Neuroscience Methods

• Mapping the brain’s electrical activity

  • Cognitive functioning involves coordinated activity of networks of different brain areas

    • Identifying networks goes beyond anatomical activity → studies what goes on in the brain when performing particular tasks

    • One way is by mapping brain’s electrical activity

  • Electrical activity is a good index of activity in neurons

    • When neurons fire they generate electricity

• Various techniques for measuring brain’s electrical activity

  • Single cell recordings

    • Microelectrode is placed close to individual neuron to record discharge of action potentials in cell

    • Has been used to identify neurons that respond to particular stimuli

    • Ex: mirror neurons fire both when a monkey performs specific action and when it observes that action being performed by an observer

  • Electroencephalogram (EEG)

    • **function

    • Electrodes attached to skull and wired up to a computer

    • Technique provides amplified recording of waves of electrical activity that sweep across brain’s surface

      • Each electrode sensitive to electrical activity of thousands of neurons, closest neurons making largest contribution

      • Coordinated activity of neural populations seen as oscillatory waves at different frequencies

        • Useful in clinical contexts for diagnosing epilepsy and tumors

    • Also provide way of measuring event-related potentials (ERPs)

      • ERP activity provoked by specific stimulus

      • ERPs have very fine temporal resolution, low spatial resolution

    • Most widespread and least expensive technique for studying electrical activity of a large population of neurons

• Gamma

  • Very high frequency waves, 26-42+ Hz

  • Signal active exchange of information between cortical and other areas of brain

  • Conscious state or REM

• Beta

  • Irregular, low-amplitude waves, 12-25 Hz

  • Most evident in frontal, usually seen on both sides of brain in symmetrical distribution

  • State of arousal or alertness

• Alpha

  • Synchronous waves, 7.5-13 Hz

  • Relaxed awake state

• Theta

  • Synchronous waves, 3.5-7.5 Hz

  • Transition between sleep and wakefulness

  • Deep meditation, hypnagogic state, creativity, memory retrieval

• Delta

  • Low frequency, high-amplitude waves, <4 Hz

  • Deepest stages of sleep, loss of consciousness (coma)

• Quantitative Electroencephalography (qEEG)

  • New variant of EEG

    • Processes recorded EEG using computer algorithms

  • Digital data statistically analyzed

    • Sometimes comparing values with “normative” database reference values

  • Processed EEG commonly converted into color maps of brian functioning (“brain maps”)

• MEG (magnetoencephalography)

  • Large numbers (up to 300) of magnetically sensitive sensors placed on scalp

  • Measures magnetic fields created by brain’s electrical activity

  • Allows finer spatial resolution than EEGs

  • Less susceptible to distortions from skull than EEG

  • Must be carried out in room specially constructed to block all alien magnetic influences (earth’s magnetic field etc)

    • Very expensive

    • Primarily used in medical diagnosis

• CT (computed tomography) or CAT scan

  • **structure

  • Series of x-ray photographs taken from different angles, combines by computer → composite representation of a slice through brain or body

• PET (positron emission tomography) Scan

  • **function

  • Visual display of brain activity, shows where a radioactive form of glucose goes while brain performs a given task

  • Radioactive isotype decays into nonradioactive atom after about a minue

  • May be all sorts of activity going on in brain that aren’t specific to particular experiment that participant is performing

    • Ways must be found to filter out potentially irrelevant background activity

      • Using subtraction paradigm

      • Ex: asking people to look at words flashed on screen without responding then asking them to say the words out loud

• MRI (magnetic resonance imaging)

  • **structure

  • Uses magnetic fields and radio waves to produce computer-generated images that distinguish among different types of soft tissue

    • Allows us to see structures within the brain

• fMRI (functional magnetic resonance imaging)

  • Variant of MRI

  • Measures level of activity in different parts of the brain

  • Has superseded PET in many domains

  • Oxygenated and deoxygenated blood respond differently to magnetic field, so fMRI can detect increases in blood oxygen, providing measure of blood flow and cognitive activity

    • Difference between oxygenated and deoxygenated blood is known as the BOLD (blood oxygen level dependent) contrast

    • fMRI measures BOLD signal

  • Event related fMRI

    • Emerged 1990s

    • Able to measure BOLD signal associated with individual rapidly occurring neural events

      • Ex: which areas of brain show increased activation when one views picture well remembered vs familiar or not remembered

        • Participants viewed 96 color pictures, indoor and outdoor scenes (while in fMRI scanner)

        • Given unanticipated memory test 30 min later

          • Shown 128 pictures including 96 previous, asked to identify which seen before and how confident

        • Pictures classified as well remembered, familiar, forgotten

        • Parahippocampus and right dorsolateral prefrontal cortex correlated with levels of memory performance for individual events

• VBM (voxel based morphometry)

  • Uses structural MRI scans to reveal differences between group’s regional brain volume and tissue concentration

    • Each brain is superimposed on a template, then brain image is smoothed so that each voxel represents the average of itself and its neighbors

    • Image volume then compared across brains at every voxel

  • One of first well-know VBM studies showed posterior hippocampi of London taxicab drivers were significantly larger than that of controls

• Diffusion Tensor Imaging (DTI) and fractional anisotropy (FA)

  • Special type of MRI

  • Sensitive to hindrance of water diffusion due to local tissue boundaries

  • FA is a DTI-derived quantitative measure of directional dependence of water diffusion

  • Reflects anatomical features of white matter

    • Axon caliber

    • Fiber density

    • Myelination

• f/ALFF (fractional amplitude of low frequency fluctuations)

