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Article ; Online: In memoriam: Joel D. Greenspan 1952 to 2021.

Meeker, Timothy J / Quiton, Raimi L / Moulton, Eric A

2023 Volume 162, Issue 10, Page(s) 2459–2463

Language	English
Publishing date	2023-08-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	193153-2
ISSN	1872-6623 ; 0304-3959
ISSN (online)	1872-6623
ISSN	0304-3959
DOI	10.1097/j.pain.0000000000002393
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Article: Supraspinal Mechanisms Underlying Ocular Pain.

Pondelis, Nicholas J / Moulton, Eric A

Frontiers in medicine

2022 Volume 8, Page(s) 768649

Abstract: Supraspinal mechanisms of pain are increasingly understood to underlie neuropathic ocular conditions previously thought to be exclusively peripheral in nature. Isolating individual causes of centralized chronic conditions and differentiating them is ... ...

Abstract	Supraspinal mechanisms of pain are increasingly understood to underlie neuropathic ocular conditions previously thought to be exclusively peripheral in nature. Isolating individual causes of centralized chronic conditions and differentiating them is critical to understanding the mechanisms underlying neuropathic eye pain and ultimately its treatment. Though few functional imaging studies have focused on the eye as an end-organ for the transduction of noxious stimuli, the brain networks related to pain processing have been extensively studied with functional neuroimaging over the past 20 years. This article will review the supraspinal mechanisms that underlie pain as they relate to the eye.
Language	English
Publishing date	2022-02-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2021.768649
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Article ; Online: Is blue light a red herring in a rodent model of "computer vision syndrome"?

Moulton, Eric A / Galor, Anat / Ciolino, Joseph B / Jacobs, Deborah S

Pain

2023 Volume 164, Issue 7, Page(s) 1640

MeSH term(s)	Light/adverse effects ; Rodentia ; Animals ; Disease Models, Animal ; Asthenopia ; Computers
Language	English
Publishing date	2023-06-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	193153-2
ISSN	1872-6623 ; 0304-3959
ISSN (online)	1872-6623
ISSN	0304-3959
DOI	10.1097/j.pain.0000000000002941
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Article ; Online: Supraspinal Mechanisms Underlying Ocular Pain

Nicholas J. Pondelis / Eric A. Moulton

Frontiers in Medicine, Vol

2022 Volume 8

Abstract	Supraspinal mechanisms of pain are increasingly understood to underlie neuropathic ocular conditions previously thought to be exclusively peripheral in nature. Isolating individual causes of centralized chronic conditions and differentiating them is critical to understanding the mechanisms underlying neuropathic eye pain and ultimately its treatment. Though few functional imaging studies have focused on the eye as an end-organ for the transduction of noxious stimuli, the brain networks related to pain processing have been extensively studied with functional neuroimaging over the past 20 years. This article will review the supraspinal mechanisms that underlie pain as they relate to the eye.
Keywords	pain ; eye ; neuroimaging ; fMRI ; supraspinal ; brain ; Medicine (General) ; R5-920
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: C-Fiber Assays in the Cornea vs. Skin.

Moulton, Eric A / Borsook, David

Brain sciences

2019 Volume 9, Issue 11

Abstract: C-fibers are unmyelinated nerve fibers that transmit high threshold mechanical, thermal, and chemical signals that are associated with pain sensations. This review examines current literature on measuring altered peripheral nerve morphology and discusses ...

Abstract	C-fibers are unmyelinated nerve fibers that transmit high threshold mechanical, thermal, and chemical signals that are associated with pain sensations. This review examines current literature on measuring altered peripheral nerve morphology and discusses the most relevant aspects of corneal microscopy, especially whether corneal imaging presents significant method advantages over skin biopsy. Given its relative merits, corneal confocal microscopy would seem to be a more practical and patient-centric approach than utilizing skin biopsies.
Language	English
Publishing date	2019-11-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci9110320
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Article ; Online: The long-term impact of cerebellar tumor resection on executive functioning, anxiety, and fear of pain: A mixed methodology pilot study.

