Download Schizophrenia and Gamma Oscillations

SCHIZOPHRENIA AND
GAMMA OSCILLATIONS
Shizophrenia-General Overview
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Most often occurs at 17-35 years of age and affects roughly 1% of the
population
 Schizophrenia presents in a vast variety of ways and is characterized by 4
major categories of symptoms:
i) Positive symptoms - Hearing voices, suspiciousness, feeling under constant surveillance,
delusions, or making up words without a meaning (neologisms).
ii) Negative (or deficit) symptoms - Social withdrawal, difficulty in expressing emotions (in
extreme cases called blunted affect), difficulty in taking care of themselves, inability to feel
pleasure (These symptoms cause severe impairment and are often mistaken for laziness.)
iii) Cognitive symptoms - Difficulties attending to and processing of information, in
understanding the environment, and in remembering simple tasks
iv) Affective (or mood) symptoms - Most notably depression, accounting for a very high rate of
attempted suicide in people suffering from schizophrenia
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Schizophrenia seems to be caused by an interaction between genetics and
environment and is highly heritable with twin studies yielding concordance
rates of 50%
Theories on Schizophrenia
Disconnectivity Hypothesis &
Aberrant Connectivity Hypothesis
• Genetic Factors
• NMDAR (N-methyl-D-aspartate receptor)
• Spectrum Disease
• Specific impairments of synaptic plasticity
• Corollary discharge
• NMDA antagonists (ketamine)
• Hypo and hyper activity in brain regions
• Schizophrenia in relation to gamma
Genetic Factors
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Brain development and genetics seem to be a key factor leading to
schizophrenia
Studies have found abnormalities in the genes leading to synaptic plasticity
development in schizophrenics especially in NMDARs and its regulation by
DA and ACh
Schizophrenics have decreased scripts for pre-synaptic secretory machinery
involved in glutamatergic and GABAergic neurotransmission
DISC1 effects dendritic growth and maintenance in those with
schizophrenia both are reduced implicating this gene as the culprit
NRG1: is heavily implicated in regulation of oligodendrocyte maturation and
myelin production
Reelin has been implicated in cortical layer formation and in the renewal and
maintenance of dendritic spine in interneurons
Genetic Factors Cont.
“Collectively, the experimental evidence summarized above indicates that
schizophrenia is a spectrum disease that may be caused by different genetic
mechanisms and pathophysiological processes; these processes, however,
appear to converge onto the same functional pathway, ie, the regulation of
NMDAR-controlled plasticity of glutamatergic synapses by neuromodulatory
transmitters like DA, 5-HT, and Ach.”(Stephan, Klaas., et al. 2009)
Corollary Discharge
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Corollary discharges are self monitoring mechanisms which are supposed to be
malfunctioning in schizophrenics
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When movements are self-generated, the sensory areas receive a signal from motor
areas, informing them about the intended movement and thus allowing them to
predict the proprioceptive input they should be receiving. This signal has been called
a ‘‘corollary discharge,’’ or ‘‘efference copy.’’ (Stephan, Klaas., et al. 2009)
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This goes back to the presentation we had on perrisaccadic eye movements and is the
same kind of concept but has to do with all somatosensory movements that are selfgenerated
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In people with schizophrenia the motor movement and the sensory movement may
fail to coordinate
Corollary Discharge Cont.
