Pub Date : 2023-11-16DOI: 10.1093/braincomms/fcad305
Samantha C. Burnham, L. Iaccarino, M. Pontecorvo, Adam S Fleisher, M. Lu, Emily C. Collins, Michael D Devous
Alzheimer’s disease is defined by the presence of β-amyloid plaques and neurofibrillary tau tangles potentially preceding clinical symptoms by many years. Previously only detectable postmortem, these pathological hallmarks are now identifiable using biomarkers, permitting an in vivo definitive diagnosis of Alzheimer’s disease. 18F-flortaucipir (previously known as 18F-T807; 18F-AV-1451) was the first tau positron emission tomography tracer to be introduced and is the only Food and Drug Administration approved tau positron emission tomography tracer (Tauvid™). It has been widely adopted and validated in a number of independent research and clinical settings. In this review, we present an overview of the published literature on flortaucipir for positron emission tomographyimaging of neurofibrillary tau tangles. We considered all accessible peer-reviewed literature pertaining to flortaucipir through April 30, 2022. We found 474 relevant peer-reviewed publications, which were organized into the following categories based on their primary focus: Typical Alzheimer’s disease, mild cognitive impairment, and pre-symptomatic populations; atypical Alzheimer’s disease; non- Alzheimer’s disease neurodegenerative conditions; head-to-head comparisons with other Tau positron emission tomography tracers; and technical considerations. The available flortaucipir literature provides substantial evidence for the use of this positron emission tomographytracer in assessing neurofibrillary tau tangles in Alzheimer’s disease and limited support for its use in other neurodegenerative disorders. Visual interpretation and quantitation approaches, although heterogeneous, mostly converge and demonstrate the high diagnostic and prognostic value of flortaucipir in Alzheimer’s disease.
阿尔茨海默病的定义是存在β-淀粉样蛋白斑块和神经纤维tau缠结，可能比临床症状出现早很多年。这些病理特征以前只能在死后检测到，现在可以利用生物标记物进行识别，从而可以在体内明确诊断阿尔茨海默病。18F-flortaucipir（以前称为 18F-T807；18F-AV-1451）是第一个推出的 tau 正电子发射断层扫描示踪剂，也是唯一获得美国食品药品管理局批准的 tau 正电子发射断层扫描示踪剂 (Tauvid™)。该示踪剂已被大量独立研究和临床机构广泛采用和验证。在本综述中，我们概述了已发表的有关氟替瑞匹用于神经纤维tau缠结正电子发射断层成像的文献。我们研究了截至 2022 年 4 月 30 日所有与氟替卡韦相关的同行评审文献。我们找到了 474 篇相关的同行评议出版物，根据其主要关注点分为以下几类：典型阿尔茨海默病、轻度认知障碍和症状前人群；非典型阿尔茨海默病；非阿尔茨海默病神经退行性疾病；与其他 Tau 正电子发射断层扫描示踪剂的头对头比较；以及技术考虑因素。现有的氟陶西泮文献提供了大量证据，证明这种正电子发射断层扫描示踪剂可用于评估阿尔茨海默病的神经纤维tau缠结，但对其在其他神经退行性疾病中的应用支持有限。目视解释和定量方法虽然不尽相同，但大多趋于一致，证明了氟替瑞匹在阿尔茨海默病中具有很高的诊断和预后价值。
{"title":"A review of the flortaucipir literature for PET imaging of tau neurofibrillary tangles","authors":"Samantha C. Burnham, L. Iaccarino, M. Pontecorvo, Adam S Fleisher, M. Lu, Emily C. Collins, Michael D Devous","doi":"10.1093/braincomms/fcad305","DOIUrl":"https://doi.org/10.1093/braincomms/fcad305","url":null,"abstract":"Alzheimer’s disease is defined by the presence of β-amyloid plaques and neurofibrillary tau tangles potentially preceding clinical symptoms by many years. Previously only detectable postmortem, these pathological hallmarks are now identifiable using biomarkers, permitting an in vivo definitive diagnosis of Alzheimer’s disease. 18F-flortaucipir (previously known as 18F-T807; 18F-AV-1451) was the first tau positron emission tomography tracer to be introduced and is the only Food and Drug Administration approved tau positron emission tomography tracer (Tauvid™). It has been widely adopted and validated in a number of independent research and clinical settings. In this review, we present an overview of the published literature on flortaucipir for positron emission tomographyimaging of neurofibrillary tau tangles. We considered all accessible peer-reviewed literature pertaining to flortaucipir through April 30, 2022. We found 474 relevant peer-reviewed publications, which were organized into the following categories based on their primary focus: Typical Alzheimer’s disease, mild cognitive impairment, and pre-symptomatic populations; atypical Alzheimer’s disease; non- Alzheimer’s disease neurodegenerative conditions; head-to-head comparisons with other Tau positron emission tomography tracers; and technical considerations. The available flortaucipir literature provides substantial evidence for the use of this positron emission tomographytracer in assessing neurofibrillary tau tangles in Alzheimer’s disease and limited support for its use in other neurodegenerative disorders. Visual interpretation and quantitation approaches, although heterogeneous, mostly converge and demonstrate the high diagnostic and prognostic value of flortaucipir in Alzheimer’s disease.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"11 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139266702","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}
Abstract Cognitive flexibility, the ability of adapting to an everchanging environment, declines with aging and impaired in early stages of dementia. Although recent studies have indicated there is a relationship between the intestinal microbiota and cognitive function, few studies have shown relationships between intestinal microbiota and cognitive flexibility because of limited behavioral tasks in mice. We recently established a novel cognitive flexibility task for mice using a touchscreen operant apparatus and found that probiotic treatment with a mixture of Bifidobacterium animalis subsp. lactis LKM512 and arginine (LKM + Arg) improved cognitive flexibility in young adult mice. To confirm the effects of the probiotic treatment on cognitive flexibility and to determine whether it is effective even in older age, we here examined the effects of long-term treatment with LKM + Arg on cognitive flexibility in middle aged mice. From 8 to 15 months of age, mice received LKM + Arg or vehicle (controls) orally three times per week and were subjected to the cognitive flexibility task at 13–15 months old. In one of indices of cognitive flexibility, both LKM + Arg and vehicle treated mice showed progressively improved performance by repeating reversal tasks, with a small trend that LKM + Arg treated mice showed better learning performance through reversal phases. With respect to the other index of cognitive flexibility, LKM + Arg treated mice showed significantly fewer error choices than control mice at the reversal phase, i.e., LKM + Arg improved the performance of behavioral sequencing acquired in the previous phase, which allowed LKM + Arg treated mice to show an early onset of shift to reversal contingency. Taken together, long-term treatment with LKM + Arg was found to improve cognitive flexibility in middle aged mice, indicating that probiotic treatment might contribute to prevention of age-related cognitive decline.
