scholarly journals Altered sleep intensity upon DBS to hypothalamic sleep-wake centers in rats

2021 ◽  
Author(s):  
Sophie Masneuf ◽  
Lukas L. Imbach ◽  
Fabian Buechele ◽  
Giovanni Colacicco ◽  
Marco Penner ◽  
...  
Keyword(s):  
High Frequency ◽  
Slow Wave Sleep ◽  
Spectral Power ◽  
High Frequency Stimulation ◽  
Delta Power ◽  
Bipolar Stimulation ◽  
Frequency Stimulation ◽  
Ventrolateral Preoptic Nucleus ◽  
And Behavior ◽  
Deep Brain

Deep brain stimulation (DBS) has been scarcely investigated in the field of sleep research. We hypothesize that DBS onto hypothalamic sleep- and wake-promoting centers will produce significant neuromodulatory effects, and potentially become a therapeutic strategy for patients suffering severe, drug-refractory sleep-wake disturbances. We aimed to investigate whether continuous electrical high-frequency DBS, such as that often implemented in clinical practice, in the ventrolateral preoptic nucleus (VLPO) or the perifornical area of the posterior lateral hypothalamus (PeFLH), significantly modulates sleep-wake characteristics and behavior. We implanted healthy rats with electroencephalographic/electromyographic electrodes and recorded vigilance states in parallel to bilateral bipolar stimulation of VLPO and PeFLH at 125 Hz at 90 microA over 24 h to test the modulating effects of DBS on sleep-wake proportions, stability and spectral power in relation to baseline. We unexpectedly found that VLPO DBS at 125 Hz deepens slow-wave sleep as measured by increased delta power, while sleep proportions and fragmentation remain unaffected. Thus, the intensity, but not the amount of sleep or its stability, is modulated. Similarly, the proportion and stability of vigilance states remained altogether unaltered upon PeFLH DBS but, in contrast to VLPO, 125 Hz stimulation unexpectedly weakened SWS, evidenced by reduced delta power. This study provides novel insights into non-acute functional outputs of major sleep-wake centers in the rat brain in response to electrical high-frequency stimulation, a paradigm frequently used in human DBS. In the conditions assayed, while exerting no major effects on sleep-wake architecture, hypothalamic high-frequency stimulation arises as a provocative sleep intensity-modulating approach.

scholarly journals Altered sleep intensity upon DBS to hypothalamic sleep–wake centers in rats

2021 ◽  
Vol 12 (1) ◽  
pp. 611-625
Author(s):  
Sophie Masneuf ◽  
Lukas L. Imbach ◽  
Fabian Büchele ◽  
Giovanni Colacicco ◽  
Marco Penner ◽  
...  
Keyword(s):  
High Frequency ◽  
Slow Wave Sleep ◽  
Spectral Power ◽  
High Frequency Stimulation ◽  
Delta Power ◽  
Bipolar Stimulation ◽  
Frequency Stimulation ◽  
Ventrolateral Preoptic Nucleus ◽  
And Behavior ◽  
Deep Brain

Abstract Deep brain stimulation (DBS) has been scarcely investigated in the field of sleep research. We hypothesize that DBS onto hypothalamic sleep- and wake-promoting centers will produce significant neuromodulatory effects and potentially become a therapeutic strategy for patients suffering severe, drug-refractory sleep–wake disturbances. We aimed to investigate whether continuous electrical high-frequency DBS, such as that often implemented in clinical practice, in the ventrolateral preoptic nucleus (VLPO) or the perifornical area of the posterior lateral hypothalamus (PeFLH), significantly modulates sleep–wake characteristics and behavior. We implanted healthy rats with electroencephalographic/electromyographic electrodes and recorded vigilance states in parallel to bilateral bipolar stimulation of VLPO and PeFLH at 125 Hz and 90 µA over 24 h to test the modulating effects of DBS on sleep–wake proportions, stability and spectral power in relation to the baseline. We unexpectedly found that VLPO DBS at 125 Hz deepens slow-wave sleep (SWS) as measured by increased delta power, while sleep proportions and fragmentation remain unaffected. Thus, the intensity, but not the amount of sleep or its stability, is modulated. Similarly, the proportion and stability of vigilance states remained altogether unaltered upon PeFLH DBS but, in contrast to VLPO, 125 Hz stimulation unexpectedly weakened SWS, as evidenced by reduced delta power. This study provides novel insights into non-acute functional outputs of major sleep–wake centers in the rat brain in response to electrical high-frequency stimulation, a paradigm frequently used in human DBS. In the conditions assayed, while exerting no major effects on the sleep–wake architecture, hypothalamic high-frequency stimulation arises as a provocative sleep intensity-modulating approach.

