Changju Lee Visual System Neural Network Lab. Department of Bio and Brain Engineering

Content Introduction - Neural oscillation & Neural synchronization - Schizophrenia (SCZ) Result - Neural oscillation in SCZ - Neurobiology of abnormal oscillations - Neurodevelopmental hypothesis of SCZ Conclusion

Introduction – Neural oscillation Global cortical network Local cortical network Fundamental mechanism for enabling coordinated activity during normal brain functioning

Introduction – Neural synchronization Courtesy of D. Nikolić, Max-Planck Institute for Brain Research Fell & Axmacher (2011), Nat. Rev. Neurosci. Correlations or coupling between spikes in two regions Neural oscillations and synchrony Aperiodic signal Quasi-periodic signal

Introduction – Schizophrenia (SCZ) Schizophrenia (SCZ) : a mental disorder often characterized by abnormal social behavior and failure to recognize what is real. Self-portrait of Craig Finn  Positive symptom : A range of psychotic symptoms that most individuals do not normally experience. e.g., sensory hallucination, delusion  Negative symptom : an absence of behavior e.g., poverty of speech, inability to experience pleasure, lack of motivation  Causes of SCZ are still unknown  Distributed impairment involving many cortical areas and their connectivity  Mechanisms that mediate the generation of coherent and coordinated activity in cortical circuits will be the key understanding pathophysiology of SCZ

 Role of dysfunctional neural oscillations in SCZ with EEG and MEG  Possible neurobiological causes of impaired oscillations of SCZ  Neurodevelopmental hypothesis and oscillations of SCZ In this review article,

Result – Neural oscillation in SCZ Steady-state stimulation SSEP Measuring neural oscillations in EEG and MEG signals  Probe the ability of neuronal networks to generate and maintain oscillatory activity Measurement of steady-state evoked potentials (SSEPs) Measurement of evoked and induced oscillatory activity  Evoked activity reflects bottom-up sensory transmission  Induced oscillations represent the internal dynamics of cortical networks Courtesy of F. Roux, Max-Planck Institute for Brain Research

Result – Neural oscillation in SCZ Kwon (1999), Arch. Gen. Psychiatry Gallinat et al.(2004), Clin. Neurophysiol Uhlhaas et al. (2006), J. Neurosci. Neural oscillations and synchrony in SCZ  Dysfunction in the auditory SSEP, in particular at 40 Hz.  Dysfunction in early sensory processes.  Dysfunctional phase synchrony during Gestalt perception in SCZ.  Impairments in neural oscillations are a candidate mechanism for network in SCZ

Result – Neurobiology of abnormal oscillations Mechanisms underlying the generation of gamma oscillations and synchrony  Negative feedback inhibition of pyramidal cells by GABAergic PV + interneurons  Cortico-cortical connections mediate long-distance synchronization with high precision Engel et al. (1991), Science. Berlucchi (1972), Brain res. Excitatory input Mutual inhibition Pyramidal cells fire repeat

Result – Neurobiology of abnormal oscillations Neurobiological correlates of deficits in neural oscillations and synchrony in SCZ Hashimoto et al. (2003), J. Neurosci. Lodge et al. (2009), J. Neurosci.  Changes in connectivity between healthy controls and patients with SCZ according to Diffusion Tensor Imaging (DTI)  Ability of PV + interneurons to express important genes is impaired in SCZ  Reduction of PV + neurons in the mPFC in an animal model of SCZ Rotarska-Jagiela et al. (2008), Neuroimage. AnteriorPosterior

Result – Neurodevelopmental hypothesis of SCZ Uhlhaas et al. (2009), Proc. Natl Acad. Sci. USA. Hashimoto et al. (2009), Biol. Psychiatry. Emergence of high frequency oscillations and synchrony during the transition from adolescence to adulthood  Gamma oscillations increase significantly during the transition from adolescence to adulthood  Cortical networks reorganize during the transition from adolescence to adulthood  Provide one mechanism for the late maturation of high frequency oscillations in EEG data.  Predominance of GABA α 2 subunit during early development, whereas α 1 subunit is expressed in adults

Conclusion Abnormalities in the synchronized oscillatory activity of neurons may have a central role in the pathophysiology of SCZ PV + interneurons generate gamma oscillation synchrony in local neural networks, and corpus callosum transmits Interhemispheric information with high precision SCZ is characterized by abnormal brain maturation at several stages of development, and typically manifests during late adolescence and early adulthood

Supplementary information Fractional anisotropy