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. 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
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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
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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
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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.
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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)
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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
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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.
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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
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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.
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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
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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
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