Brain Communications最新文献

{"title":"1H and 31P magnetic resonance spectroscopy reveal potential pathogenic and biomarker metabolite alterations in Lafora disease","authors":"Kimberly L. Chan, Aparna Panatpur, Souad Messahel, Hamza Dahshi, Talon Johnson, Anke Henning, Jimin Ren, B. Minassian","doi":"10.1093/braincomms/fcae104","DOIUrl":"https://doi.org/10.1093/braincomms/fcae104","url":null,"abstract":"\u0000 Lafora disease is a fatal teenage-onset progressive myoclonus-epilepsy and neurodegenerative disease associated with polyglucosan bodies. Polyglucosans are long-branched and as a result precipitation and aggregation-prone glycogen. In mouse models, downregulation of glycogen synthase, the enzyme that elongates glycogen branches, prevents polyglucosan formation and rescues Lafora disease. Mouse work, however, has not yet revealed the mechanisms of polyglucosan generation, and few in vivo human studies have been performed. Here, non-invasive in vivo magnetic resonance spectroscopy (1H and 31P) was applied to test scan feasibility, and assess neurotransmitter balance and energy metabolism in Lafora disease toward a better understanding of pathogenesis. Macromolecule-suppressed GABA-edited 1H magnetic resonance spectroscopy and 31P magnetic resonance spectroscopy at 3 Tesla and 7 Tesla, respectively, were performed in 4 Lafora disease patients and a total of 21 healthy controls (12 for the 1H- magnetic resonance spectroscopy and 9 for the 31P-magnetic resonance spectroscopy). Spectra were processed using in-house software and fit to extract metabolite concentrations. From the 1H spectra, we found 33% lower GABA concentrations (p = 0.013), 34% higher glutamate + glutamine concentrations (p = 0.011), and 24% lower N-acetylaspartate concentrations (p = 0.0043) in Lafora disease patients compared to controls. From the 31P spectra, we found 34% higher phosphoethanolamine concentrations (p = 0.016), 23% lower nicotinamide adenine dinucleotide concentrations (p = 0.003), 50% higher uridine diphosphate glucose concentrations (p = 0.004) and 225% higher glucose 6-phosphate concentrations in Lafora disease patients versus controls (p = 0.004). Uridine diphosphate glucose is the substrate of glycogen synthase and glucose 6-phosphate is its extremely potent allosteric activator. The observed elevated uridine diphosphate glucose and glucose 6-phosphate levels are expected to hyperactivate glycogen synthase and may underlie the generation of polyglucosans in Lafora disease. The increased glutamate + glutamine and reduced GABA indicate altered neurotransmission and energy metabolism, which may contribute to the disease’s intractable epilepsy. These results suggest a possible basis of polyglucosan formation and potential contributions to the epilepsy of Lafora disease. If confirmed in larger human and animal model studies, measurements of the dysregulated metabolites by magnetic resonance spectroscopy could be developed into non-invasive biomarkers for clinical trials.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"84 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140377851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mRNA encoded antibody approach for targeting extracellular and intracellular tau","authors":"Patricia Wongsodirdjo, Alayna C Caruso, Alicia K Yong, Madeleine A. Lester, Laura J Vella, Ya Hui Hung, Rebecca M. Nisbet","doi":"10.1093/braincomms/fcae100","DOIUrl":"https://doi.org/10.1093/braincomms/fcae100","url":null,"abstract":"\u0000 Monoclonal antibodies have emerged as a leading therapeutic agent for the treatment of disease, including Alzheimer’s disease. In the last year, two anti-amyloid monoclonal antibodies, lecanemab and aducanumab, have been approved in the USA for the treatment of Alzheimer’s disease, whilst several tau-targeting monoclonal antibodies are currently in clinical trials. Such antibodies, however, are expensive and timely to produce and require frequent dosing regimens to ensure disease-modifying effects. Synthetic in vitro-transcribed mRNA encoding antibodies for endogenous protein expression holds the potential to overcome many of the limitations associated with protein antibody production. Here, we have generated synthetic in vitro-transcribed mRNA encoding a tau specific antibody as a full-sized immunoglobulin and as a single-chain variable fragment. In vitro transfection of human neuroblastoma SH-SY5Y cells demonstrated the ability of the synthetic mRNA to be translated into a functional tau-specific antibody. Furthermore, we show that the translation of the tau-specific single-chain variable fragment as an intrabody results in the specific engagement of intracellular tau. This work highlights the utility of mRNA for the delivery of antibody therapeutics, including intrabodies, for the targeting of tau in Alzheimer’s disease and other tauopathies.