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Article ; Online: Effects of Hallucination Proneness and Sensory Resolution on Prior Biases in Human Perceptual Inference of Time Intervals.

Duhamel, Emeline / Mihali, Andra / Horga, Guillermo

The Journal of neuroscience : the official journal of the Society for Neuroscience

2023 Volume 43, Issue 29, Page(s) 5365–5377

Abstract: Bayesian models of perception posit that percepts result from the optimal integration of new sensory information and prior expectations. In turn, prominent models of perceptual disturbances in psychosis frame hallucination-like phenomena as percepts ... ...

Abstract	Bayesian models of perception posit that percepts result from the optimal integration of new sensory information and prior expectations. In turn, prominent models of perceptual disturbances in psychosis frame hallucination-like phenomena as percepts excessively biased toward perceptual prior expectations. Despite mounting support for this notion, whether this hallucination-related prior bias results secondarily from imprecise sensory representations at early processing stages or directly from alterations in perceptual priors-both suggested candidates potentially consistent with Bayesian models-remains to be tested. Using modified interval timing paradigms designed to arbitrate between these alternative hypotheses, we show in human participants (16 females and 24 males) from a nonclinical population that hallucination proneness correlates with a circumscribed form of prior bias that reflects selective differences in weighting of contextual prior variance, a prior bias that is unrelated to the effect of sensory noise and to a separate index of sensory resolution. Our results thus suggest distinct mechanisms underlying prior biases in perceptual inference and favor the notion that hallucination proneness could reflect direct alterations in the representation or use of perceptual priors independent of sensory noise.
MeSH term(s)	Male ; Female ; Humans ; Bayes Theorem ; Hallucinations ; Psychotic Disorders ; Illusions ; Bias
Language	English
Publishing date	2023-06-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.0692-22.2023
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Article ; Online: Altered hierarchical gradients of intrinsic neural timescales in mild cognitive impairment and Alzheimer's disease.

Zhang, Aiying / Wengler, Kenneth / Zhu, Xi / Horga, Guillermo / Goldberg, Terry E / Lee, Seonjoo

The Journal of neuroscience : the official journal of the Society for Neuroscience

2024

Abstract: Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects millions of seniors in the US. Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to study neurophysiology in AD and its prodromal condition, mild ... ...

Abstract	Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects millions of seniors in the US. Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to study neurophysiology in AD and its prodromal condition, mild cognitive impairment (MCI). The intrinsic neural timescale (INT), which can be estimated through the magnitude of the autocorrelation of neural signals from rs-fMRI, is thought to quantify the duration that neural information is stored in a local circuit. Such heterogeneity of the timescales forms a basis of the brain functional hierarchy and captures an aspect of circuit dynamics relevant to excitation/inhibition balance, which is broadly relevant for cognitive functions. Given that, we applied rs-fMRI to test whether distinct changes of INT at different hierarchies are present in people with MCI, those progressing to AD (called Converter), and AD patients of both sexes. Linear mixed effect model was implemented to detect altered hierarchical gradients across populations followed by pairwise comparisons to identify regional differences. High similarities between AD and Converter were observed. Specifically, the inferior temporal, caudate, pallidum areas exhibit significant alterations in both AD and Converter. Distinct INT related pathological changes in MCI and AD were found. For AD/Converter, neural information is stored for a longer time in lower hierarchical areas, while higher levels of hierarchy seem to be preferentially impaired in MCI leading to a less pronounced hierarchical gradients. These results inform that the INT holds great potential as an additional measure for AD prediction, even a stable biomarker for clinical diagnosis.
Language	English
Publishing date	2024-04-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.2024-23.2024
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Article ; Online: Introspective inference counteracts perceptual distortion.

Mihali, Andra / Broeker, Marianne / Ragalmuto, Florian D M / Horga, Guillermo

Nature communications

2023 Volume 14, Issue 1, Page(s) 7826

Abstract: Introspective agents can recognize the extent to which their internal perceptual experiences deviate from the actual states of the external world. This ability, also known as insight, is critically required for reality testing and is impaired in ... ...

