Brain communications最新文献

{"title":"Impact of fixation duration on messenger RNA detectability in human formalin-fixed paraffin-embedded brain tissue.","authors":"Charlene-Annett Hurler, Sabine Liebscher, Thomas Arzberger, Sarah Jäkel","doi":"10.1093/braincomms/fcae430","DOIUrl":"10.1093/braincomms/fcae430","url":null,"abstract":"<p><p>Technologies to study mRNA in post-mortem human brain samples have greatly advanced our understanding of brain pathologies. With ongoing improvements, particularly in formalin-fixed paraffin-embedded tissue, these technologies will continue to enhance our knowledge in the future. Despite various considerations for tissue and mRNA quality, such as pre-mortem health status and RNA integrity, the impact of the tissue fixation time has not been addressed in a systemic fashion yet. In this study, we employed RNAscope to assess mRNA detectability in human post-mortem brain tissue in relation to fixation time. Our results reveal a dynamic change in mRNA detection across varying fixation durations, accompanied by an increase in signal derived from the negative probe and autofluorescence background. These findings highlight the critical relevance of standardized fixation protocols for the collection of human brain tissue in order to probe mRNA abundancy to ensure reliable and comparable results.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae430"},"PeriodicalIF":4.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell analysis reveals expanded CD8⁺  <i>GZMK</i> ^high T cells in CSF and shared peripheral clones in sporadic amyotrophic lateral sclerosis.","authors":"Hyo Jae Kim, Jae-Jun Ban, Junho Kang, Hye-Ryeong Im, Sun Hi Ko, Jung-Joon Sung, Sung-Hye Park, Jong-Eun Park, Seok-Jin Choi","doi":"10.1093/braincomms/fcae428","DOIUrl":"10.1093/braincomms/fcae428","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons in the brain and spinal cord. Despite the crucial role of aberrant immune responses in ALS pathogenesis, studies investigating immunological profiles in the cerebrospinal fluid (CSF) of patients with ALS have reported inconsistent findings. Herein, we explored the intrathecal adaptive immune response and features of circulating T cells between CSF and blood of patients with ALS using single-cell RNA and T-cell receptor (TCR) sequencing. This study comprised a total of 11 patients with apparently sporadic ALS and three controls with non-inflammatory diseases. We collected CSF from all participants, and for three patients with ALS, we additionally obtained paired samples of peripheral blood mononuclear cells (PBMCs). Utilizing droplet-based single-cell RNA and TCR sequencing, we analysed immunological profiles, gene expression characteristics and clonality. Furthermore, we examined T-cell characteristics in both PBMC and CSF samples, evaluating the shared T-cell clones across these compartments. In the CSF, patients with ALS exhibited a lower proportion of CD4⁺ T cells (45.2 versus 61.2%, <i>P</i> = 0.005) and a higher proportion of CD8⁺  <i>GZMK</i> ^hi effector memory T cells (TEMs) than controls (21.7 versus 16.8%, <i>P</i> = 0.060). Higher clonality was observed in CD8⁺ TEMs in patients with ALS compared with controls. In addition, CSF macrophages of patients with ALS exhibited a significant increase in chemokines recruiting CD8⁺ TEMs. Immunohistochemical analysis showed slightly higher proportions of T cells in the perivascular and parenchymal spaces in patients with ALS than in controls, and CD8⁺ TEMs co-localized with neurons or astrocytes in the motor cortices of patients with ALS. Clonally expanded CD8⁺  <i>GZMK</i> ^hi TEMs primarily comprised shared T-cell clones between CSF and PBMCs. Moreover, the shared CD8⁺ TEMs of PBMCs exhibited gene expression profiles similar to CSF T cells. Patients with ALS showed an increase in proportion and clonality of CD8⁺  <i>GZMK</i> ^hi TEMs and activated features of macrophages in CSF. The shared T-cell clone between CSF and blood was mainly composed of expanded CD8⁺  <i>GZMK</i> ^hi TEMs. In conclusion, single-cell immune profiling provided novel insights into the pathogenesis of ALS, characterized by activated macrophages and clonally expanded CD8⁺ T cells potentially communicating with the central nervous system and peripheral circulation.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae428"},"PeriodicalIF":4.