Modulation of saccades in humans by electrical stimulation of the posterior subthalamic area

2020 ◽  
Vol 132 (4) ◽  
pp. 1218-1226
Author(s):  
Omar K. Bangash ◽  
Arosha S. Dissanayake ◽  
Shirley Knight ◽  
John Murray ◽  
Megan Thorburn ◽  
...  
Keyword(s):  
Eye Movements ◽  
High Frequency ◽  
Animal Studies ◽  
Saccadic Eye Movements ◽  
Zona Incerta ◽  
High Frequency Stimulation ◽  
Guide Tube ◽  
Active Electrode ◽  
Frequency Stimulation ◽  
Deep Brain

OBJECTIVEPosterior subthalamic area (PSA) deep brain stimulation (DBS) targeting the zona incerta (ZI) is an emerging treatment for tremor syndromes, including Parkinson’s disease (PD) and essential tremor (ET). Evidence from animal studies has indicated that the ZI may play a role in saccadic eye movements via pathways between the ZI and superior colliculus (incerto-collicular pathways). PSA DBS permitted testing this hypothesis in humans.METHODSSixteen patients (12 with PD and 4 with ET) underwent DBS using the MRI-directed implantable guide tube technique. Active electrode positions were confirmed at the caudal ZI. Eye movements were tested using direct current electrooculography (EOG) in the medicated state pre- and postoperatively on a horizontal predictive task subtending 30°. Postoperative assessments consisted of stimulation-off, constituting a microlesion (ML) condition, and high-frequency stimulation (HFS; frequency = 130 Hz) up to 3 V.RESULTSWith PSA HFS, the first saccade amplitude was significantly reduced by 10.4% (95% CI 8.68%–12.2%) and 12.6% (95% CI 10.0%–15.9%) in the PD and ET groups, respectively. With HFS, peak velocity was reduced by 14.7% (95% CI 11.7%–17.6%) in the PD group and 27.7% (95% CI 23.7%–31.7%) in the ET group. HFS led to PD patients performing 21% (95% CI 16%–26%) and ET patients 31% (95% CI 19%–38%) more saccadic steps to reach the target.CONCLUSIONSPSA DBS in patients with PD and ET leads to hypometric, slowed saccades with an increase in the number of steps taken to reach the target. These effects contrast with the saccadometric findings observed with subthalamic nucleus DBS. Given the location of the active contacts, incerto-collicular pathways are likely responsible. Whether the acute finding of saccadic impairment persists with chronic PSA stimulation is unknown.

Stereotactic coordinates associated with facial musculature contraction during high-frequency stimulation of the subthalamic nucleus

2009 ◽  
Vol 110 (6) ◽  
pp. 1317-1321 ◽  
Author(s):  
Alessandra A. Gorgulho ◽  
Donald C. Shields ◽  
Dennis Malkasian ◽  
Eric Behnke ◽  
Antonio A. F. DeSalles
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
High Frequency ◽  
Electrical Current ◽  
High Frequency Stimulation ◽  
Facial Musculature ◽  
Frequency Stimulation ◽  
Deep Brain ◽  
Stimulation Of

