المؤلفون: Kourdougli, Nazim, Suresh, Anand, Liu, Benjamin, Juarez, Pablo, Lin, Ashley, Chung, David T, Graven Sams, Anette, Gandal, Michael J, Martínez-Cerdeño, Verónica, Buonomano, Dean V, Hall, Benjamin J, Mombereau, Cédric, Portera-Cailliau, Carlos

المصدر: Neuron. 111(18)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Neurosciences, Brain Disorders, Fragile X Syndrome, Rare Diseases, Pediatric, Intellectual and Developmental Disabilities (IDD), 2.1 Biological and endogenous factors, Aetiology, Neurological, Humans, Mice, Animals, Parvalbumins, Fragile X Mental Retardation Protein, Interneurons, Neurons, Touch, Mice, Knockout, Disease Models, Animal, Kv3.1, RNA-seq, autism spectrum disorders, calcium imaging, intellectual disability, medial ganglionic eminence, parvalbumin, tactile defensiveness, transcriptomics, two-photon, Psychology, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology

الوصف: Changes in the function of inhibitory interneurons (INs) during cortical development could contribute to the pathophysiology of neurodevelopmental disorders. Using all-optical in vivo approaches, we find that parvalbumin (PV) INs and their immature precursors are hypoactive and transiently decoupled from excitatory neurons in postnatal mouse somatosensory cortex (S1) of Fmr1 KO mice, a model of fragile X syndrome (FXS). This leads to a loss of parvalbumin INs (PV-INs) in both mice and humans with FXS. Increasing the activity of future PV-INs in neonatal Fmr1 KO mice restores PV-IN density and ameliorates transcriptional dysregulation in S1, but not circuit dysfunction. Critically, administering an allosteric modulator of Kv3.1 channels after the S1 critical period does rescue circuit dynamics and tactile defensiveness. Symptoms in FXS and related disorders could be mitigated by targeting PV-INs.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5z08c7kwTest

المؤلفون: Harde, Eva, Hierl, Markus, Weber, Michael, Waiz, David, Wyler, Roger, Wach, Jean-Yves, Haab, Rachel, Gundlfinger, Anja, He, Weiping, Schnider, Patrick, Paina, Manuel, Rolland, Jean-Francois, Greiter-Wilke, Andrea, Gasser, Rodolfo, Reutlinger, Michael, Dupont, Amanda, Roberts, Sonia, O'Connor, Eoin C., Bartels, Björn, Hall, Benjamin J.

المصدر: Cell Chemical Biology ; volume 31, issue 3, page 577-592.e23 ; ISSN 2451-9456

مصطلحات موضوعية: Clinical Biochemistry, Drug Discovery, Pharmacology, Molecular Biology, Molecular Medicine, Biochemistry

الإتاحة: https://doi.org/10.1016Test/j.chembiol.2023.11.004
https://api.elsevier.com/content/article/PII:S2451945623004191?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2451945623004191?httpAccept=text/plainTest

المؤلفون: Wilhelm, Maria, Sych, Yaroslav, Fomins, Aleksejs, Alatorre Warren, José Luis, Lewis, Christopher, Serratosa Capdevila, Laia, Boehringer, Roman, Amadei, Elizabeth A, Grewe, Benjamin, O’Connor, Eoin C, Hall, Benjamin J, Helmchen, Fritjof

المصدر: Wilhelm, Maria; Sych, Yaroslav; Fomins, Aleksejs; Alatorre Warren, José Luis; Lewis, Christopher; Serratosa Capdevila, Laia; Boehringer, Roman; Amadei, Elizabeth A; Grewe, Benjamin; O’Connor, Eoin C; Hall, Benjamin J; Helmchen, Fritjof (2023). Striatum-projecting prefrontal cortex neurons support working memory maintenance. Nature Communications, 14(1):7016.