Abstract	Introspective agents can recognize the extent to which their internal perceptual experiences deviate from the actual states of the external world. This ability, also known as insight, is critically required for reality testing and is impaired in psychosis, yet little is known about its cognitive underpinnings. We develop a Bayesian modeling framework and a psychophysics paradigm to quantitatively characterize this type of insight while people experience a motion after-effect illusion. People can incorporate knowledge about the illusion into their decisions when judging the actual direction of a motion stimulus, compensating for the illusion (and often overcompensating). Furthermore, confidence, reaction-time, and pupil-dilation data all show signatures consistent with inferential adjustments in the Bayesian insight model. Our results suggest that people can question the veracity of what they see by making insightful inferences that incorporate introspective knowledge about internal distortions.
MeSH term(s)	Humans ; Perceptual Distortion ; Illusions ; Bayes Theorem ; Psychophysics ; Psychotic Disorders ; Motion Perception
Language	English
Publishing date	2023-11-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-42813-2
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Article ; Online: Publisher Correction: An integrative framework for perceptual disturbances in psychosis.

Horga, Guillermo / Abi-Dargham, Anissa

Nature reviews. Neuroscience

2020 Volume 21, Issue 5, Page(s) 297

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Language	English
Publishing date	2020-03-03
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	2034150-7
ISSN	1471-0048 ; 1471-0048 ; 1471-003X
ISSN (online)	1471-0048
ISSN	1471-0048 ; 1471-003X
DOI	10.1038/s41583-020-0290-6
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Zs.A 5473: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Altered hierarchical gradients of intrinsic neural timescales in mild cognitive impairment and Alzheimer's disease.

Zhang, Aiying / Wengler, Kenneth / Zhu, Xi / Horga, Guillermo / Goldberg, Terry E / Lee, Seonjoo

bioRxiv : the preprint server for biology

2023

Abstract: Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects millions of older adults in the US and worldwide. Resting-state functional magnetic resonance imaging (rs-fMRI) has become a widely used neuroimaging tool to study ... ...

Abstract	Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects millions of older adults in the US and worldwide. Resting-state functional magnetic resonance imaging (rs-fMRI) has become a widely used neuroimaging tool to study neurophysiology in AD and its prodromal condition, mild cognitive impairment (MCI). The intrinsic neural timescale (INT), which can be estimated through the magnitude of the autocorrelation of intrinsic neural signals using rs-fMRI, is thought to quantify the duration that neural information is stored in a local cortical circuit. The heterogeneity of the timescales is considered to be a basis of the functional hierarchy in the brain. In addition, INT captures an aspect of circuit dynamics relevant to excitation/inhibition (E/I) balance, which is thought to be broadly relevant for cognitive functions. Here we examined its relevance to AD. We used rs-fMRI data of 904 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The subjects were divided into 4 groups based on their baseline and end-visit clinical status, which were cognitively normal (CN), stable MCI, Converter, and AD groups. Linear mixed effect model and pairwise comparison were implemented to investigate the large-scale hierarchical organization and local differences. We observed high similarities between AD and Converter groups. Specifically, among the eight identified ROIs with distinct INT alterations in AD, three ROIs (inferior temporal, caudate, pallidum areas) exhibit stable and significant alteration in AD converter. In addition, distinct INT related pathological changes in stable MCI and AD/Converter were found. For AD and Converter groups, neural information is stored for a longer time in lower hierarchical order areas, while higher levels of hierarchy seem to be preferentially impaired in stable MCI leading to a less pronounced hierarchical gradient effect. These results inform that the INT holds great potential as an additional measure for AD prediction, a stable biomarker for clinical diagnosis and an important therapeutic target in AD.
Language	English
Publishing date	2023-09-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.26.559549
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Article: Gender similarities and differences in skeletal muscle and body composition: an MRI study of recreational cyclists.

Belzunce, Martin Alberto / Henckel, Johann / Di Laura, Anna / Horga, Laura Maria / Hart, Alister James

BMJ open sport & exercise medicine

2023 Volume 9, Issue 3, Page(s) e001672

Abstract: Objectives: This study aims to quantitatively evaluate whether there are muscle mass differences between male and female recreational cyclists and compare muscle quality and body composition in the pelvis region between two well-matched groups of fit ... ...

