Medial Prefrontal Cortex Brain Magnetic Stimulation in Autism
17 de agosto de 2026 actualizado por: National Taiwan University Hospital
The Efficacy and Brain Mechanism of Deep Transcranial Magnetic Stimulation in Autism: A Pilot Study Targeting Medial Prefrontal Cortex
Despite decades of research, no definitive, effective biological treatments exist for core symptoms of Autism Spectrum Disorder (ASD). Emerging evidence suggests that conventional Transcranial Magnetic Stimulation (TMS) targeting the dorsolateral prefrontal cortex or posterior superior temporal sulcus may reduce repetitive behaviors, but its efficacy on social communication remains inconsistent.
Deep Transcranial Magnetic Stimulation (dTMS) allows for the stimulation of deeper brain structures. Deep social brain networks, such as the medial prefrontal cortex (mPFC), play a critical role in social cognition and mentalizing processes. Targeting the mPFC with dTMS holds potential for improving core impairments in social cognition among individuals with ASD. This pilot study aims to evaluate the efficacy of dTMS on social cognition, mPFC-related functional connectivity, and clinical symptoms (autism severity, stereotyped behaviors, sensory symptoms, and emotion regulation).
Descripción general del estudio
Estado
Estado
Aún no reclutando
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Descripción detallada
Conventional repetitive Transcranial Magnetic Stimulation (rTMS) and intermittent Theta Burst Stimulation (iTBS) targeting regions such as the dorsolateral prefrontal cortex (DLPFC) or posterior superior temporal sulcus (pSTS) have shown moderate efficacy in reducing repetitive behaviors and irritability in Autism Spectrum Disorder (ASD). However, their therapeutic effects on core social communication deficits remain inconsistent (~30% response rate in pSTS studies). A key physical limitation of standard TMS/TBS figure-of-eight coils is their shallow stimulation depth (0.7 to 1.1 cm), which restricts their ability to directly reach deeper cortical structures within the "social brain" network.Deep Transcranial Magnetic Stimulation (dTMS) utilizes specialized coil geometry (such as H-coils) to deliver magnetic fields to deeper brain structures (1.8 to 3.5 cm) over larger volumes. The medial prefrontal cortex (mPFC) is a central hub of the social brain network, playing a vital role in social cognition, emotion processing, and mentalization. Preliminary evidence suggests that targeting the mPFC/dorsomedial PFC with dTMS can improve emotion recognition, reduce self-oriented social anxiety, and alleviate core autistic symptoms in high-functioning adults. This pilot study aims to evaluate the safety, clinical efficacy, neural mechanism, and predictive biomarkers of mPFC-targeted dTMS in autistic adults.Study Objectives & Research QuestionsThis single-arm/pilot clinical trial is designed to address the following specific research questions and objectives:Safety and Tolerability: Evaluate the overall safety, side-effect profile, and tolerability of high-frequency dTMS targeting the mPFC in adults with ASD.
Clinical Efficacy:
Assess whether 10 sessions of high-frequency dTMS lead to significant improvements in core ASD domains, with emotion recognition (social cognition) as the primary outcome measure. Secondary outcomes include overall autism severity, repetitive/stereotyped behaviors, sensory processing abnormalities, and emotional regulation.Neural Connectivity (fMRI): Utilize functional Magnetic Resonance Imaging (fMRI) to evaluate post-treatment changes in functional connectivity between the mPFC and other key nodes of the social brain network (e.g., amygdala, orbitofrontal cortex, superior temporal sulcus, anterior cingulate cortex, and temporoparietal junction). Predictive Biomarkers (EEG E/I Balance): Investigate whether acute electroencephalography (EEG) shifts in the excitation/inhibition (E/I) balance-estimated via changes in the aperiodic exponent after a single initial dTMS session-can serve as a neurophysiological biomarker to predict final clinical and neural connectivity responses.
All participants will receive the same deep rTMS intervention. Following treatment, participants will grouped into high response and low response subgroups based on changes of their aperiodic exponent before and after the single-session dTMS for further analysis.
