Neuroplasticity in Health and Disease Notes

Learning Outcomes

  • Common diseases/injuries to the CNS (Central Nervous System)
  • Principles of neuroplasticity
  • Mechanisms of Neuroplasticity
  • Linking Pathophysiology to recovery mechanism

Brain Anatomy

  • Cerebrum:
    • Higher functions: Interpreting touch, vision, hearing, speech, reasoning, emotions, learning, and fine motor control.
  • Cerebellum:
    • Coordinates muscle movements, maintains posture, and balance.
  • Brainstem:
    • Relay center between the cerebrum and cerebellum.
    • Controls autonomic functions.

Cerebral Hemispheres

  • Right and Left Hemispheres
  • Corpus Callosum:
    • Facilitates message transmission between hemispheres (crossover effect).
    • Left Hemisphere:
      • Dominant for speech, comprehension, arithmetic, and writing (92% dominance).
    • Right Hemisphere:
      • Specialized for reactivity, spatial ability, artistic, and musical skills.

Lobes of the Brain

  • Frontal Lobe:
    • Motor control (premotor cortex).
    • Problem-solving (prefrontal area).
    • Speech production (Broca's area).
  • Parietal Lobe:
    • Touch perception (somatosensory cortex).
    • Body orientation and sensory discrimination.
  • Temporal Lobe:
    • Auditory processing (hearing).
    • Language comprehension (Wernicke's area).
    • Memory/information retrieval.
  • Occipital Lobe:
    • Sight (visual cortex).
    • Visual reception and interpretation.
  • Cerebellum:
    • Balance and coordination
  • Brainstem:
    • Involuntary responses

Higher Brain Function

  • Information flow: Peripheral nervous system → thalamus → gyrus.
  • Cortex is responsible for higher processing.
  • Key areas:
    • Primary Motor Cortex
    • Motor Association Cortex
    • Speech Center
    • Primary Somatosensory Cortex
    • Sensory Association Cortex
    • Visual Association Area
    • Visual Cortex
    • Wernicke's Area
    • Prefrontal Cortex
    • Auditory Cortex
    • Auditory Association Area

Brain structures

  • Pineal gland
  • Superior colliculi
  • Cerebrum
  • Cerebellum
  • Thalamus
  • Optic nerve
  • Pons
  • Spinal cord
  • Medulla oblongata
  • Hypothalamus
  • Gray matter
  • White matter

Neuroplasticity Pioneers

  • Michael Merzenich
  • Jerzy Konorski
  • Torsten Wiesel
  • David H. Hubel
  • David Eagleman
  • Wendy Suzuki
  • V.S. Ramachandran
  • Lormier Moseley

Neuroplasticity Defined

  • Reorganization and formation of synaptic connections.
  • Constant process, varying in strength.
  • Brain plasticity.
  • Dependent on structural changes.
  • "The ability of the nervous system to change its activity in response to intrinsic or extrinsic stimuli by reorganizing its structure, functions, or connections."

Brain Activity and Imbalances

  • Brain activity determines feelings and actions.
  • Brain imbalances or chronic emotions can affect daily life even with normal brain function.

Neurofeedback

  • Training of brain activity.
  • Brainwaves: Electrical impulses from cellular communication.
    • Monitored by QEEG brain map.
    • Electrical activity monitored by EEGs.
    • Increased activity = increased risk requiring brain training
  • Purpose of brain training

Location of Neuroplasticity

  • Subventricular zone
  • Subgranular zone
  • Cerebral cortex
  • Hippocampus
  • Oligodendrocyte progenitor cell
  • Chains of migrating neuroblasts
  • Type B astrocytes ensheath migrating cells

Neuroplasticity in Disease

  • Beneficial: Restoration of function after injury.
  • Neutral: No clinical change.
  • Negative: Pathological consequences.
  • Mechanisms:
    • Neuronal regeneration/collateral sprouting (synaptic plasticity and neurogenesis).
    • Functional reorganization (equipotentiality, vicariation, and diaschisis).

