Métodos de interferencia temporal para la estimulación cerebral profunda no invasiva, estudio 1.1
Métodos de interferencia temporal para la estimulación cerebral profunda no invasiva
In its totality, this grant aims to develop a line of research using temporal interference (TI) electrical neurostimulation technology to understand the causal role of deep brain structures in cognition. In the short term, the investigators aim to validate and characterize the effects of TI on brain activity as measured by fMRI and demonstrate its ability to focally stimulate deep brain regions without affecting overlying cortex. In the longer term, investigators aim to use these data to resolve longstanding debates about the function of deeper brain regions and lay the foundation for future clinical applications of TI for treating addiction, Obsessive-Compulsive Disorder (OCD), Parkinson's disease, and other disorders involving deep brain dysfunction. The grant supports 2 distinct aims, each of which will be evaluated through a series of independent studies.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
- Dispositivo: Temporal Interference (TI) Electrical Stimulation - NAcc TI Active
- Dispositivo: Temporal Interference (TI) Electrical Stimulation - NAcc TI Sham
- Dispositivo: Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Active
- Dispositivo: Temporal Interference (TI) Electrical Stimulation - NAcc No-TI Sham
Descripción detallada
Through the grant's duration, the investigators hypothesize that temporal interference (TI) electrical neurostimulation will be well tolerated and effective at focally manipulating deep brain activity as measured by functional MRI (fMRI) BOLD signals. The investigators will investigate whether TI stimulation can increase BOLD activity in targeted deep brain regions including the nucleus accumbens (NAcc) and dorsal anterior cingulate cortex (dACC), and whether this stimulation can influence cognitive functions controlled by these regions. TI works by applying alternating currents of slightly different frequencies through multiple electrode pairs, creating an interference pattern that can stimulate deep brain regions without significantly affecting superficial cortical areas. This method is similar to traditional transcranial direct current stimulation (tDCS), however TI can stimulate deeper brain structures that tDCS cannot reach effectively. The study is broken up into two main aims with multiple sub-studies. In Aim 1, the investigators will characterize the effects of TI on fMRI BOLD signals, test different beat frequencies, and compare TI effects in the nucleus accumbens versus dorsal anterior cingulate cortex. In Aim 2, the investigators will apply TI to the dorsal anterior cingulate cortex to test causal theories about its role in cognitive control, conflict monitoring, risk avoidance, and foraging behavior using established cognitive tasks while subjects undergo fMRI scanning.
Study 1.1 (Aim 1, Study 1) will test the ability to focally activate the nucleus accumbens without activating the overlying cortex, and also its effects on functional connectivity. Healthy subjects (n=30) will present for a single study visit during which they will be placed in the fMRI scanner and administered a temporal interference protocol. Specifically, subjects will have two pairs of carbon fiber electrodes attached to the scalp with conductive gel. They will receive one 8-minute block of stimulation at 2mA per electrode pair. The stimulation sequence will be 2 minutes on, 2 minutes off, 2 minutes on, and 2 minutes off with 30 second ramp up and ramp down beginning at the start of each 2-minute period. The first block will apply active TI stimulation with 2000Hz in one channel and 2020Hz in the other channel. The second block will be a sham TI stimulation, identical to the first block but with the "on" condition immediately ramping down as soon as it reaches 2mA after ramp up. The third and fourth blocks will be identical to the first and second blocks, except that both electrode pairs will stimulate at 2000Hz, resulting in a "NO-TI active" and "NO-TI sham" conditions. The order of blocks, and whether the "on" or "off" condition occurs first within a block, will be counterbalanced across subjects.
Tipo de estudio
Inscripción (Actual)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
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Indiana
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Bloomington, Indiana, Estados Unidos, 47408
- Indiana University Bloomington, Imaging Research Facility
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Between the ages of 18 and 50
- Must have at least a 6th grade education
- Ability to speak and read English for all phases
Exclusion Criteria:
- Currently taking psychotropic medications for ADHD, other mental illness, or medications for cancer
- History of epilepsy or seizure disorders
- History of migraines or other neurological syndromes
- History of AIDS (due to potential cognitive deficits)
- History of head trauma or cognitive impairments
- Personal experiences consistent with symptoms of psychosis (e.g., hallucinations, delusions of control or special powers)
- History of skull defects (e.g., holes bored into the skull or known cranial fissures)
- Metal implants in the head or under the scalp
- Does not meet fMRI safety screening criteria (e.g., metal implants in the body, permanent jewelry, tattoos on the head or neck)
- Uses an intrauterine device (IUD) for birth control and cannot provide documentation to verify MRI safety
- Pregnancy (self-reported; no pregnancy test administered)
- Weight over 440 lbs (scanner weight limit)
- Presence of pacemakers
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Comparador activo: NAcc TI Active, then NAcc TI Sham, then NAcc No-TI Active, then NAcc No-TI Sham
Participants in this Arm receive temporal interference (TI) electrical stimulation with two pairs of carbon fiber electrodes in this order: NAcc TI Active, then NAcc TI Sham, then NAcc No-TI Active, then NAcc No-TI Sham. |
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies (e.g., 2000 Hz and 2020 Hz) at up to 2 mA per electrode. This stimulation creates a beat frequency interference pattern (e.g., 20 Hz) that focally stimulates deep brain regions without activating overlying cortex. For the NAcc TI Active condition, 2000Hz will be administered in one channel and 2020Hz in the other. These frequencies will be administered in 2 minutes on/2 minutes off cycles with a 30 second ramp up and ramp down beginning at the start of each 2 minute period.
