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Towards a closed loop retinal prosthesis: measuring electrically evoked retinal responses using large electrodes.
(Journal of Neural Engineering, 2025-08-29) Spencer, Martin J; Hosie, Suzanne; Tong, Wei; Shivdasani, Mohit N; Garrett, David J; De León, Sorel E; Brunton, Emma K; Kameneva, Tatiana; Grayden, David B; Fallon, James B; Ibbotson, Michael R; Burkitt, Anthony N; Meffin, Hamish
Sensory prostheses use arrays of electrodes to stimulate neural tissue and restore a sense of vision or hearing. At perceptible levels of stimulation, the current from each electrode spreads and causes overlapping regions of neural activation. This lack of specificity results in perceptual deficits. Methods to overcome this reduced specificity, such as a closed loop stimulation approach require measurement of the neural response to stimulation. This investigation tests the possibility of using the large stimulating electrodes such as those required by some subretinal or suprachoroidal retinal implants to measure the neural response to stimulation, an approach similar to Evoked Compound Action Potentials measurements used in cochlear implants.tissue samples from Long Evans rats with healthy retinas and Royal College of Surgeon rats with retinal degeneration were used to investigate both stimulating and recording from electrodes of the same array. A hexagonal array was used with 20 platinum electrodes with 500m diameter and 700m pitch. Post-stimulus voltage decay was reduced with appropriate tuning of a triphasic stimulation pulse and in post-analysis with a high-pass filter. A method using alternating polarities of biphasic pulses was also trialed. A cocktail of synaptic and ion channel blockers was used to block all neural response including action potentials and thus confirm the biological origin of the signal.It was found that a neural signal was observable on electrode that were sufficiently distant from the stimulating electrodes. The signal appeared to be due to direct activation of ganglion cells or possibly mediated via inner retinal neurons.This result confirms that recording usable neural signals from large electrodes is possible, which is an essential step in implementing a closed loop stimulation strategy for a subretinal or suprachoroidal retinal prosthesis.
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Alpha-synuclein is increased in erythrocytes in parkinson's disease cases.
(Scientific Reports, 2025-08-29) Coyle, Ryan N; Roberts, Anne M; Horne, Malcolm; Fowler, Christopher; Masters, Colin L; Roberts, Blaine R
Idiopathic Parkinson's disease (iPD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Mutations in the SCNA gene, which encodes the protein alpha synuclein (α-syn), are associated with familial forms of Parkinson's disease (PD). Additionally, Lewy bodies (LBs) rich in α-synuclein are a hallmark of idiopathic Parkinson's disease (iPD) pathology. Unlike AD, there are no effective blood-based diagnostic assays for iPD. Recent studies show that measures of misfolded α-syn in cerebrospinal fluid (CSF) and skin biopsies reflect the diagnosis of iPD. The presence of misfolded α-syn suggests that the altered cellular processes in the brain that lead to aggregated α-syn may also occur in the periphery. However, CSF and skin biopsies are intrusive, highlighting the need for a blood-based diagnostic assay. Erythrocytes are the richest source of α-syn in the body, and we hypothesized that peripheral α-syn changes could be detected in erythrocytes in iPD. To test this hypothesis, we used a targeted liquid chromatography-mass spectrometry (LC-MS) assay, that included N-enriched recombinant α-syn as an internal standard. We compared the levels of α-syn in erythrocytes from iPD patients, AD patients, and healthy controls (CN). α-syn concentrations were significantly elevated in iPD (48.1 (29.7) µg mL of erythrocytes, median (IQR)) compared to CN (36.1 (28.4) µg mL) and no difference was observed in AD (33.5 (18.1) µg mL). Although α-syn levels were significantly elevated in iPD, the receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.62, indicating that erythrocytic α-syn levels alone are not sufficient for diagnostic purposes.
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Towards an Implantable Aptamer Biosensor for Monitoring in Inflammatory Bowel Disease.
(biosensors, 2025-08-19) Huang, Yanan; Duan, Wenlu; Deng, Fei; Tang, Wenxian; Payne, Sophie C; Guo, Tianruo; Goldys, Ewa M; Lovell, Nigel H; Shivdasani, Mohit N
Inflammatory bowel disease (IBD) is a relapsing-remitting condition resulting in chronic inflammation of the gastrointestinal tract. Present methods are either inadequate or not viable for continuous tracking of disease progression in individuals. In this study, we present the development towards an implantable biosensor for detecting interleukin-6 (IL-6), an important cytokine implicated in IBD. The optimised sensor design includes a gold surface functionalised with a known IL-6-specific aptamer, integrating a recognition sequence and an electrochemical redox probe. The IL-6 aptasensor demonstrated a sensitivity of up to 40% and selectivity up to 10% to the IL-6 target in vitro. Sensors were found to degrade over 7 days when exposed to recombinant IL-6, with the degradation rate rapidly increasing when exposed to intestinal mucosa. A feasibility in vivo experiment with a newly designed implantable gut sensor array confirmed rapid degradation over a 5-h implantation period. We achieved up to a 93% reduction in sensor degradation rates, with a polyvinyl alcohol-methyl acrylate hydrogel coating that aimed to reduce nonspecific interactions in complex analytes compared to uncoated sensors. Degradation was linked to desorption of the monolayer leading to breakage of gold thiol bonds. While there are key challenges to be resolved before a stable implantable IBD sensor is realised, this work highlights the potential of aptamer-based biosensors as effective tools for long-term diagnostic monitoring in IBD.
