Exploring intermediate phenotypes with EEG: Working memory dysfunction in schizophrenia

Haenschel, Corinna; Linden, David Edmund Johannes

doi:10.1016/j.bbr.2010.08.045

Cited by 45 publications

(39 citation statements)

References 250 publications

(227 reference statements)

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“…Disruption of the theta phase code provides an intuitive neural mechanism for cannabinoid-induced cognitive impairment that Melges et al (1970) called "temporal disintegration" and described as "difficulty in retaining, coordinating and serially indexing those memories, perceptions and expectations that are relevant to the goal one is pursuing." Links between cognitive impairments and aberrant network oscillations are increasingly implicated in the pathophysiology of schizophrenia (Uhlhaas and Singer, 2010;Haenschel and Linden, 2011), and alterations in rhythmic activity in the theta, alpha, beta, and gamma bands of cortical oscillations have been reported to correlate with working memory dysfunction in the disease (Haenschel et al, 2009;Haenschel and Linden, 2011). Moreover, disrupted functional coupling between dorsolateral prefrontal cortex and hippocampus has been observed in schizophrenia patients (Lawrie et al, 2002;Meyer-Lindenberg et al, 2005) as well as in healthy carriers of a genetic risk variant (Esslinger et al, 2009) and a mouse model of a chromosomal microdeletion associated with the disease (Sigurdsson et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Dysfunctional Prefrontal Cortical Network Activity and Interactions following Cannabinoid Receptor Activation

Kucewicz¹,

Tricklebank²,

Bogacz³

et al. 2011

J. Neurosci.

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Coordinated activity spanning anatomically distributed neuronal networks underpins cognition and mediates limbic-cortical interactions during learning, memory, and decision-making. We used CP55940, a potent agonist of brain cannabinoid receptors known to disrupt coordinated activity in hippocampus, to investigate the roles of network oscillations during hippocampal and medial prefrontal cortical (mPFC) interactions in rats. During quiet wakefulness and rest, CP55940 dose-dependently reduced 0.1-30 Hz local field potential power in CA1 of the hippocampus while concurrently decreasing 30 -100 Hz power in mPFC; these contrasting population-level effects were paralleled by differential effects on underlying single-unit activity in the two structures. During decision-making phases of a spatial working memory task, CP5540-induced deficits in hippocampal theta and prefrontal gamma oscillations were observed alongside disrupted theta-frequency coherence between the two structures. These changes in coordinated limbic-cortical network activities correlated with (1) reduced accuracy of task performance, (2) impaired phase-locking of prefrontal single-unit spiking to the local gamma and hippocampal theta rhythms, and (3) impaired task-dependent activity in a subset of mPFC units. In addition to highlighting the importance of CA1-mPFC network oscillations for cognition, these results implicate disrupted theta-frequency coordination of CA1-mPFC activity in the cognitive deficits caused by exogenous activation of brain cannabinoid receptors.

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Section: Discussionmentioning

confidence: 99%

Dysfunctional Prefrontal Cortical Network Activity and Interactions following Cannabinoid Receptor Activation

Kucewicz¹,

Tricklebank²,

Bogacz³

et al. 2011

J. Neurosci.

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“…To examine cognitive function relevant to schizophrenia, we used spontaneous T-maze alternation as a measure of working memory (24) due to the link between frontal cortex function, working memory, and schizophrenia (25). AAV-GFP-expressing mice perform on average 73.3 ± 6.7% correct in a series of six discrete trials over 2 days (Fig.…”

Section: Creation Of Dominant Negative Reagents To Disrupt the Synapticmentioning

confidence: 99%

Disrupting the clustering of GABA_Areceptor α2 subunits in the frontal cortex leads to reduced γ-power and cognitive deficits