مصطلحات موضوعية: Institute of Neuroinformatics, Neuroscience Center Zurich, Adaptive Brain Circuits in Development and Learning (AdaBD), 570 Life sciences, biology, General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: Neurons in the medial prefrontal cortex (mPFC) are functionally linked to working memory (WM) but how distinct projection pathways contribute to WM remains unclear. Based on optical recordings, optogenetic perturbations, and pharmacological interventions in male mice, we report here that dorsomedial striatum (dmStr)-projecting mPFC neurons are essential for WM maintenance, but not encoding or retrieval, in a T-maze spatial memory task. Fiber photometry of GCaMP6m-labeled mPFC→dmStr neurons revealed strongest activity during the maintenance period, and optogenetic inhibition of these neurons impaired performance only when applied during this period. Conversely, enhancing mPFC→dmStr pathway activity—via pharmacological suppression of HCN1 or by optogenetic activation during the maintenance period—alleviated WM impairment induced by NMDA receptor blockade. Moreover, cellular-resolution miniscope imaging revealed that >50% of mPFC→dmStr neurons are active during WM maintenance and that this subpopulation is distinct from neurons active during encoding and retrieval. In all task periods, neuronal sequences were evident. Striatum-projecting mPFC neurons thus critically contribute to spatial WM maintenance.

وصف الملف: application/pdf

العلاقة: https://www.zora.uzh.ch/id/eprint/254230/1/ZORA_s41467_023_42777_3.pdfTest; info:pmid/37919287; urn:issn:2041-1723

الإتاحة: https://doi.org/10.5167/uzh-25423010.1038/s41467-023-42777-3Test
https://www.zora.uzh.ch/id/eprint/254230Test/
https://www.zora.uzh.ch/id/eprint/254230/1/ZORA_s41467_023_42777_3.pdfTest

المؤلفون: Ejdrup, Aske L., Wellbourne-Wood, Joel, Dreyer, Jakob K., Guldhammer, Nina, Lycas, Matthew D., Gether, Ulrik, Hall, Benjamin J., Sørensen, Gunnar

المصدر: Ejdrup , A L , Wellbourne-Wood , J , Dreyer , J K , Guldhammer , N , Lycas , M D , Gether , U , Hall , B J & Sørensen , G 2023 , ' Within-Mice Comparison of Microdialysis and Fiber Photometry-Recorded Dopamine Biosensor during Amphetamine Response ' , ACS Chemical Neuroscience , vol. 14 , no. 9 . https://doi.org/10.1021/acschemneuro.2c00817Test

مصطلحات موضوعية: amphetamine, biosensors, dopamine, Fiber photometry, microdialysis, striatum

الوصف: A fundamental concept in neuroscience is the transmission of information between neurons via neurotransmitters, -modulators, and -peptides. For the past decades, the gold standard for measuring neurochemicals in awake animals has been microdialysis (MD). The emergence of genetically encoded fluorescencebased biosensors, as well as in vivo optical techniques such as fiber photometry (FP), has introduced technologically distinct means of measuring neurotransmission. To directly compare MD and FP, we performed concurrent within-animal recordings of extracellular dopamine (DA) in the dorsal striatum (DS) before and after administration of amphetamine in awake, freely behaving mice expressing the dopamine sensor dLight1.3b. We show that despite temporal differences, MD- and FP-based readouts of DA correlate well within mice. Down-sampling of FP data showed temporal correlation to MD data, with less variance observed using FP. We also present evidence that DA fluctuations periodically reach low levels, and naï ve animals have rapid, predrug DA dynamics measured with FP that correlate to the subsequent pharmacodynamics of amphetamine as measured with MD and FP. ; A fundamental concept in neuroscience is the transmission of information between neurons via neurotransmitters, -modulators, and -peptides. For the past decades, the gold standard for measuring neurochemicals in awake animals has been microdialysis (MD). The emergence of genetically encoded fluorescence-based biosensors, as well as in vivo optical techniques such as fiber photometry (FP), has introduced technologically distinct means of measuring neurotransmission. To directly compare MD and FP, we performed concurrent within-animal recordings of extracellular dopamine (DA) in the dorsal striatum (DS) before and after administration of amphetamine in awake, freely behaving mice expressing the dopamine sensor dLight1.3b. We show that despite temporal differences, MD- and FP-based readouts of DA correlate well within mice. Down-sampling of FP data showed ...

