Lecture 19: Development, Plasticity, and Aging

Question 1

Developmental Cognitive Neuroscience

Answer 1

The study of how cognitive functions develop over time, and
what brain changes underlie development

Question 2

Synaptogenesis

Answer 2

Formation of synapses
* Synapses form long before birth (prior to week 27)
* Doesn’t reach peak density until after birth (first 15 months)
* Goes “from inside out” deep (e.g., midbrain) to superficial layers
(e.g., cortex)
* At the same time, neurons are growing longer dendrites, extending
their axons and undergoing myelination

Question 3

Synaptic elimination (“pruning”)

Answer 3

Elimination of synapses
following synaptogenesis
* Lasts for more than a decade
* Considered to reflect “fine tuning” of neural connectivity, removing
redundant or non-functional connections

Question 4

Synaptogenesis & Synaptic Elimination

Answer 4

Synaptic density peaks early, starts to decline almost immediately after
Pattern is different for grey and white matter, and differs according to region

Question 5

Critical period

Answer 5

Time window in which appropriate
environmental input is essential for learning to take place,
and this learning is hard to reverse in the face of later
experience

Question 6

Filial imprinting (Lorenz)

Answer 6

Ducklings identify their parent by
forming an attachment to a moving object seen in a
particular time window (15 hours to 3 days) – hard to form
attachments to new “parents” after this time

However, subsequent research suggests that timing of window is
flexible (e.g., if no moving object is seen) and can be changed
gradually
* Suggests a sensitive period (more flexible than critical period)

Critical period for language acquisition is thought to end during
adolescence, after puberty (Lenneburg, 1967)
* However, different aspects of language may have different sensitive
periods (e.g., discriminating between phonemes is set at infancy,
whereas accents are more fluid during infancy but become harder to
change in adulthood)

Question 7

The Adolescent Brain

Answer 7

• Adolescents tend to make risky decisions and engage in
  risky behaviors
• Traditional cognitive neuroscience explanation: Frontal lobes develop slowly (not fully developed in adolescents), and as a
  consequence, adolescents show immature executive
  function and poor impulse control

However, younger kids have underdeveloped frontal lobes, yet
you don’t see as much risky behavior there…

• Alternative explanation by Casey et al. (2008): In addition to
  slow development of frontal lobes, the limbic regions
  (responsible for emotional arousal and sensitivity to reward)
  develop more quickly
  Heightened emotional
  reactivity
  (from faster-developed limbic
  regions)
  +
  Underdeveloped
  executive/impulse control
  (from slowly developing
  frontal regions)
  =
  Risky adolescent behavior!

Question 8

The Adolescent Brain
* Tested using

Answer 8

“Go/No-go task”:
* Participants see a series of faces, and are asked to make a “go”
response (i.e., press a button) to fearful faces or a “no-go” response
(i.e., don’t press button) to neutral faces

Measured amygdala activity
for fearful and neutral
expressions

Adolescents have heightened amygdala
responses, regardless of whether they’re
responding to a fearful face or not

Question 9

The Adolescent Brain: Cognitive Control in
Emotional Context

Answer 9

Question 10

Aging

Answer 10

Aging is associated with declines in speed of processing, working
memory processes, and long term memory … but it’s also
associated with increases in acquired world knowledge

Aging is associated with declines in speed of processing, working
memory processes, and long term memory … but it’s also
associated with increases in acquired world knowledge
* Brain volume decreases throughout life, but decline is not uniform
in all regions

Hippocampus,
caudate nucleus,
cerebellum, and
lateral PFC show
reductions with age

Question 11

Aging and Brain Activity During Encoding and Retrieval

Answer 11

2 commonly observed patterns:
* Under-recruitment of frontal resources
* Non-selective recruitment of frontal resources

Question 12

Under-recruitment of Frontal Resources

Answer 12

• Self-initiated encoding task: Remember a bunch of words
  from a list
• Usually, self-initiated encoding recruits the left inferior frontal
  cortex (LIFC)

Older adults significantly under-recruit LIFC (i.e., less
activity in this region) during the task, compared with young
adults

• However, if you give them a support strategy (e.g., an
  effective semantic coding task that requires deeper
  encoding), then they show same levels of LIFC activity as
  young adults

Question 13

Non-selective Recruitment of Frontal
Resources

Answer 13

• Younger adults selectively recruit the left frontal area, not the right
• However, older adults have nonselective recruitment of frontal
  resources (i.e., more equally recruit both left and right frontal regions)

With strategy support (i.e., deeper semantic encoding), both
younger and older adults show improved memory
performance, but older adults still show non-selective
recruitment of bilateral frontal areas

• Non-selective recruitment appears in many other episodic
  memory retrieval tasks (e.g., word-pair cued recall, word-stem
  cued recall, word recognition, face recognition)

Question 14

Is non-selective recruitment in older adults adaptive and
compensatory, or a sign of breakdown?