Tipo de estudio
Tipo de estudio
Intervencionista
Inscripción (Estimado)
Inscripción
20
Fase
Fase
- No aplica
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Estudio Contacto
Estudio Contacto
- Nombre: Yi-Ling Chien, MD, PhD
- Número de teléfono: 262380 866+223123456
- Correo electrónico: ntuh.peers@gmail.com
Copia de seguridad de contactos de estudio
- Nombre: Yi-Ting Lin, MD
Ubicaciones de estudio
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Taipei, Taiwán
- Department of Psychiatry, National Taiwan University Hospital
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Contacto:
- Yi-Ling Chien, MD, PhD
- Número de teléfono: 262380 886+223123456
- Correo electrónico: ntuh.peers@gmail.com
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
Acepta Voluntarios Saludables
No
Descripción
Inclusion Criteria:
- Having a diagnosis of autism spectrum disorder based on DSM-5-TR diagnosis criteria
- Aged 18-45 years old
- No change of medications in the past three months
Exclusion Criteria:
- Comorbidity of schizophrenia, substance use disorder,
- Had major medical diseases (e.g., malignancy, severe cardiac, hepatic, renal diseases, or active CNS or systemic infection) or major neurological disease (e.g., uncontrolled epilepsy, brain tumors or hemangioma, severe head trauma)
- Contraindications of MRI or TMS procedure: Ferromagnetic material in the skull, head, and neck; claustrophobia; had received neurosurgery, etc.
- Receiving electroconvulsive therapy or TMS in the past three months
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Número de brazos
1
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
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Experimental: TMS pilot group
Each participant will receive one session of magnetic stimulation and undergo resting-state electroencephalography (EEG) before and after stimulation. Subsequently, they will receive magnetic stimulation once daily for 10 days, for a total of 10 sessions. On the day of the tenth stimulation session or within three days afterward, participants will undergo post-treatment assessment and brain MRI. |
The TMS device (Brainsway Deep TMS system with an H1 coil device, Brainsway Ltd, Israel) emits brief, noninvasive electromagnetic pulses through the skull, inducing an electrical current in a specific cortical region to affect neuronal function.
Subjects will receive 10 once-daily high-frequency repetitive TMS sessions on 10 consecutive work days.
To stimulate the mPFC, the H1 coil helmet will be placed symmetrically bilaterally and with its zero mark 3 cm above the nasion on the sagittal rule.
The stimulation parameters follow the standard protocol cleared by the USFDA.
Each session consists of 55 trains of 2-sec 18-Hz stimulation, given every 20 sec (2-sec on and 18-second off, inter-train interval 20 sec), and the stimulation intensity is 120% resting motor threshold (rMT).
As such 1980 pulses will be given in around 20 minutes each session.
The rMT is the minimal stimulation intensity that can induce observable muscle contraction in at least 5 out of 10 consecutive stimulations.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Social cognitive performance on the "Reading the Mind in the Eyes" Test
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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The Reading the Mind in the Eyes Test (RMET; Baron-Cohen et al., 2001) will be used to assess recognition of emotional and mental states from facial cues.
First, participants will complete the Basic Emotion Recognition Task, identifying six basic emotions-happiness, sadness, anger, fear, disgust, and surprise-from whole-face photographs using a two-choice format.
They will then complete the standard RMET, which contains 36 photographs of the eye region depicting complex mental states.
For each image, participants select the most appropriate of four descriptors.
To examine possible cultural differences, the Taiwanese RMET (TW-RMET) is administered alongside the original UK version.
The TW-RMET includes 43 culturally adapted items and has been validated in Taiwanese populations (Li et al., 2022).
Higher scores indicates a stronger ability to accurately interpret emotional and mental cues from facial expressions.
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14 days (change from baseline to after 10 working days of intervention)
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Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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The Social Responsiveness Scale (SRS)
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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The SRS (Constantino, 2002) is a 65-item rating scale assessing the severity of ASD symptoms in natural settings.
It provides clinical description of an individual's social impairments, covering social awareness, social information processing, capacity for reciprocal social communication, social avoidance, and autistic mannerisms.
