Module 6 Flashcards
The very first requirement to obtain approval for conducting research using animals is that the science itself has been reviewed and judged to be sound and important. How is this done? How are research grants identified as having high scientific merit?
1) The leading researcher (who is often called “principal investigator”, or PI) who is overseeing the project program has obtained a research grant, that is, funding from an external organization to pay for the cost of the research.
2) In Canada, the main federal research agencies are NSERC (fundamental, basic research in the areas of biopsychology and neuroscience, including animal research), CIHR (Clinical, disease-oriented neuroscientific (human and non-human) research), and SSHRC (does not cover animal research).
True or False?
Even after a PI has successfully obtained an external research grant, they still need to obtain permission to conduct their research at the institution.
True.
The review and monitoring of animal research activities at universities is conducted by the University Animal Care Committee (UACC); federal laws and regulation mandate that each university has its own UACC.
The UACC also reviews and monitors the use of animals in teaching, such as lab courses that involve work or demonstrations with animals.
The use of animals in science at Queen’s is done with the supervision and approval of the Canadian Council on Animal Care (CCAC). What is the CCAC?
A Canadian peer-reviewed organization responsible for setting, maintaining, and overseeing the implementation of high standards for animal ethics and care in science on a national scale.
The goal of the CCAC guidelines is to strive for best research practices and optimal conditions for the animals, through constant improvement as new information on animal well-being and health becomes available. Compliance with and approval of the CCAC is mandatory in order to receive federal funding, the highest source of funding for most Canadian universities. Failure to comply with the CCAC can lead to a suspension of animal care and research programs at the university.
Why are animals used in research?
Pre-clinical trials on animals are often a legal requirement before the drug can be put to use. Regulatory agencies in most countries require evidence of drug safety before they can be used with humans and in many cases this pre-clinical testing is done on animals.
Animals are often the most valuable way to study the effects of how organ systems in the body interact with each other and to learn about the side effects that might occur with a particular treatment.
In the research path to the discovery of, for example, a better treatment for hypertension, some studies might be done in cell or tissue culture, then in animals, and ultimately in humans. Such clinical trials are very carefully regulated.
Many techniques and vaccines developed through animal research are applied to animal health practices as well as in human medicine. In this way, developments made with animal research can also benefit animals.
What is The University Animal Care Committee (UACC) ?
is a Principal’s committee that reports to the Vice Principal (Research). The UACC is mandated by the Animals for Research Act (ARA) which is administered by the Ontario Ministry of Agriculture, Food and Rural Affairs (OMAFRA) and the Canadian Council on Animal Care (CCAC). The UACC is responsible for the review of all protocols proposing the use of animals in research, teaching, or testing at or in direct affiliation with Queen’s University.
The role of the Committee is to ensure that the welfare of the animals is a prime consideration in their procurement, care and use and that the highest ethical standards, as defined by the Canadian Council on Animal Care (CCAC), are observed.
What are the UACC’s objectives?
1) To ensure that the use of animals at Queen’s University in research, teaching or testing meets or exceeds the standards of animal welfare established by the Animals for Research Act (Ontario), and the Canadian Council on Animal Care (CCAC).
2) To teach and promote the ethical use and management of animals in research, teaching and testing by providing training opportunities to personnel engaged in the care and research of animals.
3) To encourage good communication between animal users and the UACC, and to work with investigators and instructors to create a research and teaching environment that promotes animal welfare.
4) To work with the Canadian Council on Animal Care (CCAC) and the Ontario Ministry of Agriculture, Food and Rural Affairs (OMAFRA) to ensure that all animal care facilities at Queen’s University meet or exceed the standards of care set by agency guidelines and legislation, and to report accurate numbers of animals used in research and teaching to these agencies.
The UACC plays a critical role in not only the approval of research project, but also the monitoring of ongoing research activities by doing what?
They will visit labs and observe procedures being conducted on animals and ensure that the actual lab procedures match those that the UACC has approved, and that animals are always monitored for their health status and maintained under the best housing and environmental conditions.
What are the 3 R’s of ethical animal experimentation?
Replacement - whenever possible, replace use of animals with other models.
Reduction - reduce the numbers of animals used.
