and sham DBS delivered to EP. LFP activity was recorded from dorsal striatum (STR), ventroanterior thalamus (VA), primary motor cortex (M1), and the stimulation site in EP. Spontaneous and acute stimulation-induced LFP oscillation power and functional connectivity were assessed at baseline, and after 30, 60, and 90 minutes of stimulation. HF EP DBS produced widespread alterations in spontaneous and stimulus-induced LFP oscillations, with some effects similar across regions and others occurring in a region- and frequency band-specific manner. Many of these changes evolved over time. HF EP DBS produced an initial transient reduction in power in the low beta band in M1 and STR; however, phase synchronization between these regions in the low beta band was markedly suppressed at all time points. DBS also enhanced low gamma synchronization throughout the circuit. With sustained stimulation, there were significant reductions in low beta synchronization between M1-VA and STR-VA, and increases in power within regions in the faster frequency bands. HF DBS also suppressed the ability of acute EP stimulation to induce beta oscillations in all regions along the circuit. This dynamic pattern of synchronizing and desynchronizing effects of EP DBS suggests a complex modulation of activity along cortico-BG-thalamic circuits underlying the therapeutic effects of GPi DBS for conditions such as PD and dystonia.

SUBMITTER: McCracken CB

PROVIDER: S-EPMC4100931 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Precision targeting of specific white matter bundles that traverse the subcallosal cingulate (SCC) has been linked to efficacy of deep brain stimulation (DBS) for treatment resistant depression (TRD). Methods to confirm optimal target engagement in this heterogenous region are now critical to establish an objective treatment protocol. As yet unexamined are the time-frequency features of the SCC evoked potential (SCC-EP), including spectral power and phase-clustering. We examined these spectral features-evoked power and phase clustering-in a sample of TRD patients (n = 8) with implanted SCC stimulators. Electroencephalogram (EEG) was recorded during wakeful rest. Location of electrical stimulation in the SCC target region was the experimental manipulation. EEG was analyzed at the surface level with an average reference for a cluster of frontal sensors and at a time window identified by prior study (50-150 ms). Morlet wavelets generated indices of evoked power and inter-trial phase clustering. Enhanced phase clustering at theta frequency (4-7 Hz) was observed in every subject and was significantly correlated with SCC-EP magnitude, but only during left SCC stimulation. Stimulation to dorsal SCC evinced stronger phase clustering than ventral SCC. There was a weak correlation between phase clustering and white matter density. An increase in evoked delta power (2-4 Hz) was also coincident with SCC-EP, but was less consistent across participants. DBS evoked time-frequency features index mm-scale changes to the location of stimulation in the SCC target region and correlate with structural characteristics implicated in treatment optimization. Results also imply a shared generative mechanism (inter-trial phase clustering) between evoked potentials evinced by electrical stimulation and evoked potentials evinced by auditory/visual stimuli and behavioral tasks. Understanding how current injection impacts downstream cortical activity is essential to building new technologies that adapt treatment parameters to individual differences in neurophysiology.

Project description:The hyperkinetic symptoms of Parkinson's Disease (PD) are associated with the ensembles of interacting oscillators that cause excess or abnormal synchronous behavior within the Basal Ganglia (BG) circuitry. Delayed feedback stimulation is a closed loop technique shown to suppress this synchronous oscillatory activity. Deep Brain Stimulation (DBS) via delayed feedback is known to destabilize the complex intermittent synchronous states. Computational models of the BG network are often introduced to investigate the effect of delayed feedback high frequency stimulation on partially synchronized dynamics. In this study, we develop a reduced order model of four interacting nuclei of the BG as well as considering the Thalamo-Cortical local effects on the oscillatory dynamics. This model is able to capture the emergence of 34 Hz beta band oscillations seen in the Local Field Potential (LFP) recordings of the PD state. Train of high frequency pulses in a delayed feedback stimulation has shown deficiencies such as strengthening the synchronization in case of highly fluctuating neuronal activities, increasing the energy consumed as well as the incapability of activating all neurons in a large-scale network. To overcome these drawbacks, we propose a new feedback control variable based on the filtered and linearly delayed LFP recordings. The proposed control variable is then used to modulate the frequency of the stimulation signal rather than its amplitude. In strongly coupled networks, oscillations reoccur as soon as the amplitude of the stimulus signal declines. Therefore, we show that maintaining a fixed amplitude and modulating the frequency might ameliorate the desynchronization process, increase the battery lifespan and activate substantial regions of the administered DBS electrode. The charge balanced stimulus pulse itself is embedded with a delay period between its charges to grant robust desynchronization with lower amplitudes needed. The efficiency of the proposed Frequency Adjustment Stimulation (FAS) protocol in a delayed feedback method might contribute to further investigation of DBS modulations aspired to address a wide range of abnormal oscillatory behavior observed in neurological disorders.

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Time and frequency-dependent modulation of local field potential synchronization by deep brain stimulation.

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