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":" 1001","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140382306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Volumetric analysis of hippocampal subregions and subfields in left and right semantic dementia","authors":"A. Carlos, Stephen D. Weigand, Joseph R. Duffy, Heather M Clark, Rene L. Utianski, M. Machulda, H. Botha, Nha Trang Thu Pham, V. Lowe, C. Schwarz, J. Whitwell, K. Josephs","doi":"10.1093/braincomms/fcae097","DOIUrl":"https://doi.org/10.1093/braincomms/fcae097","url":null,"abstract":"Abstract Two variants of semantic dementia are recognized based on the laterality of temporal lobe involvement: a left-predominant variant associated with verbal knowledge impairment and a right-predominant variant associated with behavioural changes and non-verbal knowledge loss. This cross-sectional clinicoradiologic study aimed to assess whole hippocampal, subregion, and/or subfield volume loss in semantic dementia versus controls and across its variants. Thirty-five semantic dementia participants and 15 controls from the Neurodegenerative Research Group at Mayo Clinic who had completed 3.0-T volumetric magnetic resonance imaging and 18F-fluorodeoxyglucose-positron emission tomography were included. Classification as left-predominant (n = 25) or right-predominant (n = 10) variant was based on temporal lobe hypometabolism. Volumes of hippocampal subregions (head, body, and tail) and subfields (parasubiculum, presubiculum, subiculum, cornu ammonis 1, cornu ammonis 3, cornu ammonis 4, dentate gyrus, molecular layer, hippocampal–amygdaloid transition area, and fimbria) were obtained using FreeSurfer 7. Subfield volumes were measured separately from head and body subregions. We fit linear mixed-effects models using log-transformed whole hippocampal/subregion/subfield volumes as dependent variables; age, sex, total intracranial volume, hemisphere and a group-by-hemisphere interaction as fixed effects; and subregion/subfield nested within hemisphere as a random effect. Significant results (P < 0.05) are hereby reported. At the whole hippocampal level, the dominant (predominantly involved) hemisphere of both variants showed 23–27% smaller volumes than controls. The non-dominant (less involved) hemisphere of the right-predominant variant also showed volume loss versus controls and the left-predominant variant. At the subregional level, both variants showed 17–28% smaller dominant hemisphere head, body, and tail than controls, with the right-predominant variant also showing 8–12% smaller non-dominant hemisphere head than controls and left-predominant variant. At the subfield level, the left-predominant variant showed 12–36% smaller volumes across all dominant hemisphere subfields and 14–15% smaller non-dominant hemisphere parasubiculum, presubiculum (head and body), subiculum (head) and hippocampal–amygdaloid transition area than controls. The right-predominant variant showed 16–49% smaller volumes across all dominant hemisphere subfields and 14–22% smaller parasubiculum, presubiculum, subiculum, cornu ammonis 3, hippocampal–amygdaloid transition area (all from the head) and fimbria of non-dominant hemisphere versus controls. Comparison of dominant hemispheres showed 16–29% smaller volumes of the parasubiculum, presubiculum (head) and fimbria in the right-predominant than left-predominant variant; comparison of non-dominant hemispheres showed 12–15% smaller cornu ammonis 3, cornu ammonis 4, dentate gyrus, hippocampal–amygdaloid transition area (all from","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":" 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140383894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA guardians of the posterior cingulate cortex delay cognitive deterioration in elders","authors":"H. Soreq","doi":"10.1093/braincomms/fcae099","DOIUrl":"https://doi.org/10.1093/braincomms/fcae099","url":null,"abstract":"This scientific commentary refers to ‘MicroRNA profiles of pathology and resilience in posterior cingulate cortex of cognitively intact elders’, by Kelley et al. (https://doi.org/10.1093/braincomms/fcae082).","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"5 