SlideShare a Scribd company logo

Abnormal Neural Oscillations And Synchrony In Schizophrenia

•
•
Kyongsik Yun
Kyongsik Yun

This document summarizes research on abnormal neural oscillations and synchrony in schizophrenia. It finds that patients show dysfunctional phase synchrony and reduced gamma oscillations, associated with reduced parvalbumin expression and inhibitory function. Animal models replicating anatomical and behavioral deficits in schizophrenia also show impaired gamma oscillations. The transition from adolescence to adulthood involves increased gamma oscillations and cortical network reorganization, associated with changes in GABAA receptor-mediated inhibition.

1 of 14
Download to read offline
Abnormal neural oscillations and synchrony in schizophrenia Uhlhaas and Singer 2010 NRN Prepared for Brain Dynamics Lab Journal Club 2010.03.09, 10:30p.m. Kyongsik Yun, Ph.D. Candidate KAIST yunks@kaist.edu 1
Neural oscillations and synchrony in cortical networks The timing of rhythmic activity in cortical networks influences communication between neuronal populations. Interconnected neurons Action potentials Effective communication LFP Preventing communication 2
Synchronization between neurons in local cortical networks depends on the occurrence of gamma oscillations Oscillations in the beta and gamma range establish synchronization with great precision in local cortical networks BA17, anaesthetized cats, a drifting grating stimulus 3
Measurement of steady-state evoked potentials A steady-state stimulation at a frequency of 20 Hz Steady-state evoked potentials can probe the ability of neuronal networks to generate and maintain oscillatory activity in different frequency bands. 4
Evoked and induced oscillations reflect different aspects of information processing in cortical networks Evoked activity reflects bottom-up sensory transmission (close temporal relationship with the incoming stimulus). Induced activity represents the internal dynamics of cortical networks (higher cognitive functions) 5
Neural oscillations and synchrony in schizophrenia The presentation of click trains Visual oddball task dysfunction in early sensory processes 6
Dysfunctional phase synchrony during Gestalt perception in schizophrenia Control – ScZ Red: + Green: - Phase synchrony 7
A neocortical circuit involved in the generation of gamma-band oscillations Negative feedback inhibition of pyramidal cells by GABAergic interneurons that express the Ca2+- binding protein parvalbumin This phasic inhibition leads to the synchronization of spiking activity that can be recovered with a cross- correlogram The network of GABAergic interneurons acts as a pacemaker in the generation of high frequency oscillations by producing rhythmic inhibitory postsynaptic potentials. 8
Cortico-cortical connections mediate long- distance synchronization These data show that synchronization can occur over long distances with high precision and is crucially dependent on the integrity of cortico-cortical connections 9
Connectivity of the corpus callosum and its abnormalities in schizophrenia as reflected in diffusion tensor imaging data p < 0.05 p < 0.0055 Patients with schizophrenia show significantly less organization (lower fractional anisotropy) in subdivisions of the corpus callosum than controls. Fractional anisotropy values estimate the presence and coherence of oriented structures, such as myelinated axons. 10
Expression of parvalbumin mRNA in layers 3–4 of the dlPFC is reduced in patients with schizophrenia Expression of parvalbumin mRNA These findings suggest that the ability of parvalbumin-positive interneurons to express important genes is impaired in schizophrenia 11
Reduction in gamma oscillations and parvalbumin-positive neurons in the mPFC in an animal model of schizophrenia Methylazoxymethanol acetate (MAM) This methylazoxymethanol acetate (MAM) treated model reproduces the anatomical changes, behavioural deficits and altered neuronal information processing observed in ScZ patients. Treated rats display a regionally specific reduction in the density of parvalbumin-positive neurons throughout the mPFC, Acg, and vSub. The presentation of a tone induces a mild increase in prefrontal gamma (30– 55 Hz) oscillations in saline- but not MAM-treated rats. 12
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. 13 Uhlhaas et al. PNAS 2009
Changes in GABAA receptor-mediated neurotransmission in the monkey dlPFC during adolescence Monkey Prepubertal: 15~17 months Postpubertal: 43~47 months 30ms: 33Hz 40ms: 25Hz A higher fraction of shorter mIPSPs in postpubertal animals than in prepubertal animals As the decay time of IPSPs is a critical factor for the dominant frequency of oscillations in a network, these data provide one mechanism for the late maturation of high-frequency oscillations 14

