Chapter 7: Methods of Studying the Brain's Structures and Functions Flashcards
Functional Near-Infrared Spectroscopy (fNIRS)
noninvasive technique that gathers light transmitted through cortical tissue to image oxygen consumption, form of optical tomography
Neuropsychology
study of relationships between brain function and behavior, especially in humans
Behavioral Neuroscience
study of the biological bases or behavior in humans and other animals
Stereotaxic Apparatus
surgical instrument that permits a researcher or neurosurgeon to target a specific part of the brain
Compensation
following brain damage, the neuroplastic ability to modify behavior from that used prior to damage
Deep Brain Stimulation (DBS)
neurosurgery in which electrodes implanted in the brain stimulate a targeted area with a low-voltage electrical current to produce or facilitate behavior
Transcranial Magnetic Stimulation (TMS)
procedure in which a magnetic coil is placed over the skull to stimulate the underlying brain, used either to induce behavior or to disrupt ongoing behavior
Synthetic Biology
design and construction of biological devices, systems, and machines found in nature
Chemogenetics
transgenic technique that combines genetic and synthetic drugs to activate targeted cells in living tissue
Place Cells
hippocampal neurons maximally responsive to specific locations in the world
Electrocorticography (ECoG)
graded potentials recorded with electrodes placed directly on the surface of the brain
Alpha Rhythm
large, extremely regular brain waves with a frequency ranging from 7 to 11 Hz, found in most people when they are relaxed with eyes closed
Event-Related Potential (ERP)
complex electroencephalographic waveform related in time to a specific sensory event
Magnetoencephalogram (MEG)
magnetic potentials recorded from detectors placed outside the skull
Computed Tomography (CT)
x-ray technique that produces a static three-dimensional images (called a CT scan) of the brain in cross section
Magnetic Resonance Imaging (MRI)
technique that produces a static three-dimensional brain image by passing a strong magnetic field through the brain, followed by a radio wave, then measuring a radio-frequency signal emitted from hydrogen atoms
Diffusion Tensor Imaging (DTI)
magnetic resonance imaging method that can image fiber pathways in the brain by detecting the directional movements of water molecules
Magnetic Resonance Spectroscopy (MRS)
magnetic resonance imaging method that uses the hydrogen protein signal to determine the concentration of brain metabolites, used to identify changes in specific markers of neuronal function, which is promising for accurate diagnosis of traumatic brain injuries
How do we study the brain’s structure and functions?
measuring and manipulating brain and behavior
measuring the brain’s electrical activity
anatomical imaging techniques: CT and MRI
functional brain imaging
chemical and genetic measures of brain and behavior
comparing neuroscience research methods
using animals in brain-behavior research
What is functional near-infrared spectroscopy (fNIRS)
non-invasive technique that gathers light transmitted through cortical tissue to image oxygen consumption
form of optical tomography
What is shown in the fNIRS of babies exposed to language?
when babies were exposed to words of their parent’s language a specific pattern of activation emerges
What processes were involved in twentieth century neuroscience?
lesions and localization of function: observing how people or animals with head injuries act
What is neuropsychology?
study of the relationships between brain function and behavior
emphasis on humans
measuring brain and behavior includes noninvasive imaging, complex neuroanatomical measurement, and sophisticated behavioral analyses
What are the origins of neuropsychology?
Paul Broca discovered the link between specific damage located in the left frontal lobe region and language difficulties (1863)
What are the early origins of behavioral neuroscience?
techniques for neuroanatomy
histological: brains sectioned postmortem and tissue stained with different dyes (early 20th century)
What do contemporary techniques in behavioral neuroscience involve?
contemporary techniques identify molecular, neurochemical, and morphological differences among neuronal types
how these differences contribute to behavior
What were brain imaging techniques in the early 20th century?
light microscopic techniques allowed researchers to divide the cerebral cortex into many distinct zones based on the characteristics of neurons in those zones
researchers presumed cortical zones had specific functions
What were brain imaging techniques in the early 21st century?
researchers learned to label neurons and their connections + glial cells
Brainbow: dye specific glial cells based on different chemicals
What are the characteristics of modern day methods of brain imaging?
prioritize greater resolution and specificity
visualize living tissue instead of dead tissue
can visualize neuron’s structures
visualize synapses in 3D detail
can mount a telescope on the head of a mouse
How do modern techniques allow for the study of anatomy and behavior?
learning example
learning is correlated with neuroanatomical changes (modification of synaptic organization of specific neurons, where and how new synaptic connections were made)
modern techniques allow researchers to track these specific anatomical changes
What is ethology?
the objective study of animal behavior, especially under natural conditions
animal learning and ethology provide the basis for modern behavioral neuroscience
What is the neuropsychological testing of humans?
the brain can control a wide range of functions (movement, perception, emotion)
any analysis of behavior must be tailored to the particular functions under investigation
How are memory disturbances measured?
memory is not a single function (memory for events, colors, names, places, and motor skills)
it is rare for someone to be impaired in all forms of memory, so each must be measured separately
Why are rats used in the study of behavioral neuroscience?
rats have very large behavioral repertoires
can be independently examined
can study the neural bases on sensation, cognition, memory, movement, etc.
using mazes and other tests
What was the swimming pool tasks experiments on rats?
