Neuroplasticity and Brain Development

Neuroplasticity

• Represents the brain's ability to change through experience

Mechanisms of Plasticity

• Synaptic plasticity occurs via the addition or removal of channel-receptors at the synapse
• Synapses are added/removed during development and adulthood as a mechanism of plasticity
• Axonal sprouting is a mechanism of brain plasticity
• New neurons can be born in adulthood

Main Brain Divisions

• Forebrain
• Midbrain
• Hindbrain

Human Brain Development

• Timeline of development includes significant milestones:
  • 29 days
  • 33 days
  • 52 days
  • 59 days
  • 70 days
  • 20 weeks
  • 6 months
  • 9 months
• Stages of life considered in the context of brain development:
  • Young child
  • Teenager
  • Adult
• Human head size is limited by the birth canal
• Brain development continues after birth
• Neurons form networks and circuits

Number of Neurons in Visual Cortex

• Newborn: 0 million
• 2 weeks old: 3 million
• 3 years old: 6 million
• 5 years old: 9 million
• 11 years old: 12-15 million

Changes in Neuron Number with Age

• Neuron numbers increase prenatally and continue shortly after birth
• Number of neurons begins to decrease into adolescence

Changes in Synapse Number with Age

• Synapses peak after birth and decline thereafter
• Synapse density varies in the human visual cortex
• Synapse maturation involves strengthening and refinement
• Myelination plays a key role in brain development

Brain Matter

• Gray matter consists of neuronal somas and dendrites
• White matter consists of axons covered by myelin

Myelination

• Optic nerve myelination changes with age
• Myelination in a 14-day-old rat differs from that of a 2-month-old rat

Recovery Following Stroke

• Pedro Bach-y-Rita represents a case study, that introduces visualizing reorganization

Synaptic Plasticity

• Santiago Ramon y Cajal was a neuroanatomist who contributed significantly to the understanding of synaptic plasticity:
  • Croonian Lecture, 1894
  • Nobel Laureate, 1906
• He suggested learning doesn't require genesis of new neurons
• Memories are formed by strengthening connections between existing neurons
• Synaptic transmission changes based on activity, altering neural circuitry and behavior

Hebbian Theory

• Donald O. Hebb proposed the Hebbian Theory in 1949
• Key tenet: "Neurons that fire together wire together"
• Synaptic transmission can be altered by experience
• Synaptic plasticity involves activity-dependent changes in synaptic strength
• Long-term changes in synaptic transmission form the cellular basis for learning and memory

Long-Term Potentiation/Depression

• Long-Term potentiation (LTP)
• Long-Term depression (LTD)

Principles of Experience-Based Neuroplasticity

• Donald Hebb outlined the principles of experience-based neuroplasticity
• "Use it or lose it"
• "Use it to improve it"
• These principles rely on:
  • Repetition of Stimulation
  • Intensity of Stimulation
  • Regional and Functional Specificity
• Inefficiently used synapses are eliminated, while efficiently used synapses are maintained
• Significant axonal input stimulation leads to new synapse formation
• Plasticity occurs in specific synapses within specific circuits
• Critical periods of learning occur during development where environmental factors influence the formation of synaptic connections and circuit function

Brain Imaging Advancements

• Standard X-ray
• Computed Tomography (CT) scanner
• Computed Axial Tomography scanner
  • Resolution around several mm
• Magnetic Resonance Imaging (MRI) scanner
  • Resolution: less than 1 mm
• The strength of an MRI magnet is measured in Teslas
• Nikola Tesla (1856-1943) was a Serbian American electrical engineer who pioneered modern electrical thinking
• Center for Magnetic Resonance Imaging at the University of Minnesota:
  • Resolution: less than 1 mm
  • Has a 10.5T Magnet
• 10.5T Magnet is the world’s largest and most powerful human imaging magnet
• Capable of delivering sharpest images via magnetic resonance imaging technology
• Functional Magnetic Resonance Imaging (fMRI) scanner
  • Resolution: 2 mm

MnDRIVE

• MnDRIVE, established in 2013, is a partnership between the University and the State of Minnesota
• MnDRIVE Brain Conditions focuses on neuromodulation research
• Neuromodulation is a transdisciplinary field focused on treating nervous system disorders with technological interventions for therapeutic response:
  • Integrates basic science
  • Engineering
  • Clinical disciplines
• Therapeutic innovations developed include:
  • Electrical
  • Magnetic
  • Optogenetic
  • Ultrasound technologies

