Brain communications最新文献

{"title":"Cognitive capacity in amyotrophic lateral sclerosis: the value of diagnostic markers in cerebrospinal fluid and the influence of nutrition and pulmonary function.","authors":"Sabrina M Wölfel, Catherine N Widmann, Sergio Castro-Gomez, Patrick Weydt, Pawel Tacik, Michael T Heneka","doi":"10.1093/braincomms/fcaf137","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf137","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis is an incurable neurodegenerative disease that is fatal with a median of 3-4 years. It is characterized by degeneration of the first and second motor neurons. In addition to physical limitations, neuropsychological abnormalities occur in more than 50% of cases. This leads to a rapid loss of autonomy and increases the need for care. An individual prognosis for the course of the disease, in particular the development of cognitive and behavioural abnormalities, is not yet possible As part of our investigations, we focused on cognitive performance and behavioural abnormalities measured by the Edinburgh Cognitive and Behavioural ALS Screen in patients with amyotrophic lateral sclerosis and investigated possible prognostic biomarkers in cerebrospinal fluid as well as modifiable factors such as nutrition and lung function. A retrospective data analysis of 99 patients with amyotrophic lateral sclerosis cases examined between 2018 and 2021 at the Department for Neurodegenerative Diseases and Gerontopsychiatry at the University Hospital of Bonn, using Edinburgh Cognitive and Behavioural ALS Screen, revealed that elevated levels of total tau and phospho-tau 181 were associated with diminished performance of patients with amyotrophic lateral sclerosis on the Edinburgh Cognitive and Behavioural ALS Screen. Additionally, weight loss during the course of the disease has been observed to have a deleterious impact on cognitive performance. Moreover, we were able to demonstrate a previously insufficiently described correlation between abnormalities in the Edinburgh Cognitive and Behavioural ALS Screen and low-normal thiamine levels in serum. The hypothesis that reduced lung function has a negative effect on cognitive performance was not supported by our findings. The initial onset of amyotrophic lateral sclerosis, whether bulbar or spinal, does not appear to affect cognition and behaviour measured using Edinburgh Cognitive and Behavioural ALS Screen. Furthermore, our findings confirm the utility of the Edinburgh Cognitive and Behavioural ALS Screen in identifying a behavioural variant frontotemporal dementia in amyotrophic lateral sclerosis patients who have been previously diagnosed by experienced neurologists using the Rascovsky criteria. This development facilitates a more precise utilization of complex diagnostic instruments. Our results provide insight into the prognosis of patients with amyotrophic lateral sclerosis in terms of cognitive performance and behavioural abnormalities as the disease progresses, as well as potential therapeutic approaches to stabilize and support neuropsychological abnormalities. The importance of total tau as a widely available prognostic marker should be emphasized. Additionally, new avenues of research are emerging, particularly regarding the role of thiamine in amyotrophic lateral sclerosis.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf137"},"PeriodicalIF":4.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058696","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":"Exploring anterior thalamus functional connectivity with cortical regions in prospective memory with ultra-high-field functional MRI.","authors":"Luke Flanagan, Bruno de Matos Mansur, Christoph Reichert, Anni Richter, Soroosh Golbabaei, Jasmin M Kizilirmak, Catherine M Sweeney-Reed","doi":"10.1093/braincomms/fcaf135","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf135","url":null,"abstract":"<p><p>Prospective memory, or memory for future intentions, engages particular cortical regions. Lesion studies also implicate the thalamus, with prospective memory deterioration following thalamic stroke. Neuroimaging, anatomical and lesion studies suggest the anterior nuclei of the thalamus (ANT), in particular, are involved in episodic memory, with electrophysiological studies suggesting an active role in selecting neural assemblies underlying particular memory traces. Here, we hypothesized that the ANT are engaged in realizing prospectively-encoded intentions, detectable using ultra-high-field strength functional MRI. Using a within-subject design, participants (<i>N</i> = 14; age 20-35 years) performed an ongoing n-back working memory task with two cognitive loads, each with and without a prospective memory component, during 7-Tesla functional MRI. Seed-to-voxel whole brain functional connectivity analyses were performed to establish whether including a prospective memory component in an ongoing task results in greater connectivity between ANT and cortical regions engaged in prospective memory. Repeated measures ANOVAs were applied to behavioral and connectivity measures, with the factors <i>Task Type</i> (with