Higher scores on the SRS total scores reflect greater impairment and autistic symptoms with scores≧60 typically considered within above the clinical threshold.
The Mandarin Chinese version of the SRS has demonstrated strong psychometric properties, with satisfactory four-factor structure and high internal consistency (Cronbach's alpha, .94-.95), i.e., social communication, autistic mannerism, social awareness, and social emotion (Gau et al., 2013).
In this project, we use the SRS to measure social communication deficits and stereotyped behaviors.
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14 days (change from baseline to after 10 working days of intervention)
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The Autism-Spectrum Quotient (AQ)
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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The Autism-Spectrum Quotient (AQ; Baron-Cohen et al., 2001) is a 50-item self- or parent-report measure of autistic traits across social skills, attention switching, attention to detail, communication, and imagination.
Items use a four-point response scale, with higher scores indicating more autistic traits.
The AQ has good internal consistency (α=.82), test-retest reliability (.70), and screening validity, with a clinical threshold of 26 (Woodbury-Smith et al., 2005).
The Mandarin Chinese AQ uses a 1-4 Likert scale and has been validated in Taiwanese adults (Lau et al., 2013).
It shows good total-score internal consistency (α=.836), moderate-to-good test-retest reliability (ICC=.647),
and somewhat different factor structure from the original version.
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14 days (change from baseline to after 10 working days of intervention)
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The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R)
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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The RAADS-R (Ritvo et al., 2011) is a self-report instrument designed to assist in the identification of adult autistics older than 18 years, particularly those who may have escaped earlier diagnosis due to subclinical symptom presentation.
The RAADS-R is an updated version of the original Ritvo Autism Asperger Diagnostic Scale (RAADS) (Ritvo et al., 2008).
Questions on the initial RAADS assess developmental pathology in three symptom domains: language, social relatedness, and sensory-motor (of the DSM-IV-TR).
The revised 80-item RAADS-R includes the addition of a fourth domain-circumscribed interests, as well as two new items and multiple wording clarifications based on clinical feedback and factor analytic findings.
Subsequent factor analysis of the RAADS-R supported a four-factor structure, comprising: social-relatedness, circumscribed interests, sensory-motor behaviors, and social anxiety.
Scores above 65 strongly suggest the presence of autistic traits.
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14 days (change from baseline to after 10 working days of intervention)
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The Empathy Quotient (EQ)
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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The EQ (Baron-Cohen & Wheelwright, 2004) is a widely used self-report measure designed to assess cognitive and affective components of empathy.
Empirical evidence has demonstrated that approximately 81% of autistic individuals score below 30 on the EQ, whereas only 12% of neurotypical controls fall within this range, indicating its clinical utility in distinguishing empathic traits in ASD populations.
The EQ demonstrates excellent psychometric properties, with an internal consistency of α = .92
and a test-retest reliability of r = .97.
The Mandarin Chinese version of the EQ, developed and validated by Huang H.-Y. and Gau S.S.-F.
(unpublished), has shown satisfactory reliability and validity and will be utilized in the current study to assess empathic functioning in autistic participants.
Higher scores represent higher empathy levels, while lower indicate social and communication obstacles.
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14 days (change from baseline to after 10 working days of intervention)
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Adolescent/Adult Sensory Profile (AASP)
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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The AASP (Catana E. Brown, 2002) is a 60-item self-rating scale designed to examine sensory-related features, including preference, emotional reactions, or behavior changes prompted by perceptions.
It measures six modalities: taste/smell, movement, visual, touch, activity, and auditory processing.
It adopts a 5-point Linkert rating scale with '1' for never (0%), '2' for seldom (25%), '3' for sometimes (50%), '4' for frequently (75%), and '5' for always (100%).
Aligned with Dunn's 4-dimension model of sensory functioning (Dunn, 1997; Dunn & Brown, 1997), the scoring system includes Low Registration, Sensation Seeking, Sensory Sensitivity, and Sensation Avoiding subscales, where higher scores indicate greater sensory reactivity.