Refinement - methods to improve animal welfare (better housing, handling, pain relief, shorter experiments etc)
You are a biopsychologist who has discovered a novel neurotransmitter substance (transmitter X) released by cortical neurons. Nothing is known about the transmitter and you are preparing a grant application entitled: “The physiological and behavioural functions of transmitter X in the rodent brain”. You likely will submit this grant application to:
SSHRC
CIHR
NSERC
Queen’s University
NSERC
The Canadian Council on Animal Care (CCAC) is:
a). the committee at Queen’s that oversees the use of animals for research and teaching purposes
b). a national organization with a mandate to set standards for the care and use of animals in research in Canada
c). will review and approve animal procedures conducted at Queen’s and other universities
d). both (a) and (c) are correct
b). a national organization with a mandate to set standards for the care and use of animals in research in Canada
The University Animal Care Committee (UACC) of Queen’s…
reviews all research or teaching procedures carried out by Queen’s University personnel on animals
reviews research or teaching procedures on animals carried out only at Queen’s University
conducts unannounced inspections of Ontario universities on a yearly basis
reviews and approve animal procedures conducted at Queen’s and other universities
reviews all research or teaching procedures carried out by Queen’s University personnel on animals
The Ontario Ministry of Agriculture, Food and Rural Affairs (OMAFRA)…
conducts unannounced inspections of Ontario universities on a yearly basis
reviews animal procedures conducted at Ontario universities
offers training workshops to improve animal handling and experimental skills and techniques
all of the above are correct
conducts unannounced inspections of Ontario universities on a yearly basis
The 3Rs of ethical animal research stand for…
reduce redundancies and replication
replace, reduce, and refine
reduce, reuse, and recycle
regulation, reconstruction, and resilience
replace, reduce, and refine
As an animal researcher, you have introduced the use of a powerful and long-lasting analgesic drug, to be used after the surgical implantation of recording electrodes into the brain of rats. This is an example of…
Reduction
Replacement
Refinement
All of the above
Refinement
Let’s start with the idea of standardization by running through a hypothetical experiment.
1) First, imagine that you are a scientist working for a pharmaceutical company and you have developed a new compound (“drug N”). This compound acts as a strong and highly selective agonist at GABA receptors in the brain. (Drugs that act as GABA receptor agonist are used to treat anxiety disorders.)
2) You will probably want to explore if drug N has anxiety-reducing properties in an animal model, such as the elevated plus maze (EPM). Before testing the actual drug, you want to establish the “baseline” levels of open arm exploration in control (i.e., no drug treatment) animals. Just to be on the safe side and ensure that you can obtain consistent and reliable levels of baseline open arm exploration (and, thus, anxiety level), you actually decide to run two control groups, each of the two control groups consists of 12 rats.
3) It is desirable to have control/comparison conditions that show relatively little variability, in other words, scientists often hope for a “stable, consistent” baseline or control condition to which they then compare the group that receives an experimental manipulation (e.g., drug treatment).
How do we achieve such stable, tight control conditions? This is where standardization comes into play. By standardizing various experimental and other conditions, we hope to reduce the variability of a data set.
What can standardization involve?
1) Consistent/identical housing conditions for all animals.
2) Consistent/identical food and water supply. (For example, hunger can increase the open arm time in EPM.
3) Consistent/identical environmental conditions like room temp, lighting, humidity. (For example, reduced lighting increases open arm exporation)
4) Consistent/identical test conditions and apparatus. (Ie: the same maze)
5) Consistent/identical behavioral testing conditions (ie: time of day)
6) Consistent/identical age groups of experimental animals
7) Using animals of only one sex
What are 4 different sorts of methods for visualizing the living human brain?
x-ray-based techniques,
a radioactivity-based technique,
magnetic-field- based techniques,
an ultrasound-based technique.
Describe two x-ray-based techniques for visualizing the living human brain.
1) CONTRAST X-RAYS - injecting into one compartment of the body a substance that absorbs x-rays either less than or more than the surrounding tissue. The injected substance then heightens the contrast between the compart- ment and the surrounding tissue during x-ray photography.