{"title":"Probiotic treatment with bifidobacterium animalis subsp. lactis LKM512 + arginine improves cognitive flexibility in middle aged mice","authors":"Daisuke Joho, Masahira Takahashi, Takeru Suzuki, Kayo Ikuta, Mitsuharu Matsumoto, Masaki Kakeyama","doi":"10.1093/braincomms/fcad311","DOIUrl":"https://doi.org/10.1093/braincomms/fcad311","url":null,"abstract":"Abstract Cognitive flexibility, the ability of adapting to an everchanging environment, declines with aging and impaired in early stages of dementia. Although recent studies have indicated there is a relationship between the intestinal microbiota and cognitive function, few studies have shown relationships between intestinal microbiota and cognitive flexibility because of limited behavioral tasks in mice. We recently established a novel cognitive flexibility task for mice using a touchscreen operant apparatus and found that probiotic treatment with a mixture of Bifidobacterium animalis subsp. lactis LKM512 and arginine (LKM + Arg) improved cognitive flexibility in young adult mice. To confirm the effects of the probiotic treatment on cognitive flexibility and to determine whether it is effective even in older age, we here examined the effects of long-term treatment with LKM + Arg on cognitive flexibility in middle aged mice. From 8 to 15 months of age, mice received LKM + Arg or vehicle (controls) orally three times per week and were subjected to the cognitive flexibility task at 13–15 months old. In one of indices of cognitive flexibility, both LKM + Arg and vehicle treated mice showed progressively improved performance by repeating reversal tasks, with a small trend that LKM + Arg treated mice showed better learning performance through reversal phases. With respect to the other index of cognitive flexibility, LKM + Arg treated mice showed significantly fewer error choices than control mice at the reversal phase, i.e., LKM + Arg improved the performance of behavioral sequencing acquired in the previous phase, which allowed LKM + Arg treated mice to show an early onset of shift to reversal contingency. Taken together, long-term treatment with LKM + Arg was found to improve cognitive flexibility in middle aged mice, indicating that probiotic treatment might contribute to prevention of age-related cognitive decline.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"121 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136351614","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}
Pub Date : 2023-11-11DOI: 10.1093/braincomms/fcad298
Naomi I Kremer, Mark J Roberts, Wouter V Potters, José Dilai, Varvara Mathiopoulou, Niels Rijks, Gea Drost, Teus van Laar, J Marc C van Dijk, Martijn Beudel, Rob M A de Bie, Pepijn van den Munckhof, Marcus L F Janssen, P Richard Schuurman, Maarten Bot
Abstract Connectivity-derived 7-Tesla MRI segmentation and intraoperative microelectrode recording can both assist subthalamic nucleus targeting for deep brain stimulation in Parkinson’s disease. It remains unclear if deep brain stimulation electrodes placed in the 7-Tesla MRI segmented subdivision with predominant projections to cortical motor areas (hyperdirect pathway) achieve superior motor improvement and whether microelectrode recording can accurately distinguish the motor subdivision. In 25 Parkinson’s disease patients, deep brain stimulation electrodes were evaluated for being inside or outside the predominantly motor-connected subthalamic nucleus (motor-connected subthalamic nucleus [mc-STN] or non-motor-connected subthalamic nucleus [nmc-STN], respectively) based on 7-Tesla MRI connectivity segmentation. Hemi-body motor improvement (Movement Disorder Society Unified Parkinson’s disease Rating Scale part III), and microelectrode recording characteristics multi- and single-unit activity were compared between groups. Deep brain stimulation electrodes placed in the motor-connected subthalamic nucleus resulted in higher hemi-body motor improvement, compared to electrodes placed in the non-motor-connected subthalamic nucleus (80% vs. 52%, P < 0.0001). Multi-unit activity was found slightly higher in the motor-connected subthalamic nucleus versus the non-motor-connected subthalamic nucleus (P < 0.001, receiver operating characteristic 0.63); single-unit activity did not differ between groups. Deep brain stimulation in the connectivity-derived 7T-MRI subthalamic nucleus motor-segment had superior clinical outcome, however, microelectrode recording did not accurately distinguish this subdivision within the subthalamic nucleus.