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EEG hyperexcitability and hyperconnectivity linked to GABAergic inhibitory interneuron loss following traumatic brain injury.","authors":"Hazel G May, Konstantinos Tsikonofilos, Cornelius K Donat, Magdalena Sastre, Andriy S Kozlov, David J Sharp, Michael Bruyns-Haylett","doi":"10.1093/braincomms/fcae385","DOIUrl":"10.1093/braincomms/fcae385","url":null,"abstract":"<p><p>Traumatic brain injury represents a significant global health burden and has the highest prevalence among neurological disorders. Even mild traumatic brain injury can induce subtle, long-lasting changes that increase the risk of future neurodegeneration. Importantly, this can be challenging to detect through conventional neurological assessment. This underscores the need for more sensitive diagnostic tools, such as electroencephalography, to uncover opportunities for therapeutic intervention. Progress in the field has been hindered by a lack of studies linking mechanistic insights at the microscopic level from animal models to the macroscale phenotypes observed in clinical imaging. Our study addresses this gap by investigating a rat model of mild blast traumatic brain injury using both immunohistochemical staining of inhibitory interneurons and translationally relevant electroencephalography recordings. Although we observed no pronounced effects immediately post-injury, chronic time points revealed broadband hyperexcitability and increased connectivity, accompanied by decreased density of inhibitory interneurons. This pattern suggests a disruption in the balance between excitation and inhibition, providing a crucial link between cellular mechanisms and clinical hallmarks of injury. Our findings have significant implications for the diagnosis, monitoring, and treatment of traumatic brain injury. The emergence of electroencephalography abnormalities at chronic time points, despite the absence of immediate effects, highlights the importance of long-term monitoring in traumatic brain injury patients. The observed decrease in inhibitory interneuron density offers a potential cellular mechanism underlying the electroencephalography changes and may represent a target for therapeutic intervention. This study demonstrates the value of combining cellular-level analysis with macroscale neurophysiological recordings in animal models to elucidate the pathophysiology of traumatic brain injury. Future research should focus on translating these findings to human studies and exploring potential therapeutic strategies targeting the excitation-inhibition imbalance in traumatic brain injury.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae385"},"PeriodicalIF":4.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal dysregulation of the somatomotor network in agitated depression.","authors":"Qunjun Liang, Ziyun Xu, Shengli Chen, Shiwei Lin, Xiaoshan Lin, Ying Li, Yingli Zhang, Bo Peng, Gangqiang Hou, Yingwei Qiu","doi":"10.1093/braincomms/fcae425","DOIUrl":"10.1093/braincomms/fcae425","url":null,"abstract":"<p><p>Agitated depression (A-MDD) is a severe subtype of major depressive disorder, with an increased risk of suicidality and the potential to evolve into bipolar disorder. Despite its clinical significance, the neural basis remains unclear. We hypothesize that psychomotor agitation, marked by pressured speech and racing thoughts, is linked to disruptions in brain dynamics. To test this hypothesis, we examined brain dynamics using time delay estimation and edge-centre time series, as well as dynamic connections between the somatomotor network (SMN) and the default mode network in 44 patients with A-MDD, 75 with non-agitated MDD (NA-MDD), and 94 healthy controls. Our results revealed that the neural co-activity duration was shorter in the A-MDD group compared with both the NA-MDD and controls (A-MDD versus NA-MDD: <i>t</i> = 2.295; A-MDD versus controls: <i>t</i> = 2.192, all <i>P</i> < 0.05). In addition, the dynamic of neural fluctuation in SMN altered in the A-MDD group than in the NA-MDD group (<i>t</i> = -2.616, <i>P</i> = 0.011) and was correlated with agitation severity (<i>β</i> = -0.228, <i>P</i> = 0.011). The inter-network connection was reduced in the A-MDD group compared with the control group (<i>t</i> = 2.102, <i>P</i> = 0.037), especially at low-amplitude time points (<i>t</i> = 2.139, <i>P</i> = 0.034). These findings indicate rapid neural fluctuations and disrupted dynamic coupling between the SMN and default mode network in A-MDD, potentially underlying the psychomotor agitation characteristic of this subtype. These insights contribute to a more nuanced understanding of the heterogeneity of depression and have implications for differential diagnosis and treatment strategies.