Lunde, Claire E / Dudek, Madison R / Talbert, Cameron A / Sieberg, Christine B / Silva, Katie E / Papadelis, Christos / Ullrich, Nicole J / Manley, Peter E / Moulton, Eric A

Applied neuropsychology. Child

2024 , Page(s) 1–11

Abstract: This pilot study investigated the long-term impact of a surgery-only treatment (no exposure to other treatments, such as chemotherapy and radiation) for pediatric cerebellar low-grade gliomas on executive function, anxiety, and fear of pain (FOP) beliefs. ...

Abstract	This pilot study investigated the long-term impact of a surgery-only treatment (no exposure to other treatments, such as chemotherapy and radiation) for pediatric cerebellar low-grade gliomas on executive function, anxiety, and fear of pain (FOP) beliefs. Twelve patients who underwent surgical glioma resection during childhood (surgery age was 4-16 years, study visit age was 10-28 years), and 12 pain-free controls matched for age, sex, race, and handedness were tested. The spatial extent of resection was precisely mapped using magnetic resonance imaging (MRI). Executive function, anxiety, and FOP were assessed using validated self-report age-appropriate questionnaires for children and adults. Structured clinical interviews at a post-surgery follow-up visit were completed (average: 89 months, range: 20-99). No significant differences in FOP (FOPQ-C t[14 = 1.81,
Language	English
Publishing date	2024-04-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2673759-0
ISSN	2162-2973 ; 2162-2965
ISSN (online)	2162-2973
ISSN	2162-2965
DOI	10.1080/21622965.2024.2337208
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Article ; Online: Clinical Neuroimaging of Photophobia in Individuals With Chronic Ocular Surface Pain.

Choudhury, Anjalee / Reyes, Nicholas / Galor, Anat / Mehra, Divy / Felix, Elizabeth / Moulton, Eric A

American journal of ophthalmology

2022 Volume 246, Page(s) 20–30

Abstract: Purpose: To examine neural mechanisms underlying photophobia in individuals with chronic ocular surface pain by using functional magnetic resonance imaging (fMRI).: Design: Cross-sectional case/control analysis.: Methods: A total of 16 individuals ...

Abstract	Purpose: To examine neural mechanisms underlying photophobia in individuals with chronic ocular surface pain by using functional magnetic resonance imaging (fMRI). Design: Cross-sectional case/control analysis. Methods: A total of 16 individuals from the Miami Veterans Affairs eye clinic underwent comprehensive ocular surface evaluations and were surveyed for ocular surface symptoms. Case patients included patients who reported chronic ocular surface pain symptoms and light sensitivity at least most of the time over 1 week. Controls included persons without chronic ocular surface pain who reported no or minimal light sensitivity. All patients viewed light stimuli during 2 fMRI scans, one before and one after topical anesthetic instillation, and rated their level of pain intensity to the stimulus at the end of each scan. Areas of brain activation in response to light stimuli presentation were correlated with pain responses and examined post- vs pre-anesthesia. Results: Case patients (n = 8) reported higher pain intensity ratings than controls (n = 8) in response to light stimuli during fMRI. Case patient ratings correlated more with light-evoked activation in pain-related areas within the trigeminal brainstem, primary somatosensory cortex (S1), anterior mid-cingulate cortex (aMCC), and insula than in controls. Topical anesthesia led to varying responses in pain ratings among case patients as well as decreased light-evoked activation in S1 and aMCC. Conclusions: The trigeminal nociceptive system may contribute to photophobia in individuals with chronic ocular surface pain. We demonstrate modulation of cortical structures in this pathway with topically applied anesthetic to the eyes. Further understanding of modulatory interactions that govern ocular surface pain and photophobia is critical for developing effective, precision-based therapies.
MeSH term(s)	Humans ; Photophobia/diagnosis ; Photophobia/etiology ; Cross-Sectional Studies ; Eye Pain/diagnosis ; Eye Pain/etiology ; Pain ; Neuroimaging ; Magnetic Resonance Imaging/methods
Language	English
Publishing date	2022-10-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	80030-2
ISSN	1879-1891 ; 0002-9394
ISSN (online)	1879-1891
ISSN	0002-9394
DOI	10.1016/j.ajo.2022.09.020
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Article ; Online: Placebos in pediatrics: A cross-sectional survey investigating physicians' perspectives.