{"title":"Dorsal subthalamic nucleus targeting in deep brain stimulation: microelectrode recording versus 7-Tesla connectivity","authors":"Naomi I Kremer, Mark J Roberts, Wouter V Potters, José Dilai, Varvara Mathiopoulou, Niels Rijks, Gea Drost, Teus van Laar, J Marc C van Dijk, Martijn Beudel, Rob M A de Bie, Pepijn van den Munckhof, Marcus L F Janssen, P Richard Schuurman, Maarten Bot","doi":"10.1093/braincomms/fcad298","DOIUrl":"https://doi.org/10.1093/braincomms/fcad298","url":null,"abstract":"Abstract Connectivity-derived 7-Tesla MRI segmentation and intraoperative microelectrode recording can both assist subthalamic nucleus targeting for deep brain stimulation in Parkinson’s disease. It remains unclear if deep brain stimulation electrodes placed in the 7-Tesla MRI segmented subdivision with predominant projections to cortical motor areas (hyperdirect pathway) achieve superior motor improvement and whether microelectrode recording can accurately distinguish the motor subdivision. In 25 Parkinson’s disease patients, deep brain stimulation electrodes were evaluated for being inside or outside the predominantly motor-connected subthalamic nucleus (motor-connected subthalamic nucleus [mc-STN] or non-motor-connected subthalamic nucleus [nmc-STN], respectively) based on 7-Tesla MRI connectivity segmentation. Hemi-body motor improvement (Movement Disorder Society Unified Parkinson’s disease Rating Scale part III), and microelectrode recording characteristics multi- and single-unit activity were compared between groups. Deep brain stimulation electrodes placed in the motor-connected subthalamic nucleus resulted in higher hemi-body motor improvement, compared to electrodes placed in the non-motor-connected subthalamic nucleus (80% vs. 52%, P &lt; 0.0001). Multi-unit activity was found slightly higher in the motor-connected subthalamic nucleus versus the non-motor-connected subthalamic nucleus (P &lt; 0.001, receiver operating characteristic 0.63); single-unit activity did not differ between groups. Deep brain stimulation in the connectivity-derived 7T-MRI subthalamic nucleus motor-segment had superior clinical outcome, however, microelectrode recording did not accurately distinguish this subdivision within the subthalamic nucleus.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"5 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135087124","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}
Pub Date : 2023-11-10DOI: 10.1093/braincomms/fcad310
Junhua Ding, Erica L Middleton, Daniel Mirman
Abstract Aphasia is a common consequence of stroke with severe impacts on employability, social interactions, and quality of life. Producing discourse-relevant information in a real-world setting is the most important aspect of recovery because it is critical to successful communication. This study sought to identify the lesion correlates of impaired production of relevant information in spoken discourse in a large, unselected sample of participants with post-stroke aphasia. Spoken discourse (n=80) and structural brain scans (n=66) from participants with aphasia following left hemisphere stroke were analyzed. Each participant provided 10 samples of spoken discourse elicited in three different genres and “correct information unit” analysis was used to quantify the informativeness of speech samples. The lesion correlates were identified using multivariate lesion-symptom mapping, voxel-wise disconnection, and tract-wise analyses. Amount and speed of relevant information were highly correlated across different genres and with total lesion size. The analyses of lesion correlates converged on the same pattern: impaired production of relevant information was associated with damage to anterior dorsal white matter pathways, specifically the arcuate fasciculus, frontal aslant tract, and superior longitudinal fasciculus. Damage to these pathways may be a useful biomarker for impaired informative spoken discourse and informs development of neurorehabilitation strategies.
{"title":"Impaired discourse content in aphasia is associated with frontal white matter damage","authors":"Junhua Ding, Erica L Middleton, Daniel Mirman","doi":"10.1093/braincomms/fcad310","DOIUrl":"https://doi.org/10.1093/braincomms/fcad310","url":null,"abstract":"Abstract Aphasia is a common consequence of stroke with severe impacts on employability, social interactions, and quality of life. Producing discourse-relevant information in a real-world setting is the most important aspect of recovery because it is critical to successful communication. This study sought to identify the lesion correlates of impaired production of relevant information in spoken discourse in a large, unselected sample of participants with post-stroke aphasia. Spoken discourse (n=80) and structural brain scans (n=66) from participants with aphasia following left hemisphere stroke were analyzed. Each participant provided 10 samples of spoken discourse elicited in three different genres and “correct information unit” analysis was used to quantify the informativeness of speech samples. The lesion correlates were identified using multivariate lesion-symptom mapping, voxel-wise disconnection, and tract-wise analyses. Amount and speed of relevant information were highly correlated across different genres and with total lesion size. The analyses of lesion correlates converged on the same pattern: impaired production of relevant information was associated with damage to anterior dorsal white matter pathways, specifically the arcuate fasciculus, frontal aslant tract, and superior longitudinal fasciculus. Damage to these pathways may be a useful biomarker for impaired informative spoken discourse and informs development of neurorehabilitation strategies.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":" 494","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135186495","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}
Pub Date : 2023-11-09DOI: 10.1093/braincomms/fcad299
J Poulos, M Samuels, J Palace, D Beeson, S Robb, S Ramdas, S Chan, P Munot
Abstract Respiratory problems are a major cause of morbidity and mortality in patients with congenital myasthenic syndromes (CMS), a rare heterogeneous group of neuromuscular disorders caused by genetic defects impacting the structure and function of the neuromuscular junction. Recurrent, life-threatening episodic apnoea in early infancy and childhood, as well as progressive respiratory failure requiring ventilation are features of certain genotypes of CMS. Robb et al published empirical guidance on respiratory management of the congenital myasthenic syndromes, but other than this workshop report, there is little published longitudinal natural history data on respiratory outcomes of these disorders. We report a retrospective, single-centre study on respiratory outcomes in a cohort of 40 well characterised genetically confirmed cases of CMS, including 10 distinct subtypes (DOK7, COLQ, RAPSN, CHAT, CHRNA1, CHRNG, COL13A1, CHRNE, CHRNE fast channel syndrome and CHRNA1 slow channel syndrome), with many followed up over 20 years in our centre. A quantitative and longitudinal analysis of key spirometry and sleep study parameters, as well as a description of historical hospital admissions for respiratory decompensation, provides a snapshot of the respiratory trajectory of CMS patients based on genotype.
