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Article ; Online: Challenges Associated With Neuropharmacological Challenge Studies.

Mathalon, Daniel H

2020 Volume 88, Issue 9, Page(s) 670–672

MeSH term(s)	Double-Blind Method ; Humans ; Schizophrenia
Language	English
Publishing date	2020-10-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2020.08.015
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Article ; Online: P300 in schizophrenia: Then and now.

Hamilton, Holly K / Mathalon, Daniel H / Ford, Judith M

Biological psychology

2024 Volume 187, Page(s) 108757

Abstract: The 1965 discovery of the P300 component of the electroencephalography (EEG)-based event-related potential (ERP), along with the subsequent identification of its alteration in people with schizophrenia, initiated over 50 years of P300 research in ... ...

Abstract	The 1965 discovery of the P300 component of the electroencephalography (EEG)-based event-related potential (ERP), along with the subsequent identification of its alteration in people with schizophrenia, initiated over 50 years of P300 research in schizophrenia. Here, we review what we now know about P300 in schizophrenia after nearly six decades of research. We describe recent efforts to expand our understanding of P300 beyond its sensitivity to schizophrenia itself to its potential role as a biomarker of risk for psychosis or a heritable endophenotype that bridges genetic risk and psychosis phenomenology. We also highlight efforts to move beyond a syndrome-based approach to understand P300 within the context of the clinical, cognitive, and presumed pathophysiological heterogeneity among people diagnosed with schizophrenia. Finally, we describe several recent approaches that extend beyond measuring the traditional P300 ERP component in people with schizophrenia, including time-frequency analyses and pharmacological challenge studies, that may help to clarify specific cognitive mechanisms that are disrupted in schizophrenia. Moreover, we discuss several promising areas for future research, including studies of animal models that can be used for treatment development.
MeSH term(s)	Humans ; Electroencephalography ; Event-Related Potentials, P300/physiology ; Evoked Potentials ; Psychotic Disorders ; Schizophrenia
Chemical Substances	EP300 protein, human (EC 2.3.1.48)
Language	English
Publishing date	2024-02-03
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	185105-6
ISSN	1873-6246 ; 0301-0511
ISSN (online)	1873-6246
ISSN	0301-0511
DOI	10.1016/j.biopsycho.2024.108757
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Article ; Online: Probing long-term potentiation-like visual cortical plasticity in humans using repeated visual stimulation: effects on visual evoked potentials.

Hamilton, Holly K / Mathalon, Daniel H

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2022 Volume 48, Issue 1, Page(s) 217–218

MeSH term(s)	Humans ; Evoked Potentials, Visual ; Long-Term Potentiation/physiology ; Photic Stimulation ; Visual Cortex ; Neuronal Plasticity/physiology ; Evoked Potentials, Motor ; Transcranial Magnetic Stimulation ; Evoked Potentials ; Electric Stimulation
Language	English
Publishing date	2022-08-13
Publishing country	England
Document type	News ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-022-01420-3
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Article: Spectral graph model for fMRI: a biophysical, connectivity-based generative model for the analysis of frequency-resolved resting state fMRI.

Raj, Ashish / Sipes, Benjamin S / Verma, Parul / Mathalon, Daniel H / Biswal, Bharat / Nagarajan, Srikantan

bioRxiv : the preprint server for biology

2024

Abstract: Resting state functional MRI (rs-fMRI) is a popular and widely used technique to explore the brain's functional organization and to examine if it is altered in neurological or mental disorders. The most common approach for its analysis targets the ... ...

