NeuroSEED: Closed-Loop Cortico-Striatal Reprogramming for the Non-Invasive Erasure of Addictive Drive

1. Overview

This project will develop and pilot NeuroSEED™, a non-invasive closed-loop neural intervention that disrupts addiction-related memory traces by combining real-time craving detection with targeted memory reactivation (TMR) and temporally precise transcranial stimulation. Addiction is maintained by pathological reconsolidation of cue-reward memories. NeuroSEED aims to weaken or eliminate these circuits by reactivating craving memories and then interfering with their re-encoding through phase-locked tACS. The study will use an EEG/fNIRS-based wearable to detect endogenous craving states in individuals with nicotine dependence, triggering brief exposure to individualized craving cues, followed by theta- or gamma-frequency stimulation to interrupt reconsolidation. Ethics review is in progress under protocol ID NRG-8824, and stimulation will remain within FDA-compliant non-invasive safety thresholds. Institutional equipment and data facilities are secured. The timeline spans six months: (1) participant recruitment and classifier training (2 months), (2) closed-loop intervention sessions (3 months), and (3) follow-up, data analysis, and preprint submission (1 month). All data, code, and protocols will be preregistered on ResearchHub, and results will be released under CC-BY via GitHub and Zenodo.

2. Introduction

Addiction is not merely behavioral—it is an entrenched loop of maladaptive memory encoding between environmental cues and subcortical reward pathways¹. These learned craving responses are repeatedly reconsolidated in the brain’s cortico-striatal network, particularly the ventral striatum, medial prefrontal cortex (mPFC), and insula². Recent work has demonstrated that these addiction-related memory traces can be weakened or disrupted if reactivated under specific neuromodulatory conditions³. NeuroSEED™ leverages this vulnerability by integrating real-time craving detection with Targeted Memory Reactivation (TMR) and time-locked non-invasive brain stimulation. Our central research question is whether disrupting craving-related memory reconsolidation can produce measurable and lasting reductions in addictive drive. We hypothesize:

H1: Real-time craving states can be decoded from EEG/fNIRS signals with >80% classification accuracy.

H2: TMR followed by phase-specific tACS (theta/gamma) will reduce EEG-based frontal-striatal coherence and subjective craving.

H3: Intervention effects will persist beyond 72 hours post-session, suggesting durable reconsolidation interference.

Impact Statement: If successful, NeuroSEED would establish the first non-invasive, closed-loop system for actively extinguishing addictive circuits without medication. This offers a radically new paradigm for relapse prevention and memory-based intervention in substance use and behavioral addictions.

3. Methods

Participants/Sample

We will recruit 8–10 adult participants (ages 18–45) with moderate nicotine dependence (Fagerström score ≥5), not currently undergoing cessation treatment. Exclusion criteria include psychiatric comorbidities, seizure history, or implanted electronic devices. Recruitment will occur through university mailing lists and community advertisements. This sample size allows preliminary within-subject comparisons with 80% power to detect medium effect sizes (d = 0.6–0.8) based on prior tACS craving disruption studies.

Materials and Procedures

Participants will complete a baseline craving task to collect EEG/fNIRS data during personalized cue exposure (e.g., images of smoking, scent modules, or voice prompts). These data will train a machine learning classifier (LDA or XGBoost) to detect craving states in real time. During the intervention session, participants wear an EEG+fNIRS headset (e.g., OpenBCI Galea or Kernel Flow), and when craving is detected, they are presented with a subliminal cue set designed to reactivate the addiction memory trace (visuals, sounds, olfactory triggers). Immediately afterward, theta- or gamma-band tACS is delivered via fronto-temporal electrodes for 90 seconds. Stimulation is phase-locked to peak craving epochs and remains within FDA-approved amplitude limits (≤2 mA). Subjective craving is assessed pre-, post-, and 24–72 hours post-intervention using VAS scales and QSU-Brief. HRV and pupil dilation are collected throughout.

