Brain Communications最新文献

{"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":"119 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139786337","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":"Apathy scores in Parkinson’s disease relate to EEG components in an incentivized motor task","authors":"Soojin Lee, Esther Song, Maria Zhu, S. Appel-Cresswell, Martin J. McKeown","doi":"10.1093/braincomms/fcae025","DOIUrl":"https://doi.org/10.1093/braincomms/fcae025","url":null,"abstract":"\u0000 Apathy is one of the most prevalent non-motor symptoms of Parkinson’s disease and is characterized by decreased goal-directed behavior due to a lack of motivation and/or impaired emotional reactivity. Despite its high prevalence, the neurophysiological mechanisms underlying apathy in Parkinson’s disease, which may guide neuromodulation interventions, are poorly understood. Here, we investigated the neural oscillatory characteristics of apathy in Parkinson’s disease using EEG data recorded during an incentivized motor task.\u0000 Thirteen Parkinson’s disease patients with apathy and 13 Parkinson’s disease patients without apathy as well as 12 healthy controls were instructed to squeeze a hand grip device to earn a monetary reward proportional to the grip force they used. Event-related spectral perturbations during the presentation of a reward cue and squeezing were analyzed using multi-set canonical correlation analysis to detect different orthogonal components of temporally-consistent event-related spectral perturbations across trials and participants.\u0000 The first component, predominantly located over parietal regions, demonstrated suppression of low-beta (12–20 Hz) power (i.e., beta desynchronization) during reward cue presentation that was significantly smaller in Parkinson’s disease patients with apathy compared to healthy controls. Unlike traditional event-related spectral perturbation analysis, the beta-desynchronization in this component was significantly correlated with clinical apathy scores. Higher monetary rewards resulted in larger beta desynchronization in heathy controls but not Parkinson’s disease patients. The second component contained gamma and theta frequencies and demonstrated exaggerated theta (4–8 Hz) power in Parkinson’s disease patients with apathy during the reward cue and squeezing compared to healthy controls, and this was positively correlated with Montreal Cognitive Assessment scores. The third component, over central regions, demonstrated significantly different beta power across groups, with apathetic groups having the lowest beta power.\u0000 Our results emphasize that altered low-beta and theta oscillations are critical for reward processing and motor planning in Parkinson’s disease patients with apathy, and these may provide a target for non-invasive neuromodulation.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":" 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139788365","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":"Alteration of functional connectivity network in population of objectively-defined subtle cognitive decline","authors":"Xinyi Zhang, Qingze Zeng, Yanbo Wang, Yu Jin, Tiantian Qiu, Kaicheng Li, Xiao Luo, Shuyue Wang, Xiaopei Xu, Xiaocao Liu, Shuai Zhao, Zheyu Li, L. Hong, Jixuan Li, Siyan Zhong, Tianyi Zhang, Peiyu Huang, Baorong Zhang, Min-min Zhang, Yanxing Chen","doi":"10.1093/braincomms/fcae033","DOIUrl":"https://doi.org/10.1093/braincomms/fcae033","url":null,"abstract":"\u0000 The objectively-defined subtle cognitive decline individuals had higher progression rates of cognitive decline and pathological deposition than healthy elderly, indicating a higher risk of progressing to Alzheimer’s disease. However, little is known about the brain functional alterations during this stage. Thus, we aimed to investigate the functional network patterns in objectively-defined subtle cognitive decline cohort.\u0000 Forty-two cognitive normal, 29 objectively-defined subtle cognitive decline and 55 mild cognitive impairment subjects were included based on neuropsychological measures from the Alzheimer's Disease Neuroimaging Initiative dataset. Thirty cognitive normal, 22 objectively-defined subtle cognitive decline and 48 mild cognitive impairment had longitudinal MR data. The degree centrality and eigenvector centrality for each participant were calculated by using resting-state functional MRI. For cross-sectional data, analysis of covariance (ANCOVA) was performed to detect between-group differences of degree centrality and eigenvector centrality after controlling age, sex, and education. For longitudinal data, repeated measurement ANCOVA was used for comparing the alterations during follow-up period among three groups. In order to classify the clinical significance, we correlated degree centrality and eigenvector centrality values to Alzheimer’s disease biomarkers and cognitive function.