Abstract	Resting state functional MRI (rs-fMRI) is a popular and widely used technique to explore the brain's functional organization and to examine if it is altered in neurological or mental disorders. The most common approach for its analysis targets the measurement of the synchronized fluctuations between brain regions, characterized as functional connectivity (FC), typically relying on pairwise correlations in activity across different brain regions. While hugely successful in exploring state- and disease-dependent network alterations, these statistical graph theory tools suffer from two key limitations. First, they discard useful information about the rich frequency content of the fMRI signal. The rich spectral information now achievable from advances in fast multiband acquisitions is consequently being under-utilized. Second, the analyzed FCs are phenomenological without a direct neurobiological underpinning in the underlying structures and processes in the brain. There does not currently exist a complete generative model framework for whole brain resting fMRI that is informed by its underlying biological basis in the structural connectome. Here we propose that a different approach can solve both challenges at once: the use of an appropriately realistic yet parsimonious biophysical signal generation model followed by graph spectral (i.e. eigen) decomposition. We call this model a Spectral Graph Model (SGM) for fMRI, using which we can not only quantify the structure-function relationship in individual subjects, but also condense the variable and individual-specific repertoire of fMRI signal's spectral and spatial features into a small number of biophysically-interpretable parameters. We expect this model-based inference of rs-fMRI that seamlessly integrates with structure can be used to examine state and trait characteristics of structure-function relations in a variety of brain disorders.
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.22.586305
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Article ; Online: Efference Copy, Corollary Discharge, Predictive Coding, and Psychosis.

Ford, Judith M / Mathalon, Daniel H

Biological psychiatry. Cognitive neuroscience and neuroimaging

2019 Volume 4, Issue 9, Page(s) 764–767

MeSH term(s)	Brain/physiopathology ; Efferent Pathways/physiopathology ; Electrophysiological Phenomena/physiology ; Hallucinations/etiology ; Hallucinations/physiopathology ; Humans ; Motor Activity/physiology ; Psychotic Disorders/complications ; Psychotic Disorders/physiopathology ; Thinking/physiology
Language	English
Publishing date	2019-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2879089-3
ISSN	2451-9030 ; 2451-9022
ISSN (online)	2451-9030
ISSN	2451-9022
DOI	10.1016/j.bpsc.2019.07.005
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Article: Predicting Functional Connectivity From Observed and Latent Structural Connectivity

Cummings, Jennifer A / Sipes, Benjamin / Mathalon, Daniel H / Raj, Ashish

Frontiers in neuroscience

2022 Volume 16, Page(s) 810111

Abstract: Understanding how complex dynamic activity propagates over a static structural network is an overarching question in the field of neuroscience. Previous work has demonstrated that linear graph-theoretic models perform as well as non-linear neural ... ...

Abstract	Understanding how complex dynamic activity propagates over a static structural network is an overarching question in the field of neuroscience. Previous work has demonstrated that linear graph-theoretic models perform as well as non-linear neural simulations in predicting functional connectivity with the added benefits of low dimensionality and a closed-form solution which make them far less computationally expensive. Here we show a simple model relating the eigenvalues of the structural connectivity and functional networks using the Gamma function, producing a reliable prediction of functional connectivity with a single model parameter. We also investigate the impact of local activity diffusion and long-range interhemispheric connectivity on the structure-function model and show an improvement in functional connectivity prediction when accounting for such latent variables which are often excluded from traditional diffusion tensor imaging (DTI) methods.
Language	English
Publishing date	2022-03-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2022.810111
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Article ; Online: Pons-to-Cerebellum Hypoconnectivity Along the Psychosis Spectrum and Associations With Sensory Prediction and Hallucinations in Schizophrenia.

Abram, Samantha V / Hua, Jessica P Y / Nicholas, Spero / Roach, Brian / Keedy, Sarah / Sweeney, John A / Mathalon, Daniel H / Ford, Judith M

Biological psychiatry. Cognitive neuroscience and neuroimaging

2024

Abstract: Background: Sensory prediction allows the brain to anticipate and parse incoming self-generated sensory information from externally generated signals. Sensory prediction breakdowns may contribute to perceptual and agency abnormalities in psychosis ( ... ...