Richard and Morris (1981), navigation task
place learning: rat must find platform using external cues
matching-to-place learning: platform is in a different location each day
landmark version: platform is identified by a cue on the pool walls
What was the skill reaching task involving rats?
rats were trained to reach through a slot to obtain food
movements can be broken down into segments, which are differently affected by different types of neurological perturbation
can be used to learn about deficits in fine movement induced by strokes
How are automated touchscreen platforms used to study rats?
automated touchscreen tools
cognitive and motivational testing
programmed to deliver tests
less stressful to the rat
How is manipulation of brain-behavior interactions used to study the brain?
we can manipulate some aspect of brain function and see how behavior changes
manipulation helps in developing hypotheses about how the brain affects behavior and then test the hypotheses
manipulation helps in developing animal models of neurological and psychiatric disorders
using techniques such as drugs and electrical stimulation to activate the brain and lesions to inactivate them
animals can be manipulated using diets, social interaction, exercise, sensory stimulation, etc
What are brain lesions?
the first (and simplest) technique used for brain manipulation is to ablate (remove or destroy) tissue
used by Karl Lashley (1920s) to fins location of memory in the brain
Scoville removed the hippocampus from H.M. to treat epilepsy, but produced amnesia instead
What is a stereotaxic apparatus?
surgical instrument used to target a specific part of the brain
allows the precise positioning of all brain regions relative to each other and to landmarks on the skull
used to destroy specific brain regions or to locate areas to inject drugs, etc.
What is compensation?
the neuroplastic ability to modify behavior from that used prior to the damage
to avoid compensation following permanent lesions, temporary and reversible lesion techniques are used
regional cooling prevents synaptic transmission: hollow metal coiled placed next to brain structure, chilled fluid cools brain region to prevent synaptic transmission
local administration of a GABA agonist increases local inhibition
How is brain stimulation used to study brain function?
the brain operates on both electrical and chemical energy
it is possible to selectively turn brain regions on or off by using electrical or chemical stimulation
now we can use stereotaxic instruments to place electrode or cannula in specific brain regions
goal: enhancing or blocking neuronal activity and observing behavioral effects
How is brain stimulation used on rats?
rats with electrodes in the lateral hypothalamus eat whenever the stimulation is turned on
self-stimulation: given the opportunity, rats will press a lever to obtain the current
the stimulation affects a neural circuit involving both eating and pleasure
How does brain stimulation improve movement?
electrically stimulating the intact cortex adjacent to cortex injured by stroke leads to improvement in motor behaviors
Terskey and colleagues restored motor deficits in a rat model of Parkinson disease by electrically stimulating a specific brain nucleus
What is deep-brain stimulation?
electrodes implanted in the brain stimulate a targeted area with a low-voltage electrical current to facilitate behavior
used for Parkinson disease, depression, OCD
DBS to the Globus pallidus in the basal ganglia of Parkinson patients makes movements smoother
invasive: holes must be drilled in the skull to attach the electrode in the brain
What is transcranial magnetic stimulation (TMS)?
procedure in which magnetic coil is placed over the skull to stimulate the underlying brain
a high-voltage current pulsed through the coil produces a rapid increase and subsequent decrease in the magnetic field around the coil
the magnetic field easily passes through the skull and causes a population of neurons in the cerebral cortex to depolarize and fire
used either to induce behavior or to disrupt ongoing behavior
non-invasive
motor cortex stimulation: induces body movements
visual cortex stimulation: participant sees phosphenes
How are drug manipulations used to study brain function?
drugs can pass into the bloodstream and enter the brain through an indwelling cannula that allows direct application of drugs to specific brain structures
drugs can influence the activity of specific neurons in specific brain regions
because drug effects wear off over time, it is possible to study drug effects on learned behaviors, such as skilled reaching
What is synthetic biology?
the design and construction of biological devices, systems, and machines not found in nature
techniques include inserting or deleting a genetic sequence into the genome of a living organism
What is the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) method?
cuts DNA in any cell
used to silence genes by cutting out those regions in the DNA
DNA repair can be tailored to insert a new sequence to replace previous one
What is optogenetic?
transgenic technique that combines genetics and light to control targeted cells in living tissue
based discovery that light can activate proteins
proteins that occur naturally can be inserted into cells
fiber-optic light can be delivered to selected brain regions such that all neurons exposed to the light respond immediately
great potential for research
high spatial and temporal resolution
ion channels can be placed into specific cell lines and turned on and off on millisecond time scales
What are opsins?
