The Human Brain or Just a Lump of Clay?
The brain is exactly like clay- adaptable, malleable and changeable throughout a person’s life - of course, minus the beautiful muddy aroma.
Neuroplasticity is simply like playing with pottery clay in your head!
That wrinkled dome inside our skull has the ability to change from our first cry until our last breath. Neuroplasticity is the ability of the brain to change its physical structure and function through thought, emotion and activity1.
I’m sure I am making you feel like you have a magical wand in your head. But that’s what it is.
Contrary to the age- old belief that the brain doesn’t develop beyond a certain age, Moheb Costandi elicits in his book ‘Neuroplasticity’ that “Modification of synapses can occur on a timescale of milliseconds, synapses and dendrite branches are created or destroyed in the space of several hours, and new cells may be born or killed over periods of days2.”
On the other hand, our potter (oh, yes I’m still not done with him) might sometimes have less clay, a malfunctioning wheel, or he might have even lost his upper limb (tragic music in the background). Such situations are a perfect analogy of Alzheimer's disease.
DEATH BEFORE DEATH
Alzheimer's disease (AD) is a progressive neurologic disorder that causes the brain to shrink (atrophy) and brain cells to die. It is the most common cause of dementia — a continuous decline in thinking, behavioural and social skills that affects a person's ability to function independently3.
In India, with increased life expectancy and an ageing population, it is estimated that over 5.3 million people live with dementia, of which Alzheimer’s is the most common cause. This figure is set to rise to 7.6 million in 2030, according to the Dementia in India Report 2020 published by the Alzheimer’s and Related Disorders Society of India (ARDSI)4.
Intracellular neurofibrillary tangles (NFTs) and extracellular amyloid protein deposits characterise it pathologically. The diagnosis of AD is done by evaluating the location, distribution and characteristic brain lesions5.
Now, the question is- “If the blind have figured out new ways to see and the stroke patients have recovered to show mind-blowing functionality, can Neuroplasticity bring any luck to those diagnosed with cognitive decline and Alzheimer’s disease?”
RESEARCH PAINTS NEW HOPE
Evidence suggests that older adults have been shown to utilise additional or altogether different brain areas, presumably as a compensatory mechanism for age-related cognitive decline, and may employ unique strategies for storing and recalling information as they age.
Abstracts of noteworthy publications are listed below:
Grady et al. explored the relationship between increased prefrontal rCBF (regional cerebral blood flow) using PET (imaging technique that uses radioactive substance to visualise and measure metabolic and biochemical processes in the body) and successful task performance in normal older adults and individuals with probable early-stage AD.
The AD and control groups differed in the magnitude of brain activation when completing semantic memory tasks (ability to remember factual and conceptual information-eg. the concept of what a ‘cat’ is) and episodic memory tasks (recollection of specific events, situations and experiences-eg. first day at school). Specifically, the AD group demonstrated a more extensive recruitment of brain regions in response to task demands including the prefrontal and temporo-parietal cortices bilaterally.
This greater degree of activation correlated with improved task performance such that individuals with AD who demonstrated increased brain activation in these regions were able to perform both semantic and episodic memory tasks with more accuracy than those who demonstrated less brain activation.
Pariente et al. compared fMRI results (imaging technique that measures brain activity by detecting changes associated with blood flow) during a face-name recognition task (recall tool used to diagnose early AD) in people with mild AD compared to cognitively intact controls. In addition to BOLD (blood oxygen level dependent) signal patterns, successful encoding and retrieval of each face-name pair was determined to allow for comparison with patterns of brain activation.
Compared to the control group, subjects with AD demonstrated decreased activation in the hippocampus and simultaneously increased activation in the parietal and frontal lobes during successful encoding and retrieval of information.
There is excessive cerebral kallikrein-8 (protein encoded by KLK8 gene) mRNA at incipient stages of AD and TgCRND8 mice (mouse model showing pathological features of AD).
Antibody-mediated KLK8 inhibition exerts therapeutic effects on AD along with enhancing neuroplasticity, resulting in improved spatial memory in mice.
KLK8 inhibition increased the number of hippocampal Ki-67 (marker of cell proliferation) and doublecortin (marker of neurogenesis); thus establishing proliferative neuronal progenitor cells in transgenic mice, whereas the same action in wildtypes had no effect.
KLK8 inhibition in SH-SY5Y cells or in primary neurons increased levels of the neuroplasticity-supporting KLK8 substrate ephrin receptor B2 (EPHB2) while decreasing the relative amount of phospho-tau (phosphorylated protein which accumulates in AD).
Cristopher Daniel Morrone et al. compared TgF344-AD (a unique rat model with pathological hallmarks of AD) and non-transgenic littermate rats at 9, 12, and 15 months of age.
Neurons, β-amyloid plaques and tau inclusions were quantified in hippocampus and entorhinal cortex. Hippocampus plays a critical role in learning, emotional response, spatial navigation and memory; while the entorhinal cortex is the gateway for information entering and leaving the hippocampus.
Somatostatin (SST) and parvalbumin (PVB) interneurons, i.e GABAergic inhibitory neurons which prevent signal generation were traced to examine hippocampal neuroplasticity.
