Network effects of deep brain stimulation

Alhourani, Ahmad; McDowell, Michael M.; Randazzo, Michael J.; Wozny, Thomas A.; Kondylis, Efstathios; Lipski, Witold; Beck, Sarah R.; Karp, Jordan F.; Ghuman, Avniel Singh; Richardson, R. Mark

doi:10.1152/jn.00275.2015

Cited by 62 publications

(46 citation statements)

References 175 publications

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“…In addition to these two promising drugs, there are also some new perspectives concerning DBS (Wichmann and DeLong, 2016). Indeed, it has been claimed that understanding how DBS could affect multiple cortical regions downstream, would be an important advance in its use as a therapeutic approach (Alhourani et al, 2015). Understanding also the network effects of DBS will allow tailoring the treatment based on biomarkers related to those effects.…”

Section: Future Perspectivesmentioning

confidence: 99%

Old and new challenges in Parkinson's disease therapeutics

Pires

Teixeira

Mendes-Pinheiro

et al. 2017

Progress in Neurobiology

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored.

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Section: Future Perspectivesmentioning

confidence: 99%

Old and new challenges in Parkinson's disease therapeutics

Pires

Teixeira

Mendes-Pinheiro

et al. 2017

Progress in Neurobiology

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“…Deep brain stimulation (DBS) is clinically used to treat various neurological and neuropsychiatric conditions [1,2], yet despite its widespread use, its mechanisms of action are not fully understood [3e5]. The effects of DBS in humans are often studied using noninvasive functional imaging [6,7]: H 2 O 15 positron emission tomography (PET) [8,9] and functional magnetic resonance imaging (fMRI) [10e13]. These imaging techniques measure changes in hemodynamics caused by DBS in various brain regions.…”

Section: Introductionmentioning

confidence: 99%

Neurovascular coupling during deep brain stimulation

Noor

Murari

et al. 2020

Brain Stimulation

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a b s t r a c tBackground: Deep brain stimulation (DBS) is an effective treatment for movement disorders, yet its mechanisms of action remain unclear. One method used to study its circuit-wide neuromodulatory effects is functional magnetic resonance imaging (fMRI) which measures hemodynamics as a proxy of neural activity. To interpret functional imaging data, we must understand the relationship between neural and vascular responses, which has never been studied with the high frequencies used for DBS. Objective: To measure neurovascular coupling in the rat motor cortex during thalamic DBS. Method: Simultaneous intrinsic optical imaging and extracellular electrophysiology was performed in the motor cortex of urethane-anesthetized rats during thalamic DBS at 7 different frequencies. We related Maximum Change in Reflectance (MCR) from the imaging data to Integrated Evoked Potential (IEP) and change in broadband power of multi-unit (MU) activity, computing Spearman's correlation to determine the strength of these relationships. To determine the source of these effects, we studied the contributions of antidromic versus orthodromic activation in motor cortex perfusion using synaptic blockers. Results: MCR, IEP and change in MU power increased linearly to 60 Hz and saturated at higher frequencies of stimulation. Blocking orthodromic transmission only reduced the DBS-induced change in optical signal by~25%, suggesting that activation of corticofugal fibers have a major contribution in thalamic-induced cortical activation. Conclusion: DBS-evoked vascular response is related to both evoked field potentials as well as multi-unit activity.

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“…Three potential mechanisms of HFS on neuronal activity have been proposed: inhibition, excitation, and modulation. Studies have shown that HFS may suppress neuronal firing by activation of the inhibitory synapses of neural circuits (Alhourani et al, 2015), or by depletion of the neurotransmitters of excitatory synapses (Iremonger et al, 2006). However, other studies that involved animal experiments and mathematical simulations have shown that HFS may increase the firing rate of neuronal action potentials (Deniau et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

High-frequency stimulation of afferent axons alters firing rhythms of downstream neurons

Feng

Wang

et al. 2019

J. Integr. Neurosci.

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J o u r n a l o f I n t e g r a t i v e N e u r o s c i e n c eThis is an open access article under the CC BY-NC 4.0 license (https://creativecommons.org/licenses/by-nc/4.0/) Deep brain stimulation is an emerging treatment for brain disorders. However, the mechanisms of high-frequency brain stimulation are unclear. Recent studies have suggested that high-frequency stimulation might produce therapeutic effects by eliminating pathological rhythms in neuronal firing. To test the hypothesis, the present study investigated whether stimulation of axonal afferent fibers might alter firing rhythms of downstream neurons in invivo experiments with Sprague-Dawley rats. Stimulation trains of 100 Hz with one minute duration were applied to the Schaffer collaterals of hippocampus Area CA1 in anaesthetized rats. Spikes of single interneurons and pyramidal neurons in the downstream region were analyzed. The spike rhythms before, during, and after the stimulations were evaluated by analyzing the power spectrum density of autocorrelograms of the spiking sequences. The rhythms of local field potentials were also evaluated by power spectrum density. During baseline recordings, theta rhythms were obvious in the spiking sequences of both types of neuron and in the local field potentials of the stratum radiatum. However, these theta rhythms were all suppressed significantly during the stimulations. Additionally, the results of Pearson's correlation analysis showed that 20-30% variation in the theta rhythms of neuronal firing could be explained by changes of the theta rhythms in local field potentials. High-frequency axonal stimulation might prevent the original rhythmic excitation in afferent fibers and generate new excitation by stimulation pulses per se, thereby suppressing the theta rhythms of individual neuron firing and of local field potentials in the region downstream from stimulation. The results provide new evidence to support the hypothesis that high-frequency stimulation can alter the firing rhythms of neurons, which may underlie the therapeutic effects of deep brain stimulation.

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Network effects of deep brain stimulation

Cited by 62 publications

References 175 publications

Old and new challenges in Parkinson's disease therapeutics

Old and new challenges in Parkinson's disease therapeutics

Neurovascular coupling during deep brain stimulation

High-frequency stimulation of afferent axons alters firing rhythms of downstream neurons

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