\u0000 The results of ANCOVA showed significant between-group differences of eigenvector centrality and degree centrality in left superior temporal gyrus and left precuneus respectively. Across groups, the eigenvector centrality value of left superior temporal gyrus was positively related with recognition scores in auditory verbal learning test, whereas the degree centrality value of left precuneus was positively associated with Mini-mental State Examination total score. For longitudinal data, the results of repeated measurement ANCOVA indicated objectively-defined subtle cognitive decline group had the highest declined rate of both eigenvector centrality and degree centrality values than other groups.\u0000 Our study showed an increased brain functional connectivity in objectively-defined subtle cognitive decline individuals at both local and global level, which were associated with Alzheimer’s disease pathology and neuropsychological assessment. Moreover, we also observed a faster declined rate of functional network matrix in objectively-defined subtle cognitive decline individuals during the follow-ups.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"406 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139848146","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":"Sex differences in post-acute neurological sequelae of SARS-CoV-2 and symptom resolution in adults after COVID-19 hospitalization: an international multicenter prospective observational study","authors":"Sung-Min Cho, Lavienraj Premraj, D. Battaglini, J. Fanning, Jacky Y. Suen, G. Bassi, John F. Fraser, Chiara Robba, M. Griffee, Tommy Solomon, M. G. Semple, Kenneth Baillie, L. Sigfrid, J. Scott, B. Citarella, L. Merson, Rakesh C. Arora, Glenn Whitman, D. Thomson, Nicole White, L. Abel, Amal Abrous, K. Jabal, H. Zayyad, Younes Ait Tamlihat, Aliya Mohammed Alameen, Marta Alessi, B. Alex, K. Alexandre, Adam Ali, Kazali Enagnon Alidjnou, C. Allavena, N. Allou, C. Andrejak, Andrea Angheben, F. Angoulvant, S. Ansart, J. Arlet, Elise Artaud-Macari, J. Assié, J. Auchabie, H. Aumaître, A. Auvet, Eyvind W. Axelsen, Laurène Azemar, Cécile Azoulay, Benjamin Bach, D. Bachelet, Claudine Badr, Roar Bævre-Jensen, J. Baillie, F. Bani-Sadr, W. Barclay, Marie Bartoli, J. Baruch, R. Basmaci, Jules Bauer, A. Bedossa, Husna Begum, Sylvie Behilill, Anna Beltrame, Marine Beluze, Nicolas Benech, Delphine Bergeaud, J. Sobrino, G. Bertoli, S. Bessis, Sybille Bevilcaqua, Karine Bézulier, K. Bhavsar, Z. Bisoffi, L. Bitker, Mathieu Bl","doi":"10.1093/braincomms/fcae036","DOIUrl":"https://doi.org/10.1093/braincomms/fcae036","url":null,"abstract":"\u0000 Although it is known that COVID-19 can present with a range of neurological manifestations and in-hospital complications, sparse data exist if these initial neurological symptoms of COVID-19 are closely associated with post-acute neurological sequelae of SARS-CoV-2 (PANSC) and if female versus male sex impacts the symptom resolution. In this international, multicentre, prospective observational study across 407 sites from 15 countries (January/30th/2020-April/30th/2022), we report the prevalence and risk factors of PANSC among hospitalized adults and investigate the differences between males and females on neurological symptom resolution over time.\u0000 PANSC included altered consciousness/confusion, fatigue/malaise, anosmia, dysgeusia, and muscle aches/joint pain, which were collected at the index hospitalization and during the follow-up assessments. The analysis considered time to resolution of individual and all neurological symptoms. Resulting times were modeled by Weibull regression, assuming mixed-case interval censoring, with sex and age included as covariates. Model results were summarized as cumulative probability functions and age- and sex-adjusted median times to resolution.\u0000 We included 6,862 hospitalized adults with COVID-19, who had follow-up assessments. The median age of participants was 57 years (39.2% females). Males and females had similar baseline characteristics except that more males (vs. females) were admitted to Intensive Care Unit (30.5% vs. 20.3%) and received mechanical ventilation (17.2% vs. 11.8%).\u0000 Approximately 70% of patients had multiple neurological symptoms at the first follow-up (median=102 days). Fatigue (49.9%) and myalgia/arthralgia (45.2%) were the most prevalent symptoms of PANSC at the initial follow-up. Reported prevalence in females was generally higher (vs. males) for all symptoms. At 12 months, anosmia and dysgeusia were resolved in most patients, though fatigue, altered consciousness, and myalgia remained unresolved in >10% of the cohort. Females had a longer time to resolution (5.2 vs. 3.4 months) of neurological symptoms at follow-up for those with more than one neurological symptom.\u0000 In multivariable analysis, males were associated with a shorter time to resolution of symptoms (Hazard Ratio=1.53; 95% Confidence Interval =1.39–1.69). Intensive Care Unit admission was associated with a longer time to the resolution of symptoms (Hazard Ratio =0.68; 95% Confidence Interval=0.60–0.77). Post-discharge stroke was uncommon (0.3% in females; 0.5% in males).