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Article ; Online: Vascular neuro-otology: vestibular transient ischemic attacks and chronic dizziness in the elderly.

Bronstein, Adolfo M / Kattah, Jorge

2023 Volume 37, Issue 1, Page(s) 59–65

Abstract: Purpose of review: To explore the differential diagnosis of posterior fossa transient ischemic attacks (TIA) associated with vertigo and/or imbalance.To review the contribution of cerebral small vessel (SVD) disease to balance dysfunction and dizziness ... ...

Abstract	Purpose of review: To explore the differential diagnosis of posterior fossa transient ischemic attacks (TIA) associated with vertigo and/or imbalance.To review the contribution of cerebral small vessel (SVD) disease to balance dysfunction and dizziness in the elderly. Main findings: TIAs involving vestibular structures that mediate the vestibulo-ocular and vestibulospinal reflexes remain a diagnostic challenge because they overlap with causes of benign episodic vertigo. Here, we summarize the results of multidisciplinary specialty efforts to improve timely recognition and intervention of peripheral and central vestibular ischemia. More papers confirm that SVD is a major cause of gait disability, falls and cognitive disorder in the elderly. Recent work shows that early stages of SVD may also be responsible for dizziness in the elderly. The predominant location of the white matter changes, in the frontal deep white matter and genu of the corpus callosum, explains the association between cognitive and balance dysfunction in SVD related symptoms. Summary: The evaluation of patients with intermittent vascular vertigo represent a major diagnostic challenge, recent reviews explore the ideal design approach for a multidisciplinary study to increase early recognition and intervention. Hemispheric white matter microvascular ischemia has been the subject of research progress - advanced stages are known to cause gait disorder and dementia but early stages are associated with "idiopathic" dizziness in the elderly.
MeSH term(s)	Humans ; Aged ; Dizziness/diagnosis ; Dizziness/etiology ; Ischemic Attack, Transient/complications ; Ischemic Attack, Transient/diagnosis ; Neurotology ; Vertigo/diagnosis ; Vertigo/etiology ; Ischemia/complications
Language	English
Publishing date	2023-11-30
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	1182686-1
ISSN	1473-6551 ; 1350-7540
ISSN (online)	1473-6551
ISSN	1350-7540
DOI	10.1097/WCO.0000000000001229
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Book ; Online: Setting the Record Straight on Transformer Oversmoothing

Dovonon, Gbètondji J-S / Bronstein, Michael M. / Kusner, Matt J.

2024

Abstract: Transformer-based models have recently become wildly successful across a diverse set of domains. At the same time, recent work has shown that Transformers are inherently low-pass filters that gradually oversmooth the inputs, reducing the expressivity of ... ...

Abstract	Transformer-based models have recently become wildly successful across a diverse set of domains. At the same time, recent work has shown that Transformers are inherently low-pass filters that gradually oversmooth the inputs, reducing the expressivity of their representations. A natural question is: How can Transformers achieve these successes given this shortcoming? In this work we show that in fact Transformers are not inherently low-pass filters. Instead, whether Transformers oversmooth or not depends on the eigenspectrum of their update equations. Our analysis extends prior work in oversmoothing and in the closely-related phenomenon of rank collapse. We show that many successful Transformer models have attention and weights which satisfy conditions that avoid oversmoothing. Based on this analysis, we derive a simple way to parameterize the weights of the Transformer update equations that allows for control over its spectrum, ensuring that oversmoothing does not occur. Compared to a recent solution for oversmoothing, our approach improves generalization, even when training with more layers, fewer datapoints, and data that is corrupted.
Keywords	Computer Science - Machine Learning
Publishing date	2024-01-08
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The influence of postural threat-induced anxiety on locomotor learning and updating.

Ellmers, Toby J / Durkin, Morgan / Sriranganathan, Karthigan / Harris, David J / Bronstein, Adolfo M

Journal of neurophysiology

2024 Volume 131, Issue 3, Page(s) 562–575

Abstract: The ability to adapt our locomotion in a feedforward (i.e., "predictive") manner is crucial for safe and efficient walking behavior. Equally important is the ability to quickly deadapt and update behavior that is no longer appropriate for the given ... ...