وصف الملف: application/pdf

الإتاحة: https://doi.org/10.1021/acschemneuro.2c00817Test
https://curis.ku.dk/portal/da/publications/withinmice-comparison-of-microdialysis-and-fiber-photometryrecorded-dopamine-biosensor-during-amphetamine-responseTest(175a8e51-ae49-4b83-8fb6-77a2351b50d7).html
https://curis.ku.dk/ws/files/345514901/acschemneuro.2c00817.pdfTest

المؤلفون: Gillespie, Conor S., Hall, Benjamin J., George, Alan M., Hennigan, Dawn, Sneade, Christine, Cawker, Stephanie, Silva, Adikarige Haritha Dulanka, Vloeberghs, Michael, Aquilina, Kristian, Pettorini, Benedetta

المصدر: Child's Nervous System ; volume 40, issue 1, page 171-180 ; ISSN 0256-7040 1433-0350

مصطلحات موضوعية: Neurology (clinical), General Medicine, Pediatrics, Perinatology and Child Health

الوصف: Purpose Assess the effects of selective dorsal rhizotomy (SDR) on motor function and quality of life in children with a Gross Motor Function Classification System (GMFCS) level of IV or V (non-ambulatory). Methods This is a prospective, observational study in three tertiary neurosurgery units in England, UK, performing SDR on children aged 3–18 with spastic diplegic cerebral palsy, and a GMFCS level of IV or V, between 2012 and 2019. The primary outcome measure was the change in the 66-item Gross Motor Function Measure (GMFM-66) from baseline to 24 months after SDR, using a linear mixed effects model. Secondary outcomes included spasticity, bladder function, quality of life, and pain scores. Results Between 2012 and 2019, 144 children who satisfied these inclusion criteria underwent SDR. The mean age was 8.2 years. Fifty-two percent were female. Mean GMFM-66 score was available in 77 patients (53.5%) and in 39 patients (27.1%) at 24 months after SDR. The mean increase between baseline and 24 months post-SDR was 2.4 units (95% CI 1.7–3.1, p < 0.001, annual change 1.2 units). Of the 67 patients with a GMFM-66 measurement available, a documented increase in gross motor function was seen in 77.6% ( n = 52). Of 101 patients with spasticity data available, mean Ashworth scale decreased after surgery (2.74 to 0.30). Of patients’ pain scores, 60.7% ( n = 34) improved, and 96.4% ( n = 56) of patients’ pain scores remained the same or improved. Bladder function improved in 30.9% of patients. Conclusions SDR improved gross motor function and reduced pain in most patients at 24 months after surgery, although the improvement is less pronounced than in children with GMFCS levels II and III. SDR should be considered in non-ambulant patients.

الإتاحة: https://doi.org/10.1007/s00381-023-06062-4Test

المؤلفون: Hall, Benjamin J., Duddy, John C., Apostolopoulou, Katerina, Pettorini, Benedetta

المصدر: Child's Nervous System ; ISSN 0256-7040 1433-0350

مصطلحات موضوعية: Neurology (clinical), General Medicine, Pediatrics, Perinatology and Child Health

الوصف: Purpose Neuro-endoscopic lavage (NEL) is an increasingly popular intervention for intraventricular haemorrhage (IVH) and post-haemorrhagic hydrocephalus (PHH), with considerable variation in technique dependent on clinician and clinical circumstances. Whilst efforts to standardise the technique are ongoing, this work describes a tertiary centre experience utilising NEL, highlighting potential caveats to standardisation. Methods A retrospective review of electronic case notes for patients undergoing temporising surgical intervention for IVH between 2012 and 2021 at our centre was performed. Data collected included (i) gestational age, (ii) aetiology of hydrocephalus, (iii) age at time of intervention, (iv) intervention performed, (v) need for permanent CSF diversion, (vi) ‘surgical burden’, i.e. number of procedures following primary intervention, and (vii) wound failure and infection rate. Data was handled in Microsoft Excel and statistical analysis SPSS v27.0 Results 49 neonates ( n = 25 males) were included. Overall mean gestational age was 27 weeks and at intervention 35 + 3 weeks. IVH was the predominant cause of hydrocephalus (93.8%) and primary surgical interventions included insertion of a ventriculosubgaleal shunt (VSGS) in n = 41 (83.6%) patients, NEL in n = 6 (12.2%) patients and insertion of an EVD in n = 2 (4.1%). N = 9 (18.4%) patients underwent NEL at some point during the time interval reviewed; n = 4 (8.2%) received NEL monotherapy and n = 5 (10.2%) also received a VSGS. Rate of conversion to definitive CSF diversion between NEL ( n = 8, 88.9%) and VSGS cohorts ( n = 37, 92.5%) was not significantly different ( p = 0.57), nor between NEL alone ( n = 3, 75%) and NEL + VSGS ( n = 5, 100%) ( p = 0.44). None of the patients that underwent NEL monotherapy had any wound issues or CNS infection as a result of the initial intervention, compared to n = 3 (60%) of those that underwent NEL and implantation of VSGS ( p = 0.1). Conclusion Both NEL and VSGS are effective in temporising hydrocephalus ...

