Study Evaluating the Effect of Transcranial Direct Current Stimulation (tDCS) Targeting the Right Inferior Frontal Gyrus on Inhibitory Control in Patients With PSP (TinPSP)

A Double-blind, Randomized, Sham-controlled, Crossover Pilot Study Evaluating the Effect of Transcranial Direct Current Stimulation (tDCS) Targeting the Right Inferior Frontal Gyrus on Inhibitory Control in Patients With PSP.

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease with a prevalence estimated at 6 per 100,000 in France and a rapidly progressive course. In its classic form (known as the Richardson type), it presents with a predominantly axial Parkinsonian syndrome, postural instability with early falls, oculomotor disorders, and cognitive and behavioral disturbances. Apart from levodopa, which may provide a modest improvement in Parkinsonian syndrome in some patients, the current therapeutic approach relies primarily on rehabilitation techniques, with no proven efficacy.

Cognitive-behavioral symptoms are common in this disease and are primarily characterized by impaired executive functions, linked to dysfunction of the frontal cortex. They often have a devastating effect on quality of life, are associated with an increased risk of falls, and represent a considerable burden for caregivers. Among these symptoms, apathy is the most commonly described symptom. Impulsivity, associated with impaired inhibitory control, is present in 32-74% of cases and may coexist with apathy.

Cognitive and behavioral inhibition depends on a complex brain network that includes, among others, the right inferior frontal gyrus (IFG), the dorsolateral prefrontal cortex, the supplementary motor area, the motor cortex, and the basal ganglia. It has recently been shown that patients with PSP have impaired functional connectivity between the right LFC and other brain structures in the network, and that neurotransmitter deficits in the right LFC correlate with their impulsivity Alongside pharmacological approaches, non-invasive brain stimulation techniques are rapidly expanding as a potential therapeutic tool. Transcranial direct current stimulation (tDCS), by modulating cortical excitability, is a promising technique. It is simple to administer and has demonstrated efficacy in several clinical settings.

Furthermore, a recent meta-analysis of 45 clinical studies shows that single or repeated tDCS sessions could modestly but significantly improve the inhibitory response-measured by reaction time in the stop-signal paradigm-especially when active (anodal) stimulation was applied to the right GFI. These studies primarily involved healthy subjects. A few studies have examined the effects of tDCS in neurodegenerative diseases and in PSP. These studies are still preliminary, involving small sample sizes, but are encouraging. Among these, a randomized study comparing tDCS to sham tDCS demonstrated a beneficial effect of a single-session tDCS session targeting the dorsolateral prefrontal cortex on verbal fluency in patients with PSP.

The hypothesis of our study is that applying tDCS stimulation over the right GFI will improve certain cognitive functions and reduce behavioral impulsivity in patients.

Very little data on tDCS in PSP is available to date. Only three studies have been published. With very different designs-including only one randomized trial comparing tDCS to sham tDCS-these studies evaluated the effects of tDCS applied to the dorsolateral prefrontal cortex or to motor and premotor areas on language and motor symptoms, respectively.

In this randomized, double-blind, controlled study, the investigators propose to explore the effects of tDCS on the right GFI on executive functions and, more specifically, on inhibitory control. Another strength of our study is that only patients with proven frontal cerebral hypometabolism on FDG-PET-MRI will be included, which will allow us to test the effect of tDCS on a clearly dysfunctional neural network. Furthermore, as a secondary objective, the investigators will be able to assess whether the effects of tDCS depend on the intensity and/or topography of cerebral hypometabolism.

The neurophysiological effects of a single tDCS session appear to last up to 60 to 90 minutes. In this proof-of-concept study, the assessment tests were deliberately chosen for their short administration time and low test-retest effect. Finally, the Stop Signal Test, already used in this population, is widely used and well-standardized.

This pilot study will provide initial data on the cognitive and motor effects of a tDCS session on the GFI, with a focus on inhibition. Given the limited effectiveness of symptomatic treatments-particularly pharmacological ones-having a new option capable of improving cognitive and/or behavioral performance would have a significant impact on the quality of life of patients and their families. tDCS has the advantage of being easily accessible and generally well-tolerated by patients and could eventually be administered in patients' homes.