Answer 14

Logic:
* If it’s adaptive, then older adults who perform well on memory
tasks should show greater non-selective, bilateral recruitment of
frontal regions
* If it’s a sign of breakdown, then older adults who perform well on
memory tasks should show less non-selective recruitment of
frontal regions (more left-lateralized)

Older adults who do well on tasks show more bilateral activation, whereas
older adults who do poorly show more lateralization
* Thus, non-selective recruitment seems to be a compensatory adaptation

Question 15

Brain Plasticity
Old view:

Answer 15

The adult human brain is static and fixed, growth of neurons
stops once we reach adulthood

The adult human brain is plastic and changes in response to
experience; it is also capable of neurogenesis
(formation of new neurons)

• Neurogenesis is now well established in several brain
  regions, especially the hippocampus
• Maybe helps us keep one memory separate from another?
• Amount of neurogenesis correlates positively with learning and
  hippocampal-dependent memory

Question 16

Exercise and the Hippocampus

Answer 16

The amount of exercise in rats (i.e., time spent running in an
exercise wheel) is positively correlated with increases in
brain derived neurotrophic factor (BDNF) in the hippocampus
(Neeper et al., 1995)
* BDNF promotes neurogenesis, expansion of dendrites, and also
contributes to memory formation
* i.e., the amount of exercise is positively related to the number of new
neurons in hippocampus
* Given that hippocampal volume declines with aging, can this
be applied to human aging?

Question 17

Exercise and the Hippocampus
* Erikson et al., 2009:

Answer 17

Studied 165 older adults, and measured aerobic
fitness by measuring maximum oxygen uptake (VO2 peak) during
exercise on treadmill

Question 18

Exercise and the Hippocampus
* Erikson et al., 2011

Answer 18

120 older adults were randomized into 2 groups:
(1) Aerobic exercise group: 40 min walk, 3 times a week, for 1 year
(2)Stretching control group: Stretch for identical amount of time

• 6 months later, came back to lab and performed a spatial memory task
  Remember the locations of 1, 2, or 3 dots– after a delay, a dot appears and participants
  have to respond whether the dot matches the location of a previously-shown dot
• Exercise group shows a selective increase in anterior hippocampal volume
  with aerobic exercise (no change in stretch control group)
• Anterior hippocampus is associated with associative and spatial memory tasks

Question 19

Generality of Exercise Effects

Answer 19

• fMRI evidence that exercise is related to increased function of
  several prefrontal and parietal regions involved in
  executive/attentional control during a task that requires target
  selection and inhibitory control (Colcombe et al., 2004)
• Structural imaging evidence that exercise increases grey and
  white matter volume in prefrontal cortex (Colcombe et al., 2006)
• Evidence that higher physical activity levels are associated with
  reduced risk of Alzheimer’s disease (Andel et al., 2006)
• In Alzheimer’s, hippocampal volume is drastically reduced– exercise
  might help buffer this

Question 20

Exercise seems to lead to increased in volume of

Answer 20

anterior hippocampus

Question 21

Aging associated with decreased volume in?

Answer 21

hippocampus, caudate nucleus, cerebellum, and lateral prefrontal
cortex… but V1 and entorhinal cortex don’t show reductions with age
* Aging associated with (1) under-recruitment and (2) non-selective (bilateral) recruitment of frontal lobes
(non-selective recruitment is thought to be compensatory)

Question 22

Adolescents have more developed limbic regions and slower developing frontal lobe (which may contribute tor isky behavior):
* Heightened response

Answer 22

amygdala and nucleus accumbens (associated with emotion and reward,
respectively), coupled with immature frontal lobe response

Aging associated with decreased volume in hippocampus, caudate nucleus, cerebellum, and lateral prefrontal
cortex… but V1 and entorhinal cortex don’t show reductions with age

Question 23

• What is a critical period? Describe evidence for the existence of a critical/sensitive period

Question 24

• Describe Casey et al.’s (2008) view on why adolescents tend to engage in risky behavior

Question 25

• Describe changes in speed of processing and various memory processes with aging

Question 26

Describe 2 common changes in frontal activity in older adults:
* What is under-recruitment? Which brain region is under-recruited?
* Which brain region(s) are non-selectively recruited in older adults?
* Is non-selective recruitment in older adults adaptive or compensatory?