proteins derived from microorganisms
combine a light-sensitive domain with an ion channel
channelrhodopsin-2 (ChR2): when expressed in neuron and exposed to blue light, ion channels open and depolarizes neuron = excitation
halorhodopsin (NpHR): a green-yellow light activates a chloride pump, hyperpolarizing the neuron = inhibition
What are the four major techniques for measuring the brain’s electrical activity?
single-cell recording
electroencephalography (EEG)
event-related potentials (ERP)
magnetoencephalography (MEG)
What is the process of recording action potentials from single cells?
measuring single-neuron action potentials with fine electrodes
electrodes placed next to cells (extracellular recording) or inside them (intracellular recording)
extracellular recording techniques make it possible to distinguish the activity of as many as 40 neurons at once
intracellular recording allows study and recording of a single neuron’s electrical activity
What is single cell recording?
O’Keefe & Dostrovsky (1971) showed that neurons in the rat and mouse hippocampus vigorously fire when an animal is in a specific place in the environment
these place cells code the spatial location of the animal and contribute to a spatial map of the world in the brain
won a Nobel prize in 2014 for their discoveries of cells that constitute a positioning system in the brain
What are EEGs?
EEG measures the summed graded potentials from many thousands of neurons
reveals features of the brain’s electrical activity
the EEG changes as behavior changes
an EEG recorded from the cortex displays an array of patterns, some of which are rhythmical
the living brain’s electrical activity is never silent, even when the person is asleep or comatose
What are ERPs?
largely the graded potentials on dendrites that a sensory stimulus triggers
complex EEG waveforms are related in time to a specific sensory event
to counter noise effects, the stimulus is presented repeatedly, and the recorded responses are averaged
How are ERPs detected?
in the averaging process for an auditory ERP, a tone is presented at time 0, and EEG activity in response is recorded
after many successive presentations of the tone, the EEG wave sequence develops a distinctive shape that becomes extremely clear after 100 responses are averaged
positive and negative waves that appear at different times after the stimulus presentation are used for analyses
What are the advantages and disadvantages of using EEG and ERP?
non-invasive
cost
can record from hundreds of sites
high temporal resolution
poor spatial resolution
can’t record deep brain regions
What is magnetoencephalography?
neural activity, by generating an electrical field, also produces a magnetic field
magnetic potentials are recorded from detectors placed outside the skull
permit a three-dimensional localization of the cell groups generating the measured field
higher resolution than ERP
disadvantage: high cost
What is computed tomography (CT scan)?
X-ray beams are passed through the brain at many different angles, creating many different images
images are combined with the use of computing and mathematical techniques to create a three-dimensional image of the brain
How are brain structures observed through a CT scan?
dense skull forms white border
gray matter density does not differ from white matter density enough for a CT scan to distinguish between the two
cortex and its underlying white matter show up as homogeneous gray
ventricles can be visualized because the fluid in them is far less dense
some major fissures in the cortex are rendered darker
What is magnetic resonance imaging (MRI)?
produces a static, three dimensional brain image by passing a strong magnetic field through the brain, followed by a radio wave, then measuring the radiation emitted from hydrogen atoms
What is diffusion tensor imaging (DTI)?
detects the directional movements of water molecules to image nerve giber pathways in the brain
used to delineate abnormalities in neural pathways
What is magnetic resonance spectroscopy (MRS)?
MRI method that uses the hydrogen proton signal to determine the concentration of brain metabolites
useful in detecting persisting abnormalities in brain metabolism in disorders such as concussion
What is functional brain imaging?
when a brain region is active, the amount of blood, oxygen, and glucose flowing to the region increases
possible to infer changes in brain activity by measuring either blood flow or levels of the blood’s constituents, such as oxygen, glucose, and iron
What is functional magnetic resonance imaging (fMRI)?
when neurons become active they use more oxygen
active neurons increase blood carbon dioxide levels, which signal blood vessels to dilate, increasing blood flow and bringing more oxygen to the area
the amount of oxygen in an activated brain area increases
changes in the oxygen content of the blood alter the magnetic properties of the water in the blood
oxygen-rich hemoglobin is less magnetic than oxygen-poor hemoglobin
MRI could accurately match these changes in magnetic properties to specific brain locations
fMRI allows for good spatial resolution of the brain activity’s source
What are the advantages and disadvantages of fMRI?
the dense blood vessel supply to the cerebral cortex allows for a spatial resolution of fMRI on the order of 1 millimeter (very high spatial resolution)
changes in blood flow take 1/3 second, poorer temporal resolution relative to EEG
extremely restrictive to subject
must stay motionless
What is functional near-infrared spectroscopy (fNIRS)?