Cognition was tested in the Barnes maze (a tool used in psychological lab experiments to measure spatial learning and memory in rats).
The 9-month-old TgF344-AD rats exhibited loss of neurons in the entorhinal cortex and hippocampus. Hippocampal neuronal compensation was observed in 12-month TgF344-AD rats, with upregulation of GABAergic interneuronal markers. By 15 months, the TgF344-AD rats had robust loss of excitatory and inhibitory neurons. β-Amyloid and tau pathology accumulated continuously across age. SST interneurons exhibited tau inclusions and atrophy from 9 months, whereas PVB interneurons were resilient until 15 months.
The hippocampal PVB circuit underwent neuroplastic reorganisation with increased dendritic length and complexity in 9- and 12-month-old TgF344-AD rats, before atrophy at 15 months. Strikingly, 12-month-old TgF344-AD rats were resilient in executive function and cognitive flexibility.
Cognitive resilience in TgF344-AD rats occurred as maintenance of function between 9 and 12 months of age despite progressive spatial memory deficits, and was sustained by PVB neuroplasticity. The results demonstrate the inherent neuronal processes leading to cognitive maintenance, and describe a novel finding of endogenous cognitive resilience in an AD model.
16 amnestic mild cognitive impairment (aMCI) and 6 AD patients were recruited in the study. All the patients were subjected to rTMS to the left angular gyrus (plays a key role in spatial concepts, memory retrieval, number processing and language functions) for four weeks.
Automated fiber quantification using diffusion tensor imaging (DTI) metrics and graph theory analysis on functional networks were employed to detect the neuroplasticity of brain networks. After neuro-navigated rTMS intervention, the episodic memory of aMCI patients and Montreal Cognitive Assessment (rapid screening tool for mild cognitive dysfunction) score were significantly improved.
Increased FA values (fractional anisotropy- scalar value between 0 to 1 which measures connectivity in the brain via DTI) of right anterior thalamic radiation(brain’s information relay station) among aMCI patients, while decreased functional network properties of thalamus subregions were observed, whereas similar changes were not found in AD patients. It is worth noting that the improvement of cognition was associated with the neuroplasticity of the thalamic system.
THE BRAIN INDEED HAS AN AMAZING MORPHING POWER
AD leads to insidious and irrevocable damage of neural networks; and thus neuroplasticity progressively declines. However, individuals with early-stage AD may be capable of a compensatory response to this decline that optimises cognitive function within the confines of advancing pathology. Neuroimaging evidence indicates brain activation differences in individuals with early-stage AD when compared to normal controls during cognitive tasks. These alterations in magnitude or location of brain activity are associated with improved cognitive functions and appear to be unique to age-related plasticity responses although much remains to be learned regarding the heterogeneity of responses among individuals.
The public health significance of slowing cognitive decline could be enormous given the projected numbers of people who may develop AD in the next 10 years. The possible delay in institutionalisation and the resultant cost savings have the potential to improve quality of life for older adults and their families who care for them.
The future promises us that there’s light at the end of the tunnel for our potter and that he will definitely seize the clay!
Kendra Cherry (2022, February 18). Very Well Mind. verywellmind.com. Retrieved June 27, 2022, from What is brain plasticity?
Moheb, C. (2016). Neuroplasticity [E-book]. The MIT Press, 2016. Retrieved June 27, 2022, from Neuroplasticity by Moheb Costandi
Mayo Clinic Press. (n.d.). Alzheimer’s disease. Mayoclinic.org. Retrieved June 27, 2022, from Alzheimer’s-disease
Divya Gandhi. (2020, November 22). Just a fraction of an estimated 5 million Indians with dementia and Alzheimer’s are diagnosed. Do we need a new policy to ensure their well-being? Thehindu.com. Retrieved June 27, 2022, from https://www.joghr.org/article/12221-dementia-in-india-a-call-for-action
M. Paul Murphy et al. (2010, January). Alzheimer’s Disease and the β-Amyloid Peptide. ncbi.nlm.nih.gov. Retrieved January 27, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813509/
Cheryl L Grady et al.(2003). Evidence from functional neuroimaging of a compensatory prefrontal network in Alzheimer's disease. The Journal Of Neuroscience. https://doi.org/10.1523/JNEUROSCI.23-03-00986.2003
Jérémie Pariente et al. (2005). Alzheimer’s patients engage an alternative network during a memory task. Annals Of Neurology. https://doi.org/10.1002/ana.20653
Yvonne Münster et al. (2019). Inhibition of excessive kallikrein-8 improves neuroplasticity in Alzheimer's disease mouse model. Experimental Neurology, 324. https://doi.org/10.1016/j.expneurol.2019.113115
Morrone, C.D et al. (2022). Parvalbumin neuroplasticity compensates for somatostatin impairment, maintaining cognitive function in Alzheimer’s disease. Translational Neurodegeneration. https://doi.org/10.1186/s40035-022-00300-6
Yang, Zhiyuan et al. (2022). Cognitive improvement via left angular Gyrus-Navigated repetitive transcranial magnetic stimulation inducing the neuroplasticity of thalamic system in amnestic mild cognitive impairment patients. Journal of Alzheimer’s Disease, 86, 537–551. https://doi.org/10.3233/JAD-215390