More Related Content

Abnormal Neural Oscillations And Synchrony In Schizophrenia

  • 1. Abnormal neural oscillations and synchrony in schizophrenia Uhlhaas and Singer 2010 NRN Prepared for Brain Dynamics Lab Journal Club 2010.03.09, 10:30p.m. Kyongsik Yun, Ph.D. Candidate KAIST yunks@kaist.edu 1
  • 2. Neural oscillations and synchrony in cortical networks The timing of rhythmic activity in cortical networks influences communication between neuronal populations. Interconnected neurons Action potentials Effective communication LFP Preventing communication 2
  • 3. Synchronization between neurons in local cortical networks depends on the occurrence of gamma oscillations Oscillations in the beta and gamma range establish synchronization with great precision in local cortical networks BA17, anaesthetized cats, a drifting grating stimulus 3
  • 4. Measurement of steady-state evoked potentials A steady-state stimulation at a frequency of 20 Hz Steady-state evoked potentials can probe the ability of neuronal networks to generate and maintain oscillatory activity in different frequency bands. 4
  • 5. Evoked and induced oscillations reflect different aspects of information processing in cortical networks Evoked activity reflects bottom-up sensory transmission (close temporal relationship with the incoming stimulus). Induced activity represents the internal dynamics of cortical networks (higher cognitive functions) 5
  • 6. Neural oscillations and synchrony in schizophrenia The presentation of click trains Visual oddball task dysfunction in early sensory processes 6
  • 7. Dysfunctional phase synchrony during Gestalt perception in schizophrenia Control – ScZ Red: + Green: - Phase synchrony 7
  • 8. A neocortical circuit involved in the generation of gamma-band oscillations Negative feedback inhibition of pyramidal cells by GABAergic interneurons that express the Ca2+- binding protein parvalbumin This phasic inhibition leads to the synchronization of spiking activity that can be recovered with a cross- correlogram The network of GABAergic interneurons acts as a pacemaker in the generation of high frequency oscillations by producing rhythmic inhibitory postsynaptic potentials. 8
  • 9. Cortico-cortical connections mediate long- distance synchronization These data show that synchronization can occur over long distances with high precision and is crucially dependent on the integrity of cortico-cortical connections 9
  • 10. Connectivity of the corpus callosum and its abnormalities in schizophrenia as reflected in diffusion tensor imaging data p < 0.05 p < 0.0055 Patients with schizophrenia show significantly less organization (lower fractional anisotropy) in subdivisions of the corpus callosum than controls. Fractional anisotropy values estimate the presence and coherence of oriented structures, such as myelinated axons. 10
  • 11. Expression of parvalbumin mRNA in layers 3–4 of the dlPFC is reduced in patients with schizophrenia Expression of parvalbumin mRNA These findings suggest that the ability of parvalbumin-positive interneurons to express important genes is impaired in schizophrenia 11
  • 12. Reduction in gamma oscillations and parvalbumin-positive neurons in the mPFC in an animal model of schizophrenia Methylazoxymethanol acetate (MAM) This methylazoxymethanol acetate (MAM) treated model reproduces the anatomical changes, behavioural deficits and altered neuronal information processing observed in ScZ patients. Treated rats display a regionally specific reduction in the density of parvalbumin-positive neurons throughout the mPFC, Acg, and vSub. The presentation of a tone induces a mild increase in prefrontal gamma (30– 55 Hz) oscillations in saline- but not MAM-treated rats. 12
  • 13. 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. 13 Uhlhaas et al. PNAS 2009
  • 14. Changes in GABAA receptor-mediated neurotransmission in the monkey dlPFC during adolescence Monkey Prepubertal: 15~17 months Postpubertal: 43~47 months 30ms: 33Hz 40ms: 25Hz A higher fraction of shorter mIPSPs in postpubertal animals than in prepubertal animals As the decay time of IPSPs is a critical factor for the dominant frequency of oscillations in a network, these data provide one mechanism for the late maturation of high-frequency oscillations 14