{"title":"Congenital Myasthenic Syndromes: A Retrospective Natural History Study of Respiratory Outcomes in A Single Centre","authors":"J Poulos, M Samuels, J Palace, D Beeson, S Robb, S Ramdas, S Chan, P Munot","doi":"10.1093/braincomms/fcad299","DOIUrl":"https://doi.org/10.1093/braincomms/fcad299","url":null,"abstract":"Abstract Respiratory problems are a major cause of morbidity and mortality in patients with congenital myasthenic syndromes (CMS), a rare heterogeneous group of neuromuscular disorders caused by genetic defects impacting the structure and function of the neuromuscular junction. Recurrent, life-threatening episodic apnoea in early infancy and childhood, as well as progressive respiratory failure requiring ventilation are features of certain genotypes of CMS. Robb et al published empirical guidance on respiratory management of the congenital myasthenic syndromes, but other than this workshop report, there is little published longitudinal natural history data on respiratory outcomes of these disorders. We report a retrospective, single-centre study on respiratory outcomes in a cohort of 40 well characterised genetically confirmed cases of CMS, including 10 distinct subtypes (DOK7, COLQ, RAPSN, CHAT, CHRNA1, CHRNG, COL13A1, CHRNE, CHRNE fast channel syndrome and CHRNA1 slow channel syndrome), with many followed up over 20 years in our centre. A quantitative and longitudinal analysis of key spirometry and sleep study parameters, as well as a description of historical hospital admissions for respiratory decompensation, provides a snapshot of the respiratory trajectory of CMS patients based on genotype.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":" 35","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135292057","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}
Pub Date : 2023-11-09DOI: 10.1093/braincomms/fcad309
Etienne Aumont, Aurélie Bussy, Marc-André Bedard, Gleb Bezgin, Joseph Therriault, Melissa Savard, Jaime Fernandez Arias, Viviane Sziklas, Paolo Vitali, Nina Margherita Poltronetti, Vanessa Pallen, Emilie Thomas, Serge Gauthier, Eliane Kobayashi, Nesrine Rahmouni, Jenna Stevenson, Cecile Tissot, Mallar M Chakravarty, Pedro Rosa-Neto
Abstract Hippocampal atrophy is a well-known feature of age-related memory decline, and hippocampal subfields may contribute differently to this decline. In this cross-sectional study, we investigated the associations between hippocampal subfield volumes and performance in free recall and recognition memory tasks in both verbal and visual modalities in older adults without dementia. We collected MRIs from 97 (41 males) right-handed participants aged over 60. We segmented the right and left hippocampi into 1) dentate gyrus and cornu ammonis 4 (DG/CA4); 2) CA2 and CA3 (CA2/CA3); 3) CA1; 4) strata radiatum, lacunosum and moleculare (SRLM); and 5) subiculum. Memory was assessed with verbal free recall and recognition tasks, as well as visual free recall and recognition tasks. Amyloid-β and hippocampal tau positivity were assessed using [18F]AZD4694 and [18F]MK6240 PET tracers, respectively. The verbal free recall and verbal recognition performances were positively associated with CA1 and SRLM volumes. The verbal free recall and visual free recall were positively correlated with the right DG/CA4. The visual free recall, but not verbal free recall, was also associated with the right CA2/CA3. The visual recognition was not significantly associated with any subfield volume. Hippocampal tau positivity, but not amyloid-β positivity, was associated with reduced DG/CA4, CA2/CA3 and SRLM volumes. Our results suggest that memory performances are linked to specific subfields. CA1 appears to contribute to the verbal modality, irrespective of the free recall or recognition mode of retrieval. In contrast, DG/CA4 seems to be involved in the free recall mode, irrespective of verbal or visual modalities. These results are concordant with the view that DG/CA4 plays a primary role in encoding a stimulus’ distinctive attributes, and that CA2/CA3 could be instrumental in recollecting a visual memory from one of its fragments. Overall, we show that hippocampal subfield segmentation can be useful for detecting early volume changes and improve our understanding of the hippocampal subfields’ roles in memory.
