Cherish Madu
This wiki briefly explores the methods that those interested in neuroscience most frequently employ when investigating and explaining cognitive processes in terms of brain structure and function. The advantages and disadvantages of each method will also be discussed.
Positron Emission Tomography
Overview
Positron emission tomography (PET) is a three-dimensional brain imaging technique that takes advantage of changes in metabolism to localize brain activity and functional processes in the body [1]. The most active parts of the brain use more metabolic processes than do relatively inactive parts of the brain and PET is able to track this metabolic flow. Flourine-18 or oxygen-15, the most commonly used radioactive tracer isotopes, is injected into the bloodstream where it disperses to more active parts of the brain. Inside the brain, the radioactive tracer decays into a positron and an electron. When the positron collides with an electron, two gammas rays are produced. The accumulation of these pairs of gamma rays is measured by gamma-ray detectors which are placed all around the subject's head. Computer analyses construct the radioactive tracer concentration into three-dimensional images. PET is often combined with CT or MRI scans for superimposition of the images of concentration onto anatomic images of the subject's brain.
PET is not only used in neuroimaging. It also has applications in oncology and pharmacology. Flourodeoxyglucose (FDG) is primarily used in oncology because of its ability to track glucose metabolism in cancer tissues. Flourodeoxyglucose flourine-18 (FDG-PET) is also used to detect patients at risk for stroke in cardiology.
Advantages
PET has the advantage of having high spatial resolution (approximately a centimeter). PET is also used in humans and can be used to study higher-order functioning that is relevant to our population.
Disadvantages
Radioactive isotropes need to be created by cyclotrons either on-site or near the hospitals using PET. This process is very costly. Moreover, because the positron has to travel before it collides with an electron to produce gamma-rays, temporal resolution is very low. It takes close to a minute for the concentration of gamma-rays to accumulate into a reliable signal. Also, PET is a somewhat invasive procedure because it requires the injection of radioactive molecules into the bloodstream [2]. However, the dose of radiation is reduced in isotopes with short half-lives.
Transcranial Magnetic Stimulation
Overview
Transcranial magnetic stimulation (TMS) is used to disrupt cognitive processing in normal human subjects in order to gain knowledge of the function of certain areas of the brain. A magnetic field, created by electromagnetic induction, is placed over an area of the scalp. This rapidly changing magnetic field causes activity or inactivity in the associated brain region creating a reversible 'lesion' in the subject's brain. Repetitive transcranial magnetic stimulation (rTMS) is the application of a series of TMS pulses and has been used clinically as a treatment for a number of psychiatric and neurological disorders, including but not limited to Parkinson's disease, depression, stroke, and chronic pain.
Advantages
TMS is fully non-invasive and the stimulation of particular brain areas by TMS is associated with minimal discomfort. TMS is also relatively inexpensive and simple to use.
Disadvantages
TMS has low spatial specificity and little is known about the mechanistic processes underlying TMS and its benefits. Also TMS can cause seizures, although this is a rare occurrence [3].
Optogenetics
Overview
Optogenetics combines techniques from genetics and optics to deepen our understanding of neural circuitry and how it relates to behavior. Optogenetics is a tool that makes use of microbial opsins that can be activated by light. For the most part, viruses are engineered with specific promoters that drive expression of ospin genes and are injected into mice or rats.
Optogenetics has also allowed us to more fully understand some of the neurological disorders that plague our population today. 28% of the American population is afflicted with some kind of fear or anxiety disorder, 13% are afflicted with depression, and an ever increasing number have an addiction problem, whether it be to narcotics or gambling [4]. Through the use of optogenetics and rodent anxiety models, a specific population of amygdala synapses that directly affect anxious behavior was identified. Scientists were also able to find an inhibitory microcircuit that prevents fear typed behavior. These findings are all promising for our understanding of anxiety and fear disorders.
Advantages
Optogenetic manipulations can be immediately reversed and this sort of temporal specificity is unprecedented in other comparable neuroscience techniques. Because of its immediate reversibility, within-subjects testing is made possible just by turning a light on or off. Additionally, multi-day tests can occur in the space of a single session because of the rapid nature of optogenetics. The incredible spatial specificity of optogenetics is shown through transgenic rodent lines. These mouse lines make it possible to target neurons such as tyrosine hydroxylase and choline acetyltransferase that have promoters that would be too large, and thus impossible, to package into most vectors.
