The Stanford Clinical and Translational Science Award to Spectrum (NIH UL1 TR 001085) (NRW) and the Brain &#38; Behavior Research Foundation (NRW).

These experiments were conducted at the Medical University of South Carolina (MUSC) in compliance with an Investigational Device Exemption issued to Ziad Nahas and later transferred to Edward Baron Short under US Food and Drug Administration (FDA) guidance. The MUSC Institutional Review Board approved the protocol.
1. Participants
<ol>
	<li>For each subject, conduct comprehensive assessment including detailed neuropsychological testing at baseline and repeatedly after implantation. Fuse the ...

In this manuscript, we describe the method of EpCS of the bilateral DLPFC and FPC for the treatment of TRD. This first iteration of bilateral EpCS of DLPFC and FPC resulted in a remission rate of 60% at five year follow-up, and 80% shortly thereafter, in a group of severely depressed patients33. Despite years of chronic stimulation of the FPC and DLPFC, no changes were noted in neuropsychiatric measures of cognition and this method was generally well tolerated by all participants.
<p class="jo...

Nonpharmacologic brain stimulation therapies have emerged as potentially promising treatments for a variety of illnesses, including depression1. Depression is a disabling psychiatric disorder of melancholia that not only affects an individual&#39;s daily life and social functioning2, but is a leading cause of premature mortality and disability worldwide3. Large clinical trials have shown that pharmacologic interventions have limited success in treating depression4. Roughly 41% of patients fail to respond to two adequate trials of pharmacologic treatment, which is the definition of treatment resistant depression (TRD)5,6.
It is for these patients that interventional psychiatric approaches have emerged1, though they vary widely in methodology, with some options being significantly more invasive than others7. Guiding these therapies is the emerging understanding of mood disorders as functions of anatomic interconnections within brain regions8. Depression is a model illness for studying cooperative brain stimulation treatments, as studies have suggested that the left dorsolateral prefrontal cortex (DLPFC) is hypoactive while the right DLPFC is hyperactive9,10. The frontopolar cortex (FPC) is another region of interest due to its role in the mood regulatory circuit11 and is consistently found to have increased resting-state activity in patients suffering from depression12.
Research over the past decade has demonstrated the efficacy of epidural cortical stimulation (ECS)13,14 in managing intractable pain syndrome15,16,17,18, aiding in stroke recovery19, and improving Parkinson&#39;s disease and movement disorders20. These studies generally utilized chronic unilateral ECS of the primary motor cortex21. In addition, several cortical nodes including the anterior cingulate cortex, left temporoparietal junction, and dorsolateral prefrontal cortex have been targeted for tinnitus22,23,24. A form of ECS, epidural prefrontal cortical stimulation (EpCS) has been utilized to treat depression. Like subdural prefrontal cortical stimulation25,26, EpCS provides constant stimulation to cortical network nodes of interest27,28,29. EpCS is safer than subdural cortical stimulation from the standpoint of seizure induction and hemorrhage risk13,30.
In this protocol, we describe the method of bilateral EpCS, a unique therapeutic approach for cooperative stimulation of multiple brain regions of interest28. The electrical device remains separated from the cortex by the arachnoid space, making it potentially safer than deep brain stimulation (DBS), where electrodes lie within brain tissue31. EpCS may therefore be preferred over more invasive stimulation techniques in patients at high risk for surgical complications, including intracranial hemorrhage32. We observed the efficacy, safety, and durability of chronic intermittent EpCS of the DLPFC and FPC over a five-year period in 5 patients28,33.