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140381605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissociating reading and auditory comprehension in persons with aphasia","authors":"Rachael M Harrington, Sigfus Kristinsson, Janina Wilmskoetter, N. Busby, D. den Ouden, Chris Rorden, J. Fridriksson, L. Bonilha","doi":"10.1093/braincomms/fcae102","DOIUrl":"https://doi.org/10.1093/braincomms/fcae102","url":null,"abstract":"\u0000 Language comprehension is often affected in individuals with post-stroke aphasia. However, deficits in auditory comprehension are not fully correlated with deficits in reading comprehension and the mechanisms underlying this dissociation remain unclear. This distinction is important for understanding language mechanisms, predicting long-term impairments, and future development of treatment interventions. Using comprehensive auditory and reading measures from a large cohort of individuals with aphasia, we evaluated the relationship between aphasia type and reading comprehension impairments, the relationship between auditory vs. reading comprehension deficits and the crucial neuroanatomy supporting the dissociation between post-stroke reading and auditory deficits.\u0000 Scores from the Western Aphasia Battery Revised (WAB-R) from 70 participants with aphasia after a left-hemisphere stroke were utilized to evaluate both reading and auditory comprehension of linguistically equivalent stimuli. Repeated-measures and univariate analysis of variance (ANOVA) were used to assess the relationship between auditory comprehension and aphasia types and correlations were employed to test the relationship between reading and auditory comprehension deficits. Lesion symptom mapping (LSM) was used to determine the dissociation of crucial brain structures supporting reading comprehension deficits controlling for auditory deficits and vice-versa.\u0000 Participants with Broca's or global aphasia had the worst performance on reading comprehension. Auditory comprehension explained 26% of the variance in reading comprehension for sentence completion and 44% for following sequential commands. Controlling for auditory comprehension, worse reading comprehension performance was independently associated with damage to the inferior temporal gyrus, fusiform gyrus, posterior inferior temporal gyrus, inferior occipital gyrus, lingual gyrus, and posterior thalamic radiation.\u0000 Auditory and reading comprehension are only partly correlated in aphasia. Reading is an integral part of daily life and directly associated with quality of life and functional outcomes. This study demonstrated that reading performance is directly related to lesioned areas in the boundaries between visual association regions and ventral stream language areas. This behavioral and neuroanatomical dissociation provides information about the neurobiology of language and mechanisms for potential future treatment interventions.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":" 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140384375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to: Failure of the glymphatic system by increases of jugular resistance as possible link between asthma and dementia","authors":"A. Nair, Barbara B Bendlin, Douglas C Dean, M. Rosenkranz","doi":"10.1093/braincomms/fcae038","DOIUrl":"https://doi.org/10.1093/braincomms/fcae038","url":null,"abstract":"","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"108 25","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139781089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to: Failure of the glymphatic system by increases of jugular resistance as possible link between asthma and dementia","authors":"A. Nair, Barbara B Bendlin, Douglas C Dean, M. Rosenkranz","doi":"10.1093/braincomms/fcae038","DOIUrl":"https://doi.org/10.1093/braincomms/fcae038","url":null,"abstract":"","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"96 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139840830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultradian rhythms in accelerometric and autonomic data vary based on seizure occurrence in pediatric epilepsy patients","authors":"Solveig Vieluf, Sarah Cantley, Vaishnav Krishnan, Tobias Loddenkemper","doi":"10.1093/braincomms/fcae034","DOIUrl":"https://doi.org/10.1093/braincomms/fcae034","url":null,"abstract":"\u0000 Ultradian rhythms are physiological oscillations that resonate with period lengths shorter than twenty-four hours. This study examined the expression of ultradian rhythms in patients with epilepsy, a disease defined by an enduring seizure risk that may vary cyclically.