Neurobiological Background for Performing Surgical Intervention in the Inferior Thalamic Peduncle for Treatment of Major Depression Disorders

ABSTRACT OBJECTIVE: To present a review of evidence for an inhibitory thalamo-orbitofrontal system related to physiopathology of major depression disorders (MDDs) and to postulate that interfering with hyperactivity of the thalamo-orbitofrontal system by means of chronic high-frequency electrical stimulation of its main fiber connection, the inferior thalamic peduncle (ITP), may result in an improvement in patients with MDD. METHODS: Experimentally, the thalamo-orbitofrontal system has been proposed as part of the nonspecific thalamic system. Under normal conditions, the nonspecific thalamic system induces characteristic electrocortical synchronization in the form of recruiting responses that mimic some sleep stages. It also inhibits input of irrelevant sensory stimuli, thus facilitating the process of selective attention. Permanent disruption of the system, via lesioning or temporary inactivation through cooling of the ITP with cryoprobes, results in a state of hyperkinesia, increased attention, and cortical desynchronization. RESULTS: Surgical lesioning of the medial part of orbitofrontal cortex and white matter overlying area 13, which includes the ITP, may result in significant improvement in MDD. Imaging studies (functional magnetic resonance imaging and positron emission tomography) consistently demonstrate hyperactivity in the orbitofrontal cortex and midline thalamic regions during episodes of MDD. This hyperactivity decreases with efficient control of MDD by medical treatment, indicating that orbitofrontal cortex and midline thalamic overactivity are related to the depressive condition. Conversely, noradrenergic and serotoninergic systems in the frontal lobes have been implicated in the pathophysiology of MDD. Although noradrenergic receptor density in the frontal lobe is consistently increased in depressed patients who commit suicide, 5-hydroxytryptamine reuptake blockers, which are potent antidepressive drugs, decrease hypermetabolism in the orbital frontal cortex in MDD. Therefore, the serotonin hypothesis for depression postulates that norepinephrine and serotonin in the frontal lobes are required to maintain antidepressive responsiveness. Dysregulation of the secretion of both neurotransmitters initiates overactivity of orbitofrontal cortex, resulting in depression. It is possible that surgical interventions in this region, including electrical stimulation of ITP, disrupt adrenergic and serotoninergic dysregulation in patients with MDD. CONCLUSION: Circumscribed lesions or electrical stimulation of the ITP, a discrete target easily identified by electrophysiological studies, may improve MDD. Electrical stimulation may have the advantage of being less invasive and more adjustable to patient needs.

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Utility of Periurethral Electric Stimulation to Reduce Voiding Frequency in Rats

Journal of Medical Devices ◽

10.1115/1.3147250 ◽

2009 ◽

Vol 3 (2) ◽

Author(s):

A. Forrest ◽

Y. Zhang ◽

A. Bicek ◽

G. Timm

Keyword(s):