Abstract	Background: Sensory prediction allows the brain to anticipate and parse incoming self-generated sensory information from externally generated signals. Sensory prediction breakdowns may contribute to perceptual and agency abnormalities in psychosis (hallucinations, delusions). The pons, a central node in a cortico-ponto-cerebellar-thalamo-cortical circuit, is thought to support sensory prediction. Examination of pons connectivity in schizophrenia and its role in sensory prediction abnormalities is lacking. Methods: We examined these relationships using resting-state functional magnetic resonance imaging and the electroencephalography-based auditory N1 event-related potential in 143 participants with psychotic spectrum disorders (PSPs) (with schizophrenia, schizoaffective disorder, or bipolar disorder); 63 first-degree relatives of individuals with psychosis; 45 people at clinical high risk for psychosis; and 124 unaffected comparison participants. This unique sample allowed examination across the psychosis spectrum and illness trajectory. Seeding from the pons, we extracted average connectivity values from thalamic and cerebellar clusters showing differences between PSPs and unaffected comparison participants. We predicted N1 amplitude attenuation during a vocalization task from pons connectivity and group membership. We correlated participant-level connectivity in PSPs and people at clinical high risk for psychosis with hallucination and delusion severity. Results: Compared to unaffected comparison participants, PSPs showed pons hypoconnectivity to 2 cerebellar clusters, and first-degree relatives of individuals with psychosis showed hypoconnectivity to 1 of these clusters. Pons-to-cerebellum connectivity was positively correlated with N1 attenuation; only PSPs with heightened pons-to-postcentral gyrus connectivity showed this pattern, suggesting a possible compensatory mechanism. Pons-to-cerebellum hypoconnectivity was correlated with greater hallucination severity specifically among PSPs with schizophrenia. Conclusions: Deficient pons-to-cerebellum connectivity linked sensory prediction network breakdowns with perceptual abnormalities in schizophrenia. Findings highlight shared features and clinical heterogeneity across the psychosis spectrum.
Language	English
Publishing date	2024-02-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2879089-3
ISSN	2451-9030 ; 2451-9022
ISSN (online)	2451-9030
ISSN	2451-9022
DOI	10.1016/j.bpsc.2024.01.010
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Article ; Online: Mismatch Negativity and Theta Oscillations Evoked by Auditory Deviance in Early Schizophrenia.

Hua, Jessica P Y / Roach, Brian J / Ford, Judith M / Mathalon, Daniel H

Biological psychiatry. Cognitive neuroscience and neuroimaging

2023 Volume 8, Issue 12, Page(s) 1186–1196

Abstract: Background: Amplitude reduction of mismatch negativity (MMN), an event-related potential component indexing NMDA receptor-dependent auditory echoic memory and predictive coding, is widely replicated in schizophrenia. Time-frequency analyses of single- ... ...

Abstract	Background: Amplitude reduction of mismatch negativity (MMN), an event-related potential component indexing NMDA receptor-dependent auditory echoic memory and predictive coding, is widely replicated in schizophrenia. Time-frequency analyses of single-trial electroencephalography epochs suggest that theta oscillation abnormalities underlie MMN deficits in schizophrenia. However, this has received less attention in early schizophrenia (ESZ). Methods: Patients with ESZ (n = 89), within 5 years of illness onset, and healthy control subjects (n = 105) completed an electroencephalography MMN paradigm (duration-deviant, pitch-deviant, duration + pitch double-deviant). Repeated measures analyses of variance assessed group differences in MMN, theta intertrial phase coherence (ITC), and theta total power from frontocentral electrodes, after normal age adjustment. Group differences were retested after covarying MMN and theta measures. Results: Relative to healthy control subjects, patients with ESZ showed auditory deviance deficits. Patients with ESZ had MMN deficits for duration-deviants (p = .041), pitch-deviants (ps = .007), and double-deviants (ps < .047). Patients with ESZ had reduced theta ITC for standards (ps < .040) and duration-deviants (ps < .030). Furthermore, patients with ESZ had reduced theta power across deviants at central electrodes (p = .013). MMN group deficits were not fully accounted for by theta ITC and power, and neither were theta ITC group deficits fully accounted for by MMN. Group differences in theta total power were no longer significant after covarying for MMN. Conclusions: Patients with ESZ showed reduced MMN and theta total power for all deviant types. Theta ITC showed a relatively specific reduction for duration-deviants. Although MMN and theta ITC were correlated in ESZ, covarying for one did not fully account for deficits in the other, raising the possibility of their sensitivity to dissociable pathophysiological processes.
MeSH term(s)	Humans ; Schizophrenia ; Evoked Potentials, Auditory/physiology ; Acoustic Stimulation ; Evoked Potentials ; Electroencephalography
Language	English
Publishing date	2023-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2879089-3
ISSN	2451-9030 ; 2451-9022
ISSN (online)	2451-9030
ISSN	2451-9022
DOI	10.1016/j.bpsc.2023.03.004
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Article ; Online: Vocalizing and singing reveal complex patterns of corollary discharge function in schizophrenia.

