Functional Brain Imaging in Healthy Volunteers to Study Cognitive Functions
Condition: Healthy Volunteers
Study type: Observational

Summary: 
      Objective:

      The goal of this protocol is to improve understanding scale-free brain activity and conscious
      vs. unconscious processing by performing small behavioral, electrophysiological, neuroimaging
      and brain stimulation pilot substudies. This research is expected to help develop techniques
      and hypotheses for future research on these topics.

      We will conduct:

        -  Pilot Substudy: Pilot substudies are exploratory in nature, in order to develop enough
           information to generate a hypothesis. The criterion for transition to a new full
           protocol will be acquisition of sufficient information to generate a power analysis.
           There are no enrollment limitations for pilot substudies.

        -  Hypothesis-Testing Substudy is defined as a study with a specific hypothesis to be
           tested that can be completed with a few healthy volunteers or patients.
           Hypothesis-testing substudies will undergo statistical and PIRC reviews after 6 subjects
           (if there is one group) or after 12 (6 per arm) if two groups are studied before
           additional subjects are recruited. In the event of subject dropout or unsuccessful
           recording, replacement will be recruited. Together, the P.I. and PIRC will decide
           whether to continue the hypothesis substudy with more subjects without an amendment or
           whether an amendment or new protocol would be necessary. A memo requesting a review of
           hypothesis-testing substudies for possible additional enrollment will be sent to PIRC
           and the statistical reviewer. The memo will be forwarded to the CNS IRB.

        -  Technical development of new experimental paradigms and data analysis methods.

      This protocol includes only non-invasive techniques with minimal risk (MRI, EEG, MEG, EMG,
      tDCS).

      Study Population:

      We plan to recruit up to 120 healthy volunteers aged 18-65.

      Design:

      We will design small projects that are pertinent to the theme of scale-free brain activity
      and conscious/unconscious processing. We will investigate healthy volunteers in the resting
      state or while they perform simple motor or sensory tasks. If a hypothesis testing substudy
      leads to results of interest and if a larger population is necessary to reach statistical
      significance, a separate protocol will be submitted with a priori hypotheses, specific study
      design and power analysis adapted from the pilot or exploratory substudies performed in the
      present protocol.

      In the substudies, brain activity of healthy human volunteers will be monitored by functional
      magnetic resonance imaging (fMRI), magnetoencephalography (MEG), electroencephalography
      (EEG), or simultaneous MEG-EEG. Anatomical MRI will be collected in some subjects to allow
      better localization of brain dynamics. Because transcranial direct-current stimulation (tDCS)
      is ideally suited to modulate the slow component of scale-free brain activity, we will also
      investigate the effect of tDCS on brain activity and/or behavioral performance in cognitive
      tasks. tDCS will be administered sequentially, but not simultaneously, with brain-activity
      monitoring by fMRI/MEG/EEG. Most experiments will be conducted in conjunction with cognitive
      tasks. In some experiments, we will study resting-state brain function, during which
      spontaneous brain activity is collected without a specific externally administered task.

      Outcome Measures:

      MRI: to analyze measures such as the anatomical structures of the brain (using structural
      MRI); amplitude of the blood-oxygenation-level-dependent (BOLD) signal (using fMRI); cerebral
      blood flow [using arterial spin labeling (ASL)] and different neurotransmitter levels in
      brain regions of interest [using magnetic resonance spectroscopy (MRS)].

      EEG and MEG: to quantify measures such as power spectrum, event- or task-related potentials,
      synchronization/desynchronization, and coherence between sensors or sources located close to
      the brain areas of interest.

      tDCS: to analyze changes in behavioral measures and/or fMRI/EEG/MEG activity caused by tDCS.

      Behavioral measures: to quantify measures such as hit rate, reaction times, electromyography
      (EMG) patterns.

      We may measure autonomic data during the course of the experiment (such as heart rate,
      respiration, end-tidal CO2, skin conductance), which will be correlated with the outcome
      measures.
    