\u0000 Despite the methodological challenges of survey data, this international multicentre prospective cohort study demonstrates that PANSC following index hospitalization is high. Symptom prevalence was higher and took longer to resolve in females than in males. This supports that whilst males were sicker during acute illness, females were disproportionately affected by PANSC.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"49 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139847592","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":"Alteration of functional connectivity network in population of objectively-defined subtle cognitive decline","authors":"Xinyi Zhang, Qingze Zeng, Yanbo Wang, Yu Jin, Tiantian Qiu, Kaicheng Li, Xiao Luo, Shuyue Wang, Xiaopei Xu, Xiaocao Liu, Shuai Zhao, Zheyu Li, L. Hong, Jixuan Li, Siyan Zhong, Tianyi Zhang, Peiyu Huang, Baorong Zhang, Min-min Zhang, Yanxing Chen","doi":"10.1093/braincomms/fcae033","DOIUrl":"https://doi.org/10.1093/braincomms/fcae033","url":null,"abstract":"\u0000 The objectively-defined subtle cognitive decline individuals had higher progression rates of cognitive decline and pathological deposition than healthy elderly, indicating a higher risk of progressing to Alzheimer’s disease. However, little is known about the brain functional alterations during this stage. Thus, we aimed to investigate the functional network patterns in objectively-defined subtle cognitive decline cohort.\u0000 Forty-two cognitive normal, 29 objectively-defined subtle cognitive decline and 55 mild cognitive impairment subjects were included based on neuropsychological measures from the Alzheimer's Disease Neuroimaging Initiative dataset. Thirty cognitive normal, 22 objectively-defined subtle cognitive decline and 48 mild cognitive impairment had longitudinal MR data. The degree centrality and eigenvector centrality for each participant were calculated by using resting-state functional MRI. For cross-sectional data, analysis of covariance (ANCOVA) was performed to detect between-group differences of degree centrality and eigenvector centrality after controlling age, sex, and education. For longitudinal data, repeated measurement ANCOVA was used for comparing the alterations during follow-up period among three groups. In order to classify the clinical significance, we correlated degree centrality and eigenvector centrality values to Alzheimer’s disease biomarkers and cognitive function.\u0000 The results of ANCOVA showed significant between-group differences of eigenvector centrality and degree centrality in left superior temporal gyrus and left precuneus respectively. Across groups, the eigenvector centrality value of left superior temporal gyrus was positively related with recognition scores in auditory verbal learning test, whereas the degree centrality value of left precuneus was positively associated with Mini-mental State Examination total score. For longitudinal data, the results of repeated measurement ANCOVA indicated objectively-defined subtle cognitive decline group had the highest declined rate of both eigenvector centrality and degree centrality values than other groups.\u0000 Our study showed an increased brain functional connectivity in objectively-defined subtle cognitive decline individuals at both local and global level, which were associated with Alzheimer’s disease pathology and neuropsychological assessment. Moreover, we also observed a faster declined rate of functional network matrix in objectively-defined subtle cognitive decline individuals during the follow-ups.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":" 57","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139788090","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":"Sex differences in post-acute neurological sequelae of SARS-CoV-2 and symptom resolution in adults after COVID-19 hospitalization: an international multicenter prospective observational study","authors":"Sung-Min Cho, Lavienraj Premraj, D. Battaglini, J. Fanning, Jacky Y. Suen, G. Bassi, John F. Fraser, Chiara Robba, M. Griffee, Tommy Solomon, M. G. Semple, Kenneth Baillie, L. Sigfrid, J. Scott, B. Citarella, L. Merson, Rakesh C. Arora, Glenn Whitman, D. Thomson, Nicole White, L. Abel, Amal Abrous, K. Jabal, H. Zayyad, Younes Ait Tamlihat, Aliya Mohammed Alameen, Marta Alessi, B. Alex, K. Alexandre, Adam Ali, Kazali Enagnon Alidjnou, C. Allavena, N. Allou, C. Andrejak, Andrea Angheben, F. Angoulvant, S. Ansart, J. Arlet, Elise Artaud-Macari, J. Assié, J. Auchabie, H. Aumaître, A. Auvet, Eyvind W. Axelsen, Laurène Azemar, Cécile Azoulay, Benjamin Bach, D. Bachelet, Claudine Badr, Roar Bævre-Jensen, J. Baillie, F. Bani-Sadr, W. Barclay, Marie Bartoli, J. Baruch, R. Basmaci, Jules Bauer, A. Bedossa, Husna Begum, Sylvie Behilill, Anna Beltrame, Marine Beluze, Nicolas Benech, Delphine