Faria, Vanda / Talbert, Cameron / Goturi, Nathan / Borsook, David / Lebel, Alyssa / Kaptchuk, Ted J / Kirsch, Irving / Kelley, John M / Moulton, Eric A

Journal of psychosomatic research

2023 Volume 172, Page(s) 111421

Abstract: Objective: Placebo responses are significantly higher in children than in adults, suggesting a potential underused treatment option in pediatric care. To facilitate the clinical translation of these beneficial effects, we explored physicians' current ... ...

Abstract	Objective: Placebo responses are significantly higher in children than in adults, suggesting a potential underused treatment option in pediatric care. To facilitate the clinical translation of these beneficial effects, we explored physicians' current practice, opinions, knowledge, and likelihood of recommending placebos in the future. Methods: A cross-sectional web-based survey administered by REDCap was conducted at Boston Children's Hospital between October 2021 and March 2022. Physicians (n = 1157) were invited to participate through an email containing a link to a 23-item survey designed to assess physicians' attitudes and perceptions towards the clinical use of placebo in pediatrics. Results: From 207 (18%) returned surveys, 109 (9%) were fully completed. Most respondents (79%) believed that enhancing the therapeutic components that contribute to the placebo response may be a way of improving pediatric care. However, whereas most (62%) found placebo treatments permissible, only one-third reported recommending them. In pediatrics, placebos are typically introduced as a medicine that "might help" (43%). The most common treatments recommended to enhance placebo effects are physical therapy, vitamins, and over-the-counter analgesics. Physicians most frequently recommend placebos for occasional pain, headaches, and anxiety disorders. Finally, the great majority of physicians (87%) stated they would be more likely to recommend placebo treatments if there were safety and ethical guidelines for open-label placebos. Conclusions: Placebo treatments seem permissible to physicians in pediatric care, but the development of safety and ethical guidelines may be necessary before physicians systematically incorporate the benefits of the placebo effect in pediatrics.
MeSH term(s)	Child ; Humans ; Attitude of Health Personnel ; Cross-Sectional Studies ; Pediatrics ; Physicians ; Practice Patterns, Physicians' ; Surveys and Questionnaires
Language	English
Publishing date	2023-06-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80166-5
ISSN	1879-1360 ; 0022-3999
ISSN (online)	1879-1360
ISSN	0022-3999
DOI	10.1016/j.jpsychores.2023.111421
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Article: Disentangling the neurological basis of chronic ocular pain using clinical, self-report, and brain imaging data: use of K-means clustering to explore patient phenotypes.

Holmes, Scott / Reyes, Nicholas / Huang, Jaxon J / Galor, Anat / Pattany, Pradip M / Felix, Elizabeth R / Moulton, Eric A

Frontiers in neurology

2023 Volume 14, Page(s) 1265082

Abstract: Introduction: The factors that mediate the expression of ocular pain and the mechanisms that promote chronic ocular pain symptoms are poorly understood. Central nervous system involvement has been postulated based on observations of pain out of ... ...