Detailed description: 
      Objective:

      The goal of this protocol is to improve understanding scale-free brain activity and conscious
      vs. unconscious processing by performing small behavioral, electrophysiological, neuroimaging
      and brain stimulation pilot substudies. This research is expected to help develop techniques
      and hypotheses for future research on these topics.

      We will conduct:

        -  Pilot Substudy: Pilot substudies are exploratory in nature, in order to develop enough
           information to generate a hypothesis. The criterion for transition to a new full
           protocol will be acquisition of sufficient information to generate a power analysis.
           There are no enrollment limitations for pilot substudies.

        -  Hypothesis-Testing Substudy is defined as a study with a specific hypothesis to be
           tested that can be completed with a few healthy volunteers or patients.
           Hypothesis-testing substudies will undergo statistical and PIRC reviews after 6 subjects
           (if there is one group) or after 12 (6 per arm) if two groups are studied before
           additional subjects are recruited. In the event of subject dropout or unsuccessful
           recording, replacement will be recruited. Together, the P.I. and PIRC will decide
           whether to continue the hypothesis substudy with more subjects without an amendment or
           whether an amendment or new protocol would be necessary. A memo requesting a review of
           hypothesis-testing substudies for possible additional enrollment will be sent to PIRC
           and the statistical reviewer. The memo will be forwarded to the CNS IRB.

        -  Technical development of new experimental paradigms and data analysis methods.

      This protocol includes only non-invasive techniques with minimal risk (MRI, EEG, MEG, EMG,
      tDCS).

      Study Population:

      We plan to recruit up to 200 healthy volunteers aged 18-65.

      Design:

      We will design small projects that are pertinent to the theme of scale-free brain activity
      and conscious/unconscious processing. We will investigate healthy volunteers in the resting
      state or while they perform simple motor or sensory tasks. If a hypothesis testing substudy
      leads to results of interest and if a larger population is necessary to reach statistical
      significance, a separate protocol will be submitted with a priori hypotheses, specific study
      design and power analysis adapted from the pilot or exploratory substudies performed in the
      present protocol.

      In the substudies, brain activity of healthy human volunteers will be monitored by functional
      magnetic resonance imaging (fMRI), magnetoencephalography (MEG), electroencephalography
      (EEG), or simultaneous MEG-EEG. Anatomical MRI will be collected in some subjects to allow
      better localization of brain dynamics. Because transcranial direct-current stimulation (tDCS)
      is ideally suited to modulate the slow component of scale-free brain activity, we will also
      investigate the effect of tDCS on brain activity and/or behavioral performance in cognitive
      tasks. tDCS will be administered sequentially, but not simultaneously, with brain-activity
      monitoring by fMRI/MEG/EEG. Most experiments will be conducted in conjunction with cognitive
      tasks. In some experiments, we will study resting-state brain function, during which
      spontaneous brain activity is collected without a specific externally administered task.

      Outcome Measures:

      MRI: to analyze measures such as the anatomical structures of the brain (using structural
      MRI); amplitude of the blood-oxygenation-level-dependent (BOLD) signal (using fMRI); cerebral
      blood flow [using arterial spin labeling (ASL)] and different neurotransmitter levels in
      brain regions of interest [using magnetic resonance spectroscopy (MRS)].

      EEG and MEG: to quantify measures such as power spectrum, event- or task-related potentials,
      synchronization/desynchronization, and coherence between sensors or sources located close to
      the brain areas of interest.

      tDCS: to analyze changes in behavioral measures and/or fMRI/EEG/MEG activity caused by tDCS.

      Behavioral measures: to quantify measures such as hit rate, reaction times, electromyography
      (EMG) patterns.

      We may measure autonomic data during the course of the experiment (such as heart rate,
      respiration, end-tidal CO2, skin conductance), which will be correlated with the outcome
      measures.
    

Observational model: Cohort
Time perspective: Prospective
Keywords: Magnetic Resonance Imaging (MRI); Functional Imaging; BOLD Effect; EEG; MEG