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae425"},"PeriodicalIF":4.1,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional network disruption in cognitively unimpaired autosomal dominant Alzheimer's disease: a magnetoencephalography study.","authors":"Anne M van Nifterick, Willem de Haan, Cornelis J Stam, Arjan Hillebrand, Philip Scheltens, Ronald E van Kesteren, Alida A Gouw","doi":"10.1093/braincomms/fcae423","DOIUrl":"10.1093/braincomms/fcae423","url":null,"abstract":"<p><p>Understanding the nature and onset of neurophysiological changes, and the selective vulnerability of central hub regions in the functional network, may aid in managing the growing impact of Alzheimer's disease on society. However, the precise neurophysiological alterations occurring in the pre-clinical stage of human Alzheimer's disease remain controversial. This study aims to provide increased insights on quantitative neurophysiological alterations during a true early stage of Alzheimer's disease. Using high spatial resolution source-reconstructed magnetoencephalography, we investigated regional and whole-brain neurophysiological changes in a unique cohort of 11 cognitively unimpaired individuals with pathogenic mutations in the presenilin-1 or amyloid precursor protein gene and a 1:3 matched control group (<i>n</i> = 33) with a median age of 49 years. We examined several quantitative magnetoencephalography measures that have been shown robust in detecting differences in sporadic Alzheimer's disease patients and are sensitive to excitation-inhibition imbalance. This includes spectral power and functional connectivity in different frequency bands. We also investigated hub vulnerability using the hub disruption index. To understand how magnetoencephalography measures change as the disease progresses through its pre-clinical stage, correlations between magnetoencephalography outcomes and various clinical variables like age were analysed. A comparison of spectral power between mutation carriers and controls revealed oscillatory slowing, characterized by widespread higher theta (4-8 Hz) power, a lower posterior peak frequency and lower occipital alpha 2 (10-13 Hz) power. Functional connectivity analyses presented a lower whole-brain (amplitude-based) functional connectivity in the alpha (8-13 Hz) and beta (13-30 Hz) bands, predominantly located in parieto-temporal hub regions. Furthermore, we found a significant hub disruption index for (phase-based) functional connectivity in the theta band, attributed to both higher functional connectivity in 'non-hub' regions alongside a hub disruption. Neurophysiological changes did not correlate with indicators of pre-clinical disease progression in mutation carriers after multiple comparisons correction. Our findings provide evidence that oscillatory slowing and functional connectivity differences occur before cognitive impairment in individuals with autosomal dominant mutations leading to early onset Alzheimer's disease. The nature and direction of these alterations are comparable to those observed in the clinical stages of Alzheimer's disease, suggest an early excitation-inhibition imbalance, and fit with the activity-dependent functional degeneration hypothesis. These insights may prove useful for early diagnosis and intervention in the future.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae423"},"PeriodicalIF":4.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns and predictors of multiple sclerosis phenotype transition.","authors":"Luigi Pontieri, Nupur Greene, Malthe Faurschou Wandall-Holm, Svend Sparre Geertsen, Nasrin Asgari, Henrik Boye Jensen, Zsolt Illes, Jakob Schäfer, Rikke Marie Jensen, Tobias Sejbæk, Arkadiusz Weglewski, Mie Reith Mahler, Mai Bang Poulsen, Sivagini Prakash, Morten Stilund, Matthias Kant, Peter Vestergaard Rasmussen, Kristina Bacher Svendsen, Finn Sellebjerg, Melinda Magyari","doi":"10.1093/braincomms/fcae422","DOIUrl":"10.1093/braincomms/fcae422","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Currently, there are limited therapeutic options for patients with non-active secondary progressive multiple sclerosis. Therefore, real-world studies have investigated differences between patients with relapsing-remitting multiple sclerosis, non-active secondary progressive multiple sclerosis and active secondary progressive multiple sclerosis. Here, we explore patterns and predictors of transitioning between these phenotypes. We performed a cohort study using data from The Danish Multiple Sclerosis Registry. We included patients with a relapsing-remitting phenotype, registered changes to secondary progressive multiple sclerosis and subsequent transitions between relapsing and non-relapsing secondary progressive multiple sclerosis, which was defined