Object High-frequency stimulation of the subthalamic nucleus (STN) in patients with parkinsonian symptoms is often used to ameliorate debilitating motor symptoms associated with this condition. However, individual variability in the shape and orientation of this relatively small nucleus results in multiple side effects related to the spread of electrical current to surrounding structures. Specifically, contraction of the muscles of facial expression is noted in a small percentage of patients, although the precise mechanism remains poorly understood. Methods Facial muscle contraction was triggered by high-frequency stimulation of 49 contacts in 18 patients undergoing deep brain stimulation of the STN. The mean coordinates of these individual contacts relative to the anterior commissure–posterior commissure midpoint (also called the midcommissural point) were calculated to determine the location or structure(s) most often associated with facial contraction during physiological macrostimulation. Results The x, y, and z coordinates associated with contraction of the facial musculature were found to be 11.52, 1.29, and 1.15 mm lateral, posterior, and inferior to the midcommissural point, respectively. This location, along the lateral-anterior-superior border of the STN, may allow for the spread of electrical current to the fields of Forel, zona incerta, and/or descending corticospinal/corticobulbar tracts. Because stimulation of corticobulbar tracts produces similar findings, these results are best explained by the spread of electrical current to nearby internal capsule axons coursing lateral to the STN. Conclusions Thus, if intraoperative deep brain stimulation lead testing results in facial musculature contraction, placement of the electrode in a more medial, posterior position may reduce the amount of current spread to corticobulbar fibers and resolve this side effect.

scholarly journals Deep Brain Stimulation Alleviates Parkinsonian Bradykinesia by Regularizing Pallidal Activity

2010 ◽  
Vol 104 (2) ◽  
pp. 911-921 ◽  
Author(s):  
Alan D. Dorval ◽  
Alexis M. Kuncel ◽  
Merrill J. Birdno ◽  
Dennis A. Turner ◽  
Warren M. Grill
Keyword(s):  
Deep Brain Stimulation ◽  
Basal Ganglia ◽  
Brain Stimulation ◽  
High Frequency ◽  
High Frequency Stimulation ◽  
Motor Symptoms ◽  
Transmission Errors ◽  
Symptom Alleviation ◽  
Frequency Stimulation ◽  
Deep Brain

Deep brain stimulation (DBS) of the basal ganglia can alleviate the motor symptoms of Parkinson's disease although the therapeutic mechanisms are unclear. We hypothesize that DBS relieves symptoms by minimizing pathologically disordered neuronal activity in the basal ganglia. In human participants with parkinsonism and clinically effective deep brain leads, regular (i.e., periodic) high-frequency stimulation was replaced with irregular (i.e., aperiodic) stimulation at the same mean frequency (130 Hz). Bradykinesia, a symptomatic slowness of movement, was quantified via an objective finger tapping protocol in the absence and presence of regular and irregular DBS. Regular DBS relieved bradykinesia more effectively than irregular DBS. A computational model of the relevant neural structures revealed that output from the globus pallidus internus was more disordered and thalamic neurons made more transmission errors in the parkinsonian condition compared with the healthy condition. Clinically therapeutic, regular DBS reduced firing pattern disorder in the computational basal ganglia and minimized model thalamic transmission errors, consistent with symptom alleviation by clinical DBS. However, nontherapeutic, irregular DBS neither reduced disorder in the computational basal ganglia nor lowered model thalamic transmission errors. Thus we show that clinically useful DBS alleviates motor symptoms by regularizing basal ganglia activity and thereby improving thalamic relay fidelity. This work demonstrates that high-frequency stimulation alone is insufficient to alleviate motor symptoms: DBS must be highly regular. Descriptive models of pathophysiology that ignore the fine temporal resolution of neuronal spiking in favor of average neural activity cannot explain the mechanisms of DBS-induced symptom alleviation.

scholarly journals Therapeutic mechanisms of high-frequency stimulation in Parkinson’s disease and neural restoration via loop-based reinforcement

