Formation,

Modification, and
Repair of Neuronal
Connections

OTD 341
Dr. Lou Jensen
Fall 2023

1
 Reminders

• Neuro Book Club Preference Survey Due

Thursday - complete survey on course
website
 OTD 341: Neuroanatomy

Unit 1 Unit 2 Unit 3 Unit 4

Session 1: Session 9: Session 14: Session 21:

Organization of Assessments: Electrical Assessments: Thalamus and Hearing &
Nervous System Signaling Internal Capsule Assessments: Balance
Assessments: Exam 2 Neuro Book
Neuroscience
Practice Exam Session 2: Session 10: Club
Session 15: Reflection Session 22:
Exam 1 Development of Sensory Exam 3
Nervous System System
Cranial Nerves Exam 4 Cerebral Cortex

Session 11: Sessions 16 &

Sessions 3 & 4: Session 23:
Neuroplasticity
Spinal Cord 17: Visual Limbic System
& Brainstem System

Session 5: Session 18: Session

Session 12:
Meninges & Cranial Nerve & 24: Blood
Ventricles Pathways Vision Review Supply
Session 6: Session 25:
Session 13: Sessions 19 & 20:
Gross Course
Anatomy ANS & Spinal Motor Systems
Review
Cord
Sessions 7 & 8: Conditions
Begin Finish
Neurons and
with the with the
Glia
BIG BIG
PICTURE PICTURE
! Micro Level (e.g., cells) Meso Level (e.g., systems) Macro Level (e.g., humans in environments !
 1. Define neuroplasticity and what
facilitates this phenomenon
2. Describe the production of neurons
and connections during development
3. Discuss how synaptic connections are
Session Learning adjusted throughout life

Objectives 4. Identify, describe and apply the

various types of memory and which
types are most affected by various
injuries or diseases
5. Compare and contrast PNS and CNS
repair

4
 NEUROPLASTICITY
http://www.normandoidge.com/

5
 Introduction
• Systematic study of neuroanatomy sometimes makes it seem as if
interconnections between various structures are rigid, exact, and
genetically predetermined
• Nature vs. nurture debate
– Nature: general layout of the nervous system
– Nurture: various connections are adjusted to meet demands of
environment; also known as neuroplasticity
• Neuroplasticity is most prominent during critical periods of
development, and then is reduced (not abolished, as scientists once
believed)
– Critical periods: early development
– Ongoing adjustments: learning and memory; constraint-induced movement
therapy; etc.

6
 Neuroplasticity Defined
• Ability of the brain to change its own structure
and function through activity and thought
• Neurons and their connections adjust to
match the nervous system to the:
– Body (e.g., after-effects of being on a boat)
– Environment (e.g., London cabbies & swimmers)

7
 Examples and
Applications of
Neuroplasticity
1. Neurogenesis: creating new neurons
2. Re-wiring: creating new neuronal
pathways
3. Unmasking: uncovering existing, but
rarely used neuronal pathways
4. Cortical re-organization: reassigning
cortical “real estate”
5. Changes in synaptic efficiency: basis of
learning and memory

8
 • It was once believed that all neurons
were produced during development and
that neurons lost to disease or damage
could not be replaced
• The existence of neural stem cells- cells
that can produce new CNS neurons or
glial cells- has disproved this belief
• Stem cells have been found in the
following places:
– walls of the ventricles (but remain
1. Neurogenesis latent)
– hippocampus (subgranular zone of
the dentate gyrus) (produce
newborn neurons)
– subventricular zone of lateral
ventricles that migrate to olfactory
bulb (produce newborn neurons)
• These discoveries offer potential for
using stem cells to replace dead brain
cells

9
2. Re-wiring

https://youtu.be/MFzDaBzBlL0

10
3. Unmasking
11
4. Cortical
Re-organization

12
 5. Changes in
Synaptic Efficiency
• Neurons communicate primarily through
chemical transmission via neurotransmitters
• Hebb’s principle asserts that “neurons that fire
together wire together”: structural changes at
synapses increase ease of neurotransmission
and create a network
– Potentiation: an increase in synaptic
efficiency
– Depression: a decrease in synaptic
efficiency (“neurons
that fire apart, wire apart”)
• Duration of changes in synaptic efficiency can
vary
– Short-term potentiation or depression:
lasts a few minutes; general consequence
of activity
– Long-term potentiation or depression:
produces lasting changes (hours to years);
basis of learning and memory AND what
we hope to affect in neurorehabilitation

