A&A Chapter 4 Notes 2022 (1).pptx

Chapter 4: Changes to the Brain: Methods of Investigation, Aging, and Neuroplasticity Copyright © Springer Publishing Company, LLC. All Rights Reserved. Defining “neuroplasticity”  “Plasticity, then, in the wide sense of the word means the possession of...

Chapter 4: Changes to the Brain: Methods of Investigation, Aging, and Neuroplasticity Copyright © Springer Publishing Company, LLC. All Rights Reserved. Defining “neuroplasticity”  “Plasticity, then, in the wide sense of the word means the possession of a structure weak enough to yield to an influence, but strong enough not to yield all at once... Organic matter, especially nervous tissue, seems endowed with a very ordinary degree of plasticity of this sort...” (James, 1890, vol. I, p. 105) James, W. (1890). Principles of psychology. London, United Kingdom: MacMillan. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Figure 4.6 Drivers of neuroplasticity. Source: Zatorre, Fields, and Johansen-Berg (2012, p. 531). Adapted by permission from Macmillan Publishers Ltd. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Principles of Neural Plasticity (Kleim & Jones, 2008)  Use it or lose it  Time  Use it and improve it  Salience  Specificity  Age  Repetition  Transference  Intensity  Interference Kleim, J. A., & Jones, T. A. (2008). Principles of experience-dependent neural plasticity: Implications for rehabilitation after brain damage. Journal of Speech, Language, and Hearing Research, 51, S225–S239. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Part 1: Neuroimaging Techniques Used to Study the Aging Brain Copyright © Springer Publishing Company, LLC. All Rights Reserved. Computerized Tomography (CT)  Relies on X-rays to visualize brain tissue, and then reconstructs a series of slices to allow for a visualization of the brain.  CT scans have relatively poor spatial resolution—They produce fuzzy or grainy-looking pictures of the brain that do not have optimal detail. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Computerized Tomography (CT) (cont’d)  CT is still preferred method of brain imaging in some situations: ‒ When cost is a concern (CT scans are much cheaper than MRI scans) ‒ If rapid scanning is needed ‒ In cases where MRI is contraindicated (such as when an individual has a pacemaker, metal fragment, or any other implant that is susceptible to magnetic forces, or is in an agitated state) Copyright © Springer Publishing Company, LLC. All Rights Reserved. Magnetic Resonance Imaging  Allows for a much better spatial resolution (and thus crisper brain images) than CT imaging Figure 4.1 Comparison of a CT image (left) and MRI image (right), illustrating the superior spatial resolution of MRI. Prominent features, which are seen in more detail on the MRI, include the gyri and sulci that make up the outer perimeter of the cerebral hemispheres. The MRI image also offers more contrast of the gray matter (the gyri and sulci) from the white matter (the fiber tracts that run deep through the brain). The darker areas on both the CT and MRI images are spaces filled with cerebrospinal fluid Copyright (CSF). © Springer Publishing Company, LLC. All Rights Reserved. How Does MRI Work?  Person lies on a table that slides into a large, powerful magnet.  Magnet lines up all the protons in the body.  Radio frequency pulse is released from the scanner, causing all the protons to move out of alignment.  After the radio frequency pulse stops, the protons realign themselves, because the magnet remains on. Copyright © Springer Publishing Company, LLC. All Rights Reserved. How Does MRI Work? (cont’d)  As the protons get realigned, a computer records: ‒ The time it takes for the protons to be realigned ‒ The amount of energy they release to get realigned  Based on this information, a computer can determine the type of tissue or fluid a proton is part of, such as bone, blood, cerebrospinal fluid, white matter, and so forth).  The computer then creates brain images based on this information. Copyright © Springer Publishing Company, LLC. All Rights Reserved. How Does MRI Work? (cont’d)  Current MRI scanners have a spatial resolution on the order of millimeters.  Tesla (T; named after Nikola Tesla) refers to strength of the magnetic field—the higher the magnetic field, the sharper the image.  MRI scanners used for clinical purposes have a strength of 1.5 to 3 T (Tesla), and scanners used for research range from 3 T up to 7 T.  This is separate from T1 vs. T2 …. Copyright © Springer Publishing Company, LLC. All Rights Reserved. What’s T1 and T2?  Scanner parameters can vary the relaxation times for protons to return to equilibrium after being perturbed by the radio frequency pulse.  Sequences can be T1 or T2, where “T” is a time constant.  These relaxation time parameters lead to brain images that vary with respect to signal intensity.  Fluid appears dark on T1 images but appears bright on T2 images. Copyright © Springer Publishing Company, LLC. All Rights Reserved. What’s “FLAIR” Imaging?  Fluid-attenuated inversion recovery (FLAIR) imaging.  With FLAIR sequences, the signal from cerebrospinal fluid is suppressed to allow for more sensitivity to smaller changes/lesions in brain tissue that might otherwise be missed. Copyright © Springer Publishing Company, LLC. All Rights Reserved. T1, T2, and FLAIR Figure 4.2 MRI slices in the axial plane (i.e., parallel to the ground), showing the distinction in images produced with T1-weighted (left), T2- weighted (middle), and FLAIR (right) sequences. