Centromedian-Parafascicular Deep Brain Stimulation Induces Differential Functional Inhibition of the Motor, Associative, and Limbic Circuits in Large Animals

Kim, Joo Pyung; Min, Hoon Ki; Knight, Emily; Duffy, Penelope S.; Abulseoud, Osama A.; Marsh, Michael P.; Kelsey, Katherine M.; Blaha, Charles D.; Bennet, Kevin E.; Frye, Mark A.; Lee, Kendall H.

doi:10.1016/j.biopsych.2013.06.024

Cited by 47 publications

(47 citation statements)

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“…Given the ability of fornix stimulation to modulate dopaminergic transmission in the NAc, global BOLD changes were determined following pharmacological blockade of dopamine and glutamate receptors in the NAc to determine the functional connectivity between the medial limbic and corticolimbic circuits (Kim et al, 2013; Min et al, 2012). Rather than investigating differential dopamine D1-like and D2-like receptor actions in the NAc the D1/D2 dopamine receptor antagonist α-flupenthixol was employed.…”

Section: Resultsmentioning

confidence: 99%

“…All experiments began with stimulating lead implantation in the fornix, followed by fMRI and intracranial drug microinfusions or carbon fiber microelectrode implantation and FSCV (Figure 1A). In order to accurately and consistently implant the DBS electrode lead while minimizing inter-subject variability, high-resolution image-based targeting was performed as previously described (Min et al, 2012; Kim et al, 2013). The DBS electrode was implanted anterior and parallel to the medial portion of the fornix, in order to avoid penetrating the tract, as damage to these fibers is known to cause memory deficits (Laxton et al, 2010; Tsivilis et al, 2008; Vann et al, 2009; Wilson et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

“…DBS electrode targeting and implantation was performed with an MR image-guided Leksell stereotactic targeting system (Elekta Inc., Stockholm, Sweden) modified for large animals (Min et al, 2012; Kim et al, 2013). A 3 Tesla MR scanner (General Electric Healthcare, Wakasha, WI; Signa HDx, 16× software) with a custom four-channel transmit-receive radiofrequency coil was used for preoperative anatomical imaging.…”

Section: Methodsmentioning

confidence: 99%

“…Double-gamma hemodynamic response function (onset = 6 sec, time to response peak = 11 sec, time to undershoot peak = 21 sec, response undershoot ratio = 3) correlated voxel-wise BOLD signal changes with the given stimulus protocol were calculated by linear regression. For group analysis, the fMRI data were co-registered to the anatomical 3D MPRAGE images using acquired 2D GRE-EPI images and 3D swine brain atlas, as previously described (Min et al, 2012; Kim et al, 2013). …”

Section: Methodsmentioning

confidence: 99%

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Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens

et al. 2016

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Introduction Deep brain stimulation (DBS) is a circuit-based treatment shown to relieve symptoms from multiple neurologic and neuropsychiatric disorders. In order to treat the memory deficit associated with Alzheimer's disease (AD), several clinical trials have tested the efficacy of DBS near the fornix. Early results from these studies indicated that patients who received fornix DBS experienced an improvement in memory and quality of life, yet the mechanisms behind this effect remain controversial. It is known that transmission between the medial limbic and corticolimbic circuits plays an integral role in declarative memory, and dysfunction at the circuit level results in various forms of dementia, including AD. Here, we aimed to determine the potential underlying mechanism of fornix DBS by examining the functional circuitry and brain structures engaged by fornix DBS. Methods A multimodal approach was employed to examine global and local temporal changes that occur in an anesthetized swine model of fornix DBS. Changes in global functional activity were measured by functional MRI (fMRI), and local neurochemical changes were monitored by fast scan cyclic voltammetry (FSCV) during electrical stimulation of the fornix. Additionally, intracranial microinfusions into the nucleus accumbens (NAc) were performed to investigate the global activity changes that occur with dopamine and glutamate receptor-specific antagonism. Results Hemodynamic responses in both medial limbic and corticolimbic circuits measured by fMRI were induced by fornix DBS. Additionally, fornix DBS resulted in increases in dopamine oxidation current (corresponding to dopamine efflux) monitored by FSCV in the NAc. Finally, fornix DBS-evoked hemodynamic responses in the amygdala and hippocampus decreased following dopamine and glutamate receptor antagonism in the NAc. Conclusions The present findings suggest that fornix DBS modulates dopamine release on presynaptic dopaminergic terminals in the NAc, involving excitatory glutamatergic input, and that the medial limbic and corticolimbic circuits interact in a functional loop.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens

et al. 2016

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“…In this regard, a recent study investigating centromedial/parafascicular DBS in a large animal model supports that thalamic DBS has an inhibitory effect in regions that contribute to impaired sensory-motor and emotional processing (Kim et al, 2013). Only more recently the GPi has also been considered as a DBS target to treat Tourette syndrome.…”

Section: Current Theory Of Dbs On Modulating Bg Dysfunctionmentioning

confidence: 93%

Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation

Cunha

Boschen

Gómez-A

et al. 2015

Neuroscience & Biobehavioral Reviews

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This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson’s disease, Huntington’s disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms.

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CM‐Pf deep brain stimulation in polyneuromodulation for epilepsy

Tatum,

Freund,

Middlebrooks

et al. 2024

Epileptic Disorders

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ObjectiveNeuromodulation is a viable option for patients with drug‐resistant epilepsies. We reviewed the management of patients with two deep brain neurostimulators. In addition, patients implanted with a device targeting the centromedian‐parafascicular (CM‐Pf) nuclear complex supplements this report to provide an illustrative case to implantation and programming a patient with three active devices.MethodsA narrative review using PubMed and Embase identified patients with drug‐resistant epilepsy implanted with more than one neurostimulator was performed. Combinations of vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS) were identified. We provide a background of a newly reported case of an adult with a triple implant eventually responding to CM‐Pf DBS as the third implant following suboptimal benefit from VNS and RNS.ResultsIn review of the literature, dual‐device therapy is increasing in reports of use with combinations of VNS, RNS, and DBS to treat patients with drug‐resistant epilepsy. We review dual‐device implants with thalamic DBS device combinations, functional neural networks, and programming patients with dual devices. CM‐Pf is a new target for DBS and has shown a variable response in focal epilepsy. We report the unique case of 28‐year‐old male with drug‐resistant focal epilepsy who experienced a 75% seizure reduction with CM‐Pf DBS as his third device after suboptimal responses to VNS and RNS. After 9 months, he also experienced seizure freedom from recurrent focal to bilateral tonic–clonic seizures. No medical or surgical complications or safety issues were encountered.ConclusionWe demonstrate safety and feasibility in an adult combining active VNS, RNS, and CM‐Pf DBS. Patients with dual‐device therapy who experience a suboptimal response to initial device use at optimized settings should not be considered a neuromodulation “failure.” Strategies to combine devices require a working knowledge of brain networks.

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Centromedian-Parafascicular Deep Brain Stimulation Induces Differential Functional Inhibition of the Motor, Associative, and Limbic Circuits in Large Animals

Cited by 47 publications

References 111 publications

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens

Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation

CM‐Pf deep brain stimulation in polyneuromodulation for epilepsy

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