Deep Brain Stimulation for Medication-Refractory Aggressive and Injurious Behavior

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

Journal of Neurosurgery ◽

10.3171/2016.4.jns141704 ◽

2017 ◽

Vol 126 (4) ◽

pp. 1158-1164 ◽

Cited By ~ 4

Author(s):

Robert Micieli ◽

Adriana Lucia Lopez Rios ◽

Ricardo Plata Aguilar ◽

Luis Fernando Botero Posada ◽

William D. Hutchison

Keyword(s):

Deep Brain Stimulation ◽

Aggressive Behavior ◽

Firing Rate ◽

Brain Stimulation ◽

Single Unit ◽

Red Nucleus ◽

Posterior Hypothalamus ◽

Firing Rates ◽

Microelectrode Recordings ◽

Deep Brain

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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Patterned low-frequency deep brain stimulation induces motor deficits and modulates cortex-basal ganglia neural activity in healthy rats

Journal of Neurophysiology ◽

10.1152/jn.00929.2017 ◽

2018 ◽

Vol 120 (5) ◽

pp. 2410-2422 ◽

Cited By ~ 5

Author(s):

Chintan S. Oza ◽

David T. Brocker ◽

Christina E. Behrend ◽

Warren M. Grill

Keyword(s):

Deep Brain Stimulation ◽

Basal Ganglia ◽

Brain Stimulation ◽

Movement Disorders ◽

Neural Activity ◽

Low Frequency ◽

Oscillatory Activity ◽

Motor Deficits ◽

Motor Symptoms ◽

Deep Brain

Deep brain stimulation (DBS) is an effective therapy for movement disorders, including Parkinson’s disease (PD), although the mechanisms of action remain unclear. Abnormal oscillatory neural activity is correlated with motor symptoms, and pharmacological or DBS treatment that alleviates motor symptoms appears to suppress abnormal oscillations. However, whether such oscillatory activity is causal of motor deficits such as tremor remains unclear. Our goal was to generate abnormal oscillatory activity in the cortex-basal ganglia loop using patterned subthalamic nucleus DBS and to quantify motor behavior in awake healthy rats. Stimulation patterns were designed via model-based optimization to increase power in the low-frequency (7–11 Hz) band because these oscillations are associated with the emergence of motor symptoms in the 6-hydroxydopamine lesioned rat model of parkinsonism. We measured motor activity using a head-mounted accelerometer, as well as quantified neural activity in cortex and globus pallidus (GP), in response to 5 stimulation patterns that generated a range of 7- to 11-Hz spectral power. Stimulation patterns induced oscillatory activity in the low-frequency band in the cortex and GP and caused tremor, whereas control patterns and regular 50-Hz DBS did not generate any such effects. Neural and motor-evoked responses observed during stimulation were synchronous and time-locked to stimulation bursts within the patterns. These results identified elements of irregular patterns of stimulation that were correlated with tremor and tremor-related neural activity in the cortex and basal ganglia and may lead to the identification of the oscillatory activity and structures associated with the generation of tremor activity. NEW & NOTEWORTHY Subthalamic nucleus deep brain stimulation is a promising therapy for movement disorders such as Parkinson’s disease. Several groups reported correlation between suppression of abnormal oscillatory activity in the cortex-basal ganglia and motor symptoms, but it remains unclear whether such oscillations play a causal role in the emergence of motor symptoms. We demonstrate generation of tremor and pathological oscillatory activity in otherwise healthy rats by stimulation with patterns that produced increases in low-frequency oscillatory activity.

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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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The Effect of Deep Brain Stimulation for Movement Disorders on Emotions

PsycEXTRA Dataset ◽

10.1037/e626972012-165 ◽

2008 ◽

Author(s):

Jonathan D. Richards ◽

Paul M. Wilson ◽

Pennie S. Seibert ◽

Carin M. Patterson ◽

Caitlin C. Otto ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Movement Disorders ◽

Deep Brain

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Reoperation for device infection and erosion following deep brain stimulation implantable pulse generator placement

Journal of Neurosurgery ◽

10.3171/2019.3.jns183023 ◽

2020 ◽

Vol 133 (2) ◽

pp. 403-410 ◽

Cited By ~ 1

Author(s):

Travis J. Atchley ◽

Nicholas M. B. Laskay ◽

Brandon A. Sherrod ◽

A. K. M. Fazlur Rahman ◽

Harrison C. Walker ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Movement Disorders ◽

Pulse Generator ◽

Rank Test ◽

Implantable Pulse Generator ◽

Device Infection ◽

Deep Brain

OBJECTIVEInfection and erosion following implantable pulse generator (IPG) placement are associated with morbidity and cost for patients with deep brain stimulation (DBS) systems. Here, the authors provide a detailed characterization of infection and erosion events in a large cohort that underwent DBS surgery for movement disorders.METHODSThe authors retrospectively reviewed consecutive IPG placements and replacements in patients who had undergone DBS surgery for movement disorders at the University of Alabama at Birmingham between 2013 and 2016. IPG procedures occurring before 2013 in these patients were also captured. Descriptive statistics, survival analyses, and logistic regression were performed using generalized linear mixed effects models to examine risk factors for the primary outcomes of interest: infection within 1 year or erosion within 2 years of IPG placement.RESULTSIn the study period, 384 patients underwent a total of 995 IPG procedures (46.4% were initial placements) and had a median follow-up of 2.9 years. Reoperation for infection occurred after 27 procedures (2.7%) in 21 patients (5.5%). No difference in the infection rate was observed for initial placement versus replacement (p = 0.838). Reoperation for erosion occurred after 16 procedures (1.6%) in 15 patients (3.9%). Median time to reoperation for infection and erosion was 51 days (IQR 24–129 days) and 149 days (IQR 112–285 days), respectively. Four patients with infection (19.0%) developed a second infection requiring a same-side reoperation, two of whom developed a third infection. Intraoperative vancomycin powder was used in 158 cases (15.9%) and did not decrease the infection risk (infected: 3.2% with vancomycin vs 2.6% without, p = 0.922, log-rank test). On logistic regression, a previous infection increased the risk for infection (OR 35.0, 95% CI 7.9–156.2, p < 0.0001) and a lower patient BMI was a risk factor for erosion (BMI ≤ 24 kg/m2: OR 3.1, 95% CI 1.1–8.6, p = 0.03).CONCLUSIONSIPG-related infection and erosion following DBS surgery are uncommon but clinically significant events. Their respective timelines and risk factors suggest different etiologies and thus different potential corrective procedures.

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