Relationships between cognitive event-related brain potential measures in patients at clinical high risk for psychosis

Lepock, Jennifer R.; Ahmed, Sarah; Mizrahi, Romina; Gerritsen, Cory; Maheandiran, Margaret; Drvaric, Lauren; Bagby, R. Michael; Korostil, Michèle; Light, Gregory A.; Kiang, Michael

doi:10.1016/j.schres.2019.01.014

Cited by 33 publications

(34 citation statements)

References 86 publications

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“…Consistent with our hypothesis, we found a reduction in 40-Hz-ASSR amplitudes in both FEP and CHR-P participants in auditory and thalamic regions. This contrasts with several recent EEG-studies that found intact 40-Hz-ASSRs in both CHR-P (27) and FEP-groups (28). One possible explanation are differences in recording techniques of 40-Hz-ASSRs.…”

Section: Discussioncontrasting

confidence: 98%

40 Hz Auditory Steady-State Responses Predict Transition to Psychosis in Clinical-High-Risk Participants: A MEG Study

Grent-‘t-Jong

Gajwani

Groß

et al. 2020

Preprint

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Objective: To examine whether 40-Hz Auditory Steady-State Responses (ASSR) in participants at clinical high-risk for psychosis predict clinical outcomes. Method: In this study, magnetoencephalography (MEG) data were collected during a 40-Hz ASSR paradigm in 116 participants meeting clinical high-risk (CHR-P) for psychosis criteria, a clinical control group characterized by affective disorders and/or substance abuse (CHR-N: n=38), 32 first-episode psychosis patients (FEP, 14 antipsychotic-naive), and 49 healthy controls. We examined 40-Hz-ASSR- source-activity in bilateral Heschl's gyrus, superior temporal gyrus, Rolandic operculum, and the thalamus. Group differences in ASSR amplitudes were tested and correlated with neuropsychological scores, psychosocial functioning, and clinical symptoms. Linear discriminant analyses was used to assess whether 40-Hz-ASSR predicts transition to psychosis and persistence of APS. Results: Compared to controls, 40-Hz-ASSR responses in CHR-Ps were impaired in right Rolandic operculum (d=0.41) and right thalamus (d=0.43), particularly in those with combined UHR/BS symptoms and CHR-Ps who transitioned to psychosis (n=11). FEP-patients showed significant impairments in the right thalamus (d=0.58), while the CHR-N group was unaffected. Importantly, right thalamus 40-Hz-ASSRs predicted transition to psychosis (transitioned [n=11] vs non-transitioned [n=105]); classification accuracy 73.3%, AUC=0.827), whereas this was not the case for persistent APS (Persistent [n=41] vs non-Persistent [n=37]; classification accuracy 56.4%). Conclusions: The current study indicates that MEG-recorded 40-Hz-ASSRs constitute a potential biomarker for predicting transition to psychosis in CHR-P participants.

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Section: Discussioncontrasting

confidence: 98%

40 Hz Auditory Steady-State Responses Predict Transition to Psychosis in Clinical-High-Risk Participants: A MEG Study

Grent-‘t-Jong

Gajwani

Groß

et al. 2020

Preprint

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“…Participants included 35 CHR patients. We previously reported N400 data from a subset of this sample and healthy control participants (Lepock, Ahmed, et al, 2019). CHR participants were help‐seeking outpatients referred to the Focus on Youth Psychosis Prevention clinic at the Centre for Addiction and Mental Health (CAMH) in Toronto.…”

Section: Methodsmentioning

confidence: 99%

N400 event‐related brain potential as an index of real‐world and neurocognitive function in patients at clinical high risk for schizophrenia

