Schizophrenia is a severe psychotic disorder with prominent cognitive dysfunctions. The pathophysiological mechanisms that give rise to the signs and symptoms of the disorder are still unclear, however.
Neural oscillations and their synchronization may be core pathophysiological mechanisms in schizophrenia, as neural oscillations are fundamental for coordinated neural activity during normal brain functioning.
Recent evidence shows that schizophrenia is associated with deficits in neural oscillations, especially in the beta- and gamma-band frequencies. These impairments closely correlate with cognitive dysfunctions and the core symptoms of the disorder.
Dysfunctions in neural synchrony could result from deficits in GABA (γ-aminobutyric acid)-ergic neurotransmission and the reduced integrity of cortico-cortical connections, which are crucially involved in the generation of synchronized, oscillatory activity.
Developmentally, neural oscillations are involved in the maturation of cortical networks during early and late critical periods that have been implicated in the pathophysiology of schizophrenia.
Converging evidence from electrophysiological, physiological and anatomical studies suggests that abnormalities in the synchronized oscillatory activity of neurons may have a central role in the pathophysiology of schizophrenia. Neural oscillations are a fundamental mechanism for the establishment of precise temporal relationships between neuronal responses that are in turn relevant for memory, perception and consciousness. In patients with schizophrenia, the synchronization of beta- and gamma-band activity is abnormal, suggesting a crucial role for dysfunctional oscillations in the generation of the cognitive deficits and other symptoms of the disorder. Dysfunctional oscillations may arise owing to anomalies in the brain's rhythm-generating networks of GABA (γ-aminobutyric acid) interneurons and in cortico-cortical connections.
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The authors declare no competing financial interests.
- Negative symptoms
An absence of behaviour, characterized by flat or blunted affect and emotion, poverty of speech (alogia), inability to experience pleasure (anhedonia) and lack of motivation (avolition).
- Perceptual grouping
The ability of perceptual systems to organize sensory information into coherent representations that can serve as the basis of our phenomenal experience of the world.
- Transcranial magnetic stimulation
(TMS). A non-invasive method to excite neurons in the brain by inducing weak electric currents in the tissue using rapidly changing magnetic fields.
- Mismatch negativity
An event-related potential that is elicited when a sequence of repeated stimuli (standards) is interrupted by stimuli that deviate in sensory characteristics such as intensity, frequency or duration (deviants).
A neurophysiological, neuroanatomical, cognitive or neuropsychological marker that points to the genetic underpinnings of a clinical syndrome. An endophenotype must be heritable and state independent, and within families the endophenotype and illness must co-segregate.
- Positive symptoms
A range of psychotic symptoms that most individuals do not normally experience. Typical symptoms are hallucinations in various modalities (auditory, visual and tactile) and delusions (paranoid delusions and delusions of reference).
- Phase synchrony
Phase synchrony and coherence are estimates of the synchrony of brain oscillations. Phase synchrony provides an estimate of synchrony independent of the amplitude of oscillations. This contrasts with measures of coherence, in which synchrony and amplitude are intertwined.
- Corollary discharge
The estimate of sensory feedback that is derived from the internal copy of the motor signal (the efference copy).
- Diffusion tensor imaging
(DTI). An MRI technique used to map three-dimensional diffusion of water in brain tissue. It provides information about the microstructural integrity of the white matter, including axonal density and thickness, myelinationand axonal fibre direction.
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Uhlhaas, P., Singer, W. Abnormal neural oscillations and synchrony in schizophrenia. Nat Rev Neurosci 11, 100–113 (2010). https://doi.org/10.1038/nrn2774
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