One contrast x-ray technique, cerebral angiography, uses the infusion of a radio-opaque dye into a cerebral artery to visualize the cerebral circulatory system during x-ray photography. Cerebral angiograms are most useful for localizing vascular damage, but the dis- placement of blood vessels from their normal position also can indicate the location of a tumor.
2) COMPUTED TOMOGRAPHY (CT) - is a computer-assisted x-ray procedure that can be used to visualize the brain and other internal structures of the living body. During cerebral computed tomography, the neurological patient lies with his or her head positioned in the center of a large cylinder. On one side of the cylinder is an x-ray tube that proj- ects an x-ray beam through the head to an x-ray detector mounted on the other side. The x-ray tube and detector rotate rapidly around the head of the patient at one level of the brain, taking many individual x-ray photographs as they rotate. The meager information in each x-ray photograph is combined by a computer to generate a CT scan of one horizontal section of the brain. Then the x-ray tube and detector are moved along the axis of the patient’s body to another level of the brain, and the process is repeated. Scans of eight or nine horizontal brain sections are typically obtained from a patient. When combined, these images provide three-dimensional representations of the brain.
Describe the positron emission tomography (PET) technique.
-first brain-imaging technique to provide images of brain activity (functional brain images) rather than images of brain structure.
-a colored map of the amount of radioactivity in each of the tiny cubic voxels (volume pixels)
-Radioactive fluorodeoxyglucose (FDG) is injected into the patient’s carotid artery. Because of its similarity to glucose, the primary metabolic fuel of the brain, fluorodeoxyglucose is rapidly taken up by active (energy-consuming) cells and cannot be metabolized; so it accumulates in active neurons and astrocytes until it is gradually broken down.
-Current application of PET technology is its use in identifying the distribution of particular molecules (e.g., neurotransmitters, receptors, transporters) in the brain by injecting volunteers with radioactively labeled ligands (ions or molecules that bind to other molecules). Then, PET scans can document the distribution of radioactivity in the brain.
Describe Magnetic resonance imaging (MRI).
- structural brain-imaging procedure in which high-resolution images are constructed from the measurement of radio-frequency waves that hydrogen atoms emit as they align with a powerful magnetic field.
-Such imaging is possible because: (1) water contains two hydrogen atoms (H2O) and (2) different brain structures contain different amounts of water. This, in turn, means that the number of hydrogen atoms differs between brain structures, and, therefore, the radio-frequency waves emitted by a particular brain structure will be different from its neighboring brain structures.
-MRI provides clearer images of the brain than does CT
-Provides HIGH spatial resolution (the ability to detect and represent differences in spatial location), MRI can produce images in 3D
Describe diffusion tensor MRI.
- a method of identifying those pathways along which water molecules rapidly diffuse. Because tracts (bundles of axons) are the major routes of rapid water diffusion in the brain, diffusion tensor imaging provides an image of major tracts.
-Most brain research focuses on the structures of the brain. However, in order to understand how the brain works, it is imperative to understand the connections among those structures—the so-called connectome.
Describe functional MRI.
-produces images representing the increase in oxygenated blood flow to active areas of the brain.
- Functional MRI is possible because of two attributes of oxygenated blood. First, active areas of the brain take up more oxygenated blood than they need for their energy requirements, and thus oxygenated blood accumulates in active areas of the brain. Second, oxygenated blood has different magnetic properties than does deoxygenated blood, and this difference influences the radio-frequency waves emit- ted by hydrogen atoms in an MRI.
-The signal recorded by fMRI is called the BOLD signal (the blood-oxygen-level-dependent signal). The BOLD signal indicates the parts of the brain that are active or inactive during a cognitive or behavioral test, and thus it suggests the types of analyses the brain is performing.
- Because the BOLD signal is the result of blood flow through the brain, it is important to remember that it is not directly measuring the electrical activity of the brain.
What 3 advantages does a Functional MRI have over PET?
(1) nothing has to be injected into the volunteer;
(2) it provides both structural and functional information in the same image; and
(3) its spatial resolution is better.
True or False?
fMRI produces actual pictures of human neural activity.
False.
They are images of the BOLD signal, and the relation between the BOLD signal and neural activity is complex . Furthermore, fMRI technology has poor temporal resolution, that is, it is poor at specifying the timing of neural events. Indeed, it takes 2 or 3 seconds to measure the BOLD signal, and many neural responses, such as action potentials, occur in
the millisecond range.