Abstract	The ability to adapt our locomotion in a feedforward (i.e., "predictive") manner is crucial for safe and efficient walking behavior. Equally important is the ability to quickly deadapt and update behavior that is no longer appropriate for the given context. It has been suggested that anxiety induced via postural threat may play a fundamental role in disrupting such deadaptation. We tested this hypothesis, using the "broken escalator" phenomenon: Fifty-six healthy young adults walked onto a stationary walkway ("BEFORE" condition, 5 trials), then onto a moving walkway akin to an airport travelator ("MOVING" condition, 10 trials), and then again onto the stationary walkway ("AFTER" condition, 5 trials). Participants completed all trials while wearing a virtual reality headset, which was used to induce postural threat-related anxiety (raised clifflike drop at the end of the walkway) during different phases of the paradigm. We found that performing the locomotor adaptation phase in a state of increased threat disrupted subsequent deadaptation during AFTER trials: These participants displayed anticipatory muscular activity as if expecting the platform to move and exhibited inappropriate anticipatory forward trunk movement that persisted during multiple AFTER trials. In contrast, postural threat induced during AFTER trials did not affect behavioral or neurophysiological outcomes. These findings highlight that actions learned in the presence of postural threat-induced anxiety are strengthened, leading to difficulties in deadapting these behaviors when no longer appropriate. Given the associations between anxiety and persistent maladaptive gait behaviors (e.g., "overly cautious" gait, functional gait disorders), the findings have implications for the understanding of such conditions.
MeSH term(s)	Young Adult ; Humans ; Walking/physiology ; Learning/physiology ; Gait/physiology ; Locomotion/physiology ; Anxiety ; Postural Balance/physiology
Language	English
Publishing date	2024-02-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00364.2023
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Article ; Online: Factors influencing clinical outcome in vestibular neuritis - A focussed review and reanalysis of prospective data.

Arshad, Q / Cousins, S / Golding, J F / Bronstein, A M

Journal of the neurological sciences

2023 Volume 446, Page(s) 120579

Abstract: Following vestibular neuritis (VN), long term prognosis is not dependent on the magnitude of the residual peripheral function as measured with either caloric or the video head-impulse test. Rather, recovery is determined by a combination of visuo- ... ...

Abstract	Following vestibular neuritis (VN), long term prognosis is not dependent on the magnitude of the residual peripheral function as measured with either caloric or the video head-impulse test. Rather, recovery is determined by a combination of visuo-vestibular (visual dependence), psychological (anxiety) and vestibular perceptual factors. Our recent research in healthy individuals has also revealed a strong association between the degree of lateralisation of vestibulo-cortical processing and gating of vestibular signals, anxiety and visual dependence. In the context of several functional brain changes occurring in the interaction between visual, vestibular and emotional cortices, which underpin the aforementioned psycho-physiological features in patients with VN, we re-examined our previously published findings focusing on additional factors impacting long term clinical outcome and function. These included: (i) the role of concomitant neuro-otological dysfunction (i.e. migraine and benign paroxysmal positional vertigo (BPPV)) and (ii) the degree to which brain lateralisation of vestibulo-cortical processing influences gating of vestibular function in the acute stage. We found that migraine and BPPV interfere with symptomatic recovery following VN. That is, dizziness handicap at short-term recovery stage was significantly predicted by migraine (r = 0.523, n = 28, p = .002), BPPV (r = 0.658, n = 31, p < .001) and acute visual dependency (r = 0.504, n = 28, p = .003). Moreover, dizziness handicap in the long-term recovery stage continued to be predicted by migraine (r = 0.640, n = 22, p = .001), BPPV (r = 0.626, n = 24, p = .001) and acute visual dependency (r = 0.667, n = 22, p < .001). Furthermore, surrogate measures of vestibulo-cortical lateralisation were predictive of the amount of cortical suppression exerted over vestibular thresholds. That is, in right-sided VN patients, we observed a positive correlation between visual dependence and acute ipsilesional oculomotor thresholds (R
MeSH term(s)	Humans ; Vestibular Neuronitis ; Dizziness/complications ; Prospective Studies ; Vertigo/complications ; Migraine Disorders/complications
Language	English
Publishing date	2023-02-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80160-4
ISSN	1878-5883 ; 0022-510X ; 0374-8642
ISSN (online)	1878-5883
ISSN	0022-510X ; 0374-8642
DOI	10.1016/j.jns.2023.120579
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Article ; Online: Agricultural paraquat dichloride use and Parkinson's disease in California's Central Valley.