2015 ◽  
Vol 112 (6) ◽  
pp. E586-E595 ◽  
Author(s):  
Sabato Santaniello ◽  
Michelle M. McCarthy ◽  
Erwin B. Montgomery ◽  
John T. Gale ◽  
Nancy Kopell ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
High Frequency ◽  
Normal Activity ◽  
High Frequency Stimulation ◽  
Firing Patterns ◽  
Frequency Stimulation ◽  
Therapeutic Mechanisms ◽  
Combined Impact ◽  
Deep Brain

High-frequency deep brain stimulation (HFS) is clinically recognized to treat parkinsonian movement disorders, but its mechanisms remain elusive. Current hypotheses suggest that the therapeutic merit of HFS stems from increasing the regularity of the firing patterns in the basal ganglia (BG). Although this is consistent with experiments in humans and animal models of Parkinsonism, it is unclear how the pattern regularization would originate from HFS. To address this question, we built a computational model of the cortico-BG-thalamo-cortical loop in normal and parkinsonian conditions. We simulated the effects of subthalamic deep brain stimulation both proximally to the stimulation site and distally through orthodromic and antidromic mechanisms for several stimulation frequencies (20–180 Hz) and, correspondingly, we studied the evolution of the firing patterns in the loop. The model closely reproduced experimental evidence for each structure in the loop and showed that neither the proximal effects nor the distal effects individually account for the observed pattern changes, whereas the combined impact of these effects increases with the stimulation frequency and becomes significant for HFS. Perturbations evoked proximally and distally propagate along the loop, rendezvous in the striatum, and, for HFS, positively overlap (reinforcement), thus causing larger poststimulus activation and more regular patterns in striatum. Reinforcement is maximal for the clinically relevant 130-Hz stimulation and restores a more normal activity in the nuclei downstream. These results suggest that reinforcement may be pivotal to achieve pattern regularization and restore the neural activity in the nuclei downstream and may stem from frequency-selective resonant properties of the loop.

The regulation of adult rodent hippocampal neurogenesis by deep brain stimulation

2008 ◽  
Vol 108 (1) ◽  
pp. 132-138 ◽  
Author(s):  
Hiroki Toda ◽  
Clement Hamani ◽  
Adrian P. Fawcett ◽  
William D. Hutchison ◽  
Andres M. Lozano
Keyword(s):  
Electrical Stimulation ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
High Frequency ◽  
Hippocampal Neurogenesis ◽  
High Frequency Stimulation ◽  
Sham Surgery ◽  
Frequency Stimulation ◽  
Deep Brain ◽  
Stimulation Of

Object To examine the influence of deep brain stimulation on hippocampal neurogenesis in an adult rodent model. Methods Rats were anesthetized and treated for 1 hour with electrical stimulation of the anterior nucleus of the thalamus (AN) or sham surgery. The animals were injected with 5′-bromo-2′-deoxyuridine (BrdU) 1–7 days after surgery and killed 24 hours or 28 days later. The authors counted the BrdU-positive cells in the dentate gyrus (DG) of the hippocampus. To investigate the fate of these cells, they also stained sections for doublecortin, NeuN, and GFAP and analyzed the results with confocal microscopy. In a second set of experiments they assessed the number of DG BrdU-positive cells in animals treated with corticosterone (a known suppressor of hippocampal neurogenesis) and sham surgery, corticosterone and AN stimulation, or vehicle and sham surgery. Results Animals receiving AN high-frequency stimulation (2.5 V, 90 μsec, 130 Hz) had a 2- to 3-fold increase in the number of DG BrdU-positive cells compared with nonstimulated controls. This increase was not seen with stimulation at 10 Hz. Most BrdU-positive cells assumed a neuronal cell fate. As expected, treatment with corticosterone significantly reduced the number of DG BrdU-positive cells. This steroid-induced reduction of neurogenesis was reversed by AN stimulation. Conclusions High-frequency stimulation of the AN increases the hippocampal neurogenesis and restores experimentally suppressed neurogenesis. Interventions that increase hippocampal neurogenesis have been associated with enhanced behavioral performance. In this context, it may be possible to use electrical stimulation to treat conditions associated with impairment of hippocampal function.

Sign in / Sign up

Export Citation Format

Share Document