Question 27

What is the “new” view on brain plasticity?
* Which brain region in particular is known to show neurogenesis?

Question 28

Development of Gray & White
Matter

Answer 28

Cortical gray matter development tends to show inverted U, peaking at different
ages in different regions; white matter shows increases throughout development

Question 29

Development of Cerebral
Volume

Answer 29

Total cerebral volume (i.e. gray & white matter of
both hemispheres, assessed by structural MRI) peaks
at 14.5 yrs in males and 11.5 yrs in females
-Male brain approx. 9% larger than female (even after controlling for height/weight), but
should NOT be interpreted as providing functional advantage or disadvantage – healthy
normal children at same age can differ by as much as 50% in brain volume

Question 30

Resting State Functional
Connectivity

Answer 30

FMRI can also be used to study connections between brain
regions during rest – no task involved.
The brain is always active, even in the absence of
explicit input or output.
BOLD signal exhibits spontaneous fluctuations in activity
levels during rest – intrinsic brain activity.
These spontaneous fluctuations can be measured within
individual brain regions, and the extent to which activity
is correlated across brain regions can be measured

Resting state functional connectivity evidence indicates that
long-range connections that are present in adults are reduced or
absent in children, whereas short-range connections are present in both
and may be stronger in children.

Question 31

The Imbalance Model

Answer 31

According to our model, in
emotionally salient situations,
the more mature limbic system
will win over the prefrontal
control system. In other words,
when a poor decision is made
in an emotional context, the
adolescent may know better,
but the salience of the
emotional context biases his or
her behavior in opposite
direction of the optimal action

Question 32

testing the imbalance model

Answer 32

Go no-go task (during fMRI): Participants respond to
specific faces (e.g., fearful) and not to others (e.g., neutral)

Question 33

Nucleus accumbens and reward

Answer 33

During anticipation of reward in a learning paradigm (bigger or smaller
monetary rewards associated with specific images of pirates),
adolescents show increased nucleus accumbens response together
with immature frontal response, compared with children and
adults (Galvan et al., 2006, J. Neuroscience)

fMRI signal change in the nucleus accumbens of adolescents was
positively correlated with responses to a questionnaire assessing six
types of risk taking behaviors: risky sexual behavior, heavy drinking,
illicit drug use, aggressive and illegal behaviors, irresponsible
academic/work behaviors, and high risk sports (Galvan et al., 2007)

Question 34

Prediction error

Answer 34

refers to the discrepancy between the expectation or prediction of reward and receiving the actual reward.
Dopamine neurons in the brain, which play a major role in
reward, increase activity to “positive prediction error”: reward
received when reward is not predicted.
Dopamine neurons show little response when reward
expected and received, and reduced response when reward expected
and not received (“negative prediction error”).

Prediction error signals are often observed in neurons in the striatum, part of the
basal ganglia and the brain’s dopamine system

During reward learning, adolescents showed increased positive prediction
error signal in striatum during positive prediction errors (i.e., received reward
for correctly classifying a stimulus not expected to be associated with reward).

Question 34

Ventrolateral prefrontal cortex showed increased activity

Answer 34

with age
and high vs. low stakes performance, but these changes did not
account for high vs. low stakes performance differences.
However, vlPFC also showed increased connectivity with a reward
region (ventral striatum), which mediated the relationship between
age and high vs. low stakes performance

Question 35

Brain Plasticity

Answer 35

the brain’s ability to change as a result of experience
(Ward, p. 120)
The developing brain exhibits considerable plasticity, sometimes
re-organizing substantially after brain damage early in life to
support adaptive functioning, e.g., after early left hemisphere
damage, the right hemisphere can support normal language function.The idea that brain plasticity is greatest early in life is
Known as the Kennard Principle, named after the neurologist
Margaret Kennard (Ward, p. 124).

Relevant to cases of frontal lobotomy in children – the case of
Howard.