{"title":"Hippocampal subfield associations with memory depend on stimulus modality and retrieval mode","authors":"Etienne Aumont, Aurélie Bussy, Marc-André Bedard, Gleb Bezgin, Joseph Therriault, Melissa Savard, Jaime Fernandez Arias, Viviane Sziklas, Paolo Vitali, Nina Margherita Poltronetti, Vanessa Pallen, Emilie Thomas, Serge Gauthier, Eliane Kobayashi, Nesrine Rahmouni, Jenna Stevenson, Cecile Tissot, Mallar M Chakravarty, Pedro Rosa-Neto","doi":"10.1093/braincomms/fcad309","DOIUrl":"https://doi.org/10.1093/braincomms/fcad309","url":null,"abstract":"Abstract Hippocampal atrophy is a well-known feature of age-related memory decline, and hippocampal subfields may contribute differently to this decline. In this cross-sectional study, we investigated the associations between hippocampal subfield volumes and performance in free recall and recognition memory tasks in both verbal and visual modalities in older adults without dementia. We collected MRIs from 97 (41 males) right-handed participants aged over 60. We segmented the right and left hippocampi into 1) dentate gyrus and cornu ammonis 4 (DG/CA4); 2) CA2 and CA3 (CA2/CA3); 3) CA1; 4) strata radiatum, lacunosum and moleculare (SRLM); and 5) subiculum. Memory was assessed with verbal free recall and recognition tasks, as well as visual free recall and recognition tasks. Amyloid-β and hippocampal tau positivity were assessed using [18F]AZD4694 and [18F]MK6240 PET tracers, respectively. The verbal free recall and verbal recognition performances were positively associated with CA1 and SRLM volumes. The verbal free recall and visual free recall were positively correlated with the right DG/CA4. The visual free recall, but not verbal free recall, was also associated with the right CA2/CA3. The visual recognition was not significantly associated with any subfield volume. Hippocampal tau positivity, but not amyloid-β positivity, was associated with reduced DG/CA4, CA2/CA3 and SRLM volumes. Our results suggest that memory performances are linked to specific subfields. CA1 appears to contribute to the verbal modality, irrespective of the free recall or recognition mode of retrieval. In contrast, DG/CA4 seems to be involved in the free recall mode, irrespective of verbal or visual modalities. These results are concordant with the view that DG/CA4 plays a primary role in encoding a stimulus’ distinctive attributes, and that CA2/CA3 could be instrumental in recollecting a visual memory from one of its fragments. Overall, we show that hippocampal subfield segmentation can be useful for detecting early volume changes and improve our understanding of the hippocampal subfields’ roles in memory.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":" 21","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135291849","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}
Pub Date : 2023-11-08DOI: 10.1093/braincomms/fcad307
Wolfgang Faigle, Marco Piccirelli, Tibor Hortobágyi, Karl Frontzek, Amelia Elaine Cannon, Wolfgang Emanuel Zürrer, Tobias Granberg, Zsolt Kulcsar, Thomas Ludersdorfer, Katrin B M Frauenknecht, Regina Reimann, Benjamin Victor Ineichen
Abstract Magnetic resonance imaging (MRI) has limitations in identifying underlying tissue pathology, which is relevant for neurological diseases such as multiple sclerosis, stroke, or brain tumours. However, there are no standardized methods for correlating MRI features with histopathology. Thus, here we aimed to develop and validate a tool that can facilitate the correlation of brain MRI features to corresponding histopathology. For this, we designed the Brainbox, a waterproof and MRI-compatible 3D printed container with an integrated 3D coordinate system. We used the Brainbox to acquire post-mortem ex vivo MRI of eight human brains, fresh and formalin-fixed, and correlated focal imaging features to histopathology using the built-in 3D coordinate system. With its built-in 3D coordinate system, the Brainbox allowed correlation of MRI features to corresponding tissue substrates. The Brainbox was used to correlate different MR image features of interest to the respective tissue substrate, including normal anatomical structures such as the hippocampus or perivascular spaces, as well as a lacunar stroke. Brain volume decreased upon fixation by 7% (p = 0.01). The Brainbox enabled degassing of specimens prior to scanning, reducing susceptibility artifacts, and minimizing bulk motion during scanning. In conclusion, our proof-of-principle experiments demonstrate the usability of the Brainbox, which can contribute to improving the specificity of MRI and the standardization of the correlation between post-mortem ex vivo human brain MRI and histopathology. Brainboxes are available upon request from our institution.