Abstract	Introduction: The factors that mediate the expression of ocular pain and the mechanisms that promote chronic ocular pain symptoms are poorly understood. Central nervous system involvement has been postulated based on observations of pain out of proportion to nociceptive stimuli in some individuals. This investigation focused on understanding functional connectivity between brain regions implicated in chronic pain in persons reporting ocular pain symptoms. Methods: We recruited a total of 53 persons divided into two cohorts: persons who reported no ocular pain, and persons who reported chronic ocular pain, irrespective of ocular surface findings. We performed a resting state fMRI investigation that was focused on subcortical brain structures including the trigeminal nucleus and performed a brief battery of ophthalmological examinations. Results: Persons in the pain cohort reported higher levels of pain symptoms relating to neuropathic pain and ocular surface disease, as well as more abnormal tear metrics (stability and tear production). Functional connectivity analysis between groups evinced multiple connections exemplifying both increases and decreases in connectivity including regions such as the trigeminal nucleus, amygdala, and sub-regions of the thalamus. Exploratory analysis of the pain cohort integrating clinical and brain function metrics highlighted subpopulations that showed unique phenotypes providing insight into pain mechanisms. Discussion: Study findings support centralized involvement in those reporting ocular-based pain and allude to mechanisms through which pain treatment services may be directed in future research.
Language	English
Publishing date	2023-11-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2023.1265082
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Article ; Online: The Past, Present, and Future Role of Artificial Intelligence in Ventilation/Perfusion Scintigraphy: A Systematic Review.

Jabbarpour, Amir / Ghassel, Siraj / Lang, Jochen / Leung, Eugene / Le Gal, Grégoire / Klein, Ran / Moulton, Eric

Seminars in nuclear medicine

2023 Volume 53, Issue 6, Page(s) 752–765

Abstract: Ventilation-perfusion (V/Q) lung scans constitute one of the oldest nuclear medicine procedures, remain one of the few studies performed in the acute setting, and are amongst the few performed in the emergency setting. V/Q studies have witnessed a long ... ...

Abstract	Ventilation-perfusion (V/Q) lung scans constitute one of the oldest nuclear medicine procedures, remain one of the few studies performed in the acute setting, and are amongst the few performed in the emergency setting. V/Q studies have witnessed a long fluctuation in adoption rates in parallel to continuous advances in image processing and computer vision techniques. This review provides an overview on the status of artificial intelligence (AI) in V/Q scintigraphy. To clearly assess the past, current, and future role of AI in V/Q scans, we conducted a systematic Ovid MEDLINE(R) literature search from 1946 to August 5, 2022 in addition to a manual search. The literature was reviewed and summarized in terms of methodologies and results for the various applications of AI to V/Q scans. The PRISMA guidelines were followed. Thirty-one publications fulfilled our search criteria and were grouped into two distinct categories: (1) disease diagnosis/detection (N = 22, 71.0%) and (2) cross-modality image translation into V/Q images (N = 9, 29.0%). Studies on disease diagnosis and detection relied heavily on shallow artificial neural networks for acute pulmonary embolism (PE) diagnosis and were primarily published between the mid-1990s and early 2000s. Recent applications almost exclusively regard image translation tasks from CT to ventilation or perfusion images with modern algorithms, such as convolutional neural networks, and were published between 2019 and 2022. AI research in V/Q scintigraphy for acute PE diagnosis in the mid-90s to early 2000s yielded promising results but has since been largely neglected and thus have yet to benefit from today's state-of-the art machine-learning techniques, such as deep neural networks. Recently, the main application of AI for V/Q has shifted towards generating synthetic ventilation and perfusion images from CT. There is therefore considerable potential to expand and modernize the use of real V/Q studies with state-of-the-art deep learning approaches, especially for workflow optimization and PE detection at both acute and chronic stages. We discuss future challenges and potential directions to compensate for the lag in this domain and enhance the value of this traditional nuclear medicine scan.
MeSH term(s)	Humans ; Artificial Intelligence ; Pulmonary Embolism/diagnostic imaging ; Lung ; Radionuclide Imaging ; Perfusion Imaging ; Tomography, Emission-Computed, Single-Photon/methods
Language	English
Publishing date	2023-04-18
Publishing country	United States
Document type	Systematic Review ; Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	120248-0
ISSN	1558-4623 ; 0001-2998
ISSN (online)	1558-4623
ISSN	0001-2998
DOI	10.1053/j.semnuclmed.2023.03.002
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