Paul, Kimberly C / Cockburn, Myles / Gong, Yufan / Bronstein, Jeff / Ritz, Beate

International journal of epidemiology

2024 Volume 53, Issue 1

Abstract: Background: Paraquat dichloride is currently among the most widely used commercial herbicides in the USA. In the present study, we provide epidemiological assessment of ambient paraquat exposure and Parkinson's disease (PD) risk in a population-based ... ...

Abstract	Background: Paraquat dichloride is currently among the most widely used commercial herbicides in the USA. In the present study, we provide epidemiological assessment of ambient paraquat exposure and Parkinson's disease (PD) risk in a population-based study of PD in agricultural regions of Central California. Methods: Based on 829 PD patients and 824 community controls, we assessed associations between ambient paraquat dichloride exposure and PD. We estimated residential and workplace proximity to commercial agricultural applications in three California counties since 1974 using the CA pesticide use reporting (PUR) data and land use maps. We evaluated any, duration and average intensity [pounds (0.45 kilograms) per acre per year] of exposure for paraquat in four time windows. Results: Ambient paraquat exposure assessed at both residence and workplace was associated with PD, based on several different exposure measures. The PD patients both lived and worked near agricultural facilities applying greater amounts of the herbicide than community controls. For workplace proximity to commercial applications since 1974, working near paraquat applications every year in the window [odds ratio (OR) = 2.15, 95% confidence interval (CI) = 1.46, 3.19] and a higher average intensity of exposure [per 10 pounds (4.54 kilograms), OR = 2.08, 95% CI = 1.31, 3.38] were both associated with an increased odds of PD. Similar associations were observed for residential proximity (duration: OR = 1.91, 95% CI = 1.30, 2.83; average intensity: OR = 1.72, 95% CI = 0.99, 3.04). Risk estimates were comparable for men and women, and the strongest odds were observed for those diagnosed at ≤60 years of age. Conclusion: This study provides further indication that paraquat dichloride exposure increases the risk of Parkinson's disease.
MeSH term(s)	Male ; Humans ; Female ; Parkinson Disease/epidemiology ; Paraquat ; Pesticides ; Agriculture ; Disease Susceptibility ; California/epidemiology
Chemical Substances	Paraquat (PLG39H7695) ; Pesticides
Language	English
Publishing date	2024-02-02
Publishing country	England
Document type	Journal Article
ZDB-ID	187909-1
ISSN	1464-3685 ; 0300-5771
ISSN (online)	1464-3685
ISSN	0300-5771
DOI	10.1093/ije/dyae004
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Article: A pooled-sample draft genome assembly provides insights into host plant-specific transcriptional responses of a Solanaceae-specializing pest,

Goldberg, Jay K / Allan, Carson W / Copetti, Dario / Matzkin, Luciano M / Bronstein, Judith

Ecology and evolution

2024 Volume 14, Issue 3, Page(s) e10979

Abstract: The assembly of genomes from pooled samples of genetically heterogenous samples of conspecifics remains challenging. In this study, we show that high-quality genome assemblies can be produced from samples of multiple wild-caught individuals. We sequenced ...