Bergeaud, J. Sobrino, G. Bertoli, S. Bessis, Sybille Bevilcaqua, Karine Bézulier, K. Bhavsar, Z. Bisoffi, L. Bitker, Mathieu Bl","doi":"10.1093/braincomms/fcae036","DOIUrl":"https://doi.org/10.1093/braincomms/fcae036","url":null,"abstract":"\u0000 Although it is known that COVID-19 can present with a range of neurological manifestations and in-hospital complications, sparse data exist if these initial neurological symptoms of COVID-19 are closely associated with post-acute neurological sequelae of SARS-CoV-2 (PANSC) and if female versus male sex impacts the symptom resolution. In this international, multicentre, prospective observational study across 407 sites from 15 countries (January/30th/2020-April/30th/2022), we report the prevalence and risk factors of PANSC among hospitalized adults and investigate the differences between males and females on neurological symptom resolution over time.\u0000 PANSC included altered consciousness/confusion, fatigue/malaise, anosmia, dysgeusia, and muscle aches/joint pain, which were collected at the index hospitalization and during the follow-up assessments. The analysis considered time to resolution of individual and all neurological symptoms. Resulting times were modeled by Weibull regression, assuming mixed-case interval censoring, with sex and age included as covariates. Model results were summarized as cumulative probability functions and age- and sex-adjusted median times to resolution.\u0000 We included 6,862 hospitalized adults with COVID-19, who had follow-up assessments. The median age of participants was 57 years (39.2% females). Males and females had similar baseline characteristics except that more males (vs. females) were admitted to Intensive Care Unit (30.5% vs. 20.3%) and received mechanical ventilation (17.2% vs. 11.8%).\u0000 Approximately 70% of patients had multiple neurological symptoms at the first follow-up (median=102 days). Fatigue (49.9%) and myalgia/arthralgia (45.2%) were the most prevalent symptoms of PANSC at the initial follow-up. Reported prevalence in females was generally higher (vs. males) for all symptoms. At 12 months, anosmia and dysgeusia were resolved in most patients, though fatigue, altered consciousness, and myalgia remained unresolved in >10% of the cohort. Females had a longer time to resolution (5.2 vs. 3.4 months) of neurological symptoms at follow-up for those with more than one neurological symptom.\u0000 In multivariable analysis, males were associated with a shorter time to resolution of symptoms (Hazard Ratio=1.53; 95% Confidence Interval =1.39–1.69). Intensive Care Unit admission was associated with a longer time to the resolution of symptoms (Hazard Ratio =0.68; 95% Confidence Interval=0.60–0.77). Post-discharge stroke was uncommon (0.3% in females; 0.5% in males).\u0000 Despite the methodological challenges of survey data, this international multicentre prospective cohort study demonstrates that PANSC following index hospitalization is high. Symptom prevalence was higher and took longer to resolve in females than in males. This supports that whilst males were sicker during acute illness, females were disproportionately affected by PANSC.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":" 37","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139787824","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":"Apathy scores in Parkinson’s disease relate to EEG components in an incentivized motor task","authors":"Soojin Lee, Esther Song, Maria Zhu, S. Appel-Cresswell, Martin J. McKeown","doi":"10.1093/braincomms/fcae025","DOIUrl":"https://doi.org/10.1093/braincomms/fcae025","url":null,"abstract":"\u0000 Apathy is one of the most prevalent non-motor symptoms of Parkinson’s disease and is characterized by decreased goal-directed behavior due to a lack of motivation and/or impaired emotional reactivity. Despite its high prevalence, the neurophysiological mechanisms underlying apathy in Parkinson’s disease, which may guide neuromodulation interventions, are poorly understood. Here, we investigated the neural oscillatory characteristics of apathy in Parkinson’s disease using EEG data recorded during an incentivized motor task.\u0000 Thirteen Parkinson’s disease patients with apathy and 13 Parkinson’s disease patients without apathy as well as 12 healthy controls were instructed to squeeze a hand grip device to earn a monetary reward proportional to the grip force they used. Event-related spectral perturbations during the presentation of a reward cue and squeezing were analyzed using multi-set canonical correlation analysis to detect different orthogonal components of temporally-consistent event-related spectral perturbations across trials and participants.