The Mandarin version of the AASP has been validated in Taiwanese populations, showing acceptable internal consistency (Cronbach's α = 0.71-0.80)
and strong test-retest reliability (intraclass correlation coefficients = 0.80-0.86)
(Tseng MH, 2009).
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14 days (change from baseline to after 10 working days of intervention)
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Sensory Perception Quotient (SPQ-10)
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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The 10-item short SPQ, SPQ-10 (Greenberg et al., 2018) is a brief, self-report instrument designed to assess sensory hypersensitivity across five sensory modalities: vision, hearing, touch, taste, and smell.
The scale includes two items per modality, and each item is rated on a 4-point Likert scale ranging from 0 (strongly disagree) to 3 (strongly agree).
The total score, obtained by summing responses to all items, provides an overall index of sensory hypersensitivity, with higher scores indicating greater sensitivity.
The SPQ-10 has demonstrated strong convergent validity, with high negative correlations reported with both the full-length SPQ (r = -0.828,
p < 0.01) and the 35-item short version (r = -0.920,
p < 0.01) (Greenberg et al., 2018), supporting its construct validity and efficiency as a screening tool.
The Mandarin Chinese has been validated by our research team (paper in press).
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14 days (change from baseline to after 10 working days of intervention)
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The Schutte Emotional Intelligence Scale (SEIS)
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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The SEIS is a 33-item self-report inventory designed to assess various components of emotional intelligence.
Factor analytic studies have supported a four-factor structure for the SEIS encompassing the following domains: (Ciarrochi et al., 2001; Petrides & Furnham, 2000; Saklofske et al., 2003), including perception of emotions, managing emotions in the self, social skills or managing others' emotions, and utilizing emotions.
The SEIS was translated into Mandarin Chinese in a previous project conducted by our team, and its psychometric properties have been validated in a Taiwanese sample (Chien et al., 2023).
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14 days (change from baseline to after 10 working days of intervention)
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The Social Interaction Anxiety Scale (SIAS) (Mattick & Clarke, 1998)
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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This 20-item self-report scale measures social anxiety experienced in social situations based on DSM-IV criteria of social anxiety disorder.
Respondents rate each item on a 5-point Likert scale, ranging from 0 (not at all characteristic of me) to 4 (extremely characteristic of me), yielding a total score between 0 and 80, with higher scores indicating greater levels of social anxiety.
The Chinese version of the SIAS (Yang, 2003), has demonstrated adequate psychometric properties, including good internal consistency and construct validity.
It has been widely used in both clinical and community samples in Chinese-speaking populations.
In this project, the SIAS will be employed as a measure of social anxiety severity to evaluate potential changes before and after intervention.
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14 days (change from baseline to after 10 working days of intervention)
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Beck Depression Inventory (BDI)
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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The BDI (Beck et al., 1961) is a 21-item self-report instrument measuring the severity of depression in adolescents and adults.
The BDI-II (Beck et al., 1996) was revised in 1996 to be more consistent with the DSM-IV criteria for major depressive disorder.
Each item is rated on a 4-point Likert scale ranging from 0 (not at all) to 3 (severe), producing a total score from 0 to 63, with higher scores reflecting greater depressive symptomatology.
A Mandarin Chinese version of the BDI was translated and validated by Zheng et al. (1988).
This version demonstrated good internal consistency (Cronbach's α = 0.85) and acceptable concurrent validity with clinical measures (r = 0.566), supporting its applicability in Chinese-speaking populations.
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14 days (change from baseline to after 10 working days of intervention)
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Beck Anxiety Inventory (BAI)
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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The BAI (Beck et al., 1988) is a 21-item self-report questionnaire designed to assess the severity of anxiety symptoms experienced over the past month.
The scale encompasses multiple dimensions of anxiety, including autonomic, neurophysiological, panic-related, and subjective components.
Respondents rate each item on a 4-point Likert scale, ranging from 0 (not at all) to 3 (severely), yielding a total score ranging from 0 to 63, with higher scores indicating greater anxiety severity.
The Mandarin Chinese version of the BAI was adapted by Luo et al. (2004) and further validated in clinical populations with anxiety disorders.