Abstract	The assembly of genomes from pooled samples of genetically heterogenous samples of conspecifics remains challenging. In this study, we show that high-quality genome assemblies can be produced from samples of multiple wild-caught individuals. We sequenced DNA extracted from a pooled sample of conspecific herbivorous insects (Hemiptera: Miridae:
Language	English
Publishing date	2024-03-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2635675-2
ISSN	2045-7758
ISSN	2045-7758
DOI	10.1002/ece3.10979
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Article ; Online: Gene regulation by gonadal hormone receptors underlies brain sex differences.

Gegenhuber, B / Wu, M V / Bronstein, R / Tollkuhn, J

Nature

2022 Volume 606, Issue 7912, Page(s) 153–159

Abstract: Oestradiol establishes neural sex differences in many ... ...

Abstract	Oestradiol establishes neural sex differences in many vertebrates
MeSH term(s)	Animals ; Brain/metabolism ; Estradiol/metabolism ; Estrogen Receptor alpha/metabolism ; Female ; Gene Expression Regulation ; Male ; Mice ; Sex Characteristics
Chemical Substances	Estrogen Receptor alpha ; Estradiol (4TI98Z838E)
Language	English
Publishing date	2022-05-04
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-022-04686-1
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Article: Lysosomal genes contribute to Parkinson's disease near agriculture with high intensity pesticide use.

Ngo, Kathie J / Paul, Kimberly C / Wong, Darice / Kusters, Cynthia D J / Bronstein, Jeff M / Ritz, Beate / Fogel, Brent L

NPJ Parkinson's disease

2024 Volume 10, Issue 1, Page(s) 87

Abstract: Parkinson's disease (PD), the second most common neurodegenerative disorder, develops sporadically, likely through a combination of polygenic and environmental factors. Previous studies associate pesticide exposure and genes involved in lysosomal ... ...

Abstract	Parkinson's disease (PD), the second most common neurodegenerative disorder, develops sporadically, likely through a combination of polygenic and environmental factors. Previous studies associate pesticide exposure and genes involved in lysosomal function with PD risk. We evaluated the frequency of variants in lysosomal function genes among patients from the Parkinson's, Environment, and Genes (PEG) study with ambient pesticide exposure from agricultural sources. 757 PD patients, primarily of White European/non-Hispanic ancestry (75%), were screened for variants in 85 genes using a custom amplicon panel. Variant enrichment was calculated against the Genome Aggregation Database (gnomAD). Enriched exonic variants were prioritized by exposure to a cluster of pesticides used on cotton and severity of disease progression in a subset of 386 patients subdivided by race/ethnicity. Gene enrichment analysis identified 36 variants in 26 genes in PEG PD patients. Twelve of the identified genes (12/26, 46%) had multiple enriched variants and/or a single enriched variant present in multiple individuals, representing 61% (22/36) of the observed variation in the cohort. The majority of enriched variants (26/36, 72%) were found in genes contributing to lysosomal function, particularly autophagy, and were bioinformatically deemed functionally deleterious (31/36, 86%). We conclude that, in this study, variants in genes associated with lysosomal function, notably autophagy, were enriched in PD patients exposed to agricultural pesticides suggesting that altered lysosomal function may generate an underlying susceptibility for developing PD with pesticide exposure. Further study of gene-environment interactions targeting lysosomal function may improve understanding of PD risk in individuals exposed to pesticides.
Language	English
Publishing date	2024-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819218-7
ISSN	2373-8057
ISSN	2373-8057
DOI	10.1038/s41531-024-00703-4
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Article ; Online: Vestibular loss disrupts visual reactivity in the alpha EEG rhythm.

Ibitoye, Richard T / Castro, Patricia / Ellmers, Toby J / Kaski, Diego N / Bronstein, Adolfo M

NeuroImage. Clinical

2023 Volume 39, Page(s) 103469

Abstract: The alpha rhythm is a dominant electroencephalographic oscillation relevant to sensory-motor and cognitive function. Alpha oscillations are reactive, being for example enhanced by eye closure, and suppressed following eye opening. The determinants of ... ...

