Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology

Circuit remodeling driven by pathological forms of synaptic plasticity underlies several psychiatric diseases, including addiction. Deep brain stimulation (DBS) has been applied to treat a number of neurological and psychiatric conditions, although its effects are transient and mediated by largely unknown mechanisms. Recently, optogenetic protocols that restore normal transmission at identified synapses in mice have provided proof of the idea that cocaine-adaptive behavior can be reversed in vivo. The most efficient protocol relies on the activation of metabotropic glutamate receptors, mGluRs, which depotentiates excitatory synaptic inputs onto dopamine D1 receptor medium-sized spiny neurons and normalizes drug-adaptive behavior. We discovered that acute low-frequency DBS, refined by selective blockade of dopamine D1 receptors, mimics optogenetic mGluR-dependent normalization of synaptic transmission. Consequently, there was a long-lasting abolishment of behavioral sensitization.

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Real-time removal of stimulation artifacts in closed-loop deep brain stimulation

Journal of Neural Engineering ◽

10.1088/1741-2552/ac3cc5 ◽

2021 ◽

Author(s):

Yingnan Nie ◽

Xuanjun Guo ◽

Xiao Li ◽

Xinyi Geng ◽

Yan Li ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Real Time ◽

Brain Stimulation ◽

Sampling Method ◽

Closed Loop ◽

Low Frequency ◽

Irregular Sampling ◽

Neural Feedback ◽

Deep Brain

Abstract Objective. Closed-loop deep brain stimulation (DBS) with neural feedback has shown great potential in improving the therapeutic effect and reducing side effects. However, the amplitude of stimulation artifacts is much larger than the local field potentials, which remains a bottleneck in developing a closed-loop stimulation strategy with varied parameters. Approach. We proposed an irregular sampling method for the real-time removal of stimulation artifacts. The artifact peaks were detected by applying a threshold to the raw recordings, and the samples within the contaminated period of the stimulation pulses were excluded and replaced with the interpolation of the samples prior to and after the stimulation artifact duration. This method was evaluated with both simulation signals and in vivo closed-loop DBS applications in Parkinsonian animal models. Main results. The irregular sampling method was able to remove the stimulation artifacts effectively with the simulation signals. The relative errors between the power spectral density of the recovered and true signals within a wide frequency band (2-150 Hz) were 2.14%, 3.93%, 7.22%, 7.97% and 6.25% for stimulation at 20 Hz, 60 Hz, 130 Hz, 180 Hz, and stimulation with variable low and high frequencies, respectively. This stimulation artifact removal method was verified in real-time closed-loop DBS application in vivo, and the artifacts were effectively removed during stimulation with frequency continuously changing from 130 Hz to 1 Hz and stimulation adaptive to beta oscillations. Significance. The proposed method provides an approach for real-time removal in closed-loop DBS applications, which is effective in stimulation with low frequency, high frequency, and variable frequency. This method can facilitate the development of more advanced closed-loop DBS strategies.

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Deep Brain Stimulation of the Posterior Insula in Chronic Pain: A Theoretical Framework

Brain Sciences ◽

10.3390/brainsci11050639 ◽

2021 ◽

Vol 11 (5) ◽

pp. 639

Author(s):

David Bergeron ◽

Sami Obaid ◽

Marie-Pierre Fournier-Gosselin ◽

Alain Bouthillier ◽

Dang Khoa Nguyen

Keyword(s):

Chronic Pain ◽

Electrical Stimulation ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

High Frequency ◽

Brain Lesion ◽

Low Frequency ◽

Posterior Insula ◽

Deep Brain ◽

Stimulation Of

Introduction: To date, clinical trials of deep brain stimulation (DBS) for refractory chronic pain have yielded unsatisfying results. Recent evidence suggests that the posterior insula may represent a promising DBS target for this indication. Methods: We present a narrative review highlighting the theoretical basis of posterior insula DBS in patients with chronic pain. Results: Neuroanatomical studies identified the posterior insula as an important cortical relay center for pain and interoception. Intracranial neuronal recordings showed that the earliest response to painful laser stimulation occurs in the posterior insula. The posterior insula is one of the only regions in the brain whose low-frequency electrical stimulation can elicit painful sensations. Most chronic pain syndromes, such as fibromyalgia, had abnormal functional connectivity of the posterior insula on functional imaging. Finally, preliminary results indicated that high-frequency electrical stimulation of the posterior insula can acutely increase pain thresholds. Conclusion: In light of the converging evidence from neuroanatomical, brain lesion, neuroimaging, and intracranial recording and stimulation as well as non-invasive stimulation studies, it appears that the insula is a critical hub for central integration and processing of painful stimuli, whose high-frequency electrical stimulation has the potential to relieve patients from the sensory and affective burden of chronic pain.

