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

Summary: 
      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
    


Intervention name(s): real tDCS
Intervention type(s): Device
Intervention description(s): In active stimulation, the "Transcranial Direct Current Stimulation" device will produce a direct current of 1 mA from one electrode to the other for 30 min with a ramp up at the beginning and a ramp down at the end of the stimulation of 30 s. The sham or active mode is chosen by a numeric code.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science