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fNIRS reproducibility varies with data quality, analysis pipelines, and researcher experience.
(Communications Biology, 2025-08-04) Yücel, Meryem A; Luke, Robert; Mesquita, Rickson C; von Lühmann, Alexander; Mehler, David M A; Lührs, Michael; Gemignani, Jessica; Abdalmalak, Androu; Albrecht, Franziska; de Almeida Ivo, Iara; Artemenko, Christina; Ashton, Kira; Augustynowicz, Paweł; Bajracharya, Aahana; Bannier, Elise; Barth, Beatrix; Bayet, Laurie; Behrendt, Jacqueline; Khani, Hadi Borj; Borot, Lenaic; Borrell, Jordan A; Brigadoi, Sabrina; Brink, Kolby; Bulgarelli, Chiara; Caruyer, Emmanuel; Chen, Hsin-Chin; Copeland, Christopher; Corouge, Isabelle; Cutini, Simone; Di Lorenzo, Renata; Dresler, Thomas; Eggebrecht, Adam T; Ehlis, Ann-Christine; Erdoğan, Sinem B; Evenblij, Danielle; Ferdous, Talukdar Raian; Fracalossi, Victoria; Franzén, Erika; Gallagher, Anne; Gerloff, Christian; Gervain, Judit; Goldhamer, Noy; Gossé, Louisa K; Guérin, Ségolène M R; Guevara, Edgar; Hosseini, S M Hadi; Innes-Brown, Hamish; Int-Veen, Isabell; Jaffe-Dax, Sagi; Jégou, Nolwenn; Kawaguchi, Hiroshi; Kelsey, Caroline; Kent, Michaela; Kessler, Roman; Kherbawy, Nadeen; Klein, Franziska; Kochavi, Nofar; Kolisnyk, Matthew; Koren, Yogev; Kroczek, Agnes; Kvist, Alexander; Lin, Chen-Hao Paul; Löw, Andreas; Luan, Siying; Mao, Darren; Martins, Giovani G; Middell, Eike; Montero-Hernandez, Samuel; Mutlu, Murat Can; Novi, Sergio L; Paquette, Natacha; Paranawithana, Ishara; Parmet, Yisrael; Peelle, Jonathan E; Peng, Ke; Peng, Tommy; Pereira, João; Pinti, Paola; Pollonini, Luca; Jounghani, Ali Rahimpour; Reindl, Vanessa; Ringels, Wiebke; Schopp, Betti; Schulte, Alina; Schulte-Rüther, Martin; Segel, Ari; Ala, Tirdad Seifi; Shader, Maureen J; Shavit, Hadas; Sherafati, Arefeh; Soltanlou, Mojtaba; Sorger, Bettina; Speh, Emma; Stubbs, Kevin D; Stute, Katharina; Sullivan, Eileen F; Tak, Sungho; Tipado, Zeus; Tremblay, Julie; Vahidi, Homa; Van Eeckhoutte, Maaike; Vannasing, Phetsamone; Vergotte, Gregoire; Vincent, Marion A; Weiss, Eileen; Yang, Dalin; Yükselen, Gülnaz; Zapała, Dariusz; Zemanek, Vit
As data analysis pipelines grow more complex in brain imaging research, understanding how methodological choices affect results is essential for ensuring reproducibility and transparency. This is especially relevant for functional Near-Infrared Spectroscopy (fNIRS), a rapidly growing technique for assessing brain function in naturalistic settings and across the lifespan, yet one that still lacks standardized analysis approaches. In the fNIRS Reproducibility Study Hub (FRESH) initiative, we asked 38 research teams worldwide to independently analyze the same two fNIRS datasets. Despite using different pipelines, nearly 80% of teams agreed on group-level results, particularly when hypotheses were strongly supported by literature. Teams with higher self-reported analysis confidence, which correlated with years of fNIRS experience, showed greater agreement. At the individual level, agreement was lower but improved with better data quality. The main sources of variability were related to how poor-quality data were handled, how responses were modeled, and how statistical analyses were conducted. These findings suggest that while flexible analytical tools are valuable, clearer methodological and reporting standards could greatly enhance reproducibility. By identifying key drivers of variability, this study highlights current challenges and offers direction for improving transparency and reliability in fNIRS research.
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Abdominal Vagus Nerve Stimulation Increases Firing in the Rat Locus Coeruleus.
(Neuromodulation: Technology at the Neural Interface, 2025-06-20) Hyakumura, Tomoko; Payne, Sophie C; Matarazzo, Jerico V; Adams, Wendy K; Fallon, James B
Cervical vagus nerve stimulation (VNS) is a clinically available treatment for refractory epilepsy and depression. Animal studies show that electrical activation of the noradrenergic brain region, locus coeruleus (LC), is essential for the therapeutic effects of cervical VNS for the treatment of these conditions. Cervical VNS often causes side effects such as coughing, headache, and apnea-hypopnea. Such side effects can be mitigated by reducing stimulation intensity; however, evidence suggests this reduces efficacy of treatment. Abdominal VNS, targeting the vagus nerve below the nerve branches that cause these side effects, is an alternative strategy to deliver VNS.