الإتاحة: https://doi.org/10.1007/s00381-023-06214-6Test

المؤلفون: Hall, Benjamin J., Ali, Ahmad M.S., Hennigan, Dawn, Pettorini, Benedetta

المصدر: Child's Nervous System ; ISSN 0256-7040 1433-0350

مصطلحات موضوعية: Neurology (clinical), General Medicine, Pediatrics, Perinatology and Child Health

الوصف: Purpose Extremely premature neonates diagnosed with post-haemorrhagic hydrocephalus (PHH) are recognised to have particularly poor outcomes. This study assessed the impact of a number of variables on outcomes in this cohort, in particular the choice of shunt valve mechanism. Methods Electronic case notes were retrospectively reviewed of all premature neonates admitted to our centre for management of hydrocephalus between 2012 and 2021. Data included (i) gestational age, (ii) birth weight, (iii) hydrocephalus aetiology, (iv) surgical intervention, (v) shunt system, (vi) ‘surgical burden’ and (vii) wound failure and infection rate. Data was handled in Microsoft Excel and statistical analysis performed in SPSS v27.0 Results N = 53 premature hydrocephalic patients were identified ( n = 28 (52.8%) female). Median gestational age at birth was 27 weeks (range: 23–36 + 6 weeks), with n = 35 extremely preterm patients and median birth weight of 1.9 kg (range: 0.8–3.6 kg). Total n = 99 programmable valves were implanted ( n = 28 (28.3%) de novo, n = 71 (71.2%) revisions); n = 28 (28.3%) underwent n ≥ 1 pressure alterations, after which n = 21 (75%) patients had symptoms improve. In n = 8 patients exchanged from fixed to programmable valves, a mean reduction of 1.9 revisions per patient after exchange was observed (95%CI: 0.36–3.39, p = 0.02). Mean overall shunt survival was 39.5 weeks (95%CI: 30.6–48.5); 33.2 weeks (95%CI: 25.2–41.1) in programmable valves and 35.1 weeks (95%CI: 19.5–50.6) in fixed pressure ( p = 0.22) with 12-month survival rates of 25.7% and 24.7%, respectively ( p = 0.22). Shorter de novo shunt survival was associated with higher operation count overall (Pearson’s R : − 0.54, 95%CI: − 0.72 to − 0.29, p < 0.01). Wound failure, gestational age and birth weight were significantly associated with shorter de novo shunt survival in a Cox regression proportional hazards model; gestational age had the greatest impact on shunt survival (Exp(B): 0.71, 95%CI: 0.63–0.81, p < 0.01). Conclusion ...

الإتاحة: https://doi.org/10.1007/s00381-023-06204-8Test

المؤلفون: Hall, Benjamin J., Duddy, John C., Apostolopoulou, Katerina, David, Raenette, Kurzbuch, Arthur, Nadkarni, Abhishek, Trichinopoly Krishna, Sandhya, Cooper, Ben, Gouldbourne, Hayley, Hennigan, Dawn, Dawes, William, Ellenbogen, Jonathan, Parks, Christopher, Pettorini, Benedetta, Sinha, Ajay, Mallucci, Conor

المصدر: Pediatric Neurosurgery ; volume 58, issue 4, page 215-222 ; ISSN 1016-2291 1423-0305