Its psychometric properties have been well established, demonstrating high internal consistency (Cronbach's α = 0.95) and good construct validity (Che et al., 2006).
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14 days (change from baseline to after 10 working days of intervention)
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WHO Quality of Life (WHOQOL-BREF)
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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The WHOQOL-100 was originally developed by the WHOQOL research group as a comprehensive instrument to evaluate quality of life across diverse cultural settings.
A shorter version, the WHOQOL-BREF, was later developed to enhance feasibility in clinical and research contexts (The WHOQOL Group, 1998).
The WHOQOL-BREF comprises 28 items, covering four major domains: physical health (7 items), psychological health (6 items), social relationships (3 items), and environment (8 items).
In addition, it includes two general items assessing overall quality of life and general satisfaction with health A Taiwanese version of the WHOQOL-BREF has been developed and culturally adapted.
Each item is rated on a five-point Likert scale ranging from 1 (very dissatisfied/poor) to 5 (very satisfied/good), with higher scores indicating better perceived quality of life.
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14 days (change from baseline to after 10 working days of intervention)
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Resting-state functional connectivity of the mPFC on the MRI
Periodo de tiempo: 14 days (change from baseline to after 10 working days of intervention)
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Images will be acquired using a Siemens MAGNETOM Trio 3.0 Tesla.
High resolution T1 structural image will serve for frameless stereotaxy navigation of TMS experiments.
For the resting-state functional imaging, subjects will be instructed to remain awake with their eyes open.
Forty-seven contiguous horizontal slices parallel to the intercommissural plane will be acquired by using a gradient echo T2*-weighted sequence (TR 2500 msec, TE 30 msec, flip angle 90°).
The Statistical Parametric Mapping 12 (SPM12, Wellcome Centre for Human Neuroimaging, University College London, UK) and the SPMbased CONN (Whitfield-Gabrieli & Nieto-Castanon, 2012) will be used to preprocess and analyze the fMRI data.
The preprocessing consists of realignment and unwrapping of the functional data, slice-timing correction, outlier identification, direct segmentation and normalization of functional and anatomical data, functional smoothing, and denoising by linear regression and temporal band-pass filtering.
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14 days (change from baseline to after 10 working days of intervention)
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Otras medidas de resultado
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Stratification biomarker: Resting-state EEG: aperiodic exponent (1/f)
Periodo de tiempo: 30 mintues (change between baseline and immediately after initial 20-minute dTMS treatment)
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Resting-state EEG will be recorded for 3 minutes under eyes-open (EO) and eyes-closed (EC) conditions, with condition order counterbalanced.
During EO, participants fixate on a central white cross while remaining still and relaxed; during EC, they close their eyes and relax without engaging in specific mental activity.
To quantify aperiodic activity, the power spectrum is separated into periodic oscillations and the 1/f-like aperiodic component using the Fitting Oscillations and One-Over-F (FOOOF) algorithm (Donoghue et al., 2020).
The aperiodic fit is estimated from 35-45 Hz to reduce contamination from oscillatory peaks and residual line noise.
The slope of the linear fit in log-log space is extracted as an index of excitation/inhibition balance.
Slopes are calculated for each electrode and averaged by region: frontal (Fz, F3, F4, F7, F8) and posterior (Pz, P3, P4, P7, P8, O1, O2), for group comparisons and correlation analyses.
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30 mintues (change between baseline and immediately after initial 20-minute dTMS treatment)
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Patrocinador
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Estimado)
Inicio del estudio
1 de diciembre de 2026
Finalización primaria (Estimado)
Finalización primaria
31 de diciembre de 2028
Finalización del estudio (Estimado)
Finalización del estudio
31 de diciembre de 2028
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
3 de agosto de 2026
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
17 de agosto de 2026
Publicado por primera vez (Actual)
Publicado por primera vez
18 de agosto de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
18 de agosto de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
17 de agosto de 2026
Última verificación
Última verificación
1 de julio de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- 202508055DINA
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
producto fabricado y exportado desde los EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .