Methodology in Cognitive Neuroscience
Explain the typical procedure for a TMS experiment.
1. localize the scalp area overlying the cortical area to be stimulated (achieved with neuronavigated stereotactic localization) 2. optimal TMS intensity is determined for each participant individually 3. TMS is applied to influence brain activity and behavior - pulses can be applied online during task performance - pulses can be applied just before task performance, in an offline fashion, to produce neural after-effects ini which normal functional contributions of stimulated area and interconnected brain areas are markedly reduced. 4. behavioral consequences of TMS stimulation compared to baseline control condition
what are common electrical imaging techniques?
EEG and MEG - exceptional temporal resolution - only measure signals from superficial cortical regions - low spatial certainty about anatomical origin of recorded signals
What is temporal resolution?
Frequency of recording imagery of a particular area. -frequency in time w/ which measurements or manipulations can be made
what is a common disadvantage of all measurement techniques?
cannot conclusively determine the causal role the identified neural components may play in behavior
How can microstimulation be used?
- can be used to induce neural activity in spatially and temporally precise fashion - can be applied to any cortical or deeper-lying neural structure. - animal is unaware it is being stimulated - studies often don't require stimulation of a control site
how are specific brain lesions achieved in animals?
- mechanical removal of tissue (irreversible) - local injection of neurotoxin (irreversible) - applying strong electric current to damage tissue (irreversible) - insert probe that can be cooled to a temperature that prevents normal functioning (reversible)
What is the typical procedure for lesion experiments in animals?
1. both experimental and control groups are trained to complete a task 2. pre-operation performance measured 3. surgery is performed and the designated lesions are made. 4. behavioral tests are conducted to measure how task performance has changed as a result of the lesion 5. extent of lesions is documented by detailed post mortem neuroanatomical & neurochemical examination
What is the typical procedure for human lesion studies?
1. identify group of patients w/ more or less selective damage to the brain area being studied 2. reconstruction of full extent and overlap of the lesions, ideally w/. MRI 3. identify a suitable control group fr behavioral comparison, must be closely matched w/ respect to relevant factors such as age, intelligence, socioeconomic status, etc. 4. measure & compare behavioral performance across groups using series of tasks designed to isolate specific aspects of cognition or behavior
what is the typical procedure for a TMS study?
1. localize the scalp site 2. determine where the reference electrode should be attached (the electrode w/ effects that are not of interest in a given study); determines direction of current flow 3. tDCS is applied by running current for about 10-20 min
What is the procedure of EEG?
1. participant completes paperwork 2. practices experimental task while electrodes are put in place 3. participant performs an experimental task repeatedly, often w/i a session that lasts 30-120 min 4. after data collection, experimenter applies processing algorithms to minimize data quality issues & extracts. trial-by-trial responses in each electrode for further analyses. 5. Most EEG studies combine data from 10-40 participants to improve statistical significance/power.
What is the procedure for MEG experiment?
1. participant sits upright in the meg system 2. participant views the experimental stimuli on a screen in front of her & responds using a button box or keyboard positioned on her lap
What is the procedure for single-unit recording?
1. place electrode 2. experiment begins; data can be collected for a period of min to hours 3. results are shown in raw or averaged forms
What is magnetoencephalography (MEG)?
Magnetoencephalography (MEG) is a functional neuroimaging technique for mapping brain activity by recording magnetic fields produced by electrical currents occurring naturally in the brain, using very sensitive magnetometers. - fluctuations in the megnetic fields can be analyzed as either oscillatory activity (like EEG) or as changes in activity time-locked to stimulus events (like ERPs) with msec resolution
What are manipulation techniques?
Manipulation techniques examine how perturbations of the brain's function- by transiently changing neuronal firing rates or neurotransmitter levels or by permanently damaging tissue- change cognitive functions or behavior. "causal" approaches
What are the two main categories of cognitive neuroscience techniques?
Measurement techniques and manipulation techniques
What are measurement techniques?
Measurement techniques measure changes in brain function while a research participant (human or animal) engages in some cognitive activity. "correlational" approaches Ex: recording changes in neuronal firing or BOLD activity during simple choice tasks.
What is microstimulation?
Microstimulation is an invasive stimulation method used in animals where microelectrodes are inserted into the brain and used to induce neural activity via application of weak electrical currents. - in some cases used in humans to treat chronic and severe brain disorders - both anodal and cathodal deep brain stimulation result in action potentials being generated, but more reliably in cathodal mode
How do invasive and non-invasive differ?
Non-invasive techniques record endogenous brain signals using sensors outside of the body, and can be conducted repeatedly in human volunteer participants, with no serious risk. Invasive techniques introduce a chemical or a recording device into the body. It is more difficult to find participants as some invasive techniques can be used in human volunteers and others can only be used in human patients and/or non-human animals.
What is transcranial magnetic stimulation (TMS)?