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Nucleus Accumbens Deep Brain Stimulation Produces Region-Specific Alterations in Local Field Potential Oscillations and Evoked Responses In Vivo

Journal of Neuroscience ◽

10.1523/jneurosci.0131-09.2009 ◽

2009 ◽

Vol 29 (16) ◽

pp. 5354-5363 ◽

Cited By ~ 92

Author(s):

C. B. McCracken ◽

A. A. Grace

Keyword(s):

Deep Brain Stimulation ◽

Nucleus Accumbens ◽

Local Field ◽

Brain Stimulation ◽

Local Field Potential ◽

Field Potential ◽

Evoked Responses ◽

Potential Oscillations ◽

Deep Brain

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The Effects of Levodopa and Deep Brain Stimulation on Subthalamic Local Field Low-Frequency Oscillations in Parkinson's Disease

Neurosignals ◽

10.1159/000336543 ◽

2013 ◽

Vol 21 (1-2) ◽

pp. 89-98 ◽

Cited By ~ 13

Author(s):

Gaia Giannicola ◽

Manuela Rosa ◽

Sara Marceglia ◽

Emma Scelzo ◽

Lorenzo Rossi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Local Field ◽

Brain Stimulation ◽

Low Frequency ◽

Low Frequency Oscillations ◽

Deep Brain

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Understanding Deep Brain Stimulation: In Vivo Metabolic Consequences of the Electrode Insertional Effect

BioMed Research International ◽

10.1155/2018/8560232 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Marta Casquero-Veiga ◽

David García-García ◽

Manuel Desco ◽

María Luisa Soto-Montenegro

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Statistical Parametric Mapping ◽

Metabolic Effects ◽

Metabolic Pattern ◽

Cortical Areas ◽

Positron Emission ◽

Male Wistar Rats ◽

Deep Brain

Deep brain stimulation (DBS) is a neurosurgery technique widely used in movement disorders, although its mechanism of action remains unclear. In fact, apart from the stimulation itself, the mechanical insertion of the electrode may play a crucial role. Here we aimed to distinguish between the insertional and the DBS effects on brain glucose metabolism. To this end, electrodes were implanted targeting the medial prefrontal cortex in five adult male Wistar rats. Positron Emission Tomography (PET) studies were performed before surgery (D0) and seven (D7) and nine days (D9) after that. DBS was applied during the 18FDG uptake of the D9 study. PET data were analysed with statistical parametric mapping. We found an electrode insertional effect in cortical areas, while DBS resulted in a more widespread metabolic pattern. The consequences of simultaneous electrode and DBS factors revealed a combination of both effects. Therefore, the insertion metabolic effects differed from the stimulation ones, which should be considered when assessing DBS protocols.

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Low frequency deep brain stimulation in the inferior colliculus ameliorates haloperidol-induced catalepsy and reduces anxiety in rats

PLoS ONE ◽

10.1371/journal.pone.0243438 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243438

Author(s):

Hannah Ihme ◽

Rainer K. W. Schwarting ◽

Liana Melo-Thomas

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Low Frequency ◽

Anxiolytic Effect ◽

Motor Deficits ◽

Sham Treatment ◽

Plus Maze ◽

Aversive Behavior ◽

The Brain ◽

Deep Brain

Deep brain stimulation (DBS) of the colliculus inferior (IC) improves haloperidol-induced catalepsy and induces paradoxal kinesia in rats. Since the IC is part of the brain aversive system, DBS of this structure has long been related to aversive behavior in rats limiting its clinical use. This study aimed to improve intracollicular DBS parameters in order to avoid anxiogenic side effects while preserving motor improvements in rats. Catalepsy was induced by systemic haloperidol (0.5mg/kg) and after 60 min the bar test was performed during which a given rat received continuous (5 min, with or without pre-stimulation) or intermittent (5 x 1 min) DBS (30Hz, 200–600μA, pulse width 100μs). Only continuous DBS with pre-stimulation reduced catalepsy time. The rats were also submitted to the elevated plus maze (EPM) test and received either continuous stimulation with or without pre-stimulation, or sham treatment. Only rats receiving continuous DBS with pre-stimulation increased the time spent and the number of entries into the open arms of the EPM suggesting an anxiolytic effect. The present intracollicular DBS parameters induced motor improvements without any evidence of aversive behavior, pointing to the IC as an alternative DBS target to induce paradoxical kinesia improving motor deficits in parkinsonian patients.

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