form of optical tomography
technique that operates on the principle that an object can be reconstructed by gathering light transmitted through it
optical tomography can image soft body tissue, such as the brain
What is optical tomography?
reflected infrared light is used to determine blood flow because oxygen-rich hemoglobin and oxygen-poor hemoglobin differ in their absorption spectra
by measuring the blood’s light absorption, it is possible to measure the brain’s average oxygen consumption (just like fMRI)
in fNIRS, an array of optical transmitter and receiver pairs are fitted across the scalp
What are the advantages of optical tomography?
relatively easy to hook up
can record short periods of activation
What are the disadvantages of optical tomography?
light doesn’t penetrate deeper brain tissue, restricted to cortex
spatial resolution poorer than fMRI
What is positron emission tomography (PET)?
imaging technique that detects changes in blood flow by measuring changes in the uptake of compounds such as oxygen or glucose
used to analyze the metabolic activity of neurons
radioactive molecules are injected into the bloodstream (radioactive isotope oxygen-15 are very unstable, break down in just a few minutes, relatively safe)
radioactive oxygen-15 molecules release tiny positively charged subatomic particles known as positrons
positrons are attracted to negatively charged electrons in the brain (collision of the two particles leads to a release of energy)
this energy leaves the head at the speed of light (detected by the PET camera, can target source of energy release)
What are the advantages of positron emission tomography?
can detect the decay of hundreds of radiochemicals and allows the mapping of a wide range of brain changes and conditions
can detect relative amounts of a given neurotransmitter, the density of receptors, and metabolic activities associated with learning, brain poisoning, and degenerative processes
widely used to study cognitive function
What are chemical and genetic measures of brain and behavior?
neurons are regulated by genes that encode the synthesis of particular proteins within cells
genes control the cell’s production of chemicals so it is possible to relate behavior to genes and to chemicals inside and outside the cell
the brain contains a wide mixture of chemicals, abnormalities in these chemicals leads to disruptions in behavior, low serotonin production correlated with depression
What is microdialysis?
technique used to determine the chemical constituents of extracellular fluid
catheter with semipermeable membrane is placed in the brain
fluid flows in, where it passes along the membrane
diffusion drives the passage of extracellular molecules across the membrane
fluid containing the molecules from the brain exits through tubing and is collected for analysis
How does measuring genes contribute to studies of brain and behavior?
variations in gene sequences contribute to brain organization
studying twins and adopted children allows us to tease apart environmental and genetic contributions to behavior
we can also relate the alleles of specific genes to behaviors
What does the Bueller (2006) study tell us about genes affect on brain and behavior?
the Met allele is associated with an 11% reduction in hippocampal volume and poorer memory for specific events
Val allele carriers have better episodic memory but higher incidence of anxiety disorders
two alleles produce different phenotypes, they influence brain structure differently
What is epigenetics?
genes that are expressed can change dramatically in response to environment and experience
epigenetic changes can persist throughout a lifetime and even across multiple generations
wide range of experiential factors: chronic stress, traumatic events, drugs, culture, and disease are factors, cumulative experiences affect how genes work
epigenetic changes may be related to better stroke recovery
How are neuroscience research methods compared?
some researchers focus on morphology (structure) in postmortem tissue
other investigators focus more on the ways neurons generate electrical activity in relationship to behavior or on functional changes in brain activity during specific types of cognitive processing
considerations: temporal resolution (how quickly the measurement or image is obtained), spatial resolution (how accurate localization is in the brain), degree of invasiveness
studying brain and behavior linkages by perturbing the brain is generally less costly then some imaging methods, many of which require expensive machinery
What are two important issue in using animals in brain-behavior research?
do animals actually contract the same neurological diseases as humans?
how ethical is it to use animals in research?
What are the benefits of animal models of disease?
some disorders are easy to model (eg stroke)
behavioral disorders are more difficult
What is the Kyoto SHR rat?
proposed as a good model for ADHD
known abnormalities in prefrontal dopaminergic supply that correlate with behavioral abnormalities such as hyperactivity
dopamine agonists as as methylphenidate (Ritalin) can reverse behavioral abnormalities, both in children with ADHD and in SHR rats
What is the relationship between animal welfare and scientific experimentation?
most governments regulate the use of animals in research
universities and other research organizations have additional rules governing animal use
legislation concerning the care and use of laboratory animals in the United States is set forth in the Animal Welfare Act
all accredited North American universities that receive government grant support are required to provide adequate treatment for all vertebrate animals
What are the guidelines of the Canadian Council on Animal Care?
- research needs to contribute and benefit animals and humans
- treat the animals well so the results aren’t skewed
- public confidence is needed to ensure justified animal use
- animals are used only if the researcher’s best efforts to find an alternative have failed