{"title":"The Brainbox - a tool to facilitate correlation of brain magnetic resonance imaging features to histopathology","authors":"Wolfgang Faigle, Marco Piccirelli, Tibor Hortobágyi, Karl Frontzek, Amelia Elaine Cannon, Wolfgang Emanuel Zürrer, Tobias Granberg, Zsolt Kulcsar, Thomas Ludersdorfer, Katrin B M Frauenknecht, Regina Reimann, Benjamin Victor Ineichen","doi":"10.1093/braincomms/fcad307","DOIUrl":"https://doi.org/10.1093/braincomms/fcad307","url":null,"abstract":"Abstract Magnetic resonance imaging (MRI) has limitations in identifying underlying tissue pathology, which is relevant for neurological diseases such as multiple sclerosis, stroke, or brain tumours. However, there are no standardized methods for correlating MRI features with histopathology. Thus, here we aimed to develop and validate a tool that can facilitate the correlation of brain MRI features to corresponding histopathology. For this, we designed the Brainbox, a waterproof and MRI-compatible 3D printed container with an integrated 3D coordinate system. We used the Brainbox to acquire post-mortem ex vivo MRI of eight human brains, fresh and formalin-fixed, and correlated focal imaging features to histopathology using the built-in 3D coordinate system. With its built-in 3D coordinate system, the Brainbox allowed correlation of MRI features to corresponding tissue substrates. The Brainbox was used to correlate different MR image features of interest to the respective tissue substrate, including normal anatomical structures such as the hippocampus or perivascular spaces, as well as a lacunar stroke. Brain volume decreased upon fixation by 7% (p = 0.01). The Brainbox enabled degassing of specimens prior to scanning, reducing susceptibility artifacts, and minimizing bulk motion during scanning. In conclusion, our proof-of-principle experiments demonstrate the usability of the Brainbox, which can contribute to improving the specificity of MRI and the standardization of the correlation between post-mortem ex vivo human brain MRI and histopathology. Brainboxes are available upon request from our institution.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"30 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135430042","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}
Pub Date : 2023-11-08DOI: 10.1093/braincomms/fcad308
Nicholas Yew Wei Heng, Timothy Rittman
Abstract Ethnic differences in dementia are increasingly recognised in epidemiological measures and diagnostic biomarkers. Nonetheless, ethnic diversity remains limited in many study populations. Here we provide insights into ethnic diversity in open access neuroimaging dementia datasets. Datasets comprising dementia populations with available data on ethnicity were included. Statistical analyses of sample and effect sizes were based on the Cochrane Handbook. 19 databases were included, with 17 studies of healthy groups or combination of diagnostic groups if breakdown was unavailable, and 12 of MCI and dementia groups. Combining all studies on dementia patients, the largest ethnic group was Caucasian (20,547 participants) with the next most common being Afro-Caribbean (1958), followed by Asian (1211). The smallest effect size detectable within the Caucasian group was 0.03, compared to Afro-Caribbean (0.1) and Asian (0.13). Our findings quantify the lack of ethnic diversity in openly available dementia datasets. More representative data would facilitate the development and validation of biomarkers relevant across ethnicities.
{"title":"Understanding ethnic diversity in open dementia neuroimaging datasets","authors":"Nicholas Yew Wei Heng, Timothy Rittman","doi":"10.1093/braincomms/fcad308","DOIUrl":"https://doi.org/10.1093/braincomms/fcad308","url":null,"abstract":"Abstract Ethnic differences in dementia are increasingly recognised in epidemiological measures and diagnostic biomarkers. Nonetheless, ethnic diversity remains limited in many study populations. Here we provide insights into ethnic diversity in open access neuroimaging dementia datasets. Datasets comprising dementia populations with available data on ethnicity were included. Statistical analyses of sample and effect sizes were based on the Cochrane Handbook. 19 databases were included, with 17 studies of healthy groups or combination of diagnostic groups if breakdown was unavailable, and 12 of MCI and dementia groups. Combining all studies on dementia patients, the largest ethnic group was Caucasian (20,547 participants) with the next most common being Afro-Caribbean (1958), followed by Asian (1211). The smallest effect size detectable within the Caucasian group was 0.03, compared to Afro-Caribbean (0.1) and Asian (0.13). Our findings quantify the lack of ethnic diversity in openly available dementia datasets. More representative data would facilitate the development and validation of biomarkers relevant across ethnicities.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"17 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135430328","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}
Pub Date : 2023-11-06DOI: 10.1093/braincomms/fcad301
Hilary E Miller, Emily O Garnett, Elizabeth S Heller Murray, Alfonso Nieto-Castañón, Jason A Tourville, Soo-Eun Chang, Frank H Guenther
Abstract This cross-sectional study aimed to differentiate earlier occurring neuroanatomical differences that may reflect core deficits in stuttering versus changes associated with a longer duration of stuttering by analyzing structural morphometry in a large sample of children and adults who stutter and age-matched controls. Whole-brain T1-weighted structural scans were obtained from 166 individuals who stutter (74 children, 92 adults; ages 3-58) and 191 controls (92 children, 99 adults; ages 3-53) from eight prior studies in our laboratories. Mean size and gyrification measures were extracted using FreeSurfer software for each cortical region of interest. FreeSurfer software was also used to generate subcortical volumes for regions in the automatic subcortical segmentation. For cortical analyses, separate ANOVA analyses of size (surface area, cortical thickness) and gyrification (local gyrification index) measures were conducted to test for a main effect of diagnosis (stuttering, control) and the interaction of diagnosis-group with age-group (children, adults) across cortical regions. Cortical analyses were first conducted across a set of regions that comprise the speech network and then in a second whole-brain analysis. Next, separate ANOVA analyses of volume were conducted across subcortical regions in each hemisphere. False discovery rate corrections were applied for all analyses. Additionally, we tested for correlations between structural morphometry and stuttering severity. Analyses revealed thinner cortex in children who stutter compared to controls in several key speech planning regions, with significant correlations between cortical thickness and stuttering severity. These differences in cortical size were not present in adults who stutter, who instead showed reduced gyrification in the right inferior frontal gyrus. Findings suggest that early cortical anomalies in key speech planning regions may be associated with stuttering onset. Persistent stuttering into adulthood may result from network-level dysfunction instead of focal differences in cortical morphometry. Adults who stutter may also have a more heterogeneous neural presentation than children who stutter due to their unique lived experiences.
