NeuroRehabilitation + TES for Cognitive Disorders
(PCN Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Michigan
Disqualifiers: Epilepsy, Sensory impairments, Drug abuse, others
Trial Summary
What is the purpose of this trial?As individuals grow older, a number of factors can reduce our cognitive (or thinking) abilities such as "normal" aging, neurodegenerative diseases, and cardiovascular disease. This study will evaluate whether cognitive rehabilitation and transcranial electrical stimulation (TES) can improve cognitive abilities. Cognitive rehabilitation refers to methods that are used to improve tasks people have trouble doing in everyday life. Transcranial electrical stimulation uses small amounts of electricity to try to alter brain functioning. These approaches may help improve cognitive abilities like attention, learning, memory, finding words, and problem solving as well as everyday functioning. The goal of this study is to identify how to best use these methods, either alone or in combination.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment NeuroRehabilitation + TES for Cognitive Disorders?
Research shows that transcranial alternating current stimulation (tACS) can modestly to moderately improve cognitive functions like memory and attention in various populations, including older adults and those with psychiatric conditions. Additionally, transcranial random noise stimulation (tRNS) has been found to significantly increase brain activity, suggesting potential benefits for cognitive rehabilitation.
12345Is transcranial electrical stimulation (TES) safe for humans?
Transcranial electrical stimulation (TES), including methods like tDCS, tACS, and tRNS, is generally considered safe for humans. Over 18,000 sessions have been conducted without serious adverse events, though mild effects like headaches or skin sensations can occur. Safety is established for low-intensity TES, and no serious injuries have been reported in over 33,200 sessions.
14678How is the NeuroRehabilitation + TES treatment different from other treatments for cognitive disorders?
The NeuroRehabilitation + TES treatment is unique because it combines various forms of transcranial electrical stimulation (TES) like tACS, tDCS, and tRNS with cognitive rehabilitation, aiming to enhance brain function and cognitive recovery. This approach is non-invasive, uses low-intensity electrical currents to modulate brain activity, and has shown promise in improving cognitive outcomes in conditions like traumatic brain injury and Alzheimer's disease.
39101112Eligibility Criteria
This trial is for individuals aged 50 or older who have noticed a decline in their cognitive abilities. It's open to those with and without diagnosed cognitive issues. People can't join if they have serious mental illnesses, are pregnant, might become pregnant, have metal/electronic implants in the head, history of substance abuse, or sensory/motor impairments that would limit participation.Inclusion Criteria
I am 50 years old or older.
Individuals who have reported cognitive dysfunction and cognitively intact participants
Exclusion Criteria
I do not have any sensory or motor impairments that limit my participation.
Being evaluated for TES methodology with metallic or electronic implant, or skull plates or other cranial implants that affect TES
History of serious mental illness (e.g., schizophrenia, axis 2 disorders)
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive transcranial electrical stimulation (TES) and/or cognitively based interventions tailored to individual needs, potentially including up to 260 sessions of TES
4-6 weeks
Follow-up
Participants are monitored for cognitive changes and symptomatic changes through neuropsychological testing and questionnaires
6 months
Long-term follow-up
Participants undergo additional assessments such as MRS and fMRI to evaluate long-term changes
Up to 1 year post-treatment
Participant Groups
The study tests whether cognitive rehabilitation combined with transcranial electrical stimulation (TES) improves thinking skills like attention and memory. TES involves small electric currents applied to the brain. Participants will receive either active TES (tRNS/tDCS/tACS), sham TES (placebo), or cognitively based interventions.
7Treatment groups
Experimental Treatment
Placebo Group
Group I: Sham TES + Cognitively based interventionExperimental Treatment4 Interventions
This condition combines sham TES and cognitively based interventions for some or all of the study sessions
Group II: Cognitively based interventionExperimental Treatment1 Intervention
Participants may receive a cognitively based intervention that targets the particular cognitive and/or functional abilities of interest. This includes methods of cognitive training, cognitive remediation, and cognitive rehabilitation.
Group III: Active and Sham TESExperimental Treatment6 Interventions
Participants will receive active and sham TES
Group IV: Active TES, Sham TES, Cognitively based interventionsExperimental Treatment7 Interventions
This condition combines active and sham TES with cognitively based interventions using a cross-over design
Group V: Active TES + Cognitively based interventionExperimental Treatment4 Interventions
This condition combines active TES and cognitively based interventions for some or all of the study sessions
Group VI: Active TESExperimental Treatment3 Interventions
Participants will receive "real" tES (tDCS, tACS, tRNS) in which they receive up to 4 milliamps (mA) of stimulation per electrode for up to 40 minutes for up to 260 sessions. As this may be a cross-over design, some participants may receive active and sham conditions.