Otros nombres:
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies (e.g., 2000 Hz and 2020 Hz) at up to 2 mA per electrode. This stimulation creates a beat frequency interference pattern (e.g., 20 Hz) that focally stimulates deep brain regions without activating overlying cortex. For the NAcc TI Sham condition, 2000Hz will be administered in one channel and 2020Hz in the other. These frequencies will be administered in 2 minutes on/2 minutes off cycles, however, instead of the 30 second ramp up and ramp down at the beginning of each 2 minute period (as seen in the Active TI condition), the stimulation in the NAcc TI Sham condition will immediately ramp down as soon as it reaches 2mA after ramp up.
Otros nombres:
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using the same current frequencies at up to 2 mA per electrode. For the NAcc No-TI Active condition, 2000Hz will be administered in both channels. These frequencies will be administered in 2 minutes on/2 minutes off cycles with a 30 second ramp up and ramp down beginning at the start of each 2 minute period.
Otros nombres:
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using the same current frequencies at up to 2 mA per electrode. For the NAcc No-TI Sham condition, 2000Hz will be administered in both channels. These frequencies will be administered in 2 minutes on/2 minutes off cycles, however, instead of the 30 second ramp up and ramp down at the beginning of each 2 minute period (as seen in the NAcc No-TI Active condition), the stimulation in the NAcc No-TI Sham condition will immediately ramp down as soon as it reaches 2mA after ramp up.
Otros nombres:
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Comparador activo: NAcc No-TI Active, then NAcc No-TI Sham, then NAcc TI Active, then NAcc TI Sham
Participants in this Arm receive temporal interference (TI) electrical stimulation with two pairs of carbon fiber electrodes in this order: NAcc No-TI Active, then NAcc No-TI Sham, then NAcc TI Active, then NAcc TI Sham. |
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies (e.g., 2000 Hz and 2020 Hz) at up to 2 mA per electrode. This stimulation creates a beat frequency interference pattern (e.g., 20 Hz) that focally stimulates deep brain regions without activating overlying cortex. For the NAcc TI Active condition, 2000Hz will be administered in one channel and 2020Hz in the other. These frequencies will be administered in 2 minutes on/2 minutes off cycles with a 30 second ramp up and ramp down beginning at the start of each 2 minute period.
Otros nombres:
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies (e.g., 2000 Hz and 2020 Hz) at up to 2 mA per electrode. This stimulation creates a beat frequency interference pattern (e.g., 20 Hz) that focally stimulates deep brain regions without activating overlying cortex. For the NAcc TI Sham condition, 2000Hz will be administered in one channel and 2020Hz in the other. These frequencies will be administered in 2 minutes on/2 minutes off cycles, however, instead of the 30 second ramp up and ramp down at the beginning of each 2 minute period (as seen in the Active TI condition), the stimulation in the NAcc TI Sham condition will immediately ramp down as soon as it reaches 2mA after ramp up.
Otros nombres:
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using the same current frequencies at up to 2 mA per electrode. For the NAcc No-TI Active condition, 2000Hz will be administered in both channels. These frequencies will be administered in 2 minutes on/2 minutes off cycles with a 30 second ramp up and ramp down beginning at the start of each 2 minute period.
Otros nombres:
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using the same current frequencies at up to 2 mA per electrode. For the NAcc No-TI Sham condition, 2000Hz will be administered in both channels. These frequencies will be administered in 2 minutes on/2 minutes off cycles, however, instead of the 30 second ramp up and ramp down at the beginning of each 2 minute period (as seen in the NAcc No-TI Active condition), the stimulation in the NAcc No-TI Sham condition will immediately ramp down as soon as it reaches 2mA after ramp up.
