Neurophysiological Modelling of Tonic Cortical Activity in Post-traumatic stress disorder (PTSD), Schizophrenia, First episode schizophrenia (FESz) and Attention Deficit Hyperactivity Disorder (ADHD)

Proposal details

Title: Neurophysiological Modelling of Tonic Cortical Activity in Post-traumatic stress disorder (PTSD), Schizophrenia, First episode schizophrenia (FESz) and Attention Deficit Hyperactivity Disorder (ADHD)
Research Area(s): Brain Modeling
Background: In this study a recently developed quantitative biophysical model of cortical activity is used that permits data comparison with experiment using a quantitative and standardized means. The model incorporates multiple aspects of neurophysiology including axonal transmission delays, synapto-dendritic rates, range-dependent connectivities, excitatory and inhibitory neural populations, and intrathalamic, intracortical, corticocortical and corticothalamic pathways. This study tests the ability of the model to determine unique physiological properties in a number of different data sets varying in mean age and pathology by fitting the model to individual electroencephalographic (EEG) spectra from post-traumatic stress disorder (PTSD), schizophrenia, first episode schizophrenia (FESz), attention deficit hyperactivity disorder (ADHD), and their age/sex matched controls. The results demonstrate that the model is able to distinguish each group in terms of a unique cluster of abnormal parameter deviations. The abnormal physiology inferred from these parameters is also consistent with known theoretical and experimental findings from each disorder. The model is also found to be sensitive to the effects of medication in the schizophrenia and FESz group, further supporting the biophysical validity of the model. To the author’s knowledge, this is the first study where a detailed biophysical model of the brain has been used to quantify and compare changes in neurophysiological parameters underlying a number of different clinical disorders.
Aims: The primary aim of this study was to determine whether the model could significantly discriminate these groups in terms of distinct neurophysiological parameters that reflect variation in baseline cortical function. There are some broad hypotheses given the key neurological abnormalities in these groups, however the primary goal is more exploratory, and aimed at testing the feasibility of the approach, rather than providing an extensive discussion of the mechanisms underlying each disorder.
Method: Overview of the biophysical model The structure of the model is reflected in a modest number of neurophysiological parameters, which must lie within plausible physiological limits. Variation outside these limits leads to high mismatch between model and experiment, and/or seizure like activity in the waveforms. Such variations are thus not relevant to the clinical subjects of interest and are not considered here. The model parameters appear in the expression for the theoretical EEG spectrum used in inverse modelling of experimental EEG data. The physiological features used in the model have also been justified in previous studies. In this study, the focus is on the ability of the model to provide physiological insight into tonic changes in EEG spectra due to stimulant medications, and whether the results are consistent with known physiology and the pharmacological effects of these drugs.