Invasive Decoding and Stimulation of Altered Reward Computations in Depression Patients

Official title

Invasive Decoding and Stimulation of Altered Reward Computations in Depression

Overview

Novel invasive neurostimulation stimulation strategies through neurosurgical interventions are emerging as a promising therapeutical strategy for major depressive disorder. These have been applied mostly to the anterior cingulate cortex, but other limbic brain regions have shown promise as anatomical targets for new neurostimulation strategies. The researchers seek to study neural activity in limbic brain areas implicated in decision behavior and mood regulation to identify novel targets for treatment through electrical stimulation. To do this, the study team will record local field potentials (LFPs) from the orbitofrontal cortex, hippocampus and amygdala of epilepsy participants undergoing invasive monitoring (intracranial encephalography, iEEG) during choice behavior. Leveraging the high co-morbidity of depression and intractable epilepsy (33-50%), neural responses will be compared to reward across depression status to identify abnormal responses in depression. Finally, the researchers will use these as biomarkers to guide development of neurostimulation strategies for the treatment of depression.

Detailed description

Participants (n=24) will complete a decision-making task in which participants will make decisions under uncertainty and seek to maximize rewards. The researchers will assess behavioral (risk attitudes) and neural (LFP) responses using a combination of intracranial recordings and computational modeling. A subset of patients will complete the game a second time under electrical stimulation of pre-identified anatomical targets in orbitofrontal cortex, hippocampus or amygdala. In addition, patients' depression status will be assessed through questionnaires (BDI-II and HDSA). Finally, the researchers will examine whether electrical stimulation results in behavioral or mood modulation.

Interventions

• Procedure Brain stimulation
  Brain stimulation will be performed after collection of clinical seizure data. Bipolar stimulation to one or several adjacent electrodes will be applied. Stimulation design will be either determined prior to testing or designed according to results from neurobehavioral assessments. Stimulation will consist of biphasic, constant-current trains of stimulation pulses at 100 Hz, with 100 ms pulse width or a sinusoidal wave of a predefined mean band frequency (i.e. 6Hz for θ, 11Hz for α, 20Hz for β,

Primary outcome measures

• Gambling Task [Time frame: Day 1]

Secondary outcome measures (2)

• Beck's Depression I-II (BDI-II) score [Time frame: Day 1]
• Hamilton scales for depression and anxiety (HSDA) [Time frame: Day 1]

Eligibility criteria

Inclusion criteria

\- The study will follow clinical criteria for epilepsy patient recruitment for invasive monitoring. As a results, individuals of adults of all ages are expected to be included in this study.

Exclusion criteria

• Adults over 80 years of age will be excluded as per concerns of cognitive decline.
• Children under 18 will be excluded from the study since the maturation of frontal lobes continues through adolescence and significant differences in frontal lobe functioning between children younger than 18 and adults are often observed.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Icahn School of Medicine at Mount Sinai — New York

Identifiers

NCT: NCT05239780 · STUDY-17-00258 · 1R01MH124763-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