13
 What facilitates neuroplasticity?

• Studies in mice showed that enriched environments that include novelty and
physical exercise increased the number of stem cells in their hippocampi and
prolonged the life of the cells there (Doidge, 2007)
• Intensity / redundancy (use-dependent neuroplasticity)
• Person involved in complex problem-solving for task completion
• Enhanced environments
• Individualized saliency
• Active use of affected body part needed
• Goal-driven tasks (i.e., meaningful to pt., real vs. contrived activities, etc.)

14
15
Formation of
Neural Connections

• Neurons and the connections between them are

produced in excess during prenatal and early
postnatal development
• Infants must then match neuronal connections to
their body and external environment through a
matching process
• Matching process includes dying off of surplus
neurons and retracting inappropriate connections
16
 Formation of Neural Connections (cont.)

• How do humans make sure the right

neurons survive?
– Target tissues in the body produce a limited quantity of
neurotrophic factors (e.g., nerve growth factor and
brain-derived neurotrophic factor)
– Nerve endings take up neurotrophic factors and
transport them retrogradely to neuronal cell bodies to
nourish the cell and allow it to survive
– Neuronal competition: neurons compete for
neurotrophic factors during development
17
 Formation of Neural Connections (cont.)

• How do humans make sure the right neuronal

connections last?
– Neurotrophic factors cease to be essential for survival of
neurons later in development, but continue to help
determine which dendrites and axon branches flourish and
which wither and retract
– Immature neurons receive inputs and make synaptic
connections much more easily than adult neurons
– As time goes by, connections that contribute more effectively
and efficiently to function last, and those that do not are
pruned away

18
https://onlinelibrary.wiley.com/doi/pdf/10.1002/9781118444177.ch6
19
http://newsroom.cumc.columbia.edu/blog/2014/08/21/children-autism-extra-synapses-brain/
20
 Critical Periods
• Plasticity is maximal and synapses made
during critical periods are more or less
permanent
• Critical periods vary in length for different
parts of the brain and different skills (e.g.,
refinement of synapses in multimodal
areas takes the longest)

21
 Critical Periods (cont.)
• Critical periods allow acquisition of complex skills
such as language & visual discrimination
– e.g., young children learn language more easily than adults
– very young infants can discriminate among speech sounds
of all human languages
– at 6 months, they get
better at detecting sounds
heard most often (i.e., their
native language) and start to
lose the ability to detect
sounds from other languages

22
http://www.ted.com/talks/patricia_kuhl_the_linguistic_genius_of_babies
Synaptic Connections are
Adjusted Throughout Life

• Neurodevelopmental processes and

processes during critical periods complete
the basic wiring of neuronal networks
• However, synaptic connections continue to
be adjusted throughout life on a smaller
scale, based mostly on synaptic efficiency
– Potentiation
– Depression

23
 Memory
• There are various forms of memory and most occupations involve a
combination of forms
• Memory functions are widely distributed among brain structures
• Two main types of long-term memory
– Declarative (explicit) memory: memory of facts, events, concepts, places
– Nondeclarative (implicit) memory (also known as procedural memory): how-
to memory

24
 3 Stages of Declarative (Explicit) Memory

• 1. Immediate memory (also called sensory memory or sensory

register)
– Lasts up to 3 seconds
– Snapshot of sensory input
– Processed by primary sensory and sensory association areas
of brain and is encoded for next stage
• 2. Working memory (short term memory which is effortfully
processed)
– Lasts 3-30 seconds
– Information we “keep in mind”, manipulate and rehearse

25
 3 Stages of Declarative (Explicit) Memory
(cont.)
• 3. Long term memory
– Lasts >30 seconds to remote
– Relatively permanent storage of information that has been processed in
working memory
• Recent memory: memories formed hours to weeks ago
• Remote memory: memories in more distant past
– Conversion of working memory to long term memory is called consolidation
– Cerebral cortex stores this information in diffuse neuronal networks,
interconnected by synapses

