week 4 - neuroimaging of memory

Question 1

What are strengths of using fMRI to study memory?

Answer 1

1. Capture dynamic, spatiotemporal changes (encode, store, retrieve)
   ② Applicable to study both groups and individuals in health and disease
   ③ Provides a whole-brain measure of brain structure and function
   ④ Test hypotheses about specific regions (hippocampus) and their networks
   ⑤ Neuroimaging can create hypotheses where cellular and molecular probes can be
   applied or for invasive animal studies

Question 2

What are weaknesses of using fMRI to study memory?

Answer 2

① Proxy measures of neuronal activity
② Not a measure of “structure” or “connections” per se - instead looking at correlatins
③ Results subject to methodological variation (Botvinik-Nezer et al. Nature 2020)
④ High costs associated with data collection, storage, and processing
⑤ Multiple reasons for a structural MRI signal change

Question 3

What is evidence (fmri) that the hippocampus is related to spatial memory

Answer 3

Maguire et al, 1998.
Got mice to navigate through a virtual maze. Looked at where the brain was using glucose the most on average during this task.
This showed activation in the hippocampus

Question 4

What does neuroimaging of the DMN tell us about memory?
robin et al 2015

Answer 4

• Spontaneous activity within the hippocampus is synchronized (functionally connected) with a
  network of brain regions known as the default mode network (DMN).
• The functional association of DMN with the hippocampus may vary based on cognitive
  demands.

Question 4

What is evidence (task based fmri) that the hippocampus is related to spatial memory
ryan et al 2009

Answer 4

• fMRI shows preferential involvement of hippocampal activity during episodic and spatial
  memory tasks
• Activity defined as increased blood flow (perfusion) or BOLD signal contrast increase
• Yet this tells us nothing about relevant functional connections and wider network changes

Question 5

How can fMRI study structural plasticity in memory (maguire et al 2000)

Include criticism and their response to this

Answer 5

Classic taxi driver study
Hippocampus enlarges after the knowledge

criticism:
Does this reflect training or innate expertise?
* Performance in a virtual navigation task amongst an unselected group of people was not predictable based on hippocampal volume
* The “taxi-driver effect” may be a specific consequence of extensive training
* Not explainable as an aspect of population variance (underpowered?).

Question 6

Outline why neuroimaging studies may not replicate

Answer 6

1. Sample size - using a small sample can be non replicable (Masouleh et al, 2019)
2. Variability in analysis - They might not take into account covarience
3. Variability in statistical correction - leniently or stringently correcting for multiple comparisons
4. Varaibility in analysis of hippocampus anatomy

Question 7

Outline clark et al (2020) on hippocampal volume and memory

Answer 7

tested the relationship between hippocampal grey matter
volume and scene imagination, autobiographical memory,
future thinking and spatial navigation task performance

n = 217 (large)

Little evidence that hippocampal grey
matter volume is related to task
performance
* Irrespective of methodology or
statistical approach
* Hippocampal volume may not
significantly influence performance
on tasks requiring the hippocampus
in healthy people

Question 8

Outline strengths of small animal neuroimaging when studying memory

Answer 8

Address the lack of continuity
between levels of analysis in
animal models and clinical
research
② Test hypothesis regarding
influence of genetic, of
environmental risk factors or
putative confounds
③ Link neuroimaging signal
changes to their molecular and
cellular correlates

Question 9

Describe Lerch et al’s 2011study using small animal neuroimaging to study memory

READ THIS PAPER

Answer 9

Lerch et al. Neuroimage, 2011

Spatial maze variant led to specific growth of the mouse hippocampus
* Cued version (non-spatial) led to striatal growth
* Replicates findings in humans based on different navigation strategies
* Compare in mouse models for familial Alzheimer’s disease?

When they looked at other brain regions, they did see that there was activation in other regions too

IS THIS TRAINING OR EXCERCISE?
Learning content
differed across
protocols
* Swimming content
(proxy exercise?) also
differed
* What if we compare
exercise matched
groups?
* Key volume differences
in striatum and
hippocampus remained

Possible cellular hypotheses to account for
the volume changes :
(1) alterations in neuron numbers/sizes
(2) alterations in astrocyte numbers/sizes,
(3) increased neurogenesis
(4) remodeling of neuronal processes.
Carried out immunostaining and quantification
of:
* NeuN (neurons)
* GFAP (astrocytes)
* DCX (new-born neurons)
* GAP-43 (axon marker

Axon/growth marker correlates with Δ volume
Lerch et al. Neuroimage, 2011
* Hippocampal GAP-43 staining
correlated positively with behaviour
* All structure volumes correlated with
GAP-43 staining
* GAP-43 implicated in memory storage
* Binds to cytoskeletal proteins actin and
fodrin
* Causes presynaptic morphology
changes