Single-unit analysis of the human posterior hypothalamus and red nucleus during deep brain stimulation for aggressivity

OBJECTIVE Deep brain stimulation (DBS) of the posterior hypothalamus (PH) has been reported to be effective for aggressive behavior in a number of isolated cases. Few of these case studies have analyzed single-unit recordings in the human PH and none have quantitatively analyzed single units in the red nucleus (RN). The authors report on the properties of ongoing neuronal discharges in bilateral trajectories targeting the PH and the effectiveness of DBS of the PH as a treatment for aggressive behavior. METHODS DBS electrodes were surgically implanted in the PH of 1 awake patient with Sotos syndrome and 3 other anesthetized patients with treatment-resistant aggressivity. Intraoperative extracellular recordings were obtained from the ventral thalamus, PH, and RN and analyzed offline to discriminate single units and measure firing rates and firing patterns. Target location was based on the stereotactic coordinates used by Sano et al. in their 1970 study and the location of the dorsal border of the RN. RESULTS A total of 138 units were analyzed from the 4 patients. Most of the PH units had a slow, irregular discharge (mean [± SD] 4.5 ± 2.7 Hz, n = 68) but some units also had a higher discharge rate (16.7 ± 4.7 Hz, n = 15). Two populations of neurons were observed in the ventral thalamic region as well, one with a high firing rate (mean 16.5 ± 6.5 Hz, n = 5) and one with a low firing rate (mean 4.6 ± 2.8 Hz, n = 6). RN units had a regular firing rate with a mean of 20.4 ± 9.9 Hz and displayed periods of oscillatory activity in the beta range. PH units displayed a prolonged period of inhibition following microstimulation compared with RN units that were not inhibited. Patients under anesthesia showed a trend for lower firing rates in the PH but not in the RN. All 4 patients displayed a reduction in their aggressive behavior after surgery. CONCLUSIONS During PH DBS, microelectrode recordings can provide an additional mechanism to help identify the PH target and surrounding structures to be avoided such as the RN. PH units can be distinguished from ventral thalamic units based on their response to focal microstimulation. The RN has a characteristic higher firing rate and a pattern of beta oscillations in the spike trains. The effect of the anesthetic administered should be considered when using microelectrode recordings. The results of this study, along with previous reports, suggest that PH DBS may be an effective treatment for aggression.

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Deep Brain Stimulation for Medication-Refractory Aggressive and Injurious Behavior

Deep Brain Stimulation ◽

10.1093/med/9780190647209.003.0041 ◽

2020 ◽

pp. 217-222

Author(s):

Oscar Bernal-Pacheco ◽

Adriana Martinez Perez ◽

Mary Fonseca-Ramos

Keyword(s):

Deep Brain Stimulation ◽

Aggressive Behavior ◽

Brain Stimulation ◽

Movement Disorders ◽

Allied Health ◽

Posterior Hypothalamus ◽

Psychiatric Diseases ◽

Motor Symptoms ◽

Focus Attention ◽

Deep Brain

Aggressiveness, defined as violent and angry behavior, is a special and challenging condition that is encountered in medicine. There is frequently involvement of the patient with self-aggressiveness and automutilation, and there may be a history in relatives. Allied health personal and others may be affected by injuries and trauma caused by the patient. Lesioning of the posterior hypothalamus (PHyp) is a technique that was used successfully to control aggressiveness 40 years ago. Deep brain stimulation (DBS) has been recently used for treatment of motor symptoms of movement disorders as well as for some psychiatric diseases, and groups have also suggested that it may be useful for aggressive behavior in select circumstances. This chapter reports the case of a patient with uncontrollable aggressiveness and the implantation of DBS in the PHyp. In this case, the DBS also helped to control epilepsy and to focus attention.

