Lecture 9: Psycho-patho-physiology Flashcards
Why number of publications for subthalamic nucleus increased in the beginning of 21 centrury?
because food and drug administration approved deep brain stimulation on subthalamic nucleus for essential tremor, Parkinson’s disease and dystonia
What is human model of subthalamic nucleus?
Divided into 3 parts:
-> dorsolateral motor part = target of DBS
-> central associative part
-> limbic part
What rodent research on subthalamic nucleus showed?
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.
What biased studies on subthalamic nucleus in humans?
looking for three specific functional zones only on the basis of the model
What monkey research on subthalamic nucleus showed?
That subthalamic nucleus parts were differentially connected to cortical areas.
How to study subthalamic nucleus?
tracing, cytoarchitectural approaches, structural and functional imaging, clinical observations
tracing
strengths: high level of anatomical detail, informative about connetive properties
limitations: usually low number of observations, highly dependent on injection site and volume
cytoarchitectural appraoches
strengths: high level of anatomical detail, information on chemical properties of cell populations
limitations: no information about connectivity, no functional data
structural imaging
strengths: in vivo information
limitations: low level of anatomical details
functional imaging
strengths: in vivo on distinct functions
limitations: low level of anatomical details
clinical observations
strengths: information on (dys)function
limitations: low level of anatomical detail, usually low number of observations, not always normal brain function
What is problematic in STN studies on monkeys?
Most studies are based on drawings - reports of present proteins, but no information about subdivisions.
What are evidence for structural organization of STN?
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
what is interim conclusion regarding STN?
it is not homogenous structure
What is immunocytochemical approach?
exploits the specific binding between an antibody and antigen to detect and localize specific antigens in cells and tissue
How combining approaches (merging MRI and microscopy data) helped to further study STN? What were the conclusions?
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.
How can we study tissues?
usually post-mortem -> however, in rodent research brains are healthy; whereas in human research (usually) brains are unhealthy
in vivo - studing neuropsychiatric diseases
What needs to be considered while defining inclusion and exclusion criteria in vivo?
-> literature
-> ethics
-> safety
-> number of participants (vs costs)
-> feasibility
-> scientific integrity
-> confounders
-> realistic approaches
What are techniques used to study human brains?
behavioral studies
fMRI
EEG, MEG
TMS
electrophysiology - during surgery
behavioral studies
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
what kind of things you wouldn’t want to study in human brain?
permanent lesions
differences between homosexual and heterosexuals
genes related to aggression…
ante mortem
just before death
what are exclusion and inclusion criteria for ante mortem studies?
age, gender, agonal state, medication, circadian and seasonal variation, lateralization, family history and genetic analysis
what are exclusion and inclusion criteria for post mortem studies?
post mortem delay, brain weight, pH of the brain/CSF, cause and date of death, clock time of death, freezing/fixation, storage time
How is cortisol related to depression?
Elevated cortisol levels and increased inflammation have frequently been reported in patients with depression. (mood, suicide effects)
How is vasopressin related to depression?
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)
How is oxytocin related to depression?
Oxytocin modulates stress reactions (involved in HPA axis). Morevoer, oxytocin is appetite suppressant (possible role in eating disorders).
How is thyrotropin-releasing hormone (TRH) related to depression?
Both its increase and decrease can affect mood.
How is suprachiasmatic nucleus (SCN) related to depression?
It controls circadian rhythms. Disruption of circadian rhythms may relate to mood.
What is final common pathway in depression?
hyperactive HPA
example: children bron during famine often had problems with depression
causes: glucocorticoid receptor resistence, child abuse, neglect, stroke, stressors in adulthood
How can we study effects of cortical steroids on human brain?
post-mortem studies
experimental sample: people who used cortical steroids
contol: no cortical steroids
match subjects as well as you can
How many subcortical structures are mapped vs are actually there in the middle of the brain?
actually there: 455
mapped: 7% with MRI
systematic oversight of 93% of subcortical structures
How does the probabilistic atlas of the basal ganglia look?
5 structures, Based on 105 participants * >2000 manual delineation.
How to branch in vivo and post-mortem studies?
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
What are practical problems associated with post-mortem?
air bubbles
interindividual variation
What can we stain for in post-mortem?
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
Why saying that ‘‘brain area supplied with most oxygen at the moment is most active’’ is not objective?
because it depends on how much blood is available for this structure, brain is not equally vascularized