Abstract	Objectives: This study aims to quantitatively evaluate whether there are muscle mass differences between male and female recreational cyclists and compare muscle quality and body composition in the pelvis region between two well-matched groups of fit and healthy male and female adults. Methods: This cross-sectional study involved 45 female and 42 male recreational cyclists. The inclusion criteria for both groups were to have cycled more than 7000 km in the last year, have an absence of injuries and other health problems, have no contraindication to MRI, and be 30-65 years old. Our main outcome measures were fat fraction, as a measure of intramuscular fat (IMF) content, and volume of the gluteal muscles measured using Dixon MRI. The gluteal subcutaneous adipose tissue (SAT) volume was evaluated as a secondary measure. Results: We found that there were no gender differences in the IMF content of gluteus maximus (GMAX, p=0.42), gluteus medius (GMED, p=0.69) and gluteus minimus (GMIN, p=0.06) muscles, despite women having more gluteal SAT (p<0.01). Men had larger gluteal muscles than women (p<0.01), but no differences were found when muscle volume was normalised by body weight (GMAX, p=0.54; GMED, p=0.14; GMIN, p=0.19). Conclusions: Our study shows that despite the recognised hormonal differences between men and women, there is gender equivalence in the muscle mass and quality of the gluteal muscles when matched for exercise and body weight. This new MRI study provides key information to better understand gender similarities and differences in skeletal muscle and body composition.
Language	English
Publishing date	2023-08-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2817580-3
ISSN	2055-7647
ISSN	2055-7647
DOI	10.1136/bmjsem-2023-001672
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Article ; Online: Mid-life cyclists preserve muscle mass and composition: a 3D MRI study.

Belzunce, Martin A / Henckel, Johann / Laura, Anna Di / Horga, Laura M / Hart, Alister James

BMC musculoskeletal disorders

2023 Volume 24, Issue 1, Page(s) 209

Abstract: Physical activity and a healthy lifestyle are crucial factors for delaying and reducing the effects of sarcopenia. Cycling has gained popularity in the last decades among midlife men. While the cardiovascular benefits of cycling and other endurance ... ...

Abstract	Physical activity and a healthy lifestyle are crucial factors for delaying and reducing the effects of sarcopenia. Cycling has gained popularity in the last decades among midlife men. While the cardiovascular benefits of cycling and other endurance exercises have been extensively proved, the potential benefits of lifelong aerobic exercise on muscle health have not been adequately studied. Our aim was to quantify the benefits of cycling in terms of muscle health in middle-aged men, using magnetic resonance imaging. We ran a cross-sectional study involving two groups of middle-aged male adults (mean age 49 years, range 30-65) that underwent Dixon MRI of the pelvis. The groups consisted of 28 physically inactive (PI) and 28 trained recreational cyclists. The latter had cycled more than 7000 km in the last year and have been training for 15 years on average, while the PI volunteers have not practiced sports for an average of 27 years. We processed the Dixon MRI scans by labelling and computing the fat fraction (FF), volume and lean volume of gluteus maximus (GMAX) and gluteus medius (GMED); and measuring the volume of subcutaneous adipose tissue (SAT). We found that the cyclists group had lower FF levels, a measure of intramuscular fat infiltration, compared to the PI group for GMAX (PI median FF 21.6%, cyclists median FF 14.8%, p < 0.01) and GMED (PI median FF 16.0%, cyclists median FF 11.4%, p < 0.01). Cyclists had also larger GMAX and GMED muscles than the PI group (p < 0.01), after normalizing it by body mass. Muscle mass and fat infiltration were strongly correlated with SAT volume. These results suggest that cycling could help preserve muscle mass and composition in middle-aged men. Although more research is needed to support these results, this study adds new evidence to support public health efforts to promote cycling.
MeSH term(s)	Adult ; Middle Aged ; Humans ; Male ; Aged ; Cross-Sectional Studies ; Muscle, Skeletal/diagnostic imaging ; Muscle, Skeletal/physiology ; Magnetic Resonance Imaging ; Exercise/physiology ; Exercise Therapy/methods
Language	English
Publishing date	2023-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2041355-5
ISSN	1471-2474 ; 1471-2474
ISSN (online)	1471-2474
ISSN	1471-2474
DOI	10.1186/s12891-023-06283-3
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Article ; Online: An integrative framework for perceptual disturbances in psychosis.

Horga, Guillermo / Abi-Dargham, Anissa

Nature reviews. Neuroscience

2019 Volume 20, Issue 12, Page(s) 763–778

Abstract: Perceptual disturbances in psychosis, such as auditory verbal hallucinations, are associated with increased baseline activity in the associative auditory cortex and increased dopamine transmission in the associative striatum. Perceptual disturbances are ... ...