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Exploring the brain through posterior hypothalamus surgery for aggressive behavior

Neurosurgical FOCUS ◽

10.3171/2017.6.focus17231 ◽

2017 ◽

Vol 43 (3) ◽

pp. E14 ◽

Cited By ~ 2

Author(s):

Michele Rizzi ◽

Andrea Trezza ◽

Giuseppe Messina ◽

Alessandro De Benedictis ◽

Angelo Franzini ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Aggressive Behavior ◽

Brain Stimulation ◽

Pharmacological Therapy ◽

Posterior Hypothalamus ◽

Hypothalamic Area ◽

Brain Functions ◽

Radiofrequency Surgery ◽

The 19Th Century ◽

Deep Brain

Neurological surgery offers an opportunity to study brain functions, through either resection or implanted neuromodulation devices. Pathological aggressive behavior in patients with intellectual disability is a frequent condition that is difficult to treat using either supportive care or pharmacological therapy. The bulk of the laboratory studies performed throughout the 19th century enabled the formulation of hypotheses on brain circuits involved in the generation of emotions. Aggressive behavior was also studied extensively. Lesional radiofrequency surgery of the posterior hypothalamus, which peaked in the 1970s, was shown to be an effective therapy in many reported series. As with other surgical procedures for the treatment of psychiatric disorders, however, this therapy was abandoned for many reasons, including the risk of its misuse. Deep brain stimulation (DBS) offers the possibility of treating neurological and psychoaffective disorders through relatively reversible and adaptable therapy. Deep brain stimulation of the posterior hypothalamus was proposed and performed successfully in 2005 as a treatment for aggressive behavior. Other groups reported positive outcomes using target and parameter settings similar to those of the original study. Both the lesional and DBS approaches enabled researchers to explore the role of the posterior hypothalamus (or posterior hypothalamic area) in the autonomic and emotional systems.

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Faculty Opinions recommendation of The effect of posterior hypothalamus region deep brain stimulation on sleep.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718114822.793487454 ◽

2013 ◽

Author(s):

Anna Cohen

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Posterior Hypothalamus ◽

Deep Brain

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Fully Automated Targeting Using Nonrigid Image Registration Matches Accuracy and Exceeds Precision of Best Manual Approaches to Subthalamic Deep Brain Stimulation Targeting in Parkinson Disease

Neurosurgery ◽

10.1227/neu.0000000000000714 ◽

2015 ◽

Vol 76 (6) ◽

pp. 756-765 ◽

Cited By ~ 21

Author(s):

Srivatsan Pallavaram ◽

Pierre-François D'Haese ◽

Wendell Lake ◽

Peter E. Konrad ◽

Benoit M. Dawant ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Image Registration ◽

Parkinson Disease ◽

Brain Stimulation ◽

Red Nucleus ◽

Nonrigid Image Registration ◽

Direct Targeting ◽

Fully Automatic ◽

Stn Dbs ◽

Deep Brain

Abstract BACKGROUND: Finding the optimal location for the implantation of the electrode in deep brain stimulation (DBS) surgery is crucial for maximizing the therapeutic benefit to the patient. Such targeting is challenging for several reasons, including anatomic variability between patients as well as the lack of consensus about the location of the optimal target. OBJECTIVE: To compare the performance of popular manual targeting methods against a fully automatic nonrigid image registration-based approach. METHODS: In 71 Parkinson disease subthalamic nucleus (STN)-DBS implantations, an experienced functional neurosurgeon selected the target manually using 3 different approaches: indirect targeting using standard stereotactic coordinates, direct targeting based on the patient magnetic resonance imaging, and indirect targeting relative to the red nucleus. Targets were also automatically predicted by using a leave-one-out approach to populate the CranialVault atlas with the use of nonrigid image registration. The different targeting methods were compared against the location of the final active contact, determined through iterative clinical programming in each individual patient. RESULTS: Targeting by using standard stereotactic coordinates corresponding to the center of the motor territory of the STN had the largest targeting error (3.69 mm), followed by direct targeting (3.44 mm), average stereotactic coordinates of active contacts from this study (3.02 mm), red nucleus-based targeting (2.75 mm), and nonrigid image registration-based automatic predictions using the CranialVault atlas (2.70 mm). The CranialVault atlas method had statistically smaller variance than all manual approaches. CONCLUSION: Fully automatic targeting based on nonrigid image registration with the use of the CranialVault atlas is as accurate and more precise than popular manual methods for STN-DBS.