Noninvasive use of magnetic pulsations to stimulate specific brain areas. - stimulates neurons via electromagnetic induction - uses a magnetic field, which passes easily through skull, to generate an electrical current inside the skull. - electrical current acts on the underlying neurons and triggers action potentials.
What is an event related potential (ERP)?
Part of an EEG signal caused by the presentation of a stimulus - also known as an evoked potential or EP - time locked EEG signal - researchers often investigate how an experimental manipulation or behavior influences the amplitude of a particular component of ERP signal
what are double dissociations?
Patients are grouped according to brain lesion site and compared. double dissociations are present if one lesion group shows deficits on task 1 but not task 2 and the other lesion group shows deficits on task 2 but not task 1.
Why do scientists use microstimulation in a given study?
Scientists may use microstimulation to induce surrogate neural activity in order to study how the animal's behavior is affected by action potentials generated in the stimulated area. "self stimulation studies"
What is single-unit recording?
Single-unit recording records the firing rate of a single functional unit-a neuron/group of neurons. This measurement can be used as an index of whether a stimulus changes the ongoing information processing for a particular neuron. - measurement technique - requires insertion of very fine/tiny electrode into neural tissue adjacent to the neurons of interest - quite invasive bc need to open the skull to gain access to the brain
What is transcranial direct current stimulation (tDCS)?
Two electrodes are attached to the scalp and a constant electric potential difference is applied, affecting the neurons along the path of the current - firing increased under the anode - firing decreased under the cathode - tDCS can be used in two modes: anodal tDCS to upregulate and cathodal tDCS to downregulate neural processing in a brain region - behavioral effects of activity manipulation via tDCS can be studied both during and after stimulation
What is optogenetics?
a biological technique which involves the use of light to control cells in living tissue, typically neurons, that have been genetically modified to express light-sensitive ion channels. - by switching light on/off, researcher can induce action potentials in specific cell types
What is positron emission tomography (PET)?
a method of brain imaging that assesses metabolic activity by using a radioactive substance injected into the bloodstream - researcher injects a quantity of radioactive isotope (bound to a metabolically relevant molecule like glucose or a neurotransmitter that binds to a particular type of neuron) into venous system of participant - depending on the nature of ongoing brain metabolism, the injected isotope will be differentially distributed throughout the brain (e.g. radioactive glucose will become more prevalent in areas w/ increased glucose metabolism) - as isotope decays, it emits radioactive particles called positrons that travel through the brain until they encounter an electron (usually w/in a few mm) - the collision of positrons and electrons annihilates both particles & emits gamma rays, which travel in opposite directions from the impact site - PET scanner detects coincident arrival of gamma rays in detectors around the head & can compute the likely location at which the positron was emitted. - if monitored for an extended period (minutes), enough emission events will allow estimation of rough distribution of the isotope throughout the brain, which becomes PET image
what are some advantages of animal lesion studies?
advantages: - allow full control over location & extent of lesions - animals can be randomly assigned to either lesion or control group - animals perfectly matched in terms of various relevant factors ( experience, age, etc) - effects of medication & treatment do not confound results - post mortem evaluation allows comprehensive analysis of lesion & its characteristics
advantages/limitations of TMS?
advantages: - allows non-invasive manipulation of neural processing w/ high spatial resolution & exceptional temporal resolution (msec) - can be employed very flexibly w/ respect to temporal profiles and patterns of stimulation - can be employed in almost any healthy volunteer who meets a few basic health-related criteria limitations: - only able to target. brain areas on the cortical surface - noise and tactile sensations produced by TMS can be experienced as distracting or painful by some participants - don't know the precise duration of time window of TMS after-effects
advantages/limitations of fMRI?
advantages: - allows us to map complex cognitive functions in the brains of human volunteer participants with good spatial and temporal resolution - can be conducted on typical clinical MRI scanners - data collected can be subjected to wide range of analyses - combined w/ signal processing & computer science, used to examine functional and effective connectivity and MVPA - widely accepted among researchers and understood by the public limitations: - expensive to conduct - potential safety risks associated with strong magnets - some experiments may be difficult to conduct in MRI scanner - even very small physiological variation introduces noise into the BOLD signal - no one experiment can provide definitive evidence for the mapping of a given cognitive function to a specific brain region
What are advantages/limitations of EEG?
advantages: - experimental trials can be run rapidly - non-invasive measurement technique - brain activity data can be extracted during very precise time windows w/i the experimental task (within several hundred msec) - high-temporal-resolution access the electrical activity of the brain - allows researchers to create models of ongoing dynamic processing - relatively inexpensive - good for looking at changes in activity over time, particularly for well-studied components limitations: - imprecise spatial localization - activity recorded by scalp electrodes could have been generated by any of an infinite number of potential sources (the "inverse problem") - not good for differentiating the functions of brain regions - tedious set-up time to make sure electrodes are positioned correctly
What are some advantages of lesion studies in humans?
advantages: - may provide stronger support for the behavioral necessity of a brain region - can lead to new hypotheses about brain-behavior relationships - knowledge gained is always relevant for medical care, diagnosis & treatment for patients w/ brain damage
What are advantages/limitations of MEG?