Functional Reorganization

  • Diaschisis: Functional deafferentation (loss of input from a damaged brain area).
    • Connectional vs Connectome
  • Equipotentiality: One system takes over another.
  • Vicaration: The brain's ability to substitute areas of function.

Neuronal Regeneration

Synaptic Plasticity

  • Changes in synaptic strength.
  • Involves neurotransmitters, presynaptic terminals, synaptic cleft, and postsynaptic spines.
  • Ions such as Na+Na^+ and Ca2+Ca^{2+} are involved

Parkinson's Disease (PD) Sidenote

  • Involves mutant LRRK2, Cav2.1, microtubule network, glutamatergic terminal, synaptic vesicle dynamics, CB1R, Glu, NMDAR, eCBs, AMPAR, PLC, DA, ER, DARPP-32, Gq, IP3, CaMKII, D2R, D1R, Gi, cAMP, Gs, PKA, AC, DAT, Spiny Projection Neurons, Dopaminergic terminal, and a-syn aggregates.

Mechanisms of Synaptic Plasticity

  • Spike-timing-dependent plasticity (STDP):
    • Timing of action potentials generated by pre- and postsynaptic neurons.
  • Metaplasticity:
    • Activity-dependent changes in synapses and their responsiveness.
  • Homeostatic plasticity:
    • Maintenance of homeostasis in the synaptic network.

Neurogenesis

  • Whether it occurs is disputed.
  • Subventricular zone and olfactory bulb.
  • If it occurs
    • Do neurons travel?
    • Do they mature?
    • Do they function?
    • Can they form new synapses?
    • Can it be enhanced?

Articles Discussed on Neurogenesis

  • Functional significance of adult neurogenesis
  • Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults
  • Evidences for Adult Hippocampal Neurogenesis in Humans
  • Adult Hippocampal Neurogenesis in
  • Altered adult neurogenesis and gliogenesis in enesis under Control of the Circadian System
  • Mounting evidence suggests human adult neurogenesis is unlikely

Promotion of Neuroplastic Change

  • USE IT OR LOSE IT
  • proBDNF, sortilin, p75NTR, NF-kB RhoA JNK, neuronal survival, neuronal development, apoptosis, MBDNF, TrkB, MAPK PI3K/Akt PLC-V, synaptic plasticity enhancement, CREB, dendritic growth and branching, cytoskeleton protein synthesis anti-apoptic activity neuronal development and survival

Brain Derived Neurotrophic Factor (BDNF)

  • 'Nerve growth agent' that supports, grows, and differentiates existing neurons.
  • Encoded by the BDNF gene.
  • Active in the hippocampus, cortex, and basal forebrain (learning, memory, and higher thinking).
  • Important for long-term memory and neurogenesis.

Research on BDNF

  • BDNF dysregulation and Neurodegenerative disease? (Travaglia et al. 2017)
  • BDNF activity in epilepsy (Binder 2009)
  • Can Exercise promote BDNF? (Kobilo et al. 2010)

Drivers of Plasticity

  • Brain Chemistry.
  • Stimuli $\implies$ reaction $\implies$ Chemical Emotion/Cognitive processing $\implies$ Chemical Reaction.

Philosophy of Neuro: Being Content

  • Acetylcholine: the alertness chemical
  • Seratonin: the self esteem & sleep chemical
  • Oxytocin: the trust chemical
  • Melatonin: the R&R chemical
  • Endorphins: the pain killer chemical
  • Dopamine: the reward chemical
  • Norepinephrine : the excitement chemical
  • Phenylethylmine: the bliss & infatuation chemical

Social Media and Brain Development

  • Social media (SM) usage has become a global phenomenon, with over 5.17 billion users worldwide, predominantly from Gen Z and Millennials, who are most exposed to its effects (5)
  • High levels of social media use have been linked to increased symptoms of anxiety, depression, and addictive behaviours, raising concerns about its impact on mental health (2)
  • Neuroimaging studies suggest structural and functional changes in the brain, particularly in reward and executive control systems, associated with frequent social media use (6)

AIMS AND OBJECTIVE

  • This research aimed to investigate how social media use causes structural and functional brain changes.
  • Objectives:
    • Investigate Neurological Impacts of Social Media Use on Brain Morphology
    • Explore Behavioural and Emotional Consequences of Social Usage
    • Characterise Changes to Reward Processing Mechanisms.
    • Assess Cognitive and Executive Function Alterations.