{"title":"A comparison of structural morphometry in children and adults with persistent developmental stuttering","authors":"Hilary E Miller, Emily O Garnett, Elizabeth S Heller Murray, Alfonso Nieto-Castañón, Jason A Tourville, Soo-Eun Chang, Frank H Guenther","doi":"10.1093/braincomms/fcad301","DOIUrl":"https://doi.org/10.1093/braincomms/fcad301","url":null,"abstract":"Abstract This cross-sectional study aimed to differentiate earlier occurring neuroanatomical differences that may reflect core deficits in stuttering versus changes associated with a longer duration of stuttering by analyzing structural morphometry in a large sample of children and adults who stutter and age-matched controls. Whole-brain T1-weighted structural scans were obtained from 166 individuals who stutter (74 children, 92 adults; ages 3-58) and 191 controls (92 children, 99 adults; ages 3-53) from eight prior studies in our laboratories. Mean size and gyrification measures were extracted using FreeSurfer software for each cortical region of interest. FreeSurfer software was also used to generate subcortical volumes for regions in the automatic subcortical segmentation. For cortical analyses, separate ANOVA analyses of size (surface area, cortical thickness) and gyrification (local gyrification index) measures were conducted to test for a main effect of diagnosis (stuttering, control) and the interaction of diagnosis-group with age-group (children, adults) across cortical regions. Cortical analyses were first conducted across a set of regions that comprise the speech network and then in a second whole-brain analysis. Next, separate ANOVA analyses of volume were conducted across subcortical regions in each hemisphere. False discovery rate corrections were applied for all analyses. Additionally, we tested for correlations between structural morphometry and stuttering severity. Analyses revealed thinner cortex in children who stutter compared to controls in several key speech planning regions, with significant correlations between cortical thickness and stuttering severity. These differences in cortical size were not present in adults who stutter, who instead showed reduced gyrification in the right inferior frontal gyrus. Findings suggest that early cortical anomalies in key speech planning regions may be associated with stuttering onset. Persistent stuttering into adulthood may result from network-level dysfunction instead of focal differences in cortical morphometry. Adults who stutter may also have a more heterogeneous neural presentation than children who stutter due to their unique lived experiences.","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"70 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135685213","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}
Abstract The clinical presentation of corticobasal degeneration is diverse, while the background pathology of corticobasal syndrome is also heterogeneous. Therefore, predicting the pathological background of corticobasal syndrome is extremely difficult. Herein, we investigated the clinical findings and course in patients with pathologically, genetically, and biochemically verified corticobasal degeneration and corticobasal syndrome with background pathology to determine findings suggestive of background disorder. Thirty-two patients were identified as having corticobasal degeneration. The median intervals from the initial symptoms to the onset of key milestones were as follows: gait disturbance, 0.0 year; behavioural changes, 1.0 year; falls, 2.0 years; cognitive impairment, 2.0 years; speech impairment, 2.5 years; supranuclear gaze palsy, 3.0 years; urinary incontinence, 3.0 years; and dysphagia, 5.0 years. The median survival time was 7.0 years; 50% of corticobasal degeneration were diagnosed as corticobasal degeneration/corticobasal syndrome at the final presentation. Background pathologies of corticobasal syndrome (n = 48) included corticobasal degeneration (33.3%), progressive supranuclear palsy (29.2%), and Alzheimer's disease (12.5%). The common course of corticobasal syndrome was initial gait disturbance and early fall. Additionally, corticobasal degeneration-corticobasal syndrome manifested behavioural change (2.5 years) and cognitive impairment (3.0 years), as the patient with progressive supranuclear palsy-corticobasal syndrome developed speech impairment (1.0 years) and supranuclear gaze palsy (6.0 years). The Alzheimer's disease-corticobasal syndrome patients showed cognitive impairment (1.0 years). The frequency of frozen gait at onset was higher in the corticobasal degeneration-corticobasal syndrome group than in the progressive supranuclear palsy-corticobasal syndrome group (P = 0.005, odds ratio [95% confidence interval]: 31.67 [1.46-685.34]). Dysarthria at presentation was higher in progressive supranuclear palsy-corticobasal syndrome than in corticobasal degeneration-corticobasal syndrome (P = 0.047, 6.75 [1.16-39.20]). Pyramidal sign at presentation and personality change during entire course were higher in Alzheimer's disease-corticobasal syndrome than in progressive supranuclear palsy-corticobasal syndrome (P = 0.011, 27.44 [1.25-601.61], and P = 0.013, 40.00 [1.98-807.14], respectively). In corticobasal syndrome, decision tree analysis revealed that ‘freezing at onset’ or ‘no dysarthria at presentation and age at onset under 66 years in the case without freezing at onset’ predicted corticobasal degeneration pathology with a sensitivity of 81.3% and specificity of 84.4%. ‘Dysarthria at presentation and age at onset over 61 years’ suggested progressive supranuclear palsy pathology, and ‘pyramidal sign at presentation and personality change during the entire course’ implied Alzheimer's disease pathology. In conclusion, frozen