<table>
	<tbody>
		<tr>
			<td>3T MRI Scanner</td>
			<td>Siemens</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Computer workstation</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Imaging software</td>
			<td>University of South Caroline</td>
			<td></td>
			<td>MRIcro; http://www.sph.sc.edu/comd/rorden/mricro.html</td>
		</tr>
		<tr>
			<td>Electrocardiography</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Pulse oximetry</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>End-tidal CO2</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Non-invasive blood pressure monitoring</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Fentanyl (50-250 micrograms)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Propofol infusion (25-100 micrograms/kg/min</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>2% lidocaine with epinephrine (2ccs)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Equal mixture of 1% lidocaine with epinephrine 1:100,000 and bupivacaine 0.5% (5ccs)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Skull clamp with surgical pins</td>
			<td>IntegraTM, Plainsboro, New Jersey</td>
			<td></td>
			<td>Mayfield</td>
		</tr>
		<tr>
			<td>Neuronavigation system</td>
			<td>BrainLab, Westchester, Illinois</td>
			<td></td>
			<td>VectorVision</td>
		</tr>
		<tr>
			<td>Paddle leads with extensions</td>
			<td>Medtronic Inc., Minneapolis, Minnesota</td>
			<td></td>
			<td>Resume</td>
		</tr>
		<tr>
			<td>Pulse generater with 2 channels</td>
			<td>Medtronic Inc., Minneapolis, Minnesota</td>
			<td></td>
			<td>Synergy</td>
		</tr>
		<tr>
			<td>Neurostimulator</td>
			<td>Medtronic Inc., Minneapolis, Minnesota</td>
			<td></td>
			<td>Activa PC/RC</td>
		</tr>
		<tr>
			<td>Standard aesculap power-drill</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Generic 4mm spherical diamond drill bit</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Plates and microscrews</td>
			<td>Stryker, Kalamazoo, Michigan</td>
			<td></td>
			<td>Leibinger &#34;Dog-bone&#34; style</td>
		</tr>
		<tr>
			<td>Bacitracin solution</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Vancomycin power</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Gelfoam</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>2-0 vicryl sutures</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>3-0 nylon sutures</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Sterile dressing materals</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Endotracheal anesthesia</td>
			<td></td>
			<td></td>
			<td>As dictated by patient&#39;s history and anesthesiologist&#39;s preference</td>
		</tr>
		<tr>
			<td>3-0 vicryl sutures</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>4-0 nylon sutures</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>High resolution spiral CT scan without contrast</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Opiate analgesics</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Programmer wand</td>
			<td>Medtronic Inc., Minneapolis, Minnesota</td>
			<td></td>
			<td>N&#39;Vision Clinician Programmer</td>
		</tr>
	</tbody>
</table>

description of a novel, surgically implanted neuromodulatory technique known as bilateral epidural prefrontal cortical stimulation (epcs) for treatment-resistant depression (trd)

We describe the targeting, surgical technique, intraoperative testing, and postoperative programming strategy for the invasive neuromodulatory technique termed epidural prefrontal cortical stimulation (EpCS). While EpCS has been explored by several groups, the unique approach described here involves surgical placement of four epidural cortical stimulation paddles - two over the bilateral dorsolateral prefrontal cortex (DLPFC) and two over the frontopolar cortex (FPC). The safety and efficacy of this technique for treatment-resistant depression has been described previously by the authors. 5 subjects were implanted with EpCS (3 with major depression, 2 with bipolar affective disorder I, depressive type) and their depressive symptoms were followed for five years. Application of chronic electrical stimulation (10-15mA) across all four of these paddles produced a durable antidepressant response for 3 of 5 subjects at the five-year follow-up. This manuscript discusses the unique intraoperative testing strategy as well as the programming approaches employed in this study. We aim to give guidance into improving the effect size of this novel form of stimulation.

Sample Characteristics: A total of 6 patients were enrolled in this trial. 1 withdrew prior to EpCS implantation. A total of 5 patients (3 female, mean age=44.2 years, SD=9.4 years) received EpCS implantation and completed the trial through the 5-year follow-up period. Sample characteristics are summarized in Table 1. A total of 3 subjects had a diagnosis of MDD while the 2 remaining participants had a diagnosis of bipolar affective disorder I, depressive...

We describe the implantation of 4 epidural stimulation paddles directly above the dura mater over both the left and right frontopolar and dorsolateral prefrontal cortices. Placement was verified using postoperative computed tomography (CT) coregistered with presurgical magnetic resonance imaging (MRI).

Description of a Novel, Surgically Implanted Neuromodulatory Technique Known As Bilateral Epidural Prefrontal Cortical Stimulation (Epcs) for Treatment-Resistant Depression (TRD)

We describe the targeting, surgical technique, intraoperative testing, and postoperative programming strategy for the invasive neuromodulatory technique ...

Description of a Novel, Surgically Implanted Neuromodulatory Technique Known As Bilateral Epidural Prefrontal Cortical Stimulation (Epcs) for Treatment-Resistant Depression (TRD)

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