Electrical Stimulation ◽

Electric Stimulation ◽

The United States ◽

The Body ◽

Bladder Pressure ◽

Urinary Continence ◽

Sprague Dawley ◽

Promising Alternative ◽

Surgical Interventions ◽

Stimulation Of

Urinary continence is maintained through coordination of electrical (nervous) and mechanical (muscles, ligaments and other structures) systems in the body. During micturition, the central nervous system sends a signal to the detrusor and sphincter muscles to coordinate voiding. Pathological problems can undermine either of the two systems and result in urinary incontinence (UI). Thirteen million people in the United States live with UI. Clinical treatments to date are largely mechanical in nature, restoring function through surgical interventions. However, electrically-based treatments, such as electric stimulation, offer a promising alternative. Here we investigate the utility of electrical stimulation of the periurethral neuromusculature to reduce voiding contractions in well-controlled animal experiments. Female Sprague Dawley rats were anesthetized with a ketamine/xylazine/acepromazine cocktail and the bladder was catheterized through a small incision in the bladder dome and was infused with saline. Continuous filling of the bladder triggered related cycles of voiding which was identified through bladder pressure increases and visual urination. The pubic symphysis bone was cut to expose the urethra and a stimulating electrode was placed in the periurethral region. The electrical stimulation parameters were 2.8 mA of current, 200 us pluses, and 20 Hz. The electrical stimulation was done in fifteen minute intervals. Statistically, the rats without electrical stimulation have an average contraction period of 63.1 sec (+/– 31.3 sec) and the rats with electrical stimulation have an average contraction period of 97.2 sec (+/– 43.0 sec). The results showed that the electrical stimulation of the periurethral neuromusculature in the group revealed 54.0% increase in average contraction period and decrease in voiding frequency. Electrical stimulation of the periurethral neuromusculature increases the voiding interval and void volume for the rats. This suggests the existence of an external urinary sphincter to the bladder inhibitory pathway and supports periurethral neuromusculature stimulation as an alternative to spinal nerve stimulation for the treatment of bladder overactivity.

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Propofol Suppresses Synaptic Responsiveness of Somatosensory Relay Neurons to Excitatory Input by Potentiating GABAA Receptor Chloride Channels

Molecular Pain ◽

10.1186/1744-8069-1-2 ◽

2005 ◽

Vol 1 ◽

pp. 1744-8069-1-2 ◽

Cited By ~ 28

Author(s):

Shui-Wang Ying ◽

Peter A Goldstein

Keyword(s):

Electrical Stimulation ◽

Chloride Channel ◽

Temporal Summation ◽

Brain Slices ◽

Excitatory Input ◽

Dependent Manner ◽

Sensory Stimuli ◽

Shunting Inhibition ◽

Stimulation Of ◽

Relay Neurons

Propofol is a widely used intravenous general anesthetic. Propofol-induced unconsciousness in humans is associated with inhibition of thalamic activity evoked by somatosensory stimuli. However, the cellular mechanisms underlying the effects of propofol in thalamic circuits are largely unknown. We investigated the influence of propofol on synaptic responsiveness of thalamocortical relay neurons in the ventrobasal complex (VB) to excitatory input in mouse brain slices, using both current- and voltage-clamp recording techniques. Excitatory responses including EPSP temporal summation and action potential firing were evoked in VB neurons by electrical stimulation of corticothalamic fibers or pharmacological activation of glutamate receptors. Propofol (0.6 – 3 μM) suppressed temporal summation and spike firing in a concentration-dependent manner. The thalamocortical suppression was accompanied by a marked decrease in both EPSP amplitude and input resistance, indicating that a shunting mechanism was involved. The propofol-mediated thalamocortical suppression could be blocked by a GABAA receptor antagonist or chloride channel blocker, suggesting that postsynaptic GABAA receptors in VB neurons were involved in the shunting inhibition. GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked in VB neurons by electrical stimulation of the reticular thalamic nucleus. Propofol markedly increased amplitude, decay time, and charge transfer of GABAA IPSCs. The results demonstrated that shunting inhibition of thalamic somatosensory relay neurons by propofol at clinically relevant concentrations is primarily mediated through the potentiation of the GABAA receptor chloride channel-mediated conductance, and such inhibition may contribute to the impaired thalamic responses to sensory stimuli seen during propofol-induced anesthesia.

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Electrocortical and behavioral responses elicited by acute electrical stimulation of inferior thalamic peduncle and nucleus reticularis thalami in a patient with major depression disorder

Clinical Neurophysiology ◽

10.1016/j.clinph.2005.10.023 ◽

2006 ◽

Vol 117 (2) ◽

pp. 320-327 ◽

Cited By ~ 27

Author(s):

Marcos Velasco ◽

Francisco Velasco ◽

Fiacro Jiménez ◽

José D. Carrillo-Ruiz ◽

Ana Luisa Velasco ◽

...