{"title":"Clinical course of pathologically confirmed corticobasal degeneration and corticobasal syndrome","authors":"Ikuko Aiba, Yuichi Hayashi, Takayoshi Shimohata, Mari Yoshida, Yuko Saito, Koichi Wakabayashi, Takashi Komori, Masato Hasegawa, Takeshi Ikeuchi, Aya M Tokumaru, Keita Sakurai, Shigeo Murayama, Kazuko Hasegawa, Toshiki Uchihara, Yasuko Toyoshima, Yufuko Saito, Ichiro Yabe, Satoshi Tanikawa, Keizo Sugaya, Kentaro Hayashi, Terunori Sano, Masaki Takao, Motoko Sakai, Harutoshi Fujimura, Hiroshi Takigawa, Tadashi Adachi, Ritsuko Hanajima, Osamu Yokota, Tomoko Miki, Yasushi Iwasaki, Michio Kobayashi, Nobutaka Arai, Takuya Ohkubo, Takanori Yokota, Keiko Mori, Masumi Ito, Chiho Ishida, Masaharu Tanaka, Jiro Idezuka, Masato Kanazawa, Kenju Aoki, Masashi Aoki, Takafumi Hasegawa, Hirohisa Watanabe, Atsushi Hashizume, Hisayoshi Niwa, Keizo Yasui, Keita Ito, Yukihiko Washimi, Eiichiro Mukai, Akatsuki Kubota, Tatsushi Toda, Kenji Nakashima, Yuichi Hayashi, Takayoshi Shimohata, Mari Yoshida, Yuko Saito, Koichi Wakabayashi, Takashi Komori, Masato Hasegawa, Takeshi Ikeuchi, Aya M Tokumaru, Keita Sakurai, Shigeo Murayama, Kazuko Hasegawa, Toshiki Uchihara, Yasuko Toyoshima, Yufuko Saito, Ichiro Yabe, Satoshi Tanikawa, Keizo Sugaya, Kentaro Hayashi, Terunori Sano, Masaki Takao, Motoko Sakai, Harutoshi Fujimura, Hiroshi Takigawa, Tadashi Adachi, Ritsuko Hanajima, Osamu Yokota, Tomoko Miki, Yasushi Iwasaki, Michio Kobayashi, Nobutaka Arai, Takuya Ohkubo, Takanori Yokota, Keiko Mori, Masumi Ito, Chiho Ishida, Masaharu Tanaka, Jiro Idezuka, Masato Kanazawa, Kenju Aoki, Masashi Aoki, Takafumi Hasegawa, Hirohisa Watanabe, Atsushi Hashizume, Hisayoshi Niwa, Keizo Yasui, Keita Ito","doi":"10.1093/braincomms/fcad296","DOIUrl":"https://doi.org/10.1093/braincomms/fcad296","url":null,"abstract":"Abstract The clinical presentation of corticobasal degeneration is diverse, while the background pathology of corticobasal syndrome is also heterogeneous. Therefore, predicting the pathological background of corticobasal syndrome is extremely difficult. Herein, we investigated the clinical findings and course in patients with pathologically, genetically, and biochemically verified corticobasal degeneration and corticobasal syndrome with background pathology to determine findings suggestive of background disorder. Thirty-two patients were identified as having corticobasal degeneration. The median intervals from the initial symptoms to the onset of key milestones were as follows: gait disturbance, 0.0 year; behavioural changes, 1.0 year; falls, 2.0 years; cognitive impairment, 2.0 years; speech impairment, 2.5 years; supranuclear gaze palsy, 3.0 years; urinary incontinence, 3.0 years; and dysphagia, 5.0 years. The median survival time was 7.0 years; 50% of corticobasal degeneration were diagnosed as corticobasal degeneration/corticobasal syndrome at the final presentation. Background pathologies of corticobasal syndrome (n = 48) included corticobasal degeneration (33.3%), progressive supranuclear palsy (29.2%), and Alzheimer's disease (12.5%). The common course of corticobasal syndrome was initial gait disturbance and early fall. Additionally, corticobasal degeneration-corticobasal syndrome manifested behavioural change (2.5 years) and cognitive impairment (3.0 years), as the patient with progressive supranuclear palsy-corticobasal syndrome developed speech impairment (1.0 years) and supranuclear gaze palsy (6.0 years). The Alzheimer's disease-corticobasal syndrome patients showed cognitive impairment (1.0 years). The frequency of frozen gait at onset was higher in the corticobasal degeneration-corticobasal syndrome group than in the progressive supranuclear palsy-corticobasal syndrome group (P = 0.005, odds ratio [95% confidence interval]: 31.67 [1.46-685.34]). Dysarthria at presentation was higher in progressive supranuclear palsy-corticobasal syndrome than in corticobasal degeneration-corticobasal syndrome (P = 0.047, 6.75 [1.16-39.20]). Pyramidal sign at presentation and personality change during entire course were higher in Alzheimer's disease-corticobasal syndrome than in progressive supranuclear palsy-corticobasal syndrome (P = 0.011, 27.44 [1.25-601.61], and P = 0.013, 40.00 [1.98-807.14], respectively). In corticobasal syndrome, decision tree analysis revealed that ‘freezing at onset’ or ‘no dysarthria at presentation and age at onset under 66 years in the case without freezing at onset’ predicted corticobasal degeneration pathology with a sensitivity of 81.3% and specificity of 84.4%. ‘Dysarthria at presentation and age at onset over 61 years’ suggested progressive supranuclear palsy pathology, and ‘pyramidal sign at presentation and personality change during the entire course’ implied Alzheimer's disease pathology. In conclusion, frozen ","PeriodicalId":9318,"journal":{"name":"Brain Communications","volume":"36 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135874669","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}
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