Planned Analyses

Preprocessing includes EEG artifact rejection, fNIRS filtering (short channel regression), and time-locking to cue onset.

• H1: Craving classifier accuracy tested via k-fold cross-validation.

• H2: Paired t-tests and ANOVAs on frontal-striatal coherence (via PLV and Granger causality), and craving scores pre/post.

• H3: Mixed models will assess persistence of effects across days.

Contingency: IF craving classifier fails to generalize across sessions, THEN a fixed-cue stimulation protocol will be used for fallback testing.

Ethics and Data Management

Ethical approval is under review by the institutional board (NRG-8824). All participants will provide informed consent. Stimulation is non-invasive, brief, and within clinical parameters. De-identified EEG/fNIRS, behavioral, and physiological data will be uploaded to OpenNeuro and GitHub with full analysis scripts. Code will be documented with open-source Jupyter notebooks.

4. Pilot Data (Feasibility)

Pilot feasibility data were collected from three nicotine-using participants during a passive cue-reactivity EEG task. Smoking-related imagery elicited a consistent increase in frontal theta power and right-insular beta activity relative to neutral cues. Using ~50 trials per participant, a linear discriminant analysis classifier achieved 78% mean classification accuracy (F1-score = 0.81) in distinguishing craving vs. neutral epochs based on 4 frontal electrodes. Although no stimulation or craving disruption was applied, this supports the feasibility of decoding craving states with wearable EEG. These results informed the choice of stimulation timing and window duration for the NeuroSEED protocol.

5. Budget (Itemized, Current 2025 Pricing)

Item	Vendor / Justification	Estimated Cost (USD)
EEG/fNIRS Headset Rental (3 months)	OpenBCI Galea: EEG+PPG+EOG+EMG bundle (rental via OpenBCI Research Program)	$1,500
tACS Device Rental	Neuroelectrics Starstim Home Kit (includes stimulation electrodes, software, accessories)	$1,450
Participant Compensation	$50 × 10 participants	$500
Sensory Cue Modules	Scent diffusers ($80), auditory cue software (custom) + visual LCD cue set	$300
Custom Software Development	Signal pipeline scripting (EEG decoding + stimulation trigger integration)	$650
Cloud Storage & Data Sharing	Zenodo/OSF + AWS credits for backup	$200
Total		$4,600

Remaining funds ($400) reserved for publication fees, bug fixes, or unexpected costs.

Vendor Citations:

OpenBCI Galea pricing: https://shop.openbci.com
Neuroelectrics Starstim rental: https://www.neuroelectrics.com

6. References

1. Volkow, N. D. The addicted human brain: insights from imaging studies. (National Institute on Drug Abuse, 2010).

2. Koob, G. F. & Volkow, N. D. Neurocircuitry of addiction. (Elsevier, 2016).

3. Schiller, D. & Phelps, E. A. Extinction learning and reconsolidation: mapping the temporal window. (Nature Neuroscience, 2011).

4. Herrmann, C. S., Rach, S., Neuling, T. & Strüber, D. Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes. (Frontiers in Human Neuroscience, 2013).

5. Wierenga, C. J. et al. Real-time EEG-based decoding of attentional states for closed-loop brain stimulation. (NeuroImage, 2020).

6. Arzi, A. et al. Olfactory aversive conditioning during sleep reduces cigarette-smoking behavior. (Journal of Neuroscience, 2014).

7. Reinhart, R. M. G. & Nguyen, J. A. Working memory revived in older adults by synchronizing rhythmic brain circuits. (Nature Neuroscience, 2019).

NeuroSEED: Closed-Loop Cortico-Striatal Reprogramming for the Non-Invasive Erasure of Addictive Drive

NeuroSEED: Closed-Loop Cortico-Striatal Reprogramming for the Non-Invasive Erasure of Addictive Drive

Funding Progress

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Peer Reviews

Related Funding

Request for Proposals - Neuroscience Research Project

Nonprofit Recipient

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