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218 Target Selection for Deep Brain Stimulation in Children with Secondary Dystonia Utilizing Temporary Depth Electrodes for Stimulation and Chronic Recording

Neurosurgery ◽

10.1093/neuros/nyx417.218 ◽

2017 ◽

Vol 64 (CN_suppl_1) ◽

pp. 259-259

Author(s):

Richard Aaron Robison ◽

Diana Ferman ◽

Mark A Liker ◽

Terrence Sanger

Keyword(s):

Deep Brain Stimulation ◽

Beneficial Effect ◽

Brain Stimulation ◽

Single Unit ◽

Response To Therapy ◽

Rapid Improvement ◽

Secondary Dystonia ◽

Test Stimulation ◽

Depth Electrodes ◽

Deep Brain

Abstract INTRODUCTION The optimal target for deep brain stimulation (DBS) treatment in children with secondary dystonia is not known, and the target may vary depending on the etiology and anatomic distribution of injury in each child. We present a new technique for determining optimal neuro-anatomical targets in these patients. METHODS Up to ten depth electrodes are implanted in each child in multiple brain regions, including bilateral STN, GPi, and the VLa (Vo), VLp (Vim) and VPL nuclei of the thalamus. Each electrode had both high-impedance micro contacts to identify single unit firing and macro contacts for identifying local field potentials and for performing test stimulation. Children were monitored for up to one week with continuous recording from all electrodes and intermittent test stimulation at bilateral contact pairs. RESULTS >No single consistent pattern of abnormality was found. Most often, single-unit recording showed high firing rates in GPi, and dystonic movement correlated with activity VLa or VLp. The optimal stimulation target varied between children, with rapid improvement of dystonic postures during stimulation in either VLa, VLp or VPL. Stimulation of STN caused resolution of spasms during sleep in one child. Stimulation in GPi did not produce an immediate effect during the recording period, consistent with known latency of treatment effect. All of the children were implanted with up to 4 permanent stimulation leads connected to implanted pulse generators. Preliminary clinical observations show significant beneficial effect in all children. CONCLUSION This new method of DBS targeting identified targets that varied between children. Early response to therapy suggests a beneficial effect that exceeds what would be expected for GPi stimulation alone. This technique may increase the effectiveness of DBS in secondary dystonia and may allow application to a broader range of conditions in children not previously known to respond to stimulation.

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Evaluating and Optimizing Dentato-Rubro-Thalamic-Tract Deterministic Tractography in Deep Brain Stimulation for Essential Tremor

Operative Neurosurgery ◽

10.1093/ons/opab324 ◽

2021 ◽

Author(s):

Maarten Bot ◽

Anne-Fleur van Rootselaari ◽

Vincent Odekerken ◽

Joke Dijk ◽

Rob M A de Bie ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Essential Tremor ◽

Brain Stimulation ◽

Red Nucleus ◽

Brain Regions ◽

Superior Cerebellar Peduncle ◽

Beneficial Effects ◽

Ventral Intermediate Nucleus ◽

Cerebellar Peduncle ◽

Deep Brain

Abstract BACKGROUND Dentato-rubro-thalamic tract (DRT) deep brain stimulation (DBS) suppresses tremor in essential tremor (ET) patients. However, DRT depiction through tractography can vary depending on the included brain regions. Moreover, it is unclear which section of the DRT is optimal for DBS. OBJECTIVE To evaluate deterministic DRT tractography and tremor control in DBS for ET. METHODS After DBS surgery, DRT tractography was conducted in 37 trajectories (20 ET patients). Per trajectory, 5 different DRT depictions with various regions of interest (ROI) were constructed. Comparison resulted in a DRT depiction with highest correspondence to intraoperative tremor control. This DRT depiction was subsequently used for evaluation of short-term postoperative adverse and beneficial effects. RESULTS Postoperative optimized DRT tractography employing the ROI motor cortex, posterior subthalamic area (PSA), and ipsilateral superior cerebellar peduncle and dentate nucleus best corresponded with intraoperative trajectories (92%) and active DBS contacts (93%) showing optimal tremor control. DRT tractography employing a red nucleus or ventral intermediate nucleus of the thalamus (VIM) ROI often resulted in a more medial course. Optimal stimulation was located in the section between VIM and PSA. CONCLUSION This optimized deterministic DRT tractography strongly correlates with optimal tremor control. This technique is readily implementable for prospective evaluation in DBS target planning for ET.

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