Ford, Judith M / Roach, Brian J / Mathalon, Daniel H

International journal of psychophysiology : official journal of the International Organization of Psychophysiology

2021 Volume 164, Page(s) 30–40

Abstract: Introduction: As we vocalize, our brains generate predictions of the sounds we produce to enable suppression of neural responses when intentions match vocalizations and to make adjustments when they do not. This may be instantiated by efference copy and ...

Abstract	Introduction: As we vocalize, our brains generate predictions of the sounds we produce to enable suppression of neural responses when intentions match vocalizations and to make adjustments when they do not. This may be instantiated by efference copy and corollary discharge mechanisms, which are impaired in people with schizophrenia (SZ). Although innate, these mechanisms can be affected by intentions. We asked if attending to pitch during vocalizations would take these mechanisms "off-line" and reduce suppression. Methods: Event-related potentials (ERP) were recorded from 96 SZ and 92 healthy controls (HC) as they vocalized triplets in monotone (Phrase) or sang triplets in ascending thirds (Pitch). Pre-vocalization activity (Bereitschaftspotential, BP), N1, and P2 ERP components to sounds were compared during vocalization and playback. Results: N1 was not as suppressed during Pitch as during Phrase. N1 suppression was not affected by SZ in either task when all data were collapsed across pitches (Pitch) and positions (Phrase). However, when binned according to vocalization performance, SZ showed less N1 suppression than HC at longer (>2 s) inter-stimulus intervals (Phrase) and inconsistent suppression across pitches (Pitch). Unlike N1, P2 was more suppressed during Pitch than Phrase and not affected by SZ. BP was greater during vocalization than playback but did not contribute to N1 or P2 effects. Pitch variability was inversely related to negative symptoms. Conclusions: Neural processing is not suppressed when patients and controls sing, and corollary discharge abnormalities in schizophrenia are only seen at long vocalization intervals.
MeSH term(s)	Electroencephalography ; Evoked Potentials ; Evoked Potentials, Auditory ; Humans ; Patient Discharge ; Schizophrenia ; Singing
Language	English
Publishing date	2021-02-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	605645-3
ISSN	1872-7697 ; 0167-8760
ISSN (online)	1872-7697
ISSN	0167-8760
DOI	10.1016/j.ijpsycho.2021.02.013
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Article ; Online: Phase Delay of the 40 Hz Auditory Steady-State Response Localizes to Left Auditory Cortex in Schizophrenia.

Roach, Brian J / Hirano, Yoji / Ford, Judith M / Spencer, Kevin M / Mathalon, Daniel H

Clinical EEG and neuroscience

2022 Volume 54, Issue 4, Page(s) 370–378

Abstract: Background. ...

Abstract	Background.
MeSH term(s)	Humans ; Schizophrenia/diagnosis ; Evoked Potentials, Auditory/physiology ; Electroencephalography/methods ; Auditory Cortex ; Acoustic Stimulation/methods ; Polyesters
Chemical Substances	Polyesters
Language	English
Publishing date	2022-10-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2140201-2
ISSN	2169-5202 ; 0009-9155 ; 1550-0594
ISSN (online)	2169-5202
ISSN	0009-9155 ; 1550-0594
DOI	10.1177/15500594221130896
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