Lepock

Ahmed

Mizrahi

et al. 2019

Early Intervention Psych

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Aim The N400 event‐related potential is a neurophysiological index of cognitive processing of real‐world knowledge. In healthy populations, N400 amplitude is smaller in response to stimuli that are more related to preceding context. This ‘N400 semantic priming effect’ is thought to reflect activation of contextually related information in semantic memory (SM). N400 semantic priming deficits have been found in schizophrenia, and in patients at clinical high risk (CHR) for this disorder. Because this abnormality in processing relationships between meaningful stimuli could affect ability to navigate everyday situations, we hypothesized it would be associated with real‐world functional impairment in CHR patients. Second, we hypothesized it would correlate with global neurocognitive impairment in this group. Methods We measured N400 semantic priming in 35 CHR patients who viewed prime words each followed by a related or unrelated target word, at stimulus‐onset asynchrony (SOA) of 300 or 750 ms. We measured academic/occupational and social function with the global function (GF): Role and Social scales, and cognitive function with the MATRICS Consensus Cognitive Battery (MCCB). Results Decreased N400 semantic priming at the 300‐ms SOA correlated with lower GF:Role scores. Decreased N400 semantic priming at the 750‐ms SOA correlated with lower MCCB composite scores. Conclusions Deficits in activating contextually related concepts in SM over short time intervals may contribute to functional impairment in CHR patients. Furthermore, N400 priming deficits over longer intervals may be a biomarker of global cognitive dysfunction in this population. Longitudinal studies are needed to determine whether these deficits are associated with schizophrenia risk within this population.

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“…While we cannot rule out the potential for medications to enhance or blunt gains from cognitive training, our previous studies from this sample suggest that the pro-cognitive benefits of TCT may offset the adverse cognitive effects of antipsychotic polypharmacy and anticholinergic burden 68 . Third, this study was conducted in patients with refractory psychotic disorders with well-established illness; therefore, the findings may not generalize to at-risk, early illness, or other clinical populations 28,69 . Fourth, no group-level differences were detected in ASSR measures after 1 h of TCT.…”

Section: Caveats and Limitationsmentioning

confidence: 99%

Gamma oscillations predict pro-cognitive and clinical response to auditory-based cognitive training in schizophrenia

et al. 2020

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Cognitive impairments are pervasive and disabling features of schizophrenia. Targeted cognitive training (TCT) is a “bottom-up” cognitive remediation intervention with efficacy for neurocognitive outcomes in schizophrenia, yet individual responses are variable. Gamma oscillatory measures are leading candidate biomarkers in the development of biologically informed pro-cognitive therapeutics. Forty-two schizophrenia patients were recruited from a long-term residential treatment facility. Participants were randomized to receive either 1 h of cognitive training (TCT, n = 21) or computer games (TAU, n = 21). All participants received standard-of-care treatment; the TCT group additionally completed 30 h of cognitive training. The auditory steady-state response paradigm was used to elicit gamma oscillatory power and synchrony during electroencephalogram recordings. Detailed clinical and cognitive assessments were collected at baseline and after completion of the study. Baseline gamma power predicted cognitive gains after a full course of TCT (MCCB, R2 = 0.31). A change in gamma power after 1-h TCT exposure predicted improvement in both positive (SAPS, R2 = 0.40) and negative (SANS, R2 = 0.30) symptoms. These relationships were not observed in the TAU group (MCCB, SAPS, and SANS, all R2 < 0.06). The results indicate that the capacity to support gamma oscillations, as well as the plasticity of the underlying ASSR circuitry after acute exposure to 1 h of TCT, reflect neural mechanisms underlying the efficacy of TCT, and may be used to predict individualized treatment outcomes. These findings suggest that gamma oscillatory biomarkers applied within the context of experimental medicine designs can be used to personalize individual treatment options for pro-cognitive interventions in patients with schizophrenia.

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Relationships between cognitive event-related brain potential measures in patients at clinical high risk for psychosis

Cited by 33 publications

References 86 publications

40 Hz Auditory Steady-State Responses Predict Transition to Psychosis in Clinical-High-Risk Participants: A MEG Study

40 Hz Auditory Steady-State Responses Predict Transition to Psychosis in Clinical-High-Risk Participants: A MEG Study

N400 event‐related brain potential as an index of real‐world and neurocognitive function in patients at clinical high risk for schizophrenia

Gamma oscillations predict pro-cognitive and clinical response to auditory-based cognitive training in schizophrenia

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