Abstract	The alpha rhythm is a dominant electroencephalographic oscillation relevant to sensory-motor and cognitive function. Alpha oscillations are reactive, being for example enhanced by eye closure, and suppressed following eye opening. The determinants of inter-individual variability in reactivity in the alpha rhythm (e.g. changes with amplitude following eye closure) are not fully understood despite the physiological and clinical applicability of this phenomenon, as indicated by the fact that ageing and neurodegeneration reduce reactivity. Strong interactions between visual and vestibular systems raise the theoretical possibility that the vestibular system plays a role in alpha reactivity. To test this hypothesis, we applied electroencephalography in sitting and standing postures in 15 participants with reduced vestibular function (bilateral vestibulopathy, median age = 70 years, interquartile range = 51-77 years) and 15 age-matched controls. We found participants with reduced vestibular function showed less enhancement of alpha electroencephalography power on eye closure in frontoparietal areas, compared to controls. In participants with reduced vestibular function, video head impulse test gain - as a measure of residual vestibulo-ocular reflex function - correlated with reactivity in alpha power across most of the head. Greater reliance on visual input for spatial orientation ('visual dependence', measured with the rod-and-disc test) correlated with less alpha enhancement on eye closure only in participants with reduced vestibular function, and this was partially moderated by video head impulse test gain. Our results demonstrate for the first time that vestibular function influences alpha reactivity. The results are partly explained by the lack of ascending peripheral vestibular input but also by central reorganisation of processing relevant to visuo-vestibular judgements.
MeSH term(s)	Humans ; Middle Aged ; Aged ; Alpha Rhythm ; Reflex, Vestibulo-Ocular/physiology ; Head Impulse Test ; Bilateral Vestibulopathy ; Electroencephalography
Language	English
Publishing date	2023-07-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2023.103469
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Article ; Online: Utilizing Stimuli Responsive Linkages to Engineer and Enhance Polymer Nanoparticle-Based Drug Delivery Platforms.

Hershberger, Kian K / Gauger, Andrew J / Bronstein, Lyudmila M

ACS applied bio materials

2021 Volume 4, Issue 6, Page(s) 4720–4736

Abstract: The devastating nature of cancer continues to be one of the leading causes of death in the world. Chemotherapy is among the most common forms of cancer treatment but comes with a host of adverse effects caused by the therapeutic agents damaging healthy ... ...

Abstract	The devastating nature of cancer continues to be one of the leading causes of death in the world. Chemotherapy is among the most common forms of cancer treatment but comes with a host of adverse effects caused by the therapeutic agents damaging healthy tissue and organs. To limit these side effects, scientists have been designing stimuli responsive drug delivery vessels for targeted release. This Review focuses on the incorporation of stimuli responsive linkages in targeted drug delivery systems to enhance therapeutic efficiency. These platforms are primarily employed to control the distribution of anticancer agents in the body to reduce the adverse side effects caused by their toxicities. We will outline how drug delivery vessels are constructed so that exposure to select environmental and external stimuli releases the enclosed drug only at the target site. Stimuli responsive components are integrated within drug delivery vessels in the form of cross-linkers, polymers, and surface modifications. The changes, these moieties undergo upon stimuli exposure, cascade into larger scale alterations to the platforms, resulting in complete disassembly, reversible morphological variations, and enhanced cellular uptake. The ability for these modes of delivery to be initiated exclusively under stimuli exposure allows for release of toxic therapeutic agents to be confined only to the affected area.
MeSH term(s)	Animals ; Drug Delivery Systems ; Endocytosis ; Humans ; Nanoparticles/administration & dosage ; Nanoparticles/chemistry ; Polymers/administration & dosage ; Polymers/chemistry
Chemical Substances	Polymers
Language	English
Publishing date	2021-05-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2576-6422
ISSN (online)	2576-6422
DOI	10.1021/acsabm.1c00351
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