Lecture 9: Psycho-patho-physiology

Question 1

Why number of publications for subthalamic nucleus increased in the beginning of 21 centrury?

Answer 1

because food and drug administration approved deep brain stimulation on subthalamic nucleus for essential tremor, Parkinson’s disease and dystonia

Question 2

What is human model of subthalamic nucleus?

Answer 2

Divided into 3 parts:
-> dorsolateral motor part = target of DBS
-> central associative part
-> limbic part

Question 3

What rodent research on subthalamic nucleus showed?

Answer 3

That motor area is connected to primary, premotor and somatosensory cortex. Associative area connected to dorsolateral PFC and lateral orbitofrontal cortex. Limbic part has connections to limbic and paralimbic cortex, hippocampus and amygdala.

Question 4

What biased studies on subthalamic nucleus in humans?

Answer 4

looking for three specific functional zones only on the basis of the model

Question 5

What monkey research on subthalamic nucleus showed?

Answer 5

That subthalamic nucleus parts were differentially connected to cortical areas.

Question 6

How to study subthalamic nucleus?

Answer 6

tracing, cytoarchitectural approaches, structural and functional imaging, clinical observations

Question 7

tracing

Answer 7

strengths: high level of anatomical detail, informative about connetive properties
limitations: usually low number of observations, highly dependent on injection site and volume

Question 8

cytoarchitectural appraoches

Answer 8

strengths: high level of anatomical detail, information on chemical properties of cell populations
limitations: no information about connectivity, no functional data

Question 9

structural imaging

Answer 9

strengths: in vivo information
limitations: low level of anatomical details

Question 10

functional imaging

Answer 10

strengths: in vivo on distinct functions
limitations: low level of anatomical details

Question 11

clinical observations

Answer 11

strengths: information on (dys)function
limitations: low level of anatomical detail, usually low number of observations, not always normal brain function

Question 12

What is problematic in STN studies on monkeys?

Answer 12

Most studies are based on drawings - reports of present proteins, but no information about subdivisions.

Question 13

What are evidence for structural organization of STN?

Answer 13

tracing studies: topographical organization with strict anatomical borders
cytoarchitecture: evidence pointing to complex organization of neuronal populations without clear anatomical borders between subdivisions
in vivo MRI: evidence for ion gradients
in vivo fMRI: evidence for zonation
DBS: profound effects on STN

Question 14

what is interim conclusion regarding STN?

Answer 14

it is not homogenous structure

Question 15

What is immunocytochemical approach?

Answer 15

exploits the specific binding between an antibody and antigen to detect and localize specific antigens in cells and tissue

Question 16

How combining approaches (merging MRI and microscopy data) helped to further study STN? What were the conclusions?

Answer 16

1) dead brains were put in MRI scanner
2) they were dissected into smaller parts while being continously scanned
3) stainings for proteins in tissues were performed
4) then tissues were put in paraffin and re-aligned to reconstruct STN
5) then statistical modeling was used to study distribution of proteins within structure
Results: no 3 subdivisions
Conclusions: no clear support for tripartite model - patterns are more complex.

Question 17

How can we study tissues?

Answer 17

usually post-mortem -> however, in rodent research brains are healthy; whereas in human research (usually) brains are unhealthy
in vivo - studing neuropsychiatric diseases

Question 18

What needs to be considered while defining inclusion and exclusion criteria in vivo?

Answer 18

-> literature
-> ethics
-> safety
-> number of participants (vs costs)
-> feasibility
-> scientific integrity
-> confounders
-> realistic approaches

Question 19

What are techniques used to study human brains?

Answer 19

behavioral studies
fMRI
EEG, MEG
TMS
electrophysiology - during surgery

Question 20

behavioral studies

Answer 20

testing behavioral paradigms in different groups of people (young vs old; healthy vs unhealthy); proxy of brain ffunction, but no deeper insight into neural substrates of behavior

Question 21

what kind of things you wouldn’t want to study in human brain?

Answer 21

permanent lesions
differences between homosexual and heterosexuals
genes related to aggression…

Question 22

ante mortem

Answer 22

just before death

Question 23

what are exclusion and inclusion criteria for ante mortem studies?

Answer 23

age, gender, agonal state, medication, circadian and seasonal variation, lateralization, family history and genetic analysis

Question 24

what are exclusion and inclusion criteria for post mortem studies?

Answer 24

post mortem delay, brain weight, pH of the brain/CSF, cause and date of death, clock time of death, freezing/fixation, storage time

Question 25

How is cortisol related to depression?

Answer 25

Elevated cortisol levels and increased inflammation have frequently been reported in patients with depression. (mood, suicide effects)

Question 26

How is vasopressin related to depression?

Answer 26

Postmortem studies as well as clinical investigations have described elevated levels of vasopressin in the brain and plasma of depressed patients. (mood, suicide, psychomotor effects)

Question 27

How is oxytocin related to depression?

Answer 27

Oxytocin modulates stress reactions (involved in HPA axis). Morevoer, oxytocin is appetite suppressant (possible role in eating disorders).

Question 28

How is thyrotropin-releasing hormone (TRH) related to depression?

Answer 28

Both its increase and decrease can affect mood.

Question 29

How is suprachiasmatic nucleus (SCN) related to depression?

Answer 29

It controls circadian rhythms. Disruption of circadian rhythms may relate to mood.

Question 30

What is final common pathway in depression?

Answer 30

hyperactive HPA
example: children bron during famine often had problems with depression
causes: glucocorticoid receptor resistence, child abuse, neglect, stroke, stressors in adulthood

Question 31

How can we study effects of cortical steroids on human brain?

Answer 31

post-mortem studies
experimental sample: people who used cortical steroids
contol: no cortical steroids
match subjects as well as you can

Question 32

How many subcortical structures are mapped vs are actually there in the middle of the brain?

Answer 32

actually there: 455
mapped: 7% with MRI
systematic oversight of 93% of subcortical structures

Question 33

How does the probabilistic atlas of the basal ganglia look?

Answer 33

5 structures, Based on 105 participants * >2000 manual delineation.

Question 34

How to branch in vivo and post-mortem studies?

Answer 34

MRI can be used both in vivo and post mortem
brains can be put into the scanners, then sliced and stained
it enables 3D reconstructions

Question 35

What are practical problems associated with post-mortem?

Answer 35

air bubbles
interindividual variation

Question 36

What can we stain for in post-mortem?

Answer 36

myelin - axons (myeloarchitecture) - brown
nissl (cytoarchitecture) - enables differentiation between cells (for example neurons vs glia)
hematoxylin and eosin (pathology)
calcium binding proteins (anatomical detail) - yellow

Question 37

Why saying that ‘‘brain area supplied with most oxygen at the moment is most active’’ is not objective?

Answer 37

because it depends on how much blood is available for this structure, brain is not equally vascularized