Otros nombres:
|
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Comparador activo: NAcc TI Sham, then NAcc TI Active, then NAcc No-TI Sham, then NAcc No-TI Active
Participants in this Arm receive temporal interference (TI) electrical stimulation with two pairs of carbon fiber electrodes in this order: NAcc TI Sham, then NAcc TI Active, then NAcc No-TI Sham, then NAcc No-TI Active. |
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies (e.g., 2000 Hz and 2020 Hz) at up to 2 mA per electrode. This stimulation creates a beat frequency interference pattern (e.g., 20 Hz) that focally stimulates deep brain regions without activating overlying cortex. For the NAcc TI Active condition, 2000Hz will be administered in one channel and 2020Hz in the other. These frequencies will be administered in 2 minutes on/2 minutes off cycles with a 30 second ramp up and ramp down beginning at the start of each 2 minute period.
Otros nombres:
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies (e.g., 2000 Hz and 2020 Hz) at up to 2 mA per electrode. This stimulation creates a beat frequency interference pattern (e.g., 20 Hz) that focally stimulates deep brain regions without activating overlying cortex. For the NAcc TI Sham condition, 2000Hz will be administered in one channel and 2020Hz in the other. These frequencies will be administered in 2 minutes on/2 minutes off cycles, however, instead of the 30 second ramp up and ramp down at the beginning of each 2 minute period (as seen in the Active TI condition), the stimulation in the NAcc TI Sham condition will immediately ramp down as soon as it reaches 2mA after ramp up.
Otros nombres:
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using the same current frequencies at up to 2 mA per electrode. For the NAcc No-TI Active condition, 2000Hz will be administered in both channels. These frequencies will be administered in 2 minutes on/2 minutes off cycles with a 30 second ramp up and ramp down beginning at the start of each 2 minute period.
Otros nombres:
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using the same current frequencies at up to 2 mA per electrode. For the NAcc No-TI Sham condition, 2000Hz will be administered in both channels. These frequencies will be administered in 2 minutes on/2 minutes off cycles, however, instead of the 30 second ramp up and ramp down at the beginning of each 2 minute period (as seen in the NAcc No-TI Active condition), the stimulation in the NAcc No-TI Sham condition will immediately ramp down as soon as it reaches 2mA after ramp up.
Otros nombres:
|
|
Comparador activo: NAcc No-TI Sham, then NAcc No-TI Active, then NAcc TI Sham, then NAcc TI Active
Participants in this Arm receive temporal interference (TI) electrical stimulation with two pairs of carbon fiber electrodes in this order: NAcc No-TI Sham, then NAcc No-TI Active, then NAcc TI Sham, then NAcc TI Active. |
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies (e.g., 2000 Hz and 2020 Hz) at up to 2 mA per electrode. This stimulation creates a beat frequency interference pattern (e.g., 20 Hz) that focally stimulates deep brain regions without activating overlying cortex. For the NAcc TI Active condition, 2000Hz will be administered in one channel and 2020Hz in the other. These frequencies will be administered in 2 minutes on/2 minutes off cycles with a 30 second ramp up and ramp down beginning at the start of each 2 minute period.
Otros nombres:
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using alternating current frequencies (e.g., 2000 Hz and 2020 Hz) at up to 2 mA per electrode. This stimulation creates a beat frequency interference pattern (e.g., 20 Hz) that focally stimulates deep brain regions without activating overlying cortex. For the NAcc TI Sham condition, 2000Hz will be administered in one channel and 2020Hz in the other. These frequencies will be administered in 2 minutes on/2 minutes off cycles, however, instead of the 30 second ramp up and ramp down at the beginning of each 2 minute period (as seen in the Active TI condition), the stimulation in the NAcc TI Sham condition will immediately ramp down as soon as it reaches 2mA after ramp up.
Otros nombres:
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using the same current frequencies at up to 2 mA per electrode. For the NAcc No-TI Active condition, 2000Hz will be administered in both channels. These frequencies will be administered in 2 minutes on/2 minutes off cycles with a 30 second ramp up and ramp down beginning at the start of each 2 minute period.