Describe an ultrasound-based technique for imaging the living human brain.
Functional ultrasound imaging (fUS) is a new imaging technique that uses ultrasound (sound waves of a higher frequency than we can hear) to measure changes in blood volume in particular brain regions. When a brain region becomes active, blood levels increase there, and alter the passage of ultrasound through that brain region.
As a functional brain imaging method, fUS (functional ultrasound imaging) has what three key advantages over PET and fMRI?
(1) it is cheap, (2) highly portable; and (3) can be used for imaging some individuals, such as human infants, who cannot undergo PET or fMRI.
PET, fMRI, and fUS have allowed cognitive neuroscien- tists to create images of brain activity while volunteers are engaging in particular cognitive activities. Although technically impressive, these kinds of studies of brain activity and cognition all have what same shortcoming?
They can be used to show a correlation between brain activity and cognitive activity, but they can’t prove that the brain activity caused the cognitive activity.
(For example, a brain-imaging technique may show that the cingulate cortex becomes active when volunteers view disturbing photographs, but it can’t prove that the cingulate activity causes the emotional experience—there are many other explanations.)
Describe Transcranial magnetic stimulation (TMS).
- a technique that can be used to turn off an area of human cortex by creating a magnetic field under a coil positioned next to the skull. The magnetic stimulation temporarily turns off part of the brain while the effects of the disruption on cognition and behavior are assessed.
Describe Transcranial electrical stimulation (tES).
- a technique that can be used to stimulate (“turn on”) an area of the cortex by applying an electrical current through two electrodes placed directly on the scalp. The electrical stimulation temporarily increases activity in part of the brain while the effects of the stimulation on cognition and behavior are assessed.
However, there is conflicting evidence about whether tES has beneficial effects on cognition; some studies have even reported detrimental effects.
Describe Transcranial ultrasound stimulation (tUS).
- is a technique that, like tES and TMS, can be used to activate particular brain structures. However, unlike tES and TMS, which can only be used to stimulate cortical structures, tUS can also be used to activate subcortical structures.
-To activate a brain structure using tUS, multiple sources of low-amplitude ultrasonic sound waves are placed around the head of the individual. Then, each of those sound sources is directed at the target brain structure. When the ultrasonic sound waves from each of those sources reach the target structure they sum together, such that the amplitude of the sound waves at the target brain structure is sufficiently large to stimulate activity in the cells there.
The tUS technique can also be used to make small permanent lesions to a brain structure. The procedure is the same as that for stimulation via tUS, except that the amplitude of each ultrasound source is larger, leading to a larger amplitude waveform that is sufficient to create a small (e.g., the size of a grain of rice) permanent lesion. This tUS-based lesion method has been used to treat several conditions (e.g., lesioning a thalamic nucleus to treat essential tremor)—all without having to make an incision.
What are psychophysiological recording methods?
Methods of recording physiological activity from the surface of the human body.
Describe SCALP ELECTROENCEPHALOGRAPHY (EEG).
- a measure of the gross electrical activity of the brain. It is recorded through large electrodes by a device called an electroencephalograph (EEG machine), and the technique is called electroencephalography. In EEG studies of human participants, each channel of EEG activity is usually recorded from disk-shaped electrodes, about half the size of a dime, which are attached to the scalp.
- The scalp EEG signal reflects the sum of electrical events throughout the head. These events include action potentials and postsynaptic potentials as well as electrical signals from the skin, muscles, blood, and eyes.
-Thus, the utility of the scalp EEG does not lie in its ability to provide an unclouded view of neural activity. Its value as a research and diagnostic tool rests on the fact that some EEG wave forms are associated with particular states of consciousness or particular types of cerebral pathology (e.g., epilepsy). For example, alpha waves are regular, 8- to 12-per-second, high-amplitude waves that are associated with relaxed wakefulness.
Why is it usual to record EEG activity from many sites simultaneously?
Because EEG signals decrease in amplitude as they spread from their source, a comparison of signals recorded from various sites on the scalp can sometimes indicate the origin of particular waves.