• Rehab note: It is believed that your ability to utilize your working memory is
dependent on attention
– Remediate attention
– Train compensation for memory

26
 27
https://youtu.be/seMwpP0yeu4
 Memory = hippocampus
• Primary structure
associated with
declarative memory,
specifically
consolidation, is the
hippocampus, a curved
area of cortex that lies in
the limbic lobe,
submerged in the
parahippocampus gyrus

28
 HM: Case Example

• Bilateral removal of his medial temporal lobes (which

included both hippocampi) because he had frequent,
severe epileptic seizures that originated here
• Epilepsy improved, but he had permanent memory loss
– ~1 year retrograde memory loss (couldn’t
remember events in the year before surgery)
• Retrograde amnesia: loss of memories from a
period prior to the brain injury
– Anterograde memory loss (couldn’t remember
events after surgery)
• Anterograde amnesia: deficit in forming new
memories
29
 HM (cont.)
• Implications of memory
functions
– For example, HM couldn’t
recall text he read just
minutes ago or people he
had met repeatedly since
his surgery
– He could remember
distant past events
– He was able to learn new
skills

30
 HM (cont.)

• So, the role of the hippocampus

seems to be to process memories
from short term to long term, but
memories aren’t stored in
hippocampus
• HM died in 2008 and scientists
studied his brain, slice by slice
• https://www.livescience.com/4
2898-patient-hm-postmortem-b
rain.html

31
 Diane Van •
•
Partial temporal lobectomy to reduce seizures
Ultra-marathon runner
Deren • Radio Lab where she talks about how her surgery positively
impacted her running performance. Here is a link to the
(modern day story:
https://www.wnycstudios.org/story/122291-in-running/
H.M.)
32
 Nondeclarative (Implicit) Memory
• Three general types:
– Skills and habits (basal ganglia, cerebellum, neocortex)
– Emotional associations (amygdala)
– Conditioned reflexes (cerebellum)
• Doesn’t require full conscious awareness
– Once a skill or habit is learned, little, if any, conscious attention is required to perform it
• Practice (or motor learning) is needed to store procedural (skills and habits)
memories
• Three stages involved in motor learning
– Cognitive: verbally guide motor task; requires much attention
– Associative: movement is refined and made more efficient
– Autonomous: movements are practically automatic; requires very little conscious attention
• In the case of HM, he could learn a new skill, but did not remember having
learned it
*Rehab note: Many patients with declarative memory
deficits have spared procedural memory
Errorless learning 33
 Common Diagnoses
Involved in Memory
Loss…1
• Cerebral contusions/TBI
– Areas commonly affected are anteromedial temporal lobes and
basal orbitofrontal cortex
– Usually anterograde memory more affected
– Retrograde amnesia may be present for a short time period prior
to the brain injury (and this time is variable), but it often “shrinks
forward” (that is, more remote memories come back first, with
recent memories of events just prior to injury coming back last
or not at all)
– Concussions typically involve reversible memory loss

• Stroke and anoxia

– Can affect regions involved in memory
– Hippocampus is especially vulnerable because it has a poor
blood supply

34
 • Korsakoff’s psychosis
– Seen often in people with alcoholism and
people with vitamin B12 deficiency
– Affects mammillary bodies
– Characterized by anterograde amnesia and lack
of awareness of deficits
• This lack of awareness of memory loss may
Common lead to confabulation: filling in memory
gaps by fabrication
Diagnoses
• Alzheimer’s disease
Involved in – Early stages tend to affect memory loss of
Memory Loss…2 recent events
– Preferentially affects bilateral hippocampal,
temporal, and basal forebrain structures

35
 Common Diagnoses
Involved in Memory
Loss…3
• Psychogenic amnesia
– Dissociation, repression, functional neurological
disorder (formerly called conversion disorder), and
malingering
– Linked to memory loss of an emotional event or loss of
autobiographical information