Hines

Houston

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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In schizophrenia, cognitive dysfunction is highly predictive of poor patient outcomes and is not responsive to current medications. Postmortem studies have suggested that cognitive deficits in schizophrenia are correlated with modifications in the number and size of inhibitory synapses. To test if these modifications lead to cognitive deficits, we have created a dominant-negative virus [adeno-associated (AAV)-DN1] that disrupts the clustering of γ-aminobutyric acid type A receptors (GABA A Rs) at postsynaptic inhibitory specializations. When injected into the frontal cortex of mice, AAV-DN1 impairs GABA A R α2 subunit and GABA transporter 1 (GAT-1) clustering, but increases GABA A R α1 subunit clustering on the perisomatic region, with no influence on axon-initial segment clustering. Mice expressing AAV-DN1 have prepulse inhibition deficits and impairments in working memory. Significantly, these behavioral deficits are paralleled by a reduction in electroencephalography γ-power. Collectively, our study provides functional evidence revealing that GABAergic synapses in the prefrontal cortex directly contribute to cognition and γ-power. In schizophrenia, the classical positive and negative symptoms are accompanied by striking cognitive deficits, and notably, the cognitive deficits are not ameliorated by conventional antipsychotic medications (1-3). Thus, understanding the molecular basis of these deficits is key to development of more efficacious treatments. In addition to modifications in the dopaminergic system, there is compelling evidence that modifications in signaling by γ-aminobutyric acid receptors (GABA A R) contributes to the cognitive deficits in schizophrenia. GABA A Rs are the principle mediators of fast synaptic inhibition in the brain and are pentameric heteroligomers that are principally assembled from α1-6, β1-3, γ1-3, and δ subunits (4). Within the cortex, GABA A Rs containing α2 subunits are enriched on the axoninitial segments (AIS) and perisomatic regions of neurons, where their activation has been shown to underlie oscillatory activity and cognition (5, 6).Postmortem analysis has revealed increased levels of α2 subunit immunoreactivity on the AIS of principal cortical neurons in schizophrenia and parallel deficits in the number of GABA transporter (GAT-1) positive presynaptic elements. However, whether these modifications in inhibitory synapse structure contribute to the cognitive deficits of schizophrenia remains unknown. To address this issue we have used virally encoded dominantnegative reagents to disrupt the function of inhibitory synapses containing α2 subunits in the cortex of mice. This resulted in prepulse inhibition deficits and impairments in working memory that were paralleled by a reduction in electroencephalography γ-power. Thus, α2 subunit-containing GABA A Rs are important determinants of cognition, and selectively potentiating their activity may be beneficial in improving the outcome of patients with schizophrenia. Results Creation of Dominant Negative Reagents to Disrupt the ...

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“…Coherent neuronal communications are based on neurotransmission dynamics dictated by major neurotransmitters like the amino acids glutamate and GABA. Other important neurotransmitters include acetylcholine, dopamine, adrenaline, histamine, serotonin and melatonin [24,44,48]. These action potentials activate a neighboring population of neurons which in turn may affect other populations of neurons at a distance creating a network of connectivity.…”

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confidence: 99%

Coherence a measure of the brain networks: past and present

Bowyer

2016

Neuropsychiatr Electrophysiol

257

178

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Brian connectivity describes the networks of functional and anatomical connections across the brain. The functional network communications across the brain networks dependent on neuronal oscillations. Detection of the synchronous activation of neurons can be used to determine the wellbeing or integrity of the functional connectivity in the human brain networks. Well-connected highly synchronous functional activity can be measured by Electroencephalography (EEG) or Magnetoencephalography (MEG) and then analyzed with several types of mathematical algorithms. Coherence is one mathematical method that can be used to determine if two or more sensors, or brain regions, have similar neuronal oscillatory activity with each other. Since the 1960's, coherence has generally been assessed on the similarity of the frequency content across EEG sensors. Recently coherence, after it has been imaged in the brain, has been used to assess how coherent or connected specific locations in the brain are networked together in several different neurological disorders. Statistical analysis can then be performed on the coherence results to verify evidence of normal or abnormal network activity in a patient. In this review we highlight how functional brain connectivity is assessed in Source space using coherence technique measured by MEG.

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Exploring intermediate phenotypes with EEG: Working memory dysfunction in schizophrenia

Cited by 45 publications

References 250 publications

Dysfunctional Prefrontal Cortical Network Activity and Interactions following Cannabinoid Receptor Activation

Dysfunctional Prefrontal Cortical Network Activity and Interactions following Cannabinoid Receptor Activation

Disrupting the clustering of GABA_Areceptor α2 subunits in the frontal cortex leads to reduced γ-power and cognitive deficits

Coherence a measure of the brain networks: past and present

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Exploring intermediate phenotypes with EEG: Working memory dysfunction in schizophrenia

Cited by 45 publications

References 250 publications

Dysfunctional Prefrontal Cortical Network Activity and Interactions following Cannabinoid Receptor Activation

Dysfunctional Prefrontal Cortical Network Activity and Interactions following Cannabinoid Receptor Activation

Disrupting the clustering of GABAAreceptor α2 subunits in the frontal cortex leads to reduced γ-power and cognitive deficits

Coherence a measure of the brain networks: past and present

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Disrupting the clustering of GABA_Areceptor α2 subunits in the frontal cortex leads to reduced γ-power and cognitive deficits