Imaging and cardiovascular genetics

2019-2020
Dit vak wordt in het Engels aangeboden. Omschrijvingen kunnen daardoor mogelijk alleen in het Engels worden weergegeven.

Doel vak

Students learn how brain imaging and cardiovascular imaging results can
be combined with genetics to detect genetic variations that significant
influence nervous system functions related to behavioural traits,
including cognitive and affective regulation, and psychiatric endpoints.

Inhoud vak

Human behaviour shows substantial individual variation which can be
explained to a large extent by differences in the genetic makeup of
individuals. It is therefore of crucial importance to gain knowledge of
the genetic underpinnings of normal and, in particular, abnormal
behaviour. For example, knowledge about the genetic variants that
underlie psychiatric conditions such as ADHD, depression and
schizophrenia provides keys to obtain more in-depth understanding of the
underlying pathophysiology. In addition identification of relevant genes
affords the ability to predict at risk people and can provide novel
insights to improve care and pave the way to the application of
personalised interventions.
To date the search for genetic variants that influence behaviour and
elucidation of the biological pathways through which they do so remains
a tremendous scientific challenge. This of course reflects the
complexity of behavioural traits as well as their highly polygenetic
background. An added problem is that detailed quantitative descriptions
of abnormal behaviours and psychiatric diseases are generally lacking.
Current health diagnostic systems generally entail only qualitative
appraisals of behaviour symptoms or psychiatric disorders, i.e., "one
has a symptom or disorder or not". Instead of behaviour itself,
quantitative measures of specific nervous system function that underlie
final output behaviour likely are more closely linked to genetic
variation and therefore help elucidate the pathways by which these
genetic variants influence behaviour. Measuring these biomarkers, or
"endophenotypes", can furthermore help us understand how these genes
exert their effect by highlighting the associated functional
neurobiological changes.

In this course we will focus on biomarkers from the central nervous
system (brain), obtained by Magnetic Resonance Imaging (MRI), and
biomarkers from the autonomic nervous system, obtained by the
electrocardiogram (ECG) and the impedance cardiogram (ICG). Students are
introduced to the basic methodology required to obtain the raw data for
both modalities, as well as the subsequent analysis steps needed to
arrive at final quantitative measures. For MRI this includes learning
how to obtain measures of global and local brain structure from T1
weighted images, and parameters indicating brain connectivity from
Diffusion Tensor Images (DTI), and measures of brain function and
indicators of functional networks from Echo Planar Images (EPI). For
ECG, students will learn the practical skills to record
psychophysiological signals and analyzing and scoring these signals to
obtain measures of heart rate variability and cardiac impedance
parameters such as the preejection period (PEP) and respiratory sinus
arrhythmia (RSA) related to cardiac sympathetic and parasympathetic
drive, respectively.
Based on published work from the scientific literature it will then be
demonstrated how this brain and cardiovascular imaging information can
be combined with basic molecular information on the individual’s genomes
in the context of Genome Wide Association or candidate gene designs, to
pinpoint relevant genetic variation and understand the functional
consequences of specific genes on brain and cardiac system level.
Important findings and their implications in the field of brain imaging
and cardiovascular genetics will be highlighted and discussed.

Onderwijsvorm

Tuition consists of lectures, homework assignments, computer practicals
and experimentation practicals.

Toetsvorm

A final grade based on the average grade of 2 separate assessments, a
short oral presentation on a recent brain/cardiovascular imaging
genetics paper (30%) and a final written exam (70%) consisting of
30 MC (knowledge, practical skills) and 2 Open Ended questions
(understanding).

Literatuur

- Lecture slides and practical instructions provided by the course
section accompanying the FMRIB software library that will be used for
the MRI practicals in: https://fsl.fmrib.ox.ac.uk/fslcourse/.
- Lecture slides and practical instructions provided by the course
section accompanying the VU-AMS hardware and software that will be used
for the cardiovascular practicals, including the tutorials at:
http://www.vu-ams.nl/support/tutorials/.
- Thompson PM et al (2010). Imaging genomics. Curr Opin Neurology 23
(4):368-73.
- de Geus EJ et al (2015). Genetics of Autonomic Nervous System
Activity. In: The Oxford Handbook of
Molecular Psychology (Ed Turhan Canli) Oxford University Press
- den Hoed et al (2013) Identification of heart rate-associated loci and
their effects on cardiac conduction and rhythm disorders. Nat Genetics
45(6):621-31
- Thompson PM, et al (2014). The ENIGMA Consortium: large-scale
collaborative analyses of neuroimaging and genetic data. Brain Imaging
Behavior 8(2):153-82.
- Medland SE, et al (2014). Whole-genome analyses of whole-brain data:
working within an expanded search space. Nat Neuroscience 17(6):791-800.
- Hashimoto R, et al (2015). Imaging genetics and psychiatric disorders.
Curr Mol Medicine 15(2):168-75.
During the course, additional reading material based on the latest
developments in the field will be posted on Canvas or distributed in
class.

Algemene informatie

Vakcode P_MIMCVG
Studiepunten 6 EC
Periode P4
Vakniveau 400
Onderwijstaal Engels
Faculteit Fac. der Gedrags- en Bewegingswetensch.
Vakcoördinator dr. D. van t Ent
Examinator dr. D. van t Ent
Docenten prof. dr. J.C.N. de Geus
dr. D. van t Ent

Praktische informatie

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