Oscillations and Neuronal Dynamics in Schizophrenia: The Search for Basic Symptoms and Translational Opportunities

Uhlhaas, Peter J.; Singer, Wolf

doi:10.1016/j.biopsych.2014.11.019

Cited by 219 publications

(192 citation statements)

References 110 publications

Supporting

Mentioning

180

Contrasting

Unclassified

Order By: Relevance

“…Consistent with this hypothesis, functional imaging studies in patients have repeatedly shown that schizophrenia weakens functional coupling in prefrontal networks based on reduced temporal correlations in BOLD signal across brain areas (Kang et al, 2011; Kubota et al, 2013; Lawrie et al, 2002; Mitelman et al, 2005; Mukherjee et al, 2016; Scariati et al, 2016; Tu et al, 2012, 2013). Measurements of brain activity at higher temporal resolution using electroencephalograms (EEG) and magnetoencephalography (MEG) have shown reduced synchrony in gamma band during task performance (Dale et al, 2016; Uhlhaas and Singer, 2015). The spike-timing-dependent synaptic disconnection theory is an elaboration of these prior theories extending the synchrony deficits described at larger physical scales within the brain to the level of spiking neurons, considering the impact of spike timing disruption on synaptic connectivity operating through spike-timing-dependent plasticity mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…This supports a causal theory of schizophrenia in which a distortion of spike timing occurs early in the disease, and drives the subsequent disconnection of prefrontal networks by a spike-timing-dependent, Hebbian process. We refer to this as activity-dependent disconnection , and it is closely related to several pre-existing theories of schizophrenia focusing on disrupted synchrony and disconnection in the disease (Friston, 1999; Uhlhaas and Singer, 2015). We presently investigate whether these two aspects of schizophrenia may be associated by investigating their relationship in an animal model.…”

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia

Zick

Blackman

Crowe

et al. 2018

Neuron

View full text Add to dashboard Cite

SUMMARY We employed multi-electrode array recording to evaluate the influence of NMDA receptors (NMDAR) on spike-timing dynamics in prefrontal networks of monkeys as they performed a cognitive control task measuring specific deficits in schizophrenia. Systemic, periodic administration of an NMDAR antagonist (phencyclidine) reduced the prevalence and strength of synchronous (0-lag) spike correlation in simultaneously recorded neuron pairs. We employed transfer entropy analysis to measure effective connectivity between prefrontal neurons at lags consistent with monosynaptic interactions and found that effective connectivity was persistently reduced following exposure to the NMDAR antagonist. These results suggest that a disruption of spike timing and effective connectivity might be interrelated factors in pathogenesis, supporting an activity-dependent disconnection theory of schizophrenia. In this theory, disruption of NMDAR synaptic function leads to dys-regulated timing of action potentials in prefrontal networks, accelerating synaptic disconnection through a spike-timing-dependent mechanism.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia

Zick

Blackman

Crowe

et al. 2018

Neuron

View full text Add to dashboard Cite

show abstract

“…However, decreased expression of both PV and PNN components are present in schizophrenia, suggesting that PV cell dysfunction is part of the disease process. Through a variety of mechanisms, PV and PNN-mediated alterations are likely to contribute to dysfunction of the layer 3 PV-PC local circuitry that generates γ-oscillations (Gonzalez-Burgos et al, 2015) and thus to the neural basis for the impairments in DLPFC γ-oscillations seen during cognitive tasks in individuals with schizophrenia (Uhlhaas and Singer, 2015).…”

Section: Functional Consequences Of Lower Levels Of Pv and Pnn Componmentioning

confidence: 99%

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Enwright

Sanapala

Foglio

et al. 2016

Neuropsychopharmacol

188

139

View full text Add to dashboard Cite

Alterations in cortical parvalbumin (PV)-containing neurons, including a reduced density of detectable neurons and lower PV levels, have frequently been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects. Most PV neurons are surrounded by perineuronal nets (PNNs) and the density of PNNs, as detected by Wisteria floribunda agglutinin (WFA) labeling, has been reported to be lower in schizophrenia. However, the nature of these PNN alterations, and their relationship to disease-related changes in PV neurons, has not been assessed. Using confocal microscopy, we quantified the densities and fluorescence intensities of PV neurons and PNNs labeled with WFA or immunoreactive for the major PNN protein, aggrecan, in the DLPFC from schizophrenia and matched comparison subjects. In schizophrenia, the densities of PV cells and of PNNs were not altered; however, the fluorescence intensities of PV immunoreactivity in cell bodies and of WFA labeling and aggrecan immunoreactivity in individual PNNs around PV cells were lower. These findings indicate that the normal complements of PV cells and PNNs are preserved in schizophrenia, but the levels of PV protein and of individual PNN components, especially the carbohydrate moieties on proteoglycans to which WFA binds, are lower. Given the roles of PV neurons in regulating DLPFC microcircuits and of PNNs in regulating PV cellular physiology, the identified alterations in PV neurons and their PNNs could contribute to DLPFC dysfunction in schizophrenia.

show abstract

“…Due to the prominent role of gamma band activity in cognitive function, high frequency activity has been characterized extensively in schizophrenia (Uhlhaas and Singer, 2013, 2015). Gamma band amplitude has been shown to be reduced in a wide range of cognitive and perceptual paradigms in schizophrenia, including working memory, executive control, and perceptual processing (Ford et al, 2008; Haenschel et al, 2009; Minzenberg et al, 2010).…”

Section: Clinical Findings: Cognitive Impairments and Network Distmentioning

confidence: 99%

Converging models of schizophrenia – Network alterations of prefrontal cortex underlying cognitive impairments

Sakurai

Gamo

Hikida

et al. 2015

Progress in Neurobiology

View full text Add to dashboard Cite

The prefrontal cortex (PFC) and its connections with other brain areas are crucial for cognitive function. Cognitive impairments are one of the core symptoms associated with schizophrenia, and manifest even before the onset of the disorder. Altered neural networks involving PFC contribute to cognitive impairments in schizophrenia. Both genetic and environmental risk factors affect the development of the local circuitry within PFC as well as development of broader brain networks, and make the system vulnerable to further insults during adolescence, leading to the onset of the disorder in young adulthood. Since spared cognitive functions correlate with functional outcome and prognosis, a better understanding of the mechanisms underlying cognitive impairments will have important implications for novel therapeutics for schizophrenia focusing on cognitive functions. Multidisciplinary approaches, from basic neuroscience to clinical studies, are required to link molecules, circuitry, networks, and behavioral phenotypes. Close interactions among such fields by sharing a common language on connectomes, behavioral readouts, and other concepts are crucial for this goal.

show abstract

Oscillations and Neuronal Dynamics in Schizophrenia: The Search for Basic Symptoms and Translational Opportunities

Cited by 219 publications

References 110 publications

Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia

Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Converging models of schizophrenia – Network alterations of prefrontal cortex underlying cognitive impairments

Contact Info

Product

Resources

About