Keyword(s):

Electrical Stimulation ◽

Major Depression ◽

Behavioral Responses ◽

Major Depression Disorder ◽

Nucleus Reticularis ◽

Depression Disorder ◽

Stimulation Of

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Direct Electrical Stimulation of Lateral Orbitofrontal Cortex Acutely Improves Mood in Individuals with Symptoms of Depression

Current Biology ◽

10.1016/j.cub.2018.10.026 ◽

2018 ◽

Vol 28 (24) ◽

pp. 3893-3902.e4 ◽

Cited By ~ 34

Author(s):

Vikram R. Rao ◽

Kristin K. Sellers ◽

Deanna L. Wallace ◽

Morgan B. Lee ◽

Maryam Bijanzadeh ◽

...

Keyword(s):

Electrical Stimulation ◽

Orbitofrontal Cortex ◽

Direct Electrical Stimulation ◽

Symptoms Of Depression ◽

Stimulation Of

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A Patient with a Resistant Major Depression Disorder Treated with Deep Brain Stimulation in the Inferior Thalamic Peduncle

Neurosurgery ◽

10.1227/01.neu.0000170434.44335.19 ◽

2005 ◽

Vol 57 (3) ◽

pp. 585-593 ◽

Cited By ~ 183

Author(s):

Fiacro Jiménez ◽

Francisco Velasco ◽

Rafael Salin-Pascual ◽

José A. Hernández ◽

Marcos Velasco ◽

...

Keyword(s):

Electrical Stimulation ◽

Major Depression ◽

Depression Scale ◽

Borderline Personality ◽

Hamilton Depression Scale ◽

Global Assessment Of Functioning ◽

Major Depression Disorder ◽

Depression Disorder ◽

Deep Brain ◽

Stimulation Of

ABSTRACT OBJECTIVE AND IMPORTANCE: The present report explored the effect of electrical stimulation on the inferior thalamic peduncle in a patient with resistant major depression disorder (MDD). CLINICAL PRESENTATION: This report refers to a 49-year-old woman with a history of recurrent episodes of major depression for 20 years (12 episodes and 2 hospitalizations), fulfilling Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised, criteria for MDD; in addition, the patient met criteria for borderline personality disorder and bulimia. Her longest episode of depression with suicidal ideation began 5 years before surgery. The patient's symptom array responded poorly to different combinations of antidepressants, cognitive therapy, and electroconvulsive therapy, which induced improvement only for short periods of time. Immediately before surgery, her Global Assessment of Functioning score was 20 and her Hamilton Depression Scale score ranged from 33 to 42. The patient was proposed for surgery for MDD. INTERVENTION: The patient had bilateral eight-contact electrodes stereotactically implanted for stimulation of areas at and around the inferior thalamic peduncle. Electrode position was corroborated by unilateral electrical stimulation searching for recruiting responses and regional direct current shifts in the electroencephalogram. Recording electrodes were replaced by tetrapolar electrodes for deep brain stimulation and connected to an internalized stimulation system for continuous bipolar stimulation at 130 Hz, 0.45 milliseconds, 2.5 V. Bimonthly follow-up included psychiatric and neuropsychological evaluations performed over the course of 24 months. After 8 months of ON stimulation, the patient entered a double-blind protocol with stimulators turned OFF. Improvement of depression measured by the Hamilton Depression Scale score was evident after initial placement of electrodes without electrical stimulation. Depression relapsed partially at the end of the first week. Electrical stimulation further improved depression, normalizing depression scores and neuropsychological performance. Patient depression scores ranked between 2 and 8 during 8 months of ON stimulation without antidepressant medication. After stimulation was turned OFF, spontaneous fluctuations in patient symptoms reflected by Hamilton Depression Scale and Global Assessment of Functioning scores were documented; these fluctuations disappeared after stimulation was turned on by Month 20. CONCLUSION: Complicated patients with comorbid conditions are common referrals to psychosurgery services. In this report, we present promising results of electrical stimulation of the inferior thalamic peduncle to treat recurrent unipolar depression in a patient with MDD and borderline personality disorder who responded poorly to treatment.

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