الوصف: Introduction: We present the largest series of paediatric intracranial empyemas occurring after COVID-19 infection to date, and discuss the potential implications of the pandemic on this neurosurgical pathology. Methods: Patients admitted to our centre between January 2016 and December 2021 with a confirmed radiological diagnosis of intracranial empyema were retrospectively reviewed, excluding non-otorhinological source cases. Patients were grouped according to onset before or after onset of the COVID-19 pandemic and COVID-19 status. A literature review of all post-COVID-19 intracranial empyemas was performed. SPSS v27 was used for statistical analysis. Results: Sixteen patients were diagnosed with intracranial empyema: n = 5 prior to 2020 and n = 11 after, resulting in an average annual incidence of 0.3% prior to onset of the pandemic and 1.2% thereafter. Of those diagnosed since the pandemic, 4 (25%) were confirmed to have COVID-19 on recent PCR test. Time from COVID-19 infection until empyema diagnosis ranged from 15 days to 8 weeks. Mean age for post-COVID-19 cases was 8.5 years (range: 7–10 years) compared to 11 years in non-COVID cases (range: 3–14 years). Streptococcus intermedius was grown in all cases of post-COVID-19 empyema, and 3 of 4 (75%) post-COVID-19 cases developed cerebral sinus thromboses, compared to 3 of 12 (25%) non-COVID-19 cases. All cases were discharged home with no residual deficit. Conclusion: Our post-COVID-19 intracranial empyema series demonstrates a greater proportion of cerebral sinus thromboses than non-COVID-19 cases, potentially reflecting the thrombogenic effects of COVID-19. Incidence of intracranial empyema at our centre has increased since the start of the pandemic, causes of which require further investigation and multicentre collaboration.

الإتاحة: https://doi.org/10.1159/000531753Test

المؤلفون: Cates, Rhiannon M., Hall, Benjamin J., Broughton, James, Reeves, Andrew, Ringwelski, Faith Hocutt, Zaro, Kathryn, Richards, Jenna, Roberts, Lani

المصدر: The Radical Teacher, 2020 Oct 01(118), 41-47.

الوصول الحر: https://www.jstor.org/stable/48694802Test

المؤلفون: Gillespie, Conor S, Hall, Benjamin J, George, Alan M, Hennigan, Dawn, Sneade, Christine, Cawker, Stephanie, Silva, Adikarige Haritha Dulanka, Vloeberghs, Michael, Aquilina, Kristian, Pettorini, Benedetta

مصطلحات موضوعية: Cerebral palsy, GMFCS, Multi-center, SDR, Child, Humans, Female, Male, Rhizotomy, Prospective Studies, Quality of Life, Treatment Outcome, Muscle Spasticity, Pain

الوصف: Acknowledgements: We would like to thank Christine Sneade, Carol Lever, Beata Bigas, Morag Sangster, and Colm MacEoin (Alder Hey Physiotherapy group) for their kind assistance with the study implementation, measurement of patient outcomes during the study, and the drafting and submission of the manuscript. CSG is supported by a grant from the Wolfson Foundation. ; PURPOSE: Assess the effects of selective dorsal rhizotomy (SDR) on motor function and quality of life in children with a Gross Motor Function Classification System (GMFCS) level of IV or V (non-ambulatory). METHODS: This is a prospective, observational study in three tertiary neurosurgery units in England, UK, performing SDR on children aged 3-18 with spastic diplegic cerebral palsy, and a GMFCS level of IV or V, between 2012 and 2019. The primary outcome measure was the change in the 66-item Gross Motor Function Measure (GMFM-66) from baseline to 24 months after SDR, using a linear mixed effects model. Secondary outcomes included spasticity, bladder function, quality of life, and pain scores. RESULTS: Between 2012 and 2019, 144 children who satisfied these inclusion criteria underwent SDR. The mean age was 8.2 years. Fifty-two percent were female. Mean GMFM-66 score was available in 77 patients (53.5%) and in 39 patients (27.1%) at 24 months after SDR. The mean increase between baseline and 24 months post-SDR was 2.4 units (95% CI 1.7-3.1, p < 0.001, annual change 1.2 units). Of the 67 patients with a GMFM-66 measurement available, a documented increase in gross motor function was seen in 77.6% (n = 52). Of 101 patients with spasticity data available, mean Ashworth scale decreased after surgery (2.74 to 0.30). Of patients' pain scores, 60.7% (n = 34) improved, and 96.4% (n = 56) of patients' pain scores remained the same or improved. Bladder function improved in 30.9% of patients. CONCLUSIONS: SDR improved gross motor function and reduced pain in most patients at 24 months after surgery, although the improvement is less pronounced than in children ...

وصف الملف: text/xml; application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/362815Test

الإتاحة: https://www.repository.cam.ac.uk/handle/1810/362815Test