\u0000 Using a wearable device, we recorded heart rate, body temperature, electrodermal activity, and limb accelerometry in patients admitted to the pediatric epilepsy monitoring unit. In our case-control design, we included recordings from 29 patients with tonic clonic seizures and 29 non-seizing controls. We spectrally decomposed each signal to identify cycle lengths of interest and compared average spectral power- and period-related markers between groups. Additionally, we related seizure occurrence to the phase of ultradian rhythm in patients with recorded seizures.\u0000 We observed prominent 2 and 4-hour-long ultradian rhythms of accelerometry, as well as 4-hour-long oscillations in heart rate. Patients with seizures displayed a higher peak power in the 2-hour accelerometry rhythm (U = 287, p = 0.038) and a period-lengthened 4-hour heart rate rhythm (U = 291.5, p = 0.037). Those that seized also displayed greater mean rhythmic electrodermal activity (U = 261; p = 0.013). Most seizures occurred during the falling-to-trough quarter phase of accelerometric rhythms (13 out of 27, χ2 = 8.41, p = 0.038).\u0000 Fluctuations in seizure risk or the occurrence of seizures may interrelate with ultradian rhythms of movement and autonomic function. Longitudinal assessments of ultradian patterns in larger patient samples may enable us to understand how such rhythms may improve the temporal precision of seizure forecasting models.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"47 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139782579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultradian rhythms in accelerometric and autonomic data vary based on seizure occurrence in pediatric epilepsy patients","authors":"Solveig Vieluf, Sarah Cantley, Vaishnav Krishnan, Tobias Loddenkemper","doi":"10.1093/braincomms/fcae034","DOIUrl":"https://doi.org/10.1093/braincomms/fcae034","url":null,"abstract":"\u0000 Ultradian rhythms are physiological oscillations that resonate with period lengths shorter than twenty-four hours. This study examined the expression of ultradian rhythms in patients with epilepsy, a disease defined by an enduring seizure risk that may vary cyclically.\u0000 Using a wearable device, we recorded heart rate, body temperature, electrodermal activity, and limb accelerometry in patients admitted to the pediatric epilepsy monitoring unit. In our case-control design, we included recordings from 29 patients with tonic clonic seizures and 29 non-seizing controls. We spectrally decomposed each signal to identify cycle lengths of interest and compared average spectral power- and period-related markers between groups. Additionally, we related seizure occurrence to the phase of ultradian rhythm in patients with recorded seizures.\u0000 We observed prominent 2 and 4-hour-long ultradian rhythms of accelerometry, as well as 4-hour-long oscillations in heart rate. Patients with seizures displayed a higher peak power in the 2-hour accelerometry rhythm (U = 287, p = 0.038) and a period-lengthened 4-hour heart rate rhythm (U = 291.5, p = 0.037). Those that seized also displayed greater mean rhythmic electrodermal activity (U = 261; p = 0.013). Most seizures occurred during the falling-to-trough quarter phase of accelerometric rhythms (13 out of 27, χ2 = 8.41, p = 0.038).\u0000 Fluctuations in seizure risk or the occurrence of seizures may interrelate with ultradian rhythms of movement and autonomic function. Longitudinal assessments of ultradian patterns in larger patient samples may enable us to understand how such rhythms may improve the temporal precision of seizure forecasting models.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"183 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139842303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI imaging of radiofrequency thalamotomy for tremor: what is it about?","authors":"Konstantin V Slavin","doi":"10.1093/braincomms/fcae040","DOIUrl":"https://doi.org/10.1093/braincomms/fcae040","url":null,"abstract":"This scientific commentary refers to ‘Radiofrequency thalamotomy for tremor produces focused and predictable lesions shown on magnetic resonance images ’, by Ishihara  et al. (https://doi.org/10.1093/braincomms/fcad329).","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139846142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}