\u0000 The first component, predominantly located over parietal regions, demonstrated suppression of low-beta (12–20 Hz) power (i.e., beta desynchronization) during reward cue presentation that was significantly smaller in Parkinson’s disease patients with apathy compared to healthy controls. Unlike traditional event-related spectral perturbation analysis, the beta-desynchronization in this component was significantly correlated with clinical apathy scores. Higher monetary rewards resulted in larger beta desynchronization in heathy controls but not Parkinson’s disease patients. The second component contained gamma and theta frequencies and demonstrated exaggerated theta (4–8 Hz) power in Parkinson’s disease patients with apathy during the reward cue and squeezing compared to healthy controls, and this was positively correlated with Montreal Cognitive Assessment scores. The third component, over central regions, demonstrated significantly different beta power across groups, with apathetic groups having the lowest beta power.\u0000 Our results emphasize that altered low-beta and theta oscillations are critical for reward processing and motor planning in Parkinson’s disease patients with apathy, and these may provide a target for non-invasive neuromodulation.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"357 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139848210","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":"Translatable plasma and CSF biomarkers for use in mouse models of Huntington’s disease","authors":"Marie K Bondulich, Jemima Phillips, María Cañibano-Pico, Iulia M Nita, L. Byrne, E. Wild, Gillian P Bates","doi":"10.1093/braincomms/fcae030","DOIUrl":"https://doi.org/10.1093/braincomms/fcae030","url":null,"abstract":"\u0000 Huntington’s disease is an inherited neurodegenerative disorder for which a wide range of disease-modifying therapies are in development and the availability of biomarkers to monitor treatment response is essential for the success of clinical trials. Baseline levels of NEFL (neurofilament light chain) in CSF and plasma have been shown to be effective in predicting clinical disease status, subsequent clinical progression and brain atrophy. The identification of further sensitive prognostic fluid biomarkers is an active research area and total-Tau and YKL-40 levels have been shown to be increased in CSF from Huntington’s disease mutation carriers. The use of readouts with clinical utility in the preclinical assessment of potential therapeutics, should aid in the translation of new treatments.\u0000 Here, we set out to determine how the concentrations of these three proteins change in plasma and CSF with disease progression in representative, well-established mouse models of Huntington’s disease. Plasma and CSF were collected throughout disease progression from R6/2 transgenic mice with CAG repeats of 200 or 90 codons (R6/2:Q200 and R6/2:Q90), zQ175 knock-in mice and YAC128 transgenic mice, along with their respective wild-type littermates. NEFL and total-Tau concentrations were quantified in CSF and plasma using ultrasensitive single-molecule array (SIMOA, Quanterix) assays and a novel Quanterix assay was developed for BRP-39 (breast regression protein 39, mouse homologue of YKL-40) and used to quantify BRP-39 levels in plasma. CSF levels of NEFL and plasma levels of NEFL and BRP-39 increased in wild-type biofluids with age, whereas total-Tau remained constant. NEFL and BRP-39 were elevated in the plasma and CSF from Huntington’s disease mouse models, as compared to wild-type littermates, at presymptomatic stages, whereas total-Tau was only increased at the latest disease stages analysed. Levels of biomarkers that had been measured in the same CSF or plasma samples taken at the latest stages of disease were correlated. The demonstration that BRP-39 constitutes a robust plasma biomarker in Huntington’s disease mouse models, supports the further investigation of YKL-40 as a CSF biomarker for Huntington’s disease mutation carriers. NEFL and Tau are considered markers of neuronal damage and BRP-39 is a marker of inflammation; the similarities and differences in the levels of these proteins between mouse models may provide future insights into their underlying pathology. These data will facilitate the use of fluid biomarkers in the preclinical assessment of therapeutic agents for Huntington’s disease, providing readouts with direct relevance to clinical trials.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"66 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139855879","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":"Translatable plasma and CSF biomarkers for use in mouse models of Huntington’s disease","authors":"Marie K Bondulich, Jemima Phillips, María Cañibano-Pico, Iulia M Nita, L. Byrne, E. Wild, Gillian P Bates","doi":"10.1093/braincomms/fcae030","DOIUrl":"https://doi.org/10.1093/braincomms/fcae030","url":null,"abstract":"\u0000 Huntington’s disease is an inherited neurodegenerative disorder for which a wide range of disease-modifying therapies are in development and the availability of biomarkers to monitor treatment response is essential for the success of clinical trials. Baseline levels of NEFL (neurofilament light chain) in CSF and plasma have been shown to be effective in predicting clinical disease status, subsequent clinical progression and brain atrophy. The identification of further sensitive prognostic fluid biomarkers is an active research area and total-Tau and YKL-40 levels have been shown to be increased in CSF from Huntington’s disease mutation carriers. The use of readouts with clinical utility in the preclinical assessment of potential therapeutics, should aid in the translation of new treatments.