Disadvantages
The only drawback is that lighting tends to produce heat and heat may be detrimental cell health. This means that it is necessary to maintain relevant controls in which lighting is not used so as to compare cell health.
Electroencephalography
Overview
Electroencephalograpy (EEG) recordings measure electric activity in the brain through surface electrodes that are placed along the scalp. These surface electrodes measure voltage, and the difference in voltage between the surface electrodes and a reference electrode (placed elsewhere on the head) are amplified, digitized, and then recorded [5]. EEG does not measure the elecric potential of a single neuron [6]. Instead it measures the dendritic field potentials of groups of neurons. In this way, the signal becomes large enough for EEG to detect. Event-related potentials (ERPs) are extracted from the EEG signal to relate electrical activity to neural function. ERPs can do this because they have the advantage of linking electrical activity with time.
EEG has many functional uses in assessing the global state of the brain. Clinically, EEG is used to differentiate epileptic seizures from fainting and movement disorders [7]. EEG is also used to diagnose coma and brain death.
Advantages
EEG is a non-invasive technique as it does not require surgery or the injection of hazardous materials. ERPs also have excellent temporal specificity, within milliseconds [8].
Disadvantages
EEG has poor spatial resolution because it records mainly from the most superficial layers of the cortex. Neurons within sulci, as opposed to within gyri, or other sub-cortical layers are not detected using EEG.
Functional Magnetic Resonance Imaging
Overview
Like PET, Functional magnetic resonance imaging (fMRI) results in the imaging of active brain locations. FMRI, however measures blood flow using the blood-oxygen-level-dependent (BOLD) contrast (CITE). BOLD contrasting takes advantage of the fact that oxyhemoglobin (oxygen-rich) and deoxyhemoglobin (oxygen-poor) have differing magnetic resonance signals, hence the contrast. Functioning areas of the brain require more oxygen and thus more blood flow that non-active parts of the brain.
FMRI has spurred the creation of companies that market lie-detectors based upon the imaging technique. Such companies claim that the pre-frontal cortex (PFC) is more active when individuals are planning to or contemplating a lie [9].
Advantages
FMRI is a fairly safe technique as it does not require the injection of radioactive materials, unlike PET. Also, the spatial resolution of fMRI is higher than PET, at a few millimeters. FMRI also delivers relatively high temporal resolution (a few seconds), although it does not reach the standards set by optogenetics.
Disadvantages
FMRI is an extremely costly technique because magnetic resonance scanners alone can cost upwards of $3,000,000 depending on tesla level.
References
- Bailey, D.L; D.W. Townsend, P.E. Valk, M.N. Maisey (2005). Positron Emission Tomography: Basic Sciences. Secaucus, NJ: Springer-Verlag. ISBN 1-85233-798-2.
- Brix G, Lechel U, Glatting G, et al. (April 2005). "Radiation exposure of patients undergoing whole-body dual-modality 18F-FDG PET/CT examinations". J. Nucl. Med. 46 (4): 608–13. PMID 15809483
- Rossi, S; Hallett, M; Rossini, PM; Pascual-Leone, A; Safety of TMS Consensus Group (2009). "Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research". Clinical Neurophysiology 120 (12): 2008–2039. doi:10.1016/j.clinph.2009.08.016. PMID 19833552
- Tye, K. M., & Deisseroth, K. (2012). Optogenetic investigation of neural circuits underlying brain disease in animal models. Nature Reviews Neuroscience, 13(4), 251-266.
- Tatum, W. O., Husain, A. M., Benbadis, S. R. (2008) "Handbook of EEG Interpretation" Demos Medical Publishing.
- Nunez PL, Srinivasan R (1981). Electric fields of the brain: The neurophysics of EEG. Oxford University Press.
- Atlas of EEG & Seizure Semiology. B. Abou-Khalil; Musilus, K.E.; Elsevier, 2006.
- Anderson, J. (22 October 2004). Cognitive Psychology and Its Implications (Hardcover) (6th ed.). New York, NY: Worth. p. 17. ISBN 0-7167-0110-3.
- Huettel, S. A.; Song, A. W.; McCarthy, G. (2009), Functional Magnetic Resonance Imaging (2 ed.), Massachusetts: Sinauer, ISBN 978-0-87893-286-3