Group VII: Sham TESPlacebo Group3 Interventions
Participants undergoing this condition will have the exact same procedures as the active group, with the exception that they will receive only sham stimulation for up to 260 sessions.
Active tACS is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Active tACS for:
- Investigational for cognitive rehabilitation in neurodegenerative diseases and aging-related cognitive decline
🇪🇺 Approved in European Union as Active tACS for:
- Investigational for cognitive rehabilitation in neurodegenerative diseases and aging-related cognitive decline
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Michigan - Department of PsychiatryAnn Arbor, MI
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Who Is Running the Clinical Trial?
University of MichiganLead Sponsor
References
Comparison of Three Non-Invasive Transcranial Electrical Stimulation Methods for Increasing Cortical Excitability. [2022]Transcranial direct current stimulation (tDCS) is a representative non-invasive brain stimulation method (NIBS). tDCS increases cortical excitability not only in healthy individuals, but also in stroke patients where it contributes to motor function improvement. Recently, two additional types of transcranial electrical stimulation (tES) methods have been introduced that may also prove beneficial for stimulating cortical excitability; these are transcranial random noise stimulation (tRNS) and transcranial alternating current stimulation (tACS). However, comparison of tDCS with tRNS and tACS, in terms of efficacy in cortical excitability alteration, has not been reported thus far. We compared the efficacy of the three different tES methods for increasing cortical excitability using the same subject population and same current intensity. Fifteen healthy subjects participated in this study. Similar stimulation patterns (1.0 mA and 10 min) were used for the three conditions of stimulation (tDCS, tRNS, and tACS). Cortical excitability was explored via single-pulse TMS elicited motor evoked potentials (MEPs). Compared with pre-measurements, MEPs significantly increased with tDCS, tACS, and tRNS (p < 0.05). Compared with sham measurements, significant increases in MEPs were also observed with tRNS and tACS (p < 0.05), but not with tDCS. In addition, a significant correlation of the mean stimulation effect was observed between tRNS and tACS (p = 0.019, r = 0.598). tRNS induced a significant increase in MEP compared with the Pre or Sham at all time points. tRNS resulted in the largest significant increase in MEPs. These findings suggest that tRNS is the most effective tES method and should be considered as part of a treatment plan for improving motor function in stroke patients.
A meta-analysis suggests that tACS improves cognition in healthy, aging, and psychiatric populations. [2023]Transcranial alternating current stimulation (tACS) has attracted interest as a technique for causal investigations into how rhythmic fluctuations in brain neural activity influence cognition and for promoting cognitive rehabilitation. We conducted a systematic review and meta-analysis of the effects of tACS on cognitive function across 102 published studies, which included 2893 individuals in healthy, aging, and neuropsychiatric populations. A total of 304 effects were extracted from these 102 studies. We found modest to moderate improvements in cognitive function with tACS treatment that were evident in several cognitive domains, including working memory, long-term memory, attention, executive control, and fluid intelligence. Improvements in cognitive function were generally stronger after completion of tACS ("offline" effects) than during tACS treatment ("online" effects). Improvements in cognitive function were greater in studies that used current flow models to optimize or confirm neuromodulation targets by stimulating electric fields generated in the brain by tACS protocols. In studies targeting multiple brain regions concurrently, cognitive function changed bidirectionally (improved or decreased) according to the relative phase, or alignment, of the alternating current in the two brain regions (in phase versus antiphase). We also noted improvements in cognitive function separately in older adults and in individuals with neuropsychiatric illnesses. Overall, our findings contribute to the debate surrounding the effectiveness of tACS for cognitive rehabilitation, quantitatively demonstrate its potential, and indicate further directions for optimal tACS clinical study design.
Cognitive Telerehabilitation with Transcranial Direct Current Stimulation Improves Cognitive and Emotional Functioning Following a Traumatic Brain Injury: A Case Study. [2021]Cognitive deficits following a traumatic brain injury (TBI) are a leading cause of disability in young adults and there is a critical need for novel approaches to improve cognitive outcomes in TBI survivors. Transcranial direct current stimulation (tDCS) paired with cognitive remediation has emerged as a viable, cost-effective, noninvasive approach for treating cognitive impairments in a wide variety of neurological conditions. Here, we report the first case study utilizing remotely supervised tDCS (RS-tDCS) protocol paired with cognitive remediation in a 29-year-old man with persisting cognitive and emotional sequelae following TBI.
