Enhanced Spatial Targeting in ECT Utilizing FEAST
Enhanced Spatial Targeting in ECT Utilizing FEAST
The 'principle' is that FEAST can create a focal seizure in a targeted region that has
 clinical efficacy. Standardized procedures are used to reduce impedance at ECT and EEG
 electrode sites. The d'Elia unilateral placement is used for conventional RUL ECT. FEAST will
 involve the 1.25" circular anterior electrode being centered at the measured Fp2 position by
 the 10/20 EEG system, with the posterior cathode electrode (1"x2.5") tangential to the
 mid-sagittal plain and centered at vertex. ECT is delivered with a MECTA Spectrum 5000Q. The
 only modification in the device used in this study relative to the commercial device is the
 capacity for unidirectional stimulation. A special Investigational Device Exemption for this
 research will have to be obtained from the US FDA before initiating the research at The
 University of Minnesota. The PI has substantial experience with IDE's from previous work with
 transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), deep brain
 stimulation (DBS), epidural cortical stimulation (EpCS) and of course FEAST.

 The primary outcome of this study will be and in-depth probe into the onset and seizure drive
 markers on EEG during FEAST and contrasting it to FEAST with RP or RC. The secondary
 objectives for this study are to determine remission rates as measured by HDRS and IDS-SR and
 time for re-orientation recovery after treatment.
Study Design: This study will focus on refining FEAST methods by implementing a fixed-current
 titration and dosing method (800mA; 0.3 ms), testing the optimal directionality of current
 flow, and confirming specificity of induction of seizures in right orbitofrontal cortex.
 Twenty patients in an episode of major depression will be enrolled in the initial open-label
 study. Patients are kept on current medications for at least 2 weeks prior to initiation of
 therapy and throughout the treatment course. Patients are allowed PRN lorazepam limited to 3
 mg/d but not within 10 hours of a FEAST session. Patients will undergo routine clinical care
 pre-ECT evaluations which include chemistry laboratory tests, a chest x-ray and an EKG.
 Patient will also undergo a brain MRI needed for 3D finite element modeling (FEM) to compute
 individual electric fields for each participant enrolled.

 Once treatment is initiated, patients receive a dose 6 times initial ST at all treatments
 except the first, where ST is determined. If insufficient improvement (<40% change from
 baseline HRSD-24 item, or IDS-SR) after six treatments, the dose will increase by 50% in
 charge (9 times initial ST). Patients will undergo 6 channel EEG during all treatments.
 Sessions 2, 3 and 4 will be cross-randomized across FEAST (with typical electrodes placement
 and current flow directionality configurations), RP FEAST and RC FEAST to allow a direct
 comparison of induced seizure focality. To ensure that each possible treatment sequence (ABC,
 ACB, BAC, BCA, CAB, CBA, where A=regular FEAST, B=RP FEAST, C=RC FEAST) during visits 2-4 is
 represented with approximately equal frequency, participants will be allocated to treatment
 sequence using a block randomization scheme with a block size of 6 participants. Within each
 block, each treatment sequence appears exactly once, in random order (e.g. 123456, 352641,
 etc.). In this way, the number of participants allocated to a particular sequence never
 differs by more than one from any other sequence.

 The primary measure right frontal to motor connectivity (seizure drive) and time for
 orientation recovery obtained following these sessions will permit direct comparison between
 normal configuration, RP FEAST and RC FEAST as well. Preliminary data generated by the
 investigators suggest that RP polarity FEAST will elicit the most focal seizure with the
 shortest time for reorientation and fewest amnestic side effects.

 Study Procedures: All clinical procedures performed through Fairview will be documented in
 EPIC and duplicated in the research team's RedCap database for later analysis. Treatments are
 given in the morning, 3 times per week. Pharmacological agents are standardized: atropine
 (0.4 mg IV), methohexital (0.75 mg/kg) and succinylcholine (0.75-1.0 mg/kg). [If methohexital
 is unavailable, thiopental will be substituted (2.0 mg/kg]. Patients are oxygenated by mask
 (100% O2) prior to anesthesia and until resumption of spontaneous respiration. Standardized
 procedures are used to reduce impedance at ECT and EEG electrode sites. The d'Elia unilateral
 placement[69] is used for conventional RUL ECT. FEAST will involve the 1.25" circular
 anterior electrode being centered at the measured FP2 position by the 10/20 EEG system, with
 the posterior cathode electrode (1"x2.5") tangential to the mid-sagittal plain and centered
 at vertex. FEAST is delivered with a modified MECTA Spectrum 5000Qrelative to the commercial
 device with the capacity for unidirectional stimulation.

 A baseline appointment, scheduled at the Treatment Resistant Depression Clinic in Saint Louis
 Park, will be initially scheduled with potential participants to complete the informed
 consent process as well as baseline assessments for: MINI-7, HRSD-24, Clinical Global
 Impression (CGI), Inventory of Depressive Symptoms - Self Report (IDS-SR), SSI, SSI-W, Short
 Form (SF-36), and the Quality of Life questionnaire. Participants will also undergo a
 baseline MRI that will consist of individual T1- and T2-weighted MRI scans which will be
 acquired with isotropic voxel resolution of 0.8 mm through resources located in the CMRR
 building. These structural data will be processed in the SimNIBS software to create a 3D
 volume conductor model of the subject's head. These MRI images will be constructed into 3D
 FEM models to compute non-invasive brain stimulation and electric fields for each participant
 enrolled.
Inclusion Criteria:

 -  Diagnosis of major depressive disorder using mini-7 to derive RDC; DSM-IV

 -  Pretreatment HRSC score greater than or equal to 18

 -  ECT indicated by physician evaluation

 -  Willing and capable of providing informed consent as determined by physician
 evaluation

 Exclusion Criteria:

 -  History of schizophrenia, schizoaffective disorder, other functional psychosis, or
 rapid cycling bipolar disorder as determined by mini-7; rapid cycling defined as
 greater than or equal to four episodes in past year

 -  History of neurological illness or insult other than conditions associated with
 psychotropic exposure (e.g., tardive dyskinesia) determined by physician evaluation
 and medical history

 -  Alcohol or substance abuse or dependence in the past year (RDC) determined by
 physician evaluation

 -  Secondary diagnosis of a delirium, dementia, or amnestic disorder (DSM-IV), pregnancy,
 or epilepsy determined by physician evaluation

 -  Requires especially rapid antidepressant response due to suicidality, psychosis,
 inanition, psychosocial obligations, etc. determined by physician evaluation

 -  ECT in the past six months determined by physician evaluation and medical history

 -  Pregnancy as determined by urine pregnancy test and clinical interview