Nicole LaGanke

Hebrew SeniorLife

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Álvaro Pascual‐Leone

Harvard University

Tim den Boer

University of Oxford

Davide Cappon

Berenson Allen Center for Noninvasive Brain Stimulation

Wanting Yu

Wuhan University of Science and Technology

Brad Manor

Harvard University

R. Hingston Fox

Hebrew SeniorLife

David Bartrés‐Faz

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

Ruben Perellón‐Alfonso

Departament de Salut

Gabriele Cattaneo

Institut Guttmann

Marina Brozgol

Tel Aviv Sourasky Medical Center

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Division of Undergraduate Education

Hebrew SeniorLife

Harvard University

Beth Israel Deaconess Medical Center

University of Louisville

Neurological Surgery

Institut Guttmann

Universitat Autònoma de Barcelona

University of Louisville Hospital

Feinstein Institute for Medical Research

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Tele-supervised home-based transcranial alternating current stimulation (tACS) for Alzheimer’s disease: a pilot study

Frontiers in Human Neuroscience (2023)

Davide Cappon R. Hingston Fox Tim den Boer Wanting Yu Nicole LaGanke

Over 55 million people worldwide are currently diagnosed with Alzheimer's disease (AD) and live with debilitating episodic memory deficits. Current pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high-frequency neuronal activity. Here we investigate the feasibility, safety, and preliminary effects on episodic memory of an innovative protocol where tACS is administered within the homes of older adults with AD with the help of a study companion (HB-tACS).Eight participants diagnosed with AD underwent multiple consecutive sessions of high-definition HB-tACS (40 Hz, 20-min) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14-weeks of HB-tACS with at least five sessions per week. Three participants underwent resting state electroencephalography (EEG) before and after the 14-week Acute Phase. Subsequently, participants completed a 2-3-month Hiatus Phase not receiving HB-tACS. Finally, in the Taper phase, participants received 2-3 sessions per week over 3-months. Primary outcomes were safety, as determined by the reporting of side effects and adverse events, and feasibility, as determined by adherence and compliance with the study protocol. Primary clinical outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively. Secondary outcome was EEG theta/gamma ratio. Results reported as mean ± SD.All participants completed the study, with an average of 97 HB-tACS sessions completed by each participant; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98 ± 6.8% and Taper phase was 125 ± 22.3% (rates over 100% indicates participants completed more than the minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25 ± 3.77, sustained during Hiatus 7.00 ± 4.90 and Taper 4.63 ± 2.39 Phases compared to baseline. For the three participants that underwent EEG, a decreased theta/gamma ratio in AG was observed. Conversely, participants did not show improvement in the MoCA, 1.13 ± 3.80 after the Acute Phase, and there was a modest decrease during the Hiatus -0.64 ± 3.28 and Taper -2.56 ± 5.03 Phases.This pilot study shows that the home-based, remotely-supervised, study companion administered, multi-channel tACS protocol for older adults with AD was feasible and safe. Further, targeting the left AG, memory in this sample was improved. These are preliminary results that warrant larger more definite trials to further elucidate tolerability and efficacy of the HB-tACS intervention. NCT04783350.https://clinicaltrials.gov/ct2/show/NCT04783350?term=NCT04783350&draw=2&rank=1, identifier NCT04783350.

Montreal Cognitive Assessment

10.3389/fnhum.2023.1168673

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Opioid Receptor: Its structure and how it works

The FASEB Journal (2015)

Kevin Crowthers Hiliana Melo Yixin Chen Nicole LaGanke colleen rooney

The First and Second Opium Wars were two conflicts caused by the the reaction of China over the illegal exportation of the drug opium by the British government. Opium, also known as poppy tears, is a narcotic drug extracted from the plant Papaver somniferum. This drug causes a sensation of euphoria and pain relief by binding to opioid receptors that exist on cell membranes of neurons and the digestive tract. Opioid receptors (OR) are G‐protein‐coupled receptors (GPCRs) with three main variables, μ‐OR, δ‐OR and κ‐OR. The μ‐OR is the most important opioid receptor for the management of pain. To better understand this receptor's structure and how it can impact function, the Worcester Academy SMART Team has modeled the μ‐OR using 3D printing technology. Using the irreversible antagonist β‐FNA, the μ‐OR has a complex shape, consisting of seven transmembrane α‐helices connected by three extracellular loops and three intracellular loops; transmembrane helices 5 and 6 are involved in receptor dimerization. The binding pocket is relatively open which causes a greater exposure to the extracellular surface, providing evidence as to why potent opioids like buprenorphine and etorphine have a rapid dissociation. β‐FNA interacts with 14 residues, of which nine have more interaction with the ligand and are conserved in the δ‐OR and the κ‐OR. The μ‐OR contains 11 identical amino acid residues with the the other two ORs. The only differences are the positions E229, K303 and W318, which are Asp, Trp and Leu. Further understanding of opioid receptors and their structure can lead to a way of treating pain without side effects.