Neuromodulation

• Deep Brain Stimulation involves the use of research cores
• Non-invasive Neuromodulation Laboratory exists
• Optogenetics and Neuromodulation is utilized
• Optogenetics and Neuromodulation is used for the treatment of:
  • Parkinson’s disease
  • Essential tremor
  • Dystonia
• Recent studies suggest it may be used for the treatment of:
  • Depression
  • Obsessive-compulsive disorder (OCD)
  • Tourette disorder
• Transcranial Magnetic Stimulation (TMS) is a noninvasive procedure using magnetic fields to stimulate nerve cells

Redesigning the Brain

• Michael Merzenich (1942-) is an American Neuroscientist
• Detailed "Brain Maps” in various sensory systems
• Pioneer in the field of Cortical Plasticity
• Led to the development of the Advanced Bionics Clarion cochlear implant
• Created Fast for Word and Posit Science, developing various brain training programs for children and adults
• Wilder Penfield (1891-1976) mapped sensory and motor areas of patients
• Sensory and motor cortex are topographically organized
• Stimulation of other areas of cortex triggered memories
• Penfield is one of the originators of the "homunculus" and was a Canadian Neurosurgeon

Motor and Sensory Cortex

• Involve the:
  • Central Sulcus
  • Parietal lobe
  • Frontal lobe
• The homunculus represents the topographical organization of the sensory and motor cortex
• Primary somatosensory cortex is topographically organized
  • Body areas near each other are represented near each other in the cortex
  • Somatosensory neurons are organized in specific cortical columns
• Primary motor cortex is topographically organized
  • Neurons controlling body parts near each other, are located near each other in the cortex
  • Neurons controlling the body are organized in specific cortical columns
• Vernon Mountcastle (1918-2015) is famous for his discovery of the functional organization of the cerebral cortex
• Columnar organization means all neurons in a vertical cross section of cortex respond to the same sensory signal
• Histological columnar organization exists in the cortex

Hubel and Wiesel

• David Hubel (1926-2013) and Torsten Wiesel (1924-)
• The columnar organization of the visual cortex
• Neurons in each cortical column respond to the same visual stimulus
• Ocular dominance columns describe how neurons in different columns of the visual cortex respond preferentially to either the LEFT or RIGHT eye
• Critical periods define the temporal window during development when environmental factors influence synaptic connection and circuit function
• Monocular deprivation effects include altered ocular dominance columns
• Sensory deprivation affects cortical ocular dominance columns
• Critical period for visual stimulation in newborn kittens: 3rd to 8th week of life
• Konrad Lorenz studied imprinting
• Michael Merzenich challenged the dogma of the brain and proved the plasticity of cortical maps via topographical reorganization of the sensory cortex

Digit Amputation & Cortical Maps

• Sensory cortex was mapped in monkeys before and after amputation of digit 3
• The map for digit 3 disappears, and other maps move into the cortical real estate
• Cortical maps for digits 3 and 4 merged to form a single map after digits sewn together
• fMRI scans showed activity in this combined map in humans born with webbed fingers
• Performance of refined cortical columns can be enhanced with training
• Blind individuals trained with Braille show enhanced performance with refined cortical columns

Summary of Key Principles

• Somatosensory and motor cortex are topographically organized
• Hebbian principles of cortical plasticity: "Use it or lose it" "Neurons that fire together wire together" "Use it to improve it"
• This creates a balance between hardwired brain and neuroplasticity

Cochlea and Sound

• The cochlea is tonotopically organized; tones close in frequency are represented near each other, with high frequency near the base
• The auditory cortex is tonotopically organized

Peripheral Hearing Loss

• Conductive hearing loss involves damage in the outer or middle ear
• Sensorineural hearing loss involves damage in the inner ear (most commonly, hair cells)
• Cochlear implants are small, complex electronic devices used for sensorineural hearing loss treatment:
  • The headpiece microphone picks up sounds
  • Sounds converted to electrical signals and fed into the cochlea
  • An electrode array stimulates the auditory nerve directly

