Neural network changes in schizophrenia

Neural networks in human brain change throughout life, most likely to allow for
adaptation to the environment. A neural network represents several distal gray
matter areas (neurons) and their connecting white matter (axons), together
forming a structural and functional entity. Schizophrenia, a severe psychiatric
disease characterized by hallucinations and delusions, involves abnormalities
in neural network structure. Indeed, while our Magnetic Resonance Imaging (MRI)
studies show continued growth of healthy human brain tissue in adulthood, in
schizophrenia and their family-members we find progressive decreases in
connected brain areas. However, the underlying (patho-)physiology is unknown.
This requires study of neural network functioning and detailed assessment of
the areas showing progressive brain volume loss. At the ultra high field
strength of the 7 Tesla MRI scanners this is now possible. Gray matter
activation can be measured using functional MRI. We showed functionally
connected networks of brain regions with highly synchronized intrinsic neuronal
activation during the resting state (rs-fMRI). White matter activation could
not be measured. However, we developed a method which measures white matter
activation along fiber tracts (functional DTI), which allows us to investigate
for the first time whether or not neural network structural changes (in
schizophrenia and their family-members) are directly associated with (aberrant)
neural network functioning. Combined with structural MRI for identification of
cortical layers, MR spectroscopy for chemical properties, and magnetic transfer
imaging for myelin properties, at 7 Tesla we can now study these networks.

Aim of this proposal is to unravel the changes in functional neural networks in
healthy human brain and in schizophrenia at 7T. We hypothesize a difference in
brain changes between healthy individuals and patients with schizophrenia and
abnormal neural networks in schizophrenia.

The rs-fMRI, MRS, and fDTI methods are refined at 7T and its dynamics studied
in repeated brain scans of healthy subjects. Next, these MRI methods are
applied in studies comparing patients with schizophrenia and healthy subjects,
including monozygotic and dizygotic twin-pairs for assessment of genetic and
environmental influences.

The experiment takes 3 hours (for healthy volunteers) or 4 hours (for patients
and twin pairs) in total. Volunteers will be subjected to a number of
psychological and cognitive tests and interviews. The MRI-scan takes up to 50
minutes. 4 tubes of blood will be drawn, each of 10 ml, for DNA and RNA
analysis. Subjects can indicate on the informed consent whether or not they
agree with blood withdrawal.
To date, there are no known harmfull effects of MRI.