• Normal memory loss

– Infantile amnesia
– Benign senescent forgetfulness (normal aging)
– During or shortly after awakening from sleep
– Passage of time (forgetting)
36
 • PNS nerve fibers can re-grow after injury;
typical rate of axonal regeneration is 1
mm/day (or 1 inch/month)
– Crush injuries regenerate well
because the “pipes are laid” to guide
axons where to grow
– Complete nerve transection often
leads to the axon growing aberrantly,
without the guidance of where to
connect; therefore, complete
Neuronal •
recovery is rare
CNS neurons do not typically regenerate
Repair – Glial cells impede growth by laying
down scar tissue and producing
molecules that impede neuronal
growth
– Axons do not reestablish
connections and parent cell bodies
atrophy
– If damage is to the cell body or axons
near the cell body, the whole neuron
may die

37
 1. Neurogenesis: creating new
neurons
2. Re-wiring: creating new neuronal
pathways
What is happening in this 3. Unmasking: uncovering existing,
video? but rarely used neuronal pathways
https://youtu.be/IaB5Egej0TQ 4. Cortical re-organization:
Reassigning cortical “real estate”
5. Changes in synaptic efficiency:
basis of learning and memory

38
• http://www.nytimes.com/2015/08/31/science/oliver-sacks-dies-at-82-neurologist-
and-author-explored-the-brains-quirks.html?smid=fb-nytimes&smtyp=cur&_r=1
39
 Awesome Websites on Neuroplasticity
• https://positivepsychologyprogram.com/neuroplasticity/
• https://www.heysigmund.com/dear-kids-love-from-your-brain-what-all-kids-need-t
o-know-about-the-brain/

40
• http://youtu.be/2MKNsI5CWoU (Rasmussen’s syndrome and little girl with
hemispherectomy)
• http://www.cnn.com/2009/HEALTH/12/03/brain.observatory.h.m.amnesia/index.h
tml
(News story about studying HM’s brain)
• https://youtu.be/cKaWJ72x1rI (What the Internet is Doing to Our Brains)
• https://youtu.be/Xj6lAgHroHM (Neuroplasticity and cerebral palsy; Dr. Pape,
author of “ The Boy Who Could Run But Not Walk; Understanding Neuroplasticity
in the Child's Brain“)
• https://youtu.be/WKVbRDJ-nxs (Dr. Pape has a TED Talk, too!)

Videos and Websites

41
• http://www.bigthink.com/think-again-nil-a-big-think-podcast/naturenurtureneithe
r-feat-mark-epstein
(Nature/Nurture/Neither – epigenetics)
• http://www.smithsonianmag.com/science-nature/why-are-some-people-left-hand
ed-6556937/?no-ist
(What causes handedness?)
• http://www.npr.org/sections/health-shots/2015/07/06/419519145/people-with-br
ain-injuries-heal-faster-if-they-get-up-and-get-moving
(Movement and familiar routines after TBI)
• http://www.npr.org/sections/health-shots/2014/04/23/306228476/education-may
-help-insulate-the-brain-against-traumatic-injury
(Cognitive reserve)

Videos and Websites (cont.)

42
 • Blumenfeld, H. (2002). Neuroanatomy
through clinical cases. SInauer Associates.
• Doidge, N. (2007). The brain that changes
itself. Penguin Books.
• Draw It to Know It Neuroanatomy. (n.d.).
Retrieved from
http://drawittoknowit.com/
• Gutman, S. A. (2008). Quick reference
neuroscience for rehabilitation
professionals (2nd ed.). SLACK.
• Lundy-Ekman, L. (2007). Neuroscience:
References Fundamentals for rehabililation (3rd ed.).
Elsevier.
• Siegel, A., & Sapru, H. N. (2006). Essential
neuroscience (Rev. 1st ed.). Lippincott
Williams & Wilkins.
• Vanderah, T. W., & Gould, D.J. (2021).
Nolte‘s the human brain: An introduction
to its functional anatomy (8th ed.)
Elsevier.

43
Chapter 1: A Woman
Perpetually Falling…

• “Rehab” of Bach-y-Rita’s father…OT?

• Be LOUD and PROUD and consider
yourself a neuroplastician
• Now, sit back, relax and enjoy the
show…