Psychophysiologists are often more interested in the EEG waves that accompany certain psycholog- ical events than in the background EEG signal. These accompanying EEG waves are generally referred to as _____________________.
event-related potentials (ERPs).
One commonly studied type of event-related potential is the sensory evoked potential— the change in the cortical EEG signal elicited by the momentary presentation of a sensory stimulus.
The cortical EEG that follows a sensory stimulus has two components: the response to the stimulus (the signal) and the ongoing background EEG activity (the noise). Is the signal or the noise of greater interest to psychophysiologists?
The signal is the part of any recording that is of interest; the noise is the part that isn’t.
The problem in recording sensory evoked potentials is that the noise of the background EEG is often so great that the sensory evoked potential is masked. Measuring a sensory evoked potential can be like detect- ing a whisper at a rock concert.
What is a method used to reduce the noise of the background EEG?
Signal averaging.
The analysis of average evoked potentials (AEPs) focuses on the various waves in the averaged signal. Each wave is characterized by its direction, positive or negative, and by its latency. For example, the P300 wave is the positive wave that occurs about 300 milliseconds after a momentary stimulus that has meaning for the participant (e.g., a stimulus to which the participant must respond).
In contrast, the portions of an evoked potential recorded in the first few milliseconds after a stimulus are not influenced by the meaning of the stimulus for the participant. These small waves are called far-field potentials because, although they are recorded from the scalp, they originate far away in the sensory nuclei of the brain stem.
Describe magnetoencephalography (MEG).
- measures changes in magnetic fields on the surface of the scalp that are produced by changes in underlying patterns of neural activity. Because the magnetic signals induced by neural activity are so small, only those induced near the surface of the brain can be recorded from the scalp
MEG has what two major advantages over EEG? .
It has much better spatial resolution than EEG (it can localize changes in electrical activity in the cortex with greater precision).
MEG can be used to localize sub-cortical activity with greater reliability than EEG.
True or False?
Each muscle fiber contracts in an all-or-none fashion when activated by the motor neuron that innervates it.
True.
At any given time, a few fibers in each resting muscle are likely to be contracting, thus maintaining the overall tone (tension) of the muscle. Movement results when a large number of fibers contract at the same time.
In everyday language, anxious people are commonly referred to as “tense.” This usage acknowledges the fact that anxious or otherwise aroused individuals typically display high resting levels of tension in their muscles. This is why psychophysiologists are interested in this measure; they use it as an indicator of psychological arousal.
Describe Electromyography.
is the usual procedure for measuring muscle tension. The resulting record is called an electromyogram (EMG).
EMG activity is usually recorded between two electrodes taped to the surface of the skin over the muscle of interest. The main correlate of an increase in muscle contraction is an increase in the amplitude of the raw EMG signal, which reflects the number of muscle fibers contracting at any one time.
Describe electrooculography.
- the electrophysiological technique for recording eye movements. The resulting record is called an electrooculogram (EOG).
-Electrooculography is based on the fact that a steady potential difference exists between the front (positive) and back (negative) of the eyeball. Because of this steady potential, when the eye moves, a change in the electrical potential between electrodes placed around the eye can be recorded.
-It is usual to record EOG activity between two electrodes placed on each side of the eye to measure its horizontal movements and between two electrodes placed above and below the eye to measure its vertical movements.
What are two psychophysiological measures of somatic nervous system activity?
Electromyography is the usual procedure for measuring muscle tension.
The electrophysiological technique for recording eye movements is called electrooculography.
What are two psychophysiological measures of autonomic nervous system activity?
Skin conductance & Cardiovascular activity.
Describe skin conductance level (SCL) and the skin conductance response (SCR).
- The two most commonly employed indexes of electrodermal activity
- Emotional thoughts and experiences are associated with increases in the ability of the skin to conduct electricity.
-The SCL is a measure of the background level of skin conductance that is associated with a particular situation, whereas the SCR is a measure of the transient changes in skin conductance that are associated with discrete experiences.
-there is considerable evidence implicating the sweat glands in skin conductance changes.
-the main function of sweat glands is to cool the body, but these glands tend to become active in emotional situations, causing the release of sweat that in turn increases the electrical conductivity of the skin.