Close to threshold transcranial electrical stimulation preferentially activates inhibitory networks before switching to excitation with higher intensities. [2016]Recently we have shown that transcranial random noise (tRNS) and 140 Hz transcranial alternating current stimulations (tACS), applied over the primary motor cortex (M1) and using 10 min stimulation duration and 1 mA intensity, significantly increases cortical excitability as measured by motor evoked potentials at rest before and after stimulation.
Transcranial Alternating Current Stimulation (tACS) Mechanisms and Protocols. [2020]Perception, cognition and consciousness can be modulated as a function of oscillating neural activity, while ongoing neuronal dynamics are influenced by synaptic activity and membrane potential. Consequently, transcranial alternating current stimulation (tACS) may be used for neurological intervention. The advantageous features of tACS include the biphasic and sinusoidal tACS currents, the ability to entrain large neuronal populations, and subtle control over somatic effects. Through neuromodulation of phasic, neural activity, tACS is a powerful tool to investigate the neural correlates of cognition. The rapid development in this area requires clarity about best practices. Here we briefly introduce tACS and review the most compelling findings in the literature to provide a starting point for using tACS. We suggest that tACS protocols be based on functional brain mechanisms and appropriate control experiments, including active sham and condition blinding.
A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation investigated as a treatment for several neuropsychiatric disorders. Notwithstanding tDCS-induced adverse events (AEs) are considered to be low and transient, systematic review analyses on safety and tolerability of tDCS derive mostly from single-session studies.
Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations.
Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. [2023]Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak intensities above 2mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity 'conventional' TES defined as <4mA, up to 60min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13A/m2 that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence.
Can Transcranial Electrical Stimulation Localize Brain Function? [2023]Transcranial electrical stimulation (TES) uses constant (TDCS) or alternating currents (TACS) to modulate brain activity. Most TES studies apply low-intensity currents through scalp electrodes (≤2 mA) using bipolar electrode arrangements, producing weak electrical fields in the brain (
Transcranial electrical stimulation. [2018]Transcranial electrical stimulation (tES) is a neuromodulatory technique in which low voltage constant or alternating currents are applied to the human brain via scalp electrodes. The basic idea of tES is that the application of weak currents can interact with neural processing, modify plasticity and entrain brain networks, and that this in turn can modify behaviour. The technique is now widely employed in basic and translational research, and increasingly is also used privately in sport, the military and recreation. The proposed capacity to augment recovery of brain function, by promoting learning and facilitating plasticity, has motivated a burgeoning number of clinical trials in a wide range of disorders of the nervous system.
Transcranial direct current stimulation and cognitive training in the rehabilitation of Alzheimer disease: A case study. [2015]In the present study we tested the cognitive effects of transcranial direct current stimulation (tDCS) in a case of probable Alzheimer disease (AD). The patient (male, 60 years, mild AD) underwent two cycles of treatments, separated by 2 months. In the first cycle, active stimulation (10 sessions, 2 mA for 20 min; anode over the left dorsolateral prefrontal cortex) was followed by computerised tasks (CTs) specifically chosen to engage the most impaired cognitive processes in the patient (tDCS+CT condition). In the second cycle, which was structured as the first, CTs were administered after placebo stimulation (sham+CT condition). Effects on cognitive performance were evaluated not only by the CTs, but also by neuropsychological tests assessing global cognitive functioning. Statistical analyses revealed that whereas the tDCS+CT condition had few effects on the CTs, it induced a stability of the patient's global cognitive functioning lasting approximately 3 months, which was not achieved when the patient underwent sham+CT condition. Therefore, the synergetic use of tDCS and CTs appeared to slow down the cognitive decline of our patient. This preliminary result, although in need of further confirmation, suggests the potentiality of tDCS as an adjuvant tool for cognitive rehabilitation in AD.
Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use. [2022]Transcranial direct current stimulation (tDCS) is a safe and well-tolerated noninvasive method for stimulating the brain that is rapidly developing into a treatment method for various neurological and psychiatric conditions. In particular, there is growing evidence of a therapeutic role for tDCS in ameliorating or delaying the cognitive decline in Alzheimer's disease (AD). We provide a brief overview of the current development and application status of tDCS as a nonpharmacological therapeutic method for AD and mild cognitive impairment (MCI), summarize the levels of evidence, and identify the improvements needed for clinical applications. We also suggest future directions for large-scale controlled clinical trials of tDCS in AD and MCI, and emphasize the necessity of identifying the mechanistic targets to facilitate clinical applications.