If our study demonstrates an improvement in certain cognitive/motor functions, it would lead to a larger-scale study with repeated sessions to assess its benefits over a longer period.

Finally, if an improvement in executive functions is demonstrated in PSP, this could apply to other neurodegenerative diseases.

Study Overview

• Status: Not yet recruiting
• Conditions: PSP - Progressive Supranuclear Palsy
• Intervention / Treatment: Device: tDCS, or transcranial direct current stimulation

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne-Gaëlle Dr CORBILLE; Phone Number: 0240165967; Email: ANNEGAELLE.CORBILLE@chu-nantes.fr

Study Locations

• France
  • Loire Atlantique
    • Nantes, Loire Atlantique, France, 44093
      • CHU de Nantes
      • Contact: Anne-Gaëlle Dr CORBILLE; Phone Number: 0240165967; Email: ANNEGAELLE.CORBILLE@chu-nantes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 40 to 89 years
• Patients with probable PSP according to the MDS-9 diagnostic criteria
• BREF score >10;

• 18-FDG PET-MRI performed no more than 6 months prior to enrollment and showing:

  • Glucose hypometabolism defined as > 2.5 SD compared to an atlas of healthy subjects and
  • No severe right frontal cortical atrophy according to F Pasquier's global cortical atrophy scale 53
• Concomitant treatments must have been stable for at least 4 weeks prior to enrollment and must remain stable throughout participation
• Patient must have provided written informed consent
• Patient must be enrolled in a social security program
• Patient must be able to understand French and comply with the protocol
• Women must use adequate contraceptive measures for the duration of the clinical trial (in accordance with CTFG recommendations)

Exclusion Criteria:

• Left-handed Patients;
• Patients with severe apraxia that interferes with performance of the SST (at the investigator's discretion)
• Known visual or hearing impairment that prevents performance of cognitive tests or the stop-signal test;
• History of severe psychiatric or neurological disorders other than PSP;
• Known significant brain injury(ies) (stroke, tumor, inflammation, post-traumatic, etc.), at the investigator's discretion
• Atrophy of the right frontal lobe ≥3 on the F Pasquier Global Cortical Atrophy Scale 53
• History of epilepsy and seizures (or cerebral impairment with unexplained loss of consciousness), severe cardiac disorders, neurosurgical procedures, or severe or frequent headaches;
• Presence of a cardiac, neural, drug-delivery, or cerebral stimulator
• Presence of cerebral medical devices (such as vascular clips or electronically sensitive devices), intracerebral or intracochlear metal implants,
• Patients with any electrically, magnetically, or mechanically activated implant
• Patients suffering from a serious, life-threatening condition such as congestive heart failure, chronic obstructive pulmonary disease (COPD), or active neoplasia
• Patients with skin conditions (dermatitis, psoriasis, or eczema) or lesions on the scalp or skull that preclude tDCS
• Patients under legal guardianship or protective supervision
• Pregnant or breastfeeding women
• For patients in the ancillary study, contraindication to MRI: Presence of metallic foreign bodies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: tDCS Active (first visit) + tDCS sham (second visit); Each participant will receive active tDCS then sham tDCS during two 20-minute sessions spaced one month apart	Device: tDCS, or transcranial direct current stimulation; Each participant will receive both active tDCS and sham tDCS during two 20-minute sessions spaced one month apart, with the order of the sessions determined at random.
Other: sham tDCS (fist visit) + active tDCS (second visit); Each participant will receive sham tDCS then active tDCS during two 20-minute sessions spaced one month apart	Device: tDCS, or transcranial direct current stimulation; Each participant will receive both active tDCS and sham tDCS during two 20-minute sessions spaced one month apart, with the order of the sessions determined at random.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effect of anodal tDCS targeting the right inferior frontal gyrus (IFG) on a motor-modality cognitive inhibition task, the Stop Signal Task (SST), in patients with PSP.	Stop Signal Reaction Time (SSRT) during the SST (seconds)	during the hour before each tDCS session and within 1 hour after each tDCS session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate, in PSP, the effect of anodal tDCS targeting the right GFI on the components of cognitive inhibition assessed by the SST	Results for each of the two conditions (active / sham) regarding the components of cognitive inhibition in the stop-signal test: reaction time (seconds), number of failed inhibitions, and number of unresponded-to Go stimuli will be combined to obtain a grade (low/high)	during the hour before each tDCS session and within 1 hour after each tDCS session
To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of verbal cognitive inhibition	Results for each of the two conditions (active / sham) on the Color Word Interference test from the Delis Kaplan Executive System (or Stroop D-KEFS)(scale: Preserved executive functions-Difficulty adapting to novelty)	during the hour before each tDCS session and within 1 hour after each tDCS session
To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of perseverative motor behavior	Results for each of the two conditions (active / sham) regarding the presence or absence of an applause sign and the presence or absence of palilalia	during the hour before each tDCS session and within 1 hour after each tDCS session
To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of other executive functions	Results for each of the two conditions (active / sham) on the Phonological and Categorical Verbal Fluency Test-which measures perseverations and clusters-and the Symbol-Digit Modality Test.	during the hour before each tDCS session and within 1 hour after each tDCS session
To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of social cognition	Results for each of the two conditions (active / sham) on the modified Ekman Emotion Recognition Test (6 emotions).	during the hour before each tDCS session and within 1 hour after each tDCS session
To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of overall cognitive efficiency	Results for each of the two conditions (active / sham) on the MoCA	during the hour before each tDCS session and within 1 hour after each tDCS session
To evaluate, in the PSP, the effect of anodal tDCS targeting the right GFI on motor and bulbar symptoms	Results for each of the two conditions (active / sham) on the PSP-RS scale subscores (ocular motility, bulbar examination, limb examination, gait examination)	during the hour before each tDCS session and within 1 hour after each tDCS session
To evaluate the effect of anodal tDCS targeting the right GFI on motor function in PSP	Results for each of the two conditions (active / sham) on the Timed Up and Go Test	during the hour before each tDCS session and within 1 hour after each tDCS session
To analyze the effects of tDCS on brain metabolism patterns as assessed by 18-FDG PET-MRI	Effect of tDCS as described in Sections 3 and 4 and the brain binding pattern of the FDG tracer in PET-MRI	before and after each tDCS session
To evaluate the clinical effects of tDCS on patients' clinical characteristics	Effect of tDCS as described in Sections 3 and 4, and baseline scores on the PSP-RS scales	Baseline, before and after each tDCS session
To evaluate the clinical effects of tDCS on patients' clinical characteristics	Effect of tDCS as described in Sections 3 and 4, and baseline scores on the BREF scales	Baseline, before and after each tDCS session
To evaluate the clinical effects of tDCS on patients' clinical characteristics	Effect of tDCS as described in Sections 3 and 4, and baseline scores on the NPI scale	Baseline, before and after each tDCS session
Assess participants' perception and acceptance of tDCS stimulation	Number and severity of targeted symptoms (itching, burning, pain, etc.) based on the structured questionnaire developed by Antal et al.40	within 1 hour after each tDCS session
Safety Assessment	Number of EI and Defects	within 1 hour after each tDCS session
Safety Assessment	Grades of EI and Defects	within 1 hour after each tDCS session

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): July 15, 2028
• Study Completion (Estimated): July 15, 2028

Study Registration Dates

• First Submitted: July 7, 2026
• First Submitted That Met QC Criteria: September 9, 2026
• First Posted (Actual): September 14, 2026

Study Record Updates

• Last Update Posted (Actual): September 14, 2026
• Last Update Submitted That Met QC Criteria: September 9, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Progressive Supranuclear Palsy; PSP; Transcranial direct current stimulation (tDCS); GFI
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Tauopathies; Neurodegenerative Diseases; Movement Disorders; Basal Ganglia Diseases; Cranial Nerve Diseases; Ophthalmoplegia; Ocular Motility Disorders; Paralysis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Supranuclear Palsy, Progressive; Therapeutics; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Direct Current Stimulation
• Other Study ID Numbers: RC23_0119

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No