Auditory steady state response in the schizophrenia, first-degree relatives, and schizotypal personality disorder

Rass, Olga; Forsyth, Jennifer K.; Krishnan, Giri P.; Hetrick, William P.; Klaunig, Mallory J.; Breier, Alan; O’Donnell, Brian F.; Brenner, Colleen A.

doi:10.1016/j.schres.2012.01.003

Cited by 77 publications

(79 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2012, Nakao & Nakazawa 2014). Interestingly, also in this testing paradigm, the response amplitude of single cells, in terms of relative change in mean firing rate, showed a significant decrease in Df(h15q13)/+ compared to wild‐type mice (Krishnan et al .…”

Section: Resultsmentioning

confidence: 99%

The translationally relevant mouse model of the 15q13.3 microdeletion syndrome reveals deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia

et al. 2016

View full text Add to dashboard Cite

AimTo date, the understanding and development of novel treatments for mental illness is hampered by inadequate animal models. For instance, it is unclear to what extent commonly used behavioural tests in animals can inform us on the mental and affective aspects of schizophrenia.MethodsTo link pathophysiological processes in an animal model to clinical findings, we have here utilized the recently developed Df(h15q13)/+ mouse model for detailed investigations of cortical neuronal engagement during pre‐attentive processing of auditory information from two back‐translational auditory paradigms. We also investigate if compromised putative fast‐spiking interneurone (FSI) function can be restored through pharmacological intervention using the Kv3.1 channel opener RE1. Chronic multi‐array electrodes in primary auditory cortex were used to record single cell firing from putative pyramidal and FSI in awake animals during processing of auditory sensory information.ResultsWe find a decreased amplitude in the response to auditory stimuli and reduced recruitment of neurones to fast steady‐state gamma oscillatory activity. These results resemble encephalography recordings in patients with schizophrenia. Furthermore, the probability of interneurones to fire with low interspike intervals during 80 Hz auditory stimulation was reduced in Df(h15q13)/+ mice, an effect that was partially reversed by the Kv3.1 channel modulator, RE1.ConclusionThis study offers insight into the consequences on a neuronal level of carrying the 15q13.3 microdeletion. Furthermore, it points to deficient functioning of interneurones as a potential pathophysiological mechanism in schizophrenia and suggests a therapeutic potential of Kv3.1 channel openers.

show abstract

Section: Resultsmentioning

confidence: 99%

The translationally relevant mouse model of the 15q13.3 microdeletion syndrome reveals deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Following the original and landmark observation that 40 Hz ASSR is specifically deficient in schizophrenia subjects (Kwon et al, 1999), numerous reports have broadly confirmed the finding (Brenner et al, 2003;Krishnan et al, 2009;Light et al, 2006;Spencer, 2011;Spencer et al, 2008;Vierling-Claassen et al, 2008), and extended it to first-degree relatives of schizophrenia subjects (Hong et al, 2004;Rass et al, 2012), suggesting that such a deficit may be a trait marker. However, it is pertinent to note that 40 Hz ASSR deficit is not specific to schizophrenia and extends to some neuropsychiatric conditions including bipolar disorder (Oda et al, 2012;Rass et al, 2010) and autism spectrum disorders (Rojas et al, 2011;Wilson et al, 2007).…”