advantages: - non-invasive - well-tolerated by (human) research participants - can be used within a wide range of experimental paradigms - records data from the entire brain simultaneously - can provide insight into the combined location & timing of cortical activity with precision unmatched by any other technique limitations: - inaccessible - MEG scanners, laboratory, maintenance & upkeep are very expensive - only a few hundred research MEG systems in the world - MEG is sensitive only to neurons oriented parallel to the skull - cannot unambiguously identify the generating neural sources from a MEG recording
advantages/limitations of PET imaging?
advantages: - provide information about different aspects of neural metabolism or neurotransmission (e.g. dopamine function) - can be used to analyze very precise chemical information - PET images cover the entire brain w/ moderate spatial resolution - can be conducted in human volunteer participants, human patients, and non-human animals limitations: - fairly invasive; requires injecting radioactive material into participants. - regulations on radioactive materials make PET studies more logistically complex - significant cost associated with each participant (> $1000) - limited temporal resolution
What are advantages/limitations of single-unit recording?
advantages: - provides direct information about the rate and timing of action potentials within a region - critical in identifying the core functions of brain regions - provide grounds for many computational models of brain function (identify processing associated w/ indiv. neurons & map out supporting local circuitry) limitations: - very invasive procedure limits use to non-human animals and in some cases human patients. - data collection is slow & labor intensive; data is collected serially from one neuron/unit at a time. - studies can be expensive & take very long to complete - studies focus on single brain region, limiting insight to complex cognitive processes (lower spatial imaging)
advantages/limitations of tDCS?
advantages: - well-suited for studying subtle decision processes, particularly in social situations - does not have distracting side effects - offers good control condition that is perceptually indistinguishable from active stimulation - tDCS can be (double) blinded - inexpensive and easy to use so a group of participants can be tested simultaneously - researchers can examine functional role of enhancement and reduction of neural functions limitations: - low spatial resolution - concerns of reference electrode placement can complicate interpretations of tDCS results - not temporally precise
what are some disadvantages to using experimental animal lesions?
disadvantages: - difficult to conduct in non-human primates - training, maintenance of animals can be labor-intensive & expensive - difficult to compare behavior across species
What are common metabolic imaging techniques?
fMRI and PET - accurate spatial localization - low temporal resolution - rely on correlative links b/w neural activity & neurometabolism
What is functional magnetic resonance imaging (fMRI)?
fMRI is a functional neuroimaging technique that combines imaging from MRIs with insights into the metabolic changes associated with brain activity. -magnetic field of MRI scanner causes hydrogen atoms in brain to align along the axis of the magnetic field - specialized electrical coils deliver energy in the form of radio waves to the brain, which are calibrated (it can be absorbed by the targeted atomic nuclei) - atomic nuclei give off MR signal as the radio waves are turned off and they return to their low-energy state - MRI scanner uses specialized magnetic coils to create spatial gradients in the strength of magnetic field - calibrated to detect naturally occurring changes in blood oxygenation that occur in the brain following neuronal activity.
what are single dissociations?
in human lesion studies, selective impairment relative to controls on some behavioral tests but not others
How do experimental lesions in animals work?
lesions are generated in clearly defined brain regions by various means so that therapeutic measures & time course of recovery can be examined
what are some disadvantages to lesion studies in humans?
limitations: - naturally occurring brain damage is often spatially diffuse and rarely selective to specific brain areas - difficult to find patients w/ overlapping damage in the structures of interest - offer no info about the timing of neural activity (effects of brain lesions are constant and usually irreversible) - often little is known about patient's behavior prior to accident or illness - brain injuries and illnesses & their treatment can have nonspecific sequelae
which techniques have the poorest temporal resolution?
techniques that manipulate brain function through drug effects or brain lesions (centimeters to the entire brain precision)
which techniques have intermediary temporal resolution?
techniques that measure indirect metabolic correlates of neuronal activity (ex. BOLD) (sec-min precision)
Which techniques tend to have good temporal resolution?
techniques that record neuronal activity directly through electrophysiological means (msec precision)
What are the three primary factors scientists consider when determining which research method to use?
temporal resolution, spatial resolution, and invasiveness
What are lesion studies (with humans)?
the study of behavioral deficits in patients with brain damage, shaping understanding of brain-behavior relationships
what are measurement techniques useful for?
useful for establishing the anatomical location or timing of the neural computations underlying behavior
What is electroencephalography (EEG)?
uses sensitive electrodes on the scalp to measure voltages produced by brain activity (i.e. electricity) - signal arises from synchronous changes in membrane potentials of the dendrites of many neighboring neurons - neurons with similar changes in membrane potential & share similar spatial location and orientation form collective electrical current spanning long distances w/i the brain - first demonstrated use by Hans Berger in the 1920s
How has optogenetics been used?
- to demonstrate links between the activation of certain neurons and behavior - empirically confirm long-held assumptions about causal associations