Etorphine

10.1096/fasebj.29.1_supplement.lb68

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Tele‐supervised home‐based transcranial alternating current stimulation (tACS) for Alzheimer’s disease

Alzheimer s & Dementia (2023)

R. Hingston Fox Tim den Boer Wanting Yu Nicole LaGanke Gabriele Cattaneo

Abstract Background Over 55 million people worldwide are currently diagnosed with Alzheimer’s disease (AD) and live with debilitating episodic memory deficits (World Health Organization, 2022). Current pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high‐frequency neuronal activity (Benussi et al., 2022). Our goal was to assess the safety, feasibility, and preliminary effects on episodic memory of a caregiver‐led home‐based tACS approach (HB‐tACS). Method 8 participants diagnosed with AD (Table 1) underwent high‐definition HB‐tACS (40 Hz, 20‐minutes) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14‐weeks of HB‐tACS with at least five weekly sessions. Three participants underwent resting‐state electroencephalography (EEG) before and after. Subsequently, participants completed a 2–3‐month Hiatus Phase not receiving tACS. In the Taper Phase, participants received 2‐3 sessions per week over 3‐months. Primary outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively, and EEG theta/gamma ratio. Results reported as mean±SD. Result All participants completed the study with, on average, 97 HB‐tACS sessions; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98±6.8% and Taper Phase was 125±22.3% (from minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25±3.77, sustained during Hiatus 7.00±4.90 and Taper 4.63±2.39 Phases (Table 2), and decreased theta/gamma ratio in AG (Figure 1A). Conversely, participants did not show improvement in the MoCA, 1.13±3.80 after the Acute Phase, and there was modest decrease during the Hiatus ‐0.64± 3.28 and Taper ‐2.56±5.03 phases. These results suggest the specificity of the intervention for memory functioning (Figure 1B) and relate improvement to decreased theta/gamma ratio. Conclusion This pilot study shows the feasibility of a novel, remotely supervised, caregiver‐led HB‐tACS intervention for AD. Targeting the left AG, memory was noticeably improved while global cognition was relatively stable, indicating that future interventions might benefit from multifocal neuromodulation targeting multiple cognitive domains. These results are encouraging for the prospect of safe and feasible treatment within patients’ homes.

Montreal Cognitive Assessment

10.1002/alz.074927

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Safety and Feasibility of Tele-Supervised Home-Based Transcranial Direct Current Stimulation for Major Depressive Disorder

Frontiers in Aging Neuroscience (2022)

Davide Cappon Tim den Boer Caleb Jordan Wanting Yu Alexander Lo

Major depressive disorder (MDD) is a worldwide cause of disability in older age, especially during the covid pandemic. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that has shown encouraging efficacy for treatment of depression. Here, we investigate the feasibility of an innovative protocol where tDCS is administered within the homes of older adults with MDD (patient participants) with the help of a study companion (i.e. caregiver). We further analyze the feasibility of a remotely-hosted training program that provides the knowledge and skills to administer tDCS at home, without requiring them to visit the lab. We also employed a newly developed multi-channel tDCS system with real-time monitoring designed to guarantee the safety and efficacy of home-based tDCS. Patient participants underwent a total of 37 home-based tDCS sessions distributed over 12 weeks. The protocol consisted of three phases each lasting four weeks: an acute phase, containing 28 home-based tDCS sessions, a taper phase containing nine home-based tDCS sessions, and a follow up phase, with no stimulation sessions. We found that the home-based, remotely-supervised, study companion administered, multi-channel tDCS protocol for older adults with MDD was feasible and safe. Further, the study introduces a novel training program for remote instruction of study companions in the administration of tDCS. Future research is required to determine the translatability of these findings to a larger sample. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04799405?term=NCT04799405&draw=2&rank=1, identifier NCT04799405.

Transcranial Direct Current Stimulation

Neuromodulation

Depression

10.3389/fnagi.2021.765370

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Citations (33)

Comparison of targeted web‐based advertising versus traditional methods for recruiting older adults into clinical trials

Journal of the American Geriatrics Society (2024)

Kathryn Baldyga Ike Iloputaife George E. Taffet Nicole LaGanke Brad Manor

Recruiting older adults into clinical trials can be particularly challenging. Our objective was to determine if targeted web-based advertising is an effective recruitment strategy.

Targeted advertising

10.1111/jgs.19225

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Table of Contents

Neuromodulation Technology at the Neural Interface (2024)

Jordan Levett Lior Mony Elkaïm Farbod Niazi Michael Weber

Table (database)

10.1016/s1094-7159(24)00086-2

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An Educational Program for Remote Training and Supervision of Home-Based Transcranial Electrical Stimulation: Feasibility and Preliminary Effectiveness

Neuromodulation Technology at the Neural Interface (2023)

Davide Cappon Tim den Boer Wanting Yu Nicole LaGanke R. Hingston Fox

10.1016/j.neurom.2023.04.477

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Citations (6)