human subject research

Between subjects: one group gets the real intervention and another group gets the control (fake) intervention)

Within subjects: each person gets the real intervention and the fake intervention, also called cross over study.

Ethics & Training:

  • Institituional Review Board (IRB): a working group at an institution (ex. university) and reviews all the proposals for research being conducted on human participants

  • ensured ethical and safe practices that comply with federal and state regulations

  • CITI training: Collaborative Insitutional Training Initiative, provides research ethics education to the research community, and covers research and HIPAA requirements.

Research MethodsL

  • spatial resolution: how preciesely can you measure something in space; ability to distinguish two points from each other

  • temporal resolution: how precisely can you measure something in time; ability to distinguish events happening in time

Human techniques:

  • are lower spatial and temporal resolution

  • we study humans compared to animal research because we have higher order cognition, language, descision making and social processes

  • different brains might be different across species

  • you can measure the whole brain with MRI/EEG; you might miss something if focused on a particular region or handful of regions

Research Methods

Imaging the Brain

  • structural imaging: looking at the fixed anatomy of the brain/cells

  • functional imaging: looking at the dynamics of the brain in action

Computerized axial tomography (CAT or CT):

  • x rays rotated around the body, transmitted to computer to generate an image

  • CT scans generate an anatomical map of the brain based on tissue density

  • use contrast agents to help visualize soft tissue (enhance the radiodensity, alters the way the electromagnetic radiation (x ray) passed through)

  • compared to MRI: lower resolution, faster, better for emergencies

Magnetic resonance imaging (MRI):

  • produce magnetic field → protons in body align with the field, radiofrequency current pulsed through subject, protons stimulated (strain against magnetic field), current turned off, protons relax, MRI sensors detect energy released as protons realign with magnetic field.

  • compared to CT: higher resolution images, fewer damaging effects, more expensive

  • applies to medicine in 1970s

  • utilizes hydrogen atom

  • 70-80% of atoms in body are hydrogen

  • h20 the most common

  • magent strengths are measured in Teslas: 1.5, 3.0, 4.0, 7.0

Diffusion Tensor Imaging (DTI):

  • mri, where signal is detected by movement of water molecules

  • detects how water travels along white matter tracts (axons)

  • different colors indicate direction/trajectory of axons

  • Stroke, TBI, demyelination, neurodegenerative disease

Functional Imaging:

Functional MRI (fMRI):

  • MRI + detectio of oxygenated blood flow

  • higher in active brain areas

  • Blood oxygen level dependent (BOLD) contrast

  • from changing regional blood concentrations of oxy- and deoxy-hemoglobin, which have different magnetic properties.

  • measured relative brain activity

  • can show how networks of brain structures colkaborate

Positron Emission Topography (PET):

  • radioactivity based techniques

  • tag a molecule with a radioactive tracer

  • intravenous inkection while in scanner, radioactive tracer enters brain and gets processed by certain neurons

  • tracer undergoes radioactive decay and emits photons; photos interacts with electrons to release gamma rays at 180 degree angle

  • PET scanner measures these gamma rays at a detector and localize where in the brain they originated

  • For safety, can do fewer than fmri and can’t do in kids unless required.

  • more signal in more active parts of the brain

  • lower spatial and temporal resolution than fMRI

  • good for detecting and staging many cancers

BOTH detect increased blood flow and when paired with a specific task, can indiciate which brain regions may contribute to specific functions.

  • FMRI & DTI can be combined for brain mapping before surgery, to avoid damaging speech or motor functions.

Brain Imaging:

  • Functional Near Infrared Spectroscopy (fNIRS)

    • measures changes in hemoglobin concentration (the difference in oxygenated and deoxygenated blood) via differences in optical absorption.

    • poor spatial resolution — cannot measure subcortical structures like fMRI. but better spatial resolution than eeg, and better temporal resolution than fmri.

    • affordable, allows flexbility in patient position.

Magnetoencephalography (MEG):

  • measures the tiny magnetic fields given off by brain’s electrical currents (active neurons) during certain tasks or cognitive processes, or seizures to map exact location.

Electroencephalogram (EEG):

  • electrodes applied to surface of scalp → record activity of millions of neurons working together

  • Event related potentials (ERPs): waveforms related to certain events

  • poor spatial resolution - electrical activity summated across cortical surface

  • good temporal resolution

  • compared to MEG: EEG is less expensive but has more distortion from intervening structures like skull

Recording Brain Activity

  • Electrocorticography (ECog)

    • similar to EEG but sensors placed directly on or in the brain; specific area of the brain

    • chronic ECog used for brain-computer interfaced (BCI)

      • neuroprosthesis

      • brain to speech tech

  • temporary ECog used for mapping brain function in preparation for brain surgery

    • surgery for patients with epilepsy

    • can stay in the brain for daus or weeks to evaluate epileptogenic zone

    • to precisely locate the source of epileptic seizures sEEG (Stereoelectroecncephaolography) uses minimally insvasive electrodes in the brain that can be inserted deeper into the brain.

Manipulating the Function of the Living Brain

Transcranial magnetic stimulation (TMS):

  • uses magnetic field to alter activity of discrete cortical regions (repetitive delivery of various frequencies of activity)

  • can silence neurons (virtual lesion)

  • can match (enhance?) typical activity

  • can mistmatch (disruot?) typical activity

  • can get downstream/distant effects due to connectivity of brain

  • clinical applications: treatment of depression, OCD, migraines, smoking cessation

  • research applications: cognitive neuroscience (learning, attention, visual processing, task switching, etc., when paired with task), clinical neuroscience, etc.,

Transcranial Focused Ultrasound Stimulation:

  • delivers mechanical vibrations to the brain and activates the targeted area

  • sound waves measure changes in volume

  • the same ultrasound as in pregnancy

  • very specific focal targeting

  • new tool with limited usage at this time

Electrical Stimulation: just as electricity can be recorded at many different levels, you can stimulate electrically at each of these levels

  • transcranial electrical stimulation: non invasives stimulation through pads placed on the scalp

  • Deep brain stimulation (DBS): implanted electrodes for medical purposes and research purposes in humans and animals

  • electrical microstimulation: stimulation at the microscoping level of populations of neurons