\u0000 Here, we set out to determine how the concentrations of these three proteins change in plasma and CSF with disease progression in representative, well-established mouse models of Huntington’s disease. Plasma and CSF were collected throughout disease progression from R6/2 transgenic mice with CAG repeats of 200 or 90 codons (R6/2:Q200 and R6/2:Q90), zQ175 knock-in mice and YAC128 transgenic mice, along with their respective wild-type littermates. NEFL and total-Tau concentrations were quantified in CSF and plasma using ultrasensitive single-molecule array (SIMOA, Quanterix) assays and a novel Quanterix assay was developed for BRP-39 (breast regression protein 39, mouse homologue of YKL-40) and used to quantify BRP-39 levels in plasma. CSF levels of NEFL and plasma levels of NEFL and BRP-39 increased in wild-type biofluids with age, whereas total-Tau remained constant. NEFL and BRP-39 were elevated in the plasma and CSF from Huntington’s disease mouse models, as compared to wild-type littermates, at presymptomatic stages, whereas total-Tau was only increased at the latest disease stages analysed. Levels of biomarkers that had been measured in the same CSF or plasma samples taken at the latest stages of disease were correlated. The demonstration that BRP-39 constitutes a robust plasma biomarker in Huntington’s disease mouse models, supports the further investigation of YKL-40 as a CSF biomarker for Huntington’s disease mutation carriers. NEFL and Tau are considered markers of neuronal damage and BRP-39 is a marker of inflammation; the similarities and differences in the levels of these proteins between mouse models may provide future insights into their underlying pathology. These data will facilitate the use of fluid biomarkers in the preclinical assessment of therapeutic agents for Huntington’s disease, providing readouts with direct relevance to clinical trials.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"10 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139795896","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":"High frequency oscillation network dynamics predict outcome in non-palliative epilepsy surgery","authors":"Jack Lin, Garnett C. Smith, Stephen V Gliske, Michal Zochowski, K. Shedden, William C Stacey","doi":"10.1093/braincomms/fcae032","DOIUrl":"https://doi.org/10.1093/braincomms/fcae032","url":null,"abstract":"\u0000 High frequency oscillations (HFOs) are a promising biomarker of outcome in intractable epilepsy. Prior HFO work focused on counting HFOs on individual channels, and it is still unclear how to translate those results into clinical care. We show that HFOs arise as network discharges that have valuable properties as predictive biomarkers. Here, we develop a tool to predict patient outcome before surgical resection is performed, based upon only prospective information. In addition to determining HFO rate on every channel, we performed a correlational analysis to evaluate functional connectivity of HFOs in 28 patients with intracranial electrodes. We found that HFOs were often not solitary events on a single channel, but part of a local network discharge. Eigenvector and outcloseness centrality were used to rank channel importance within the connectivity network, then used to compare patient outcome by comparison with the Seizure Onset Zone or a proportion within the proposed resected channels (Critical Resection Percentage). Combining the knowledge of each patient’s Seizure Onset Zone resection plan along with our computed HFO network centralities and HFO rate, we develop a Naïve Bayes model that predicts outcome (Positive Predictive Value: 100%) better than predicting based upon fully resecting the Seizure Onset Zone (Positive Predictive Value: 71%). Surgical margins had a large effect on outcomes: non-palliative patients in whom most of the Seizure Onset Zone was resected (‘definitive surgery’, ≥ 80% resected) had predictable outcomes, whereas palliative surgeries (< 80% resected) were not predictable. These results suggest that the addition of network properties of HFOs is more accurate in predicting patient outcome than Seizure Onset Zone alone in patients with most of the Seizure Onset Zone removed and offer great promise for informing clinical decisions in surgery for refractory epilepsy.","PeriodicalId":504765,"journal":{"name":"Brain Communications","volume":"24 38","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139795784","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}