Section: Introductionmentioning

confidence: 89%

40 Hz Auditory Steady-State Response Is a Pharmacodynamic Biomarker for Cortical NMDA Receptors

Sivarao

Chen

Senapati

et al. 2016

Neuropsychopharmacol

113

106

View full text Add to dashboard Cite

Schizophrenia patients exhibit dysfunctional gamma oscillations in response to simple auditory stimuli or more complex cognitive tasks, a phenomenon explained by reduced NMDA transmission within inhibitory/excitatory cortical networks. Indeed, a simple steady-state auditory click stimulation paradigm at gamma frequency (~40 Hz) has been reproducibly shown to reduce entrainment as measured by electroencephalography (EEG) in patients. However, some investigators have reported increased phase locking factor (PLF) and power in response to 40 Hz auditory stimulus in patients. Interestingly, preclinical literature also reflects this contradiction. We investigated whether a graded deficiency in NMDA transmission can account for such disparate findings by administering subanesthetic ketamine (1-30 mg/kg, i.v.) or vehicle to conscious rats (n = 12) and testing their EEG entrainment to 40 Hz click stimuli at various time points (~7-62 min after treatment). In separate cohorts, we examined in vivo NMDA channel occupancy and tissue exposure to contextualize ketamine effects. We report a robust inverse relationship between PLF and NMDA occupancy 7 min after dosing. Moreover, ketamine could produce inhibition or disinhibition of the 40 Hz response in a temporally dynamic manner. These results provide for the first time empirical data to understand how cortical NMDA transmission deficit may lead to opposite modulation of the auditory steady-state response (ASSR). Importantly, our findings posit that 40 Hz ASSR is a pharmacodynamic biomarker for cortical NMDA function that is also robustly translatable. Besides schizophrenia, such a functional biomarker may be of value to neuropsychiatric disorders like bipolar and autism spectrum where 40 Hz ASSR deficits have been documented.

show abstract

“…Generally, the ASSR phase locking factor (PLF) has been found to be superior in sensitivity to a Fourier power analysis in analyzing the ASSR – the PLF measures the consistency of time-locked responses to each individual stimulus in the ASSR and is reduced in schizophrenia. Importantly, the ASSR abnormality in schizophrenia appears not to be an artifact of medication [14] and is reduced in unaffected and psychotropic medication naïve 1st degree relatives of schizophrenia patients [15]. Psychotic bipolar patients also show GBO deficits but do not show the schizophrenia-specific lateralized pattern of greater deficits in the left hemisphere, where numerous MRI studies show a similarly left-lateralized reduction of cortical gray matter [14].…”

Section: Importance Of γ Band Oscillation Activity In Brain Circuit Cmentioning

confidence: 99%

Gamma band oscillations

McNally

McCarley²

2016

Current Opinion in Psychiatry

120

View full text Add to dashboard Cite

Purpose of review We review our current understanding of abnormal γ band oscillations in schizophrenia, their association with symptoms and the underlying cortical circuit abnormality, with a particular focus on the role of fast-spiking parvalbumin gamma-aminobutyric acid (GABA) neurons in the disease state. Recent findings Clinical electrophysiological studies of schizophrenia patients and pharmacological models of the disorder show an increase in spontaneous γ band activity (not stimulus-evoked) measures. These findings provide a crucial link between preclinical and clinical work examining the role of γ band activity in schizophrenia. MRI-based experiments measuring cortical GABA provides evidence supporting impaired GABAergic neurotransmission in schizophrenia patients, which is correlated with γ band activity level. Several studies suggest that stimulation of the cortical circuitry, directly or via subcortical structures, has the potential to modulate cortical γ activity, and improve cognitive function. Summary Abnormal γ band activity is observed in patients with schizophrenia and disease models in animals, and is suggested to underlie the psychosis and cognitive/perceptual deficits. Convergent evidence from both clinical and preclinical studies suggest the central factor in γ band abnormalities is impaired GABAergic neurotransmission, particularly in a subclass of neurons which express parvalbumin. Rescue of γ band abnormalities presents an intriguing option for therapeutic intervention.

show abstract

Auditory steady state response in the schizophrenia, first-degree relatives, and schizotypal personality disorder

Cited by 77 publications

References 50 publications

The translationally relevant mouse model of the 15q13.3 microdeletion syndrome reveals deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia

The translationally relevant mouse model of the 15q13.3 microdeletion syndrome reveals deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia

40 Hz Auditory Steady-State Response Is a Pharmacodynamic Biomarker for Cortical NMDA Receptors

Gamma band oscillations

Contact Info

Product

Resources

About