  • Measures spontaneous fluctuations in BOLD-fMRI signal intensity for a given region in resting brain

  • Studies suggest low-frequency oscillations arise from spontaneous neuronal activity

  • Researched extensively but actual significance unknown

  • Grit found to be negatively associated with f/ALFF in the dmPFC

• Functional near-infrared spectroscopy (fNIRS)

  • Noninvasive optical imaging technique that measure changes in hemoglobin (Hb) concentrations within the brain

  • Higher temporal resolution than fMRI but inferior spatial resolution and penetration depth

  • Advantage:

    • Robustness to motion

    • Relatively lower cost

    • Small size and high level of portability

      • Ideal candidate for multimodality studies

        • Can be combined with fMRI, EEG, TMS, tDCS, etc

Brain stimulation techniques

• Repetitive transcranial magnetic stimulation (rTMS)

  • Intense pulse of magnetic energy sent through coil placed on surface of skull, results in electrical firing of neurons beneath the scalp

    • Can briefly enhance or disrupt neural activity

    • rTMS applied to left (and sometimes right) prefrontal cortex reduces symptoms of depression w/o any side effects in ~30-40% of patients with depression

      • Treatment performed on wide-awake patients for 20-30 min daily for 2-4 weeks

      • Stimulation may energize brain’s left frontal lobe

        • Generally inactive during depression

        • Cause nerve cells to form new functioning circuits

    • Also FDA approved for treatment of OCD

• Penfield studies

  • Electrical stimulation of association areas of brain during open brain surgery while patient is fully conscious

    • Body mapped onto brain

• Electroconvulsive therapy (ECT)

  • Traced back to ancient rome

    • Roman emperor used for himself

  • Treatment for major depression

    • Person anesthetized and give drug that paralyzes muscles

    • Electrodes placed on patient’s scalp

      • Usually to non-speech-dominant hemisphere

    • Jolt of electricity applied for one twenty-fifth of a second, triggering brief seizure

      • Discovered because people with schizophrenia and epilepsy ? had a seizure, psychotic symptoms would improve

    • 3 treatments per week, 2-4 weeks

    • May work by increasing release of norepinephrine (adrenaline) or by calming neural centers overactive in depression

    • Research indicates that ECT stimulates neurogenesis and new synaptic connections within hippocampus and amygdala

  • *Advantages

    • 70% of people with depression who don’t respond to other treatments get relief with ECT

    • Improvement in symptoms much more rapid (within few days) than with antidepressants

    • Credited with saving many from suicide

      • ECT sometimes used in interim period before antidepressant drugs become effective in suicidal patients

      • ECT may be court-mandated in certain cases

  • *disadvantages

    • Prolonged and excessive use causes brain damage

      • Resulting in long-lasting impairments in memory

    • High relapse rate

• Other potential new treatments for depression

  • Transcranial direct current stimulation (tDCS)

    • Weak current applied to the scalp on the left side of dorsolateral prefrontal

    • Safer than ECT

  • Deep brain stimulation

    • Neurosurgical procedure involving placement of a neurotransmitter (“brain pacemaker”) which sends electrical impulses, through implanted electrodes, to specific targets in the brain

• Optogenetics

  • Inserting opsin genes into neurons

    • Causes neuron to manufacture light-sensitive opsin proteins and incorporate them into the membrane

    • Opsin proteins become part of ion channels in cell membrane that control whether neuron fires or not

    • Neuron can then be activated by a particular wavelength of light (ex. red)

    • Other opsin proteins can cause the neuron to produce a flash of light of a particular wavelength (ex. green) when it is activated

  • Producing hallucinations in mice using optogenetics

    • Mice shown pictures of vertical and horizontal stripes on monitor

    • Trained to lick pipe only if saw vertical

    • Using light, researchers identified neurons in visual cortex that switched on in response to vertical vs in response to horizontal

    • Then turned off monitor, mice in darkness

    • Used light to switch on neurons for vertical stripes

      • Mice licked pipe as if seeing vertical

  • Implanting false memories in mice using optogenetics

    • Neuroscientists tagged neurons associated with a certain memory

      • E.g. fear of location where they had received electric shock

    • Then using light, artificially induced those neurons to fire to make new associations between events and environments with no ties to reality

      • E.g. fear of different location

  • Scientists changed songs young zebra finches sing by implanting new memories in their brains

  • Technique can be used for precise identification of specific neurons and neural networks

  • May also potentially be used for treatment of depression, chronic pain, seizures, restoration of vision in blind in future

• Combining Resources

• Some problems with Neuroimaging Data

  • Can be noise in system, especially when voxel size is large

    • Voxel is a three-dimensional persian of a pixel (volume+pixel=voxel)

    • The smaller the voxels, the higher the spatial resolution, but lower the signal strength

      • Often necessary to increase the voxel size to capture small fluctuations in BOLD signal

      • However, increasing voxel size increases the range of different types of brain tissue occurring in each voxel, this can distort the signal

        • White matter or cerebrospinal fluid

  • Everyone’s brain is slightly different

    • Distortions can occur when data are being normalized to allow comparison across participants

• Optimizing use of techniques

  • Neuroimaging techniques are:

    • Good at telling us about functional connectivity or which brain areas are simultaneously active while participants are performing a particular task

    • Not so good at telling us about effective connectivity or order in which brain regions are activated how they influence each other

    • However, models of effective connectivity can be developed by combining different techniques, such as neuroimaging with EEG

    • It is also possible to design a series of experiments in a way that they yield information about stages of lexical processing

      • Look at areas that are active when participants are looking at a word vs. saying a word out loud