Abstract	Perceptual disturbances in psychosis, such as auditory verbal hallucinations, are associated with increased baseline activity in the associative auditory cortex and increased dopamine transmission in the associative striatum. Perceptual disturbances are also associated with perceptual biases that suggest increased reliance on prior expectations. We review theoretical models of perceptual inference and key supporting physiological evidence, as well as the anatomy of associative cortico-striatal loops that may be relevant to auditory perceptual inference. Integrating recent findings, we outline a working framework that bridges neurobiology and the phenomenology of perceptual disturbances via theoretical models of perceptual inference.
MeSH term(s)	Cerebral Cortex/metabolism ; Corpus Striatum/metabolism ; Dopamine/metabolism ; Hallucinations/metabolism ; Hallucinations/psychology ; Humans ; Nerve Net/metabolism ; Psychotic Disorders/metabolism ; Psychotic Disorders/psychology
Chemical Substances	Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2019-11-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2034150-7
ISSN	1471-0048 ; 1471-0048 ; 1471-003X
ISSN (online)	1471-0048
ISSN	1471-0048 ; 1471-003X
DOI	10.1038/s41583-019-0234-1
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Zs.A 5473: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 47: Show issues

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Article ; Online: First-in-human trial evaluating safety and pharmacokinetics of AT-752, a novel nucleotide prodrug with pan-serotype activity against dengue virus.

Zhou, Xiao-Jian / Lickliter, Jason / Montrond, Maureen / Ishak, Laura / Pietropaolo, Keith / James, Dayle / Belanger, Bruce / Horga, Arantxa / Hammond, Janet

Antimicrobial agents and chemotherapy

2024 , Page(s) e0161523

Abstract: AT-752 is a novel guanosine nucleotide prodrug inhibitor of the dengue virus (DENV) polymerase with sub-micromolar, pan-serotype antiviral activity. This phase 1, double-blind, placebo-controlled, first-in-human study evaluated the safety, tolerability, ... ...

Abstract	AT-752 is a novel guanosine nucleotide prodrug inhibitor of the dengue virus (DENV) polymerase with sub-micromolar, pan-serotype antiviral activity. This phase 1, double-blind, placebo-controlled, first-in-human study evaluated the safety, tolerability, and pharmacokinetics of ascending single and multiple oral doses of AT-752 in healthy subjects. AT-752 was well tolerated when administered as a single dose up to 1,500 mg or when administered as multiple doses up to 750 mg three times daily (TID). No serious adverse events occurred, and the majority of treatment-emergent adverse events were mild in severity and resolved by the end of the study. In those receiving single ascending doses of AT-752, no pharmacokinetic sensitivity was observed in Asian subjects, and no food effect was observed. Plasma exposure of the guanosine nucleoside metabolite AT-273, the surrogate of the active triphosphate metabolite of the drug, increased with increasing dose levels of AT-752 and exhibited a long half-life of approximately 15-25 h. Administration of AT-752 750 mg TID led to a rapid increase in plasma levels of AT-273 exceeding the target Clinical trials: Registered at ClinicalTrials.gov (NCT04722627).
Language	English
Publishing date	2024-03-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/aac.01615-23
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Zs.A 809: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Einzelsignatur: Show issues

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Article: Phase II study of bemnifosbuvir in high-risk participants in a hospital setting with moderate COVID-19.

Horga, Arantxa / Kuritzkes, Daniel R / Kowalczyk, John J / Pietropaolo, Keith / Belanger, Bruce / Lin, Kai / Perkins, Kristen / Hammond, Janet

Future virology

2023 Volume 18, Issue 8, Page(s) 489–500

Abstract: Background: Bemnifosbuvir, a novel, oral, nonmutagenic, nonteratogenic nucleotide analogue inhibits SARS-CoV-2 replication : Materials & methods: Adults in hospital settings with moderate COVID-19 were randomized 1:1 bemnifosbuvir/placebo. Study ... ...

Abstract	Background: Bemnifosbuvir, a novel, oral, nonmutagenic, nonteratogenic nucleotide analogue inhibits SARS-CoV-2 replication Materials & methods: Adults in hospital settings with moderate COVID-19 were randomized 1:1 bemnifosbuvir/placebo. Study amended to two parts after interim analysis; part B enrollment limited owing to evolving standard of care. Results: Although the study ended early and did not meet the primary efficacy end point, bemnifosbuvir was well tolerated and did not contribute to all-cause mortality. Compared with placebo, bemnifosbuvir treatment resulted in 0.61 log Conclusion: Our results suggest a potential role for bemnifosbuvir in blunting COVID-19 progression. Clinical trial registration: NCT04396106 (ClinicalTrials.gov).
Language	English
Publishing date	2023-06-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2254606-6
ISSN	1746-0808 ; 1746-0794
ISSN (online)	1746-0808
ISSN	1746-0794
DOI	10.2217/fvl-2023-0064
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