by the presence of relapses in the previous 2 years. We analysed predictors of transitioning from relapsing-remitting multiple sclerosis to relapsing and non-relapsing secondary progressive multiple sclerosis, as well as between the secondary progressive states using a multi-state Markov model. We included 4413 patients with relapsing-remitting multiple sclerosis. Within a median follow-up of 16.2 years, 962 were diagnosed with secondary progressive multiple sclerosis by their treating physician. Of these, we classified 729 as non-relapsing and 233 as relapsing secondary progressive multiple sclerosis. The risk of transitioning from relapsing-remitting to non-relapsing secondary progressive multiple sclerosis included older age (hazard ratio per increase of 1 year in age: 1.044, 95% confidence interval: 1.035-1.053), male sex (hazard ratio for female: 0.735, 95% confidence interval: 0.619-0.874), fewer relapses (hazard ratio per each additional relapse: 0.863, 95% confidence interval: 0.823-0.906), higher expanded disability status scale (hazard ratio per each additional point: 1.522, 95% confidence interval: 1.458-1.590) and longer time on disease-modifying therapies (hazard ratio per increase of 1 year in treatment, high-efficacy disease-modifying therapy: 1.095, 95% confidence interval: 1.051-1.141; hazard ratio, moderate-efficacy disease-modifying therapy: 1.073, 95% confidence interval: 1.051-1.095). We did not find significant predictors associated with the transition from relapsing secondary progressive multiple sclerosis to non-relapsing secondary progressive multiple sclerosis, whereas older age (hazard ratio per increase of 1 year in age: 0.956, 95% confidence interval: 0.942-0.971) prevented the transition from non-relapsing secondary progressive multiple sclerosis to relapsing secondary progressive multiple sclerosis. Our study suggests that transitioning from relapsing-remitting multiple sclerosis to non-relapsing secondary progressive multiple sclerosis depends on well-known factors affecting diagnosing secondary progressive multiple sclerosis. Further transitions between non-relapsing and relapsing secondary progressive multiple sclerosis are only affected by age. These findings a","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae422"},"PeriodicalIF":4.1,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent neurodegenerative patterns: Comparison of [¹⁸F] fluorodeoxyglucose-PET- and MRI-based Alzheimer's disease subtypes.","authors":"Sophia H Wheatley, Rosaleena Mohanty, Konstantinos Poulakis, Fedor Levin, J Sebastian Muehlboeck, Agneta Nordberg, Michel J Grothe, Daniel Ferreira, Eric Westman","doi":"10.1093/braincomms/fcae426","DOIUrl":"10.1093/braincomms/fcae426","url":null,"abstract":"<p><p>[¹⁸F] fluorodeoxyglucose (FDG)-PET and MRI are key imaging markers for neurodegeneration in Alzheimer's disease. It has been well established that parieto-temporal hypometabolism on FDG-PET is closely associated with medial temporal atrophy on MRI in Alzheimer's disease. Substantial biological heterogeneity, expressed as distinct subtypes of hypometabolism or atrophy patterns, has been previously described in Alzheimer's disease using data-driven and hypothesis-driven methods. However, the link between these two imaging modalities has not yet been explored in the context of Alzheimer's disease subtypes. To investigate this link, the current study utilized FDG-PET and MRI scans from 180 amyloid-beta positive Alzheimer's disease dementia patients, 339 amyloid-beta positive mild cognitive impairment and 176 amyloid-beta negative cognitively normal controls from the Alzheimer's Disease Neuroimaging Initiative. Random forest hierarchical clustering, a data-driven model for identifying subtypes, was implemented in the two modalities: one with standard uptake value ratios and the other with grey matter volumes. Five hypometabolism- and atrophy-based subtypes were identified, exhibiting both cortical-predominant and limbic-predominant patterns although with differing percentages and clinical presentations. Three cortical-predominant hypometabolism subtypes found were Cortical Predominant (32%), Cortical Predominant+ (11%) and Cortical Predominant posterior (8%), and two limbic-predominant hypometabolism subtypes found were Limbic Predominant (36%) and Limbic Predominant frontal (13%). In addition, little atrophy (minimal) and widespread (diffuse) neurodegeneration subtypes were observed from the MRI data. The five atrophy subtypes found were Cortical Predominant (19%), Limbic Predominant (27%), Diffuse (29%), Diffuse+ (6%) and Minimal (19%). Inter-modality