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Frontotemporal delta and theta band coherence that is enhanced during talking
(compared with listening) in healthy volunteers is diminished in schizophrenic
patients; the deficit is particularly pronounced in patients with auditory
hallucinations. (Ford et al., year 2008)
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A problem in communication between brain areas in schizophrenics could distinguish
between their self generated speech and external speech
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The disconnectivity leading to incongruence between different bands of oscillations
may show how different neuronal assemblies fail to communicate leading to these
hallucinations and actually studies have shown that the larger the disconnectivity
between brain regions the more symptoms of hallucinations in the patients there are
Neural Synchrony Indexes Disordered
Perception and Cognition in Schizophrenia
Spencer, K. M., et al. 2004
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Hypothesized that a clearer relationship between neural synchrony and
schizophrenic symptoms might be found if we examined oscillations that
were phase-locked to reaction time rather than stimulus onset
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They decided to do this because single unit recording studies have found
that the processes are more correlated with reaction time than stimulus
onset time
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In order to test this theory they got two groups of 20 people each one group
being schizophrenics and the other a control group
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Subjects watched a central cross and pushed a button according to whether
an illusory square was present or absent
Neural Synchrony Indexes Disordered
Perception and Cognition in Schizophrenia
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When presented with these Gestalt stimuli a gamma oscillation was elicited
in both healthy subjects and schizophrenics, however the frequency of the
oscillation in schizophrenics was lower
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This may mean that schizophrenics are unable to support high frequency
oscillations as well as healthy individuals
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The occipital response locked oscillation was different in two ways from
that in healthy people: i) the lower frequency and ii) the increases in
symptoms were associated with increased phase-locking effects
Stimulus Locked
Response Time locked
Gamma Oscillations in
Schizophrenics
 Impaired cortical circuitry would not synchronize properly and lead
to the perceptual distortions and failures of cognitive integration
that characterize schizophrenia
 Post mortem brain studies have found decreased density of
inhibitory interneurons as well as decreased somal size and spine
density of pyramidal cells
 This is evidence towards cortical hyperexcitability in schizophrenics
because of a lack of inhibition
 The abnormalities in the interneurons contribute to neural
dysynchrony with their decreased inhibitory output by increasing
pyramidal excitability while decreasing spike outbursts
Ketamine & Schizophrenia
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Ketamine is an NMDA antagonist and produces schizophrenia like symptoms in users
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Ketamine produces aberrant gamma oscillations in rodents as well as
hyperlocomotion
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These aberrant gamma oscillations were not caused by sensorimotor processing and
occurred all over the cerebral cortex and in subcortical structures related to sensory,
motor and associative/cognitive systems
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These oscillations were not conscious and gamma hyperactivity was a generalized
phenomenon not limited to sensorimotor systems
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Plateaus 1-4
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Due to similarities in the symptoms of taking ketamine including neural dysynchrony
and the antagonism of nmda to schizophrenia it may provide researchers with the
abillity to do research on animals that is as close to the mind of a
schizophrenic individual as we can get
Gamma Oscillations in
Schizophrenics Summary
 Most contemporary views on schizophrenia believe that it is a result
of dysfunctional neural synchronization more specifically in regards
to gamma oscillations and somewhat in beta oscillations
 The dysfunctional neural synchronization seems to be due to
hyperexcitation in some brain areas and hypoexcitation in others
leading to difficulty in communication and phase-locking
 Schizophrenics have varied presentation and varied brain
abnormalities leading to varied problems in synaptic plasticity which
is why it is believed in the future it will be a spectrum disease with
different types of schizophrenia diagnosed depending on which
abnormalities are present
 There is still a long way to go in the research on schizophrenia and it
will continue to help us better understand the brains global
functioning from both a top-down and bottom-up perspective
Works Cited
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Stephan, K. E., et al. (2009). Dysconnection in Schizophrenia: From Abnormal Synaptic Plasticity to
Failures of Self-monitoring. Schizophrenia Bulletin, vol. 35 no. 3 pp. 509–527.
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Gaspar, P.A., et al. (2009). The Aberrant Connectivity Hypothesis in Schizophrenia, Ch15.
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Spencer, K.M., et al. (2004). Neural synchrony indexes disordered perception and cognition in
schizophrenia. PNAS, vol. 101, no. 49. www.pnas.orgcgidoi10.1073pnas.0406074101.
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Hakami T, Jones NC, Tolmacheva EA, Gaudias J, Chaumont J, et al. (2009). NMDA Receptor
Hypofunction Leads to Generalized and Persistent Aberrant Gamma Oscillations Independent of
Hyperlocomotion and the State of Consciousness. PLoS ONE 4(8): e6755.
doi:10.1371/journal.pone.0006755
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Williams, L.M., et al. (2009). Journal of Psychiatry Neuroscience. Neural synchrony in patients with
a first episode of schizophrenia: tracking relations with grey matter and symptom profile 34(1):21-9.
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Celia J., et al. (2008). Society for the Study of Addiction. Ketamine use, cognition and psychological
wellbeing: a comparison of frequent, infrequent and ex-users with polydrug and non-using controls.
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