Otros nombres:
Non-invasive electrical brain stimulation delivered through two sets of scalp electrodes using the same current frequencies at up to 2 mA per electrode. For the NAcc No-TI Sham condition, 2000Hz will be administered in both channels. These frequencies will be administered in 2 minutes on/2 minutes off cycles, however, instead of the 30 second ramp up and ramp down at the beginning of each 2 minute period (as seen in the NAcc No-TI Active condition), the stimulation in the NAcc No-TI Sham condition will immediately ramp down as soon as it reaches 2mA after ramp up.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change From Baseline (no Stimulation) in Brain Activity in the Nucleus Accumbens During Active Versus Sham Stimulation
Periodo de tiempo: During fMRI scanning for each study session (active and sham stimulation), approximately 60 minutes
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Brain activity in the nucleus accumbens was measured using functional magnetic resonance imaging (fMRI) during active temporal interference (TI) brain stimulation compared to sham stimulation. Activity change from baseline (no stimulation) was quantified using region-of-interest (ROI) beta estimates extracted from the nucleus accumbens. The beta estimates were derived from blood-oxygen-level-dependent (BOLD) signal changes measured during fMRI and reflect the magnitude of task-related neural activation within the ROI. Higher beta values indicate greater task-related activation. Whole-brain voxelwise analyses did not identify statistically significant activation clusters after correction for multiple comparisons; therefore, descriptive ROI-level beta estimates are reported. |
During fMRI scanning for each study session (active and sham stimulation), approximately 60 minutes
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Change From Baseline (no Stimulation) in Brain Activity in the Nucleus Accumbens During No-TI Active Versus No-TI Sham High-frequency Stimulation
Periodo de tiempo: During fMRI scanning for each study session (active and sham no-TI stimulation conditions), approximately 60 minutes
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Brain activity in the nucleus accumbens was measured using functional magnetic resonance imaging (fMRI) during no-temporal interference (no-TI) control stimulation, in which both electrode pairs delivered the same frequency. Change in activity from baseline (no stimulation) was quantified using region-of-interest (ROI) beta estimates extracted from the nucleus accumbens during NO-TI active versus NO-TI sham high-frequency stimulation to determine whether high-frequency stimulation alone altered brain activity. The beta estimates were derived from blood-oxygen-level-dependent (BOLD) signal changes measured during fMRI and reflect the magnitude of task-related neural activation within the ROI. Higher beta values indicate greater task-related activation. Whole-brain voxelwise analyses did not identify statistically significant activation differences after correction for multiple comparisons; therefore, descriptive ROI-level beta estimates are reported. |
During fMRI scanning for each study session (active and sham no-TI stimulation conditions), approximately 60 minutes
|
|
Change From Baseline (no Stimulation) in Brain Activity in the Nucleus Accumbens During Active TI Stimulation Versus Active No-TI Stimulation
Periodo de tiempo: During fMRI scanning for each study session (active TI and active no-TI stimulation conditions), approximately 60 minutes
|
Brain activity in the nucleus accumbens was compared between active temporal interference (TI) stimulation and active high-frequency no-temporal interference (no-TI) stimulation using functional magnetic resonance imaging (fMRI). Change in activity from baseline (no stimulation) was quantified using region-of-interest (ROI) beta estimates extracted from the nucleus accumbens to determine whether TI stimulation produced greater task-related activation than high-frequency stimulation alone. The beta estimates were derived from blood-oxygen-level-dependent (BOLD) signal changes measured during fMRI and reflect the magnitude of task-related neural activation within the ROI. Higher beta values indicate greater task-related activation. Whole-brain voxelwise analyses did not identify statistically significant activation differences after correction for multiple comparisons; therefore, descriptive ROI-level beta estimates are reported. |
During fMRI scanning for each study session (active TI and active no-TI stimulation conditions), approximately 60 minutes
|
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Change in Brain Connectivity Between the Nucleus Accumbens and Other Brain Regions During Stimulation
Periodo de tiempo: During fMRI scanning for each study session (active and sham stimulation conditions), approximately 60 minutes
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Functional connectivity between the nucleus accumbens and other brain regions was planned to be evaluated using fMRI-based psycho-physiological interaction (PPI) analyses during active versus sham temporal interference (TI) stimulation. Higher correlation values indicate stronger functional connectivity between brain regions. The primary test statistic was the whole-brain interaction term between seed-region BOLD activity and stimulation condition (active vs. sham TI). This analysis was not performed because no statistically significant activation clusters were identified from which to define a seed region. |
During fMRI scanning for each study session (active and sham stimulation conditions), approximately 60 minutes
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Joshua W Brown, PhD, Indiana University, Bloomington
Publicaciones y enlaces útiles
Publicaciones Generales
- Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024.
- Violante IR, Alania K, Cassara AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman N. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci. 2023 Nov;26(11):1994-2004. doi: 10.1038/s41593-023-01456-8. Epub 2023 Oct 19.
- Modak P, Fine J, Colon B, Need E, Cheng H, Hulvershorn L, Finn P, Brown JW. Temporal interference electrical neurostimulation at 20 Hz beat frequency leads to increased fMRI BOLD activation in orbitofrontal cortex in humans. Brain Stimul. 2024 Jul-Aug;17(4):867-875. doi: 10.1016/j.brs.2024.07.014. Epub 2024 Jul 24.
Enlaces Útiles
- <p>Lab website for study. The Cognitive Control Lab aims to understand the neural mechanisms of goal-directed behavior, using a combination of fMRI, computational neural modeling, and neurostimulation methods in healthy and clinical human populations.</p>
- <p>Project details for the NIMH-funded study on temporal interference stimulation, including abstract, funding, and key personnel.</p>
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- 26941, Study 1.1
- 1R21MH140210-01 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
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