comparisons showed that all FDG-PET subtypes displayed medial temporal atrophy, whereas the distinct MRI subtypes showed topographically similar hypometabolic patterns. Further, allocations of FDG-PET and MRI subtypes were not consistent when compared at an individual level. Additional analysis comparing the data-driven clustering model with prior hypothesis-driven methods showed only partial agreement between these subtyping methods. FDG-PET subtypes had greater differences between limbic-predominant and cortical-predominant patterns, and MRI subtypes had greater differences in severity of atrophy. In conclusion, this study highlighted that Alzheimer's disease subtypes identified using both FDG-PET and MRI capture distinct pathways showing cortical versus limbic predominance of neurodegeneration. However, the subtypes do not share a bidirectional relationship between modalities and are thus not interchangeable.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae426"},"PeriodicalIF":4.1,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral amyloid angiopathy impacts neurofibrillary tangle burden and cognition.","authors":"Dana Godrich, Jeremy Pasteris, Eden R Martin, Tatjana Rundek, Gerard Schellenberg, Tatiana Foroud, Jeffery M Vance, Margaret A Pericak-Vance, Michael L Cuccaro, William K Scott, Walter Kukull, Thomas J Montine, Gary W Beecham","doi":"10.1093/braincomms/fcae369","DOIUrl":"10.1093/braincomms/fcae369","url":null,"abstract":"<p><p>Cerebral amyloid angiopathy commonly co-occurs with amyloid β plaques and neurofibrillary degeneration and is proposed to contribute to cognitive impairment. However, the interplay among these pathologic changes of Alzheimer disease is not well understood. Here we replicate and extend findings of a recent study that suggested the association of cerebral amyloid angiopathy and cognitive impairment is mediated by neurofibrillary degeneration. We employed similar approaches but in a larger, clinical-based (as opposed to community-based) set of 4915 autopsied National Alzheimer's Coordinating Center participants (60% with dementia). Neuropathologic lesions were measured ordinally; longitudinal change in cognition was used to measure cognitive impairment. Statistical analyses included ordinal logistic regression, mediation analyses and extension of models to include presence of <i>APOE</i> e4. We show a statistical interaction between cerebral amyloid angiopathy and neuritic plaques that impacts the burden of neurofibrillary tangles. Mediation analyses show that cerebral amyloid angiopathy is associated with cognitive impairment, but only by modifying the impact of neurofibrillary tangles on cognition. We expanded the mediation analysis to include <i>APOE</i> e4 and show similar results. Findings indicate that cerebral amyloid angiopathy plays an important role in the burden and impact of neurofibrillary degeneration contributing to cognitive impairment.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae369"},"PeriodicalIF":4.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropathic pain relief and altered brain networks after dorsal root entry zone microcoagulation in patients with spinal cord injury.","authors":"Scott Falci, Leslie Morse, Jeffrey Berliner, Mario Murakami, Abigail Welch, David Barnkow, Nguyen Nguyen, Ricardo Battaglino, Clas Linnman","doi":"10.1093/braincomms/fcae411","DOIUrl":"10.1093/braincomms/fcae411","url":null,"abstract":"<p><p>Spinal cord injury (SCI) below-level neuropathic pain is a difficult condition to treat both pharmacologically and surgically. Successful treatment using surgically created lesions of the spinal cord dorsal root entry zone (DREZ), guided by intramedullary monitoring of neuronal electrical hyperactivity, has shown that DREZs both cephalad and caudal to the level of injury can be the primary generators of SCI below-level pain. Below-level pain perception follows a unique somatotopic map of DREZ pain generators, and neuronal transmission to brain pain centres can occur primarily through sympathetic nervous system (SNS) pathways. This study evaluated changes in brain resting-state and task-based functional magnetic resonance imaging responses before and after neuroelectrically guided DREZ microcoagulation surgery. Eight persons with clinically complete SCI who suffered chronic, severe and unrelenting below-level neuropathic pain refractory to all pharmacological management were investigated before and after the surgical intervention. Baseline differences between DREZ subjects, group-matched low pain SCI and healthy controls were observed in medial primary somatosensory and motor cortex