Related Literature

  • Brocks, S. (2015). Does personal social media usage effect efficiency and well-being? Computers in Human Behavior, 46, pp.26-37. do https://doi.org/10.1016/j.chb.2014.12.053
  • Costello, C., Meniel, D. and Binder, R. (2016). Adolescents and Social Media Privacy, Brain Development and the Law Jenline] Available at:
    https://web.archive.org/web/20200321095330d http:/jaspl.org/content/jaep/44/3/313.full.pdf
  • 181 (20201 Critical appraisal tools, Jonlinel IBI Critical Appraisal Tools Available at
    https://biglobal/critical-appraisal-tools (Accessed 1 Oct, 2024)
  • Mohar, D et al. (2009. Let Evidence Guide Every New Decision (LEGEND an evidence evaluation system for point-of-care clinicians and guideline development teams, Ann Intern Med. 151 (41 pp. 264-260. DO 10.7326/0003-4819-151-4-200908180.00135
  • Petrosyan, A. (2024) Number of internet and social media users worldwide as of October 2024, Jo
    Statista Available at https://www.statista.com/statistics/617136/dgtal population worldwide. I
  • Sherman, LE. Hernandez, LM, Greenfield, P.M. and Depretto, M. (20181 What the brain Likes n correlates of providing feedback on social media Social Cognitive and Affective Neuroscience (or 107). pp 699-707. dei https//doi.org/10.1093/scan/nsy051

Neuroplasticity in Practice

Types of Stroke

  • Ischemic Stroke: Blocked blood vessel.
  • Haemorrhagic Stroke: Bleeding in the brain.

Time is Brain

  • Completed stroke: Neuronal and cell death.
  • Increased neuroplasticity due to cortical reorganization → structural change → regeneration?
  • Release of growth factors promoting synaptogenesis.
  • Is there a time limit?

Cellular Events in Stroke

  • Stroke $\implies$ Oxygen/nutrient deprivation $\implies$ Ionic imbalance & membrane depolarization $\implies$ Compromised BBB $\implies$ K+/Na+ pump failure $\implies$ Glutamate release $\implies$ Immune cell infiltration $\implies$ Cytokine release $\implies$ Microglia activation $\implies$ Cytoplasmic ion overload $\implies$ Protease activation $\implies$ Free radical production $\implies$ Caspase activation $\implies$ DNA damage $\implies$ Cell death.

Plasticity

  • Microglia
  • Neuronal Plasticity (Cell Proliferation)
  • Dendritic Plasticity
  • Synaptic Plasticity
  • Glia Plasticity Astrocyte
  • Neuromuscular Plasticity

BDNF and Stroke Recovery

  • Attenuates Stroke-Induced Cell Death.
  • Promotes Neurite Outgrowth and Neurogenesis.
  • Facilitates Functional Recovery (by overexpressing stem cells).
  • Triggers TrkB signaling $\implies$ Neuroplasticity.

Rehabilitation

  • Starts from Day 1.
  • Early mobilization is key.
  • Repeat Repeat Repeat → 10,000 hours to perfect a task.
  • Differences in LL and UL for rehabilitation → gross vs fine motor control.

Questions

  • Should we drive neuroplastic changes through rehabilitation? Why?
  • What external factors do you think neuroplasticity is dependent on?
  • If we can rewire the brain after disease through rehabilitation, can we do the same in a healthy brain? IF yes/no why?

Resources

  • https://n.neurology.org/content/98/12/505.abstract#sec-12
  • https://www.mdpi.com/2227-9067/10/8/1414
  • https://iamanetwork.com/journals/jamapediatrics/article-abstract/2800779