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DOE OSTI2024

Visibility and annoyance of the phantom array effect varies with age and history of migraine

The phantom array effect (PAE) is a series of repeated images that may be perceived when a person moves their eyes in large saccades across a light source (or a specular reflection of that light source) that is modulating in output over time. Fifty-five people, including a group of 25 who experience migraine, evaluated the visibility and annoyingness of phantom arrays produced by 85 unique temporal light modulation waveforms (including sine, rectangular, complex and DC waveforms) generated using an LED placed against a black background. Those with migraine exhibited higher average visibility compared to those without migraine ( p = 0.019) and were relatively more sensitive at higher frequencies ( p < 0.001). Younger participants also found more stimuli to be visible ( p < 0.001). The threshold sensitivity function was similar to that developed for the phantom array visibility measure (PAVM), and PAVM was effective in predicting visibility ( R 2 = 0.87 for the relevant region of PAVM < 3). While those in the migraine group did not report seeing the PAE more often in everyday life at a statistically significant level, they reported being more annoyed by it and having more unwanted physiological responses (headaches, eye fatigue and distraction/disorientation). Members of the migraine group were also more likely to have changed their behaviour in architectural spaces (such as leaving a restaurant with ‘flickering’ lights). In the four hours after completing the experiment, 64% of the migraine group (vs. 19% of the non-migraine group) reported experiencing discomfort or an adverse reaction. In particular, 41% reported experiencing a headache (vs. 8% for those in the non-migraine group).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Enhancing Acute Migraine Treatment: Exploring Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for the Nose-to-Brain Route

Migraine has a high prevalence worldwide and is one of the main disabling neurological diseases in individuals under the age of 50. In general, treatment includes the use of oral analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) for mild attacks, and, for moderate or severe attacks, triptans or 5-HT1B/1D receptor agonists. However, the administration of antimigraine drugs in conventional oral pharmaceutical dosage forms is a challenge, since many molecules have difficulty crossing the blood-brain barrier (BBB) to reach the brain, which leads to bioavailability problems. Efforts have been made to find alternative delivery systems and/or routes for antimigraine drugs. In vivo studies have shown that it is possible to administer drugs directly into the brain via the intranasal (IN) or the nose-to-brain route, thus avoiding the need for the molecules to cross the BBB. In this field, the use of lipid nanoparticles, in particular solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has shown promising results, since they have several advantages for drugs administered via the IN route, including increased absorption and reduced enzymatic degradation, improving bioavailability. Furthermore, SLN and NLC are capable of co-encapsulating drugs, promoting their simultaneous delivery to the site of therapeutic action, which can be a promising approach for the acute migraine treatment. This review highlights the potential of using SLN and NLC to improve the treatment of acute migraine via the nose-to-brain route. First sections describe the pathophysiology and the currently available pharmacological treatment for acute migraine, followed by an outline of the mechanisms underlying the nose-to-brain route. Afterwards, the main features of SLN and NLC and the most recent in vivo studies investigating the use of these nanoparticles for the treatment of acute migraine are presented.

Torres, Joana (ORCID:0000000327276229)↗
DOE OSTI2023

Integrating functional scoring and regulatory data to predict the effect of non-coding SNPs in a complex neurological disease

Abstract Most SNPs associated with complex diseases seem to lie in non-coding regions of the genome; however, their contribution to gene expression and disease phenotype remains poorly understood. Here, we established a workflow to provide assistance in prioritising the functional relevance of non-coding SNPs of candidate genes as susceptibility loci in polygenic neurological disorders. To illustrate the applicability of our workflow, we considered the multifactorial disorder migraine as a model to follow our step-by-step approach. We annotated the overlap of selected SNPs with regulatory elements and assessed their potential impact on gene expression based on publicly available prediction algorithms and functional genomics information. Some migraine risk loci have been hypothesised to reside in non-coding regions and to be implicated in the neurotransmission pathway. In this study, we used a set of 22 non-coding SNPs from neurotransmission and synaptic machinery-related genes previously suggested to be involved in migraine susceptibility based on our candidate gene association studies. After prioritising these SNPs, we focused on non-reported ones that demonstrated high regulatory potential: (1) VAMP2_rs1150 (3′ UTR) was predicted as a target of hsa-mir-5010-3p miRNA, possibly disrupting its own gene expression; (2) STX1A_rs6951030 (proximal enhancer) may affect the binding affinity of zinc-finger transcription factors (namely ZNF423) and disturb TBL2 gene expression; and (3) SNAP25_rs2327264 (distal enhancer) expected to be in a binding site of ONECUT2 transcription factor. This study demonstrated the applicability of our practical workflow to facilitate the prioritisation of potentially relevant non-coding SNPs and predict their functional impact in multifactorial neurological diseases.

Felício, Daniela↗
DOE OSTI2023

All that flashes... ...might cause crashes

Flashing lights may create challenging environments due to personnel photosensitivity. People can be photosensitive for a variety of reasons including illness, stress, and brain injury. All brains have limits. Flashing lights can be found in surprising places including reflecting off rippling water. To have environments to minimize photosensitivity, consider other people and ask before using any flashing lights including flash photography. Consider travel conditions and let your visitor rest upon arrival. Let's start a conversation to discuss lighting in our environment, our brains, and our health. The purpose of this presentation is to increase awareness of photosensitivity and encourage communication about it.

99 - GENERAL AND MISCELLANEOUS↗