NCT03056170: COMBI-STIM

Neurophysiological Impact of a Fronto-temporal tDCS Stimulation in Healthy Subjects: a Multimodal Imaging Approach

Completed NA Last updated 25 September 2025

What this trial tests

NA trial testing real tDCS in Healthy in 37 participants. Completed in 20 June 2017.

Timeline

13 November 2015

Primary endpoint
19 April 2017

20 June 2017

Quick facts

Lead sponsor	Hospices Civils de Lyon
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	basic science
Enrollment	37
Start date	13 November 2015
Primary completion	19 April 2017
Estimated completion	20 June 2017
Sites	1 location across France

Drugs / interventions tested

• real tDCS

Conditions studied

• Healthy — all drugs for Healthy →

Sponsor

Hospices Civils de Lyon — full company profile →

Who can join

Adults 18 to 45, any sex, with Healthy. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

tDCS is a technique emerging as a prospective therapy for neurologic, psychiatric and addictive disorders. Specifically, fronto-temporal tDCS, with anodal stimulation over the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation over the left temporo-parietal junction (TPJ), has been reported to reduce treatment-resistant auditory hallucinations (AH), negative symptoms and insight of the illness in schizophrenia. However, despite an increasing use in clinical settings, tDCS suffers from limitations, especially regarding the strength and the duration of therapeutic effects.

Some imaging reports suggest that tDCS effects are not restricted to the brain areas located under the electrodes, but spread through distributed cortical networks functionally connected with the targets and reach subcortical areas. Overall, these studies suggest that tDCS modulates functional connectivity within and across resting-state networks and brain activity. However, these effects are currently described at different levels depending on the imaging technique used. Moreover, the majority of studies have focused on motor cortex stimulation, while the specific effects of fronto-temporal tDCS are scarce. Finally, effects of the stimulation applied online are rarely inspected.

According to the therapeutic effects of fronto-temporal tDCS on schizophrenia and the dopaminergic pathophysiological hypothesis of schizophrenia, the effect of fronto-temporal tDCS on dopaminergic transmission is of major interest. As the cortex is densely connected with basal ganglia areas, tDCS effects are probably capable to reach subcortical dopaminergic areas. Indeed, recent fMRI studies highlighted subcortical effects of tDCS applied at the cortical level including modulations of cortico-striatal and thalamo-cortical functional connectivity. In addition, some studies suggest that cortical stimulation by other approaches, such as transcranial magnetic stimulation (rTMS) modulates dopaminergic transmission. However, tDCS effects on dopaminergic transmission have been investigated only indirectly.

Finally, information about biological effects of tDCS is scattered and creating a coherent ensemble is a mandatory and critical step to understand the mechanisms of action of tDCS.

According to the hypothesis that fronto-temporal tDCS modulates brain activity, connectivity and dopaminergic transmission, the aim of this project is to reveal the combined neurobiological impact of an online single session of fronto-temporal tDCS in a unique experiment by developing a simultaneous multimodal imaging approach (PET-MRI). The online implementation of the stimulation will allow deciphering changes induced during and after stimulation. As a first step before investigating patients with schizophrenia, healthy subjects will be involved in the present study.

The distributed changes will be explored at rest through:

* Spontaneous functional connectivity assessed by functional magnetic resonance imagery (fMRI).
* Brain activity assessed by cerebral blood flow quantitatively and directly measured by arterial spin labelling (ASL).
* Connectivity assessed by diffusion tensor imaging (DTI).
* Specific and localized dopaminergic transmission evaluated by positron emission tomography (PET) using dopaminergic D2 subtype receptor availability via \[11C\]raclopride binding.

The pioneering aspects of the project are to use an innovative simultaneous multimodal imaging system, adopt the tDCS montage used in our validated therapeutic context and apply tDCS online. We expect that our unique approach will provide an imaging biomarker essential to improve our understanding of:

1. the "normal brain" and further deficient mechanisms underlying schizophrenia as well as neurological disorders.
2. neurobiological effects of tDCS in order to:

* Bring key element of the proof of concept of tDCS
* Optimize tDCS in a therapeutic context
* Suggest a marker of the therapeutic response

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.