connectivity to the hippocampus, amygdala and medial prefrontal cortex. The DREZ surgery led to short-term (12 days) almost complete pain relief in all participants and long-term (1+ year) pain relief in all participants receiving DREZ lesioning both cephalad and caudal to the level of injury (six out of eight participants). Follow-up 12 days post-operatively indicated that DREZ surgery normalized prior negative functional coupling between primary sensory (S1) and motor (M1) cortices to the hippocampus, amygdala and the medial prefrontal cortex, increased M1 to putamen and amygdala connectivity and decreased limbic to cerebellar connectivity. DREZ hyperactivity was found both cephalad and caudal to the level of injury. The regional distribution of hyperactive regions corresponded not to classical dermatomes but rather mapped on to intermediolateral (IML) cell column end organ innervation of body regions of below-level pain perception, consistent with a non-classical SNS-mediated somatotopic map of DREZ below-level pain generators. The results indicate that neuroelectrically guided DREZ microcoagulation alters a medial prefrontal-somatosensory-limbic network that is separate from classical pain pathways. This provides further evidence that below-level SCI pain originates in hyperactive DREZs and can be relayed to the brain via the SNS.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae411"},"PeriodicalIF":4.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diffusion tensor imaging along the perivascular space: the bias from crossing fibres.","authors":"Charalampos Georgiopoulos, Alice Werlin, Samo Lasic, Sara Hall, Danielle van Westen, Nicola Spotorno, Oskar Hansson, Markus Nilsson","doi":"10.1093/braincomms/fcae421","DOIUrl":"10.1093/braincomms/fcae421","url":null,"abstract":"<p><p>Non-invasive evaluation of glymphatic function has emerged as a crucial goal in neuroimaging, and diffusion tensor imaging along the perivascular space (DTI-ALPS) has emerged as a candidate method for this purpose. Reduced ALPS index has been suggested to indicate impaired glymphatic function. However, the potential impact of crossing fibres on the ALPS index has not been assessed, which was the aim of this cross-sectional study. For this purpose, we used DTI-ALPS in a cohort with three groups: Parkinson's disease (PD) (<i>n</i> = 60, mean age 63.3 ± 1.5, 33 males), progressive supranuclear palsy (PSP) (<i>n</i> = 17, mean age 70.9 ± 1.5, 9 males) and healthy controls (<i>n</i> = 41, mean age 64.5 ± 8.4, 15 males). The ALPS index was calculated blinded to diagnosis, by manually placing two sets of regions of interest (ROI) on the projection and association fibres of each hemisphere. Annotation was performed twice: once on conventional diffusion-encoded colour maps weighted by fractional anisotropy and once on maps with weights adjusted for high incidence of crossing fibres. PSP patients had significantly lower conventional ALPS indices compared with both healthy controls (right hemisphere: <i>P</i> = 0.009; left hemisphere: <i>P</i> < 0.001) and PD patients (right hemisphere: <i>P</i> = 0.024; left hemisphere: <i>P</i> < 0.001). There were no differences between healthy controls and PD patients. After adjusting the ROI to avoid regions of crossing fibres, the ALPS index significantly decreased in healthy controls (right hemisphere: <i>P</i> < 0.001; left hemisphere: <i>P</i> < 0.001) and PD (right hemisphere: <i>P</i> < 0.001; left hemisphere: <i>P</i> < 0.001). In PSP, the adjusted ALPS index was lower compared with the conventional one only in the right hemisphere (<i>P</i> = 0.047). Overall, this adjustment led to less significant differences among diagnostic groups. Specifically, with the adjusted ALPS index, PSP patients showed significantly lower ALPS index compared with healthy controls (right hemisphere: <i>P</i> = 0.044; left hemisphere: <i>P</i> = 0.029) and PD patients (<i>P</i> = 0.003 for the left hemisphere only). Our results suggest that crossing fibres significantly inflate the ALPS index and should be considered a critical pitfall of this method. This factor could partly explain the variability observed in previous studies. Unlike previous research, we observed no differences between PD and healthy controls, likely because most patients in our cohort were in the early phase of the disease. Thus, the ALPS index may not be a sensitive indicator of glymphatic function at least in the initial stages of neurodegeneration in PD.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 6","pages":"fcae421"},"PeriodicalIF":4.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}