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Diffusion Weighted Imaging (DWI)  An additional MR sequence that provides indirect estimates of white matter in the brain  Makes use of the fact that the rate of diffusion of water molecules across axon membranes is not random but rather is constrained by the structure of these axon bundles  DWI can also be used to reconstruct directional information of the diffusion pattern as a proxy for the underlying white matter pathways Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Diffusion Weighted Imaging (DWI) (cont’d)  This directional information can then be used to generate white matter maps that show colorized reconstructions of distinct white matter pathways in the brain (known as diffusion tractography). Copyright © Springer Publishing Company, LLC. All Rights Reserved. Figure 4.3 Diffusion imaging-derived maps used to reconstruct white matter pathways in the brain. Figure courtesy of Stephanie Forkel. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Magnetic Resonance Spectroscopy (MRS)  Provides numeric information about metabolic activity as indexed by the amount of several different molecules (e.g., various amino acids, glutamate, and creatine) in a given brain region.  These MRS-derived levels are compared between an experimental group of interest (e.g., individuals with mild cognitive impairment or dementia) and a control group. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Analyzing Regions of Interest (ROIs)  Early studies used volumetric analyses, in which ROIs were manually traced on T1 MRI brain “slices.”  By early 2000s, voxel-based morphometry (VBM) techniques were developed, in which every 3D pixel (or “voxel”) is measured and differences in volume can be compared between groups. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Figure 4.4 VBM map showing significant reductions in temporal lobe gray matter in patients with dementia relative to people without dementia. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Structural Versus Functional Neuroimaging  CT and MRI, including VBM, show us the structure of a person’s brain at one point in time.  Functional neuroimaging enables researchers to measure ongoing regional brain activity.  EEG measures electrical activity of the brain through electrodes on a person’s head. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Structural Versus Functional Neuroimaging (cont’d)  One EEG measure is event-related potentials (ERPs) measure electrical activity linked to a specific event or stimulus.  EEG and ERP data have high temporal resolution but poor spatial resolution. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Functional Imaging: PET  Positron emission tomography (PET)  Single-photon emission computed tomography (SPECT)  Both PET and SPECT involve injection of a radioactive tracer (a molecule) that is taken up by active brain regions  Researchers can then see which areas are active during specific tasks while person lies in a scanner Copyright © Springer Publishing Company, LLC. All Rights Reserved. Cognitive “Subtraction” Technique During Functional Neuroimaging Complex Shows part of task (e.g., - Simpler task (e.g., reading = brain involved in solving math numbers) complex task of problems) interest (e.g., mental arithmetic) Copyright © Springer Publishing Company, LLC. All Rights Reserved. PET and SPECT Tracers  Used to track glucose metabolism, which indicates neural activity  Most commonly used PET tracer is [18F] – fluorodeoxyglucose (FDG)  FDG-PET showing decreased activity in medial temporal lobe, compared to other brain areas, is found in Alzheimer’s disease (AD) Copyright © Springer Publishing Company, LLC. All Rights Reserved. PET and SPECT Tracers (cont’d)  Radioligands are radioactive tracers attached to a molecule. They can preferentially bind to acetylcholine or dopamine receptors, for example  Pittsburgh compound B (PIB)—A radioligand that shows degree of beta-amyloid deposition in the brain Copyright © Springer Publishing Company, LLC. All Rights Reserved. Functional MRI (fMRI)  Blood oxygenation level dependent (BOLD) imaging: Signals from a MRI scanner can show changes in regional blood oxygenation, which reflects regional neuronal activity.  This became known as fMRI.  Does not require a radioactive tracer and MRI is more available and affordable than PET scanners.  However, MRI does not currently have tracers to show abnormal levels of activity. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Part 2: Changes That Occur to the Brain With Aging Copyright © Springer Publishing Company, LLC. All Rights Reserved. “Last in, First out”  The areas of the brain that develop later than others are the first to be affected by advanced age.  Areas that mature later and have thinner myelin are more vulnerable to age-related declines.  Whole brain volume starts to decrease after age 30.  The rate of volume loss increases in mid-50s to early 60s, and the rate varies across brain regions.  Ventricles and fissures increase in volume from age 60 on, more in men than women. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Frontal Lobes  Show the greatest rates of atrophy, and rate increases with advanced age.  Slow rate of reduction from age 20 to 60, and then decline accelerates.  Hypertension increases the rate of volume loss.  Women have larger frontal lobes and less reduction in frontal lobes with age than men do. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Hippocampus  Hippocampus shows second largest reduction in size with age.  Rate of atrophy stays stable until mid-50s or 60s.  Hypertension increases rate of atrophy. The more years of having hypertension, the greater the impact on atrophy.  The nearby entorhinal cortex shows little change with normal aging. Copyright © Springer Publishing Company, LLC. All Rights Reserved. What Changes Less With Age?  Parietal lobes show less atrophy than the frontal lobes.  Occipital lobes (including primary visual cortex) show the least change with age, though they do become smaller, starting around age 60.  Corpus callosum may not show change with age. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Normalcy-Pathology Homology  The areas of the brain (hippocampus, frontal lobes) that change the most with age are also the areas most susceptible to AD.  Areas like the hippocampus show large amount of plasticity (flexibility or adaptability) throughout life.  The plasticity of the hippocampus, enabling learning and memory, may make it more vulnerable to decline with age.  Decline with age may make these areas more vulnerable to AD. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Normalcy-Pathology Homology (cont’d)  Is age-related shrinkage of the hippocampus simply the start of AD? Does everyone eventually get AD?  According to Fjell et al. (2014), no—The changes observed with normal aging are not simply early signs of AD.  Rather, these areas of the brain change with age, and their loss of integrity makes them more susceptible to AD. Fjell, A. M., McEvoy, L., Holland, D., Dale, A. M., & Walhovd, K. B. (2014). What is normal in normal aging? Effects of aging, amyloid and Alzheimer’s disease on the cerebral cortex and the hippocampus. Progress in Neurobiology, 117, 20–40. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Gray and White Matter  Gray matter: Mostly cell bodies.  White matter: Parts of neurons that are enclosed in myelin, which makes tissue appear white.  Mnemonic: As one enters the brain, you go in alphabetical order through the gray matter followed by the white matter.  White matter grows in volume with myelination until around age 40, then starts to decline, and declines more rapidly than gray matter in older adulthood. Copyright © Springer Publishing Company, LLC. All Rights Reserved. White Matter Hyperintensities  Bright or “hyperintense” images on MRI scans  Found in white matter  Often found near ventricles (“periventricular”)  Associated with age, hypertension, diabetes, and smoking  Caused by ischemic damage (inadequate blood supply) of small blood vessels (“small vessel disease”)  Associated with poorer cognitive functioning Copyright © Springer Publishing Company, LLC. All Rights Reserved.  How Does the Brain Continue to Function Well?  Hemispheric Asymmetry Reduction in OLDer adults (HAROLD; Cabeza, 2002): Areas contralateral to the areas involved in a task are increasingly recruited with age to enable effective cognitive functioning.  Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH; Reuter-Lorenz & Cappell, 2008): Compensation occurs through increased activation of already-specialized brain regions and selective recruitment of alternative regions. Cabeza, R. (2002). Hemispheric asymmetry reduction in older adults: The HAROLD model. Psychology and Aging, 17, 85–100. Reuter-Lorenz, P. A., & Cappell, K. A. (2008). Neurocognitive aging and the compensation hypothesis. Current Directions in Psychological Science, 17, 177–182. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  How Does the Brain Continue to Function Well? (cont’d)  Scaffolding Theory of Aging and Cognition (STAC; Goh & Park, 2009): The aging brain maintains potential for neuroplasticity with new stimulation and learning. Goh, J. O., & Park, D. C. (2009). Neuroplasticity and cognitive aging: The scaffolding theory of aging and cognition. Restorative Neurology and Neuroscience, 27, 391–403. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Part 3: Neuroplasticity Copyright © Springer Publishing Company, LLC. All Rights Reserved. Neuroplasticity  “Plasticity, then, in the wide sense of the word means the possession of a structure weak enough to yield to an influence, but strong enough not to yield all at once” (James, 1890, Vol. I, p. 105).  Donald Hebb’s The Organization of Behavior (1949) highlighted the importance of repetitive firing of correlated synapses and neurons in the process of plasticity (commonly referred to as Hebb’s postulate). Hebb, D. O. (1949). The organization of behavior. A neuropsychological theory. New York, NY: John Wiley. James, W. (1890). Principles of psychology. London, United Kingdom: MacMillan. Copyright © Springer Publishing Company, LLC. All Rights Reserved. Neuroplasticity (cont’d) Figure 4.6 Drivers of neuroplasticity. Source: Zatorre, Fields, and Johansen-Berg (2012, p. 531). Adapted by permission from Macmillan Publishers Ltd. Copyright © Springer Publishing Company, LLC. All Rights Reserved.  Principles of Neuroplasticity (Kleim & Jones, 2008)  Use it or lose it  Use it and improve it  Specificity  Repetition  Intensity  Time  Salience  Age  Transference  Interference Kleim, J. A., & Jones, T. A. (2008). Principles of experience-dependent neural plasticity: Implications for rehabilitation after brain damage. Journal of Speech, Language, and Hearing Research, 51, S225–S239. Copyright © Springer Publishing Company, LLC. All Rights Reserved.