Neuronal Injury Recovery

• The brain represents 2% of body mass, but consumes 20% of body energy
• Neurons spend energy on:
  • Maintaining resting membrane potential
  • Restoring ionic distribution after action potentials
  • Neurotransmitter uptake to end synaptic transmission
  • Filling vesicles with neurotransmitters
  • Turnover of proteins
• Neurons need a continuous oxygen supply
• Blood cells contain hemoglobin which binds oxygen and carbon dioxide
• Functional hyperemia regulates blood flow based on activity
• Functional hyperemia provides the bases of Functional Magnetic Resonance Imaging (fMRI)
• Blood oxygenation level dependent (BOLD) imaging generates images in fMRI studies
• Oxygenated and deoxygenated hemoglobin have different paramagnetic properties
• fMRI detects relative changes in cerebral blood flow
• fMRI assess brain regions with higher activity

Strokes

• Ischemic stroke is when a blood clot blocks blood flow to the brain (80%).
• Hemorrhagic stroke is when a blood vessel bursts (20%)
• Ischemia is a lack of oxygen and nutrients
• Ischemia causes:
  • Energy failure
  • Ion gradient imbalance
  • Neuronal depolarization
  • Glutamate release
  • Intracellular calcium increase
  • Cell injury and death
• Cellular processes associated with strokes includes cell injury and death caused by the ischemia
• There can be paradoxical exacerbation of cellular dysfunction and death, following restoration of blood flow to previously ischemic tissues (Ischemia-Reperfusion Injury)
• Stroke signs include:
  • Sudden trouble walking, dizziness, or loss of balance or coordination
  • Sudden trouble seeing in one or both eyes
  • Sudden weakness of the face, arm, or leg (often on one side)
  • Sudden confusion, trouble speaking or understanding speech
  • Sudden severe headache with no known cause
• The first 3 hours after a stroke are key to effective treatment
• Thrombolytics help reestablish blood flow by breaking up clots

Stroke Risk Factors

• Controllable risk factors
  • High blood pressure
  • Atrial fibrillation
  • High cholesterol
  • Diabetes
  • Atherosclerosis
  • Circulation problems
  • Tobacco use and smoking
  • Alcohol use
  • Physical inactivity
  • Obesity
• Uncontrollable risk factors
  • Age (risk doubles with every decade after 55)
  • Gender (women have more strokes)
  • Race (African Americans, Hispanic, and Asian/Pacific Islanders have 2X risk)
  • Family History
  • Previous stroke
• Common stroke consequences (75% require rehabilitation)
  • 30% need help walking
  • 26% need help with common activities
  • 19% have language problems
  • 35% will be depressed
  • 50% have paralysis/weakness on one side
  • 26% need managed care

Approaches to Stroke Rehabilitation

• Goals are independence and quality of life.
• Consists of:
  • Repetitive practice of movements related to specific skills
  • New ways of moving to compensate for lost functions
  • Passive movements, if deficit is severe
  • Transcutaneous nerve stimulation to promote brain reorganization

Constraint-Induced Therapy

• Dr. Edward Taub did deafferentation experiments in monkeys
• Taub is credited with one of the top ten translational neuroscience accomplishments of the 20th century
• Spinal reflexes were previously seen as the basis for all movements
• Taub showed that restraining the "good arm" of a deafferented monkey made the monkey use its affected arm
• The brain, not just spinal reflexes, commands motor behavior
• The goal is to induce plasticity of brain connections controlling the affected functions.
• Involves:
  • Isolation of affected part of the body
  • Repetitive practice of individual tasks
  • Massed practice; many repetitions in a short time
• Hebb's Principles: "use it or lose it", "use it to improve it"
• To be considered for the treatment, the patient must first be able to:
  • Lift an item: washcloth
  • Drop it with the affected arm
  • Have no significant contractures
• Has to have cognitive ability and highly motivated
• CIT: increase activation in bilateral hemispheres, particularly in the unaffected hemisphere
• Control therapy: decrease in cortex activation of the affected hemisphere
• Improvement by CI Therapy can be observed by fMRI
• CI therapy increases performance on aphasia task

Aphasia

• Broca’s aphasia: damage of the Broca’s area involved in speech production
• Wernicke's Aphasia: damage of the Wernicke's area involved in speech recognition
• Those suffering from aphasia fall back on behaviors that permit them to communicate
• Constraint induced therapy on someone with aphasia significantly increased performance on a word task

Experience-Based Plasticity

• Relies on:
  • Synapses that are not efficiently used are eliminated
  • Synapses that are efficiently used are maintained
  • Regional and functional specificity, stimulating the "bad limb"
• You stop using a part of your body, other parts of your body take over the unused space in the cortex
• Post-stroke plasticity should pursue:
  • Promoting beneficial plasticity (use it to improve it)
  • Preventing detrimental plasticity (avoid use it or lose it)