prospective memory or not) and <i>N-Back</i> (2-back or 3-back). Response accuracy was greater and reaction times faster without the prospective memory component, and accuracy was higher in the 2- than 3-back condition. <i>Task Type</i> had a main effect on connectivity with an ANT seed, with greater ANT-DLPFC and ANT-STG connectivity when including a prospective memory component. <i>Post hoc</i> testing based on a significant interaction showed greater ANT-DLPFC connectivity (p-FWE = 0.007) when prospective memory was included with the low cognitive load and ANT-STG connectivity (p-FWE = 0.019) with the high cognitive load ongoing task. Direct comparison showed greater functional connectivity between these areas and the ANT than dorsomedial nucleus of the thalamus (DMNT) during prospective remembering. Enhanced ANT-DLPFC connectivity, a brain region with an established role in strategic monitoring for prospective memory cues, arose with a low cognitive load ongoing task that enabled monitoring. This connectivity was significantly less on direct comparison with increasing the cognitive load of the ongoing task without prospective memory, suggesting specificity for prospective memory. Greater ANT-STG connectivity on prospective memory inclusion in the higher cognitive load ongoing task fits with reported STG activation on prospective memory through spontaneous retrieval. Lower connectivity on direct comparison with a DMNT seed suggests ANT specificity. The findings fit with a coordinating role for the ANT in prospective remembering. Given the small sample, these findings should be considered preliminary, with replication required.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf135"},"PeriodicalIF":4.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002332","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":"Modulating limbic circuits in temporal lobe epilepsy: impacts on seizures, memory, mood and sleep.","authors":"Vaclav Kremen, Vladimir Sladky, Filip Mivalt, Nicholas M Gregg, Benjamin H Brinkmann, Irena Balzekas, Victoria Marks, Michal Kucewicz, Brian Nils Lundstrom, Jie Cui, Erik K St Louis, Paul Croarkin, Eva C Alden, Boney Joseph, Julie Fields, Karla Crockett, Jindrich Adolf, Jordan Bilderbeek, Dora Hermes, Steven Messina, Kai Joshua Miller, Jamie Van Gompel, Timothy Denison, Gregory A Worrell","doi":"10.1093/braincomms/fcaf106","DOIUrl":"10.1093/braincomms/fcaf106","url":null,"abstract":"<p><p>Temporal lobe epilepsy is a common neurological disease characterized by recurrent seizures that often originate within limbic networks involving amygdala and hippocampus. The limbic network is involved in crucial physiologic functions involving memory, emotion and sleep. Temporal lobe epilepsy is frequently drug-resistant, and people often experience comorbidities related to memory, mood and sleep. Deep brain stimulation targeting the anterior nucleus of the thalamus (ANT-DBS) is an established therapy for temporal lobe epilepsy. However, the optimal stimulation parameters and their impact on memory, mood and sleep comorbidities remain unclear. We used an investigational brain sensing-stimulation implanted device to accurately track seizures, interictal epileptiform spikes (IES), and memory, mood and sleep comorbidities in five ambulatory subjects. Wireless streaming of limbic network local field potentials (LFPs) and subject behaviour were captured on a mobile device integrated with a cloud environment. Automated algorithms applied to the continuous LFPs were used to accurately cataloged seizures, IES and sleep-wake brain state. Memory and mood assessments were remotely administered to densely sample cognitive and behavioural response during ANT-DBS in ambulatory subjects living in their natural home environment. We evaluated the effect of continuous low-frequency and duty cycle high-frequency ANT-DBS on epileptiform activity and memory, mood and sleep comorbidities. Both low-frequency and high-frequency ANT-DBS paradigms reduced seizures. However, continuous low-frequency ANT-DBS showed greater reductions in IES, electrographic seizures and better sleep and memory outcomes. These results highlight the potential of synchronized brain sensing and dense behavioural tracking during ANT-DBS for optimizing neuromodulation therapy. While studies with larger patient numbers are needed to validate the benefits of low-frequency ANT-DBS, these findings are potentially translatable to individuals currently implanted with ANT-DBS systems.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf106"},"PeriodicalIF":4.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804795","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":"Genetic aetiologies in relation to response to the ketogenic diet in 226 children with epilepsy.","authors":"Maria Dahlin, Tommy Stödberg, Elin Ekman, Virpi Töhönen, Anna Wedell","doi":"10.1093/braincomms/fcaf134","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf134","url":null,"abstract":"<p><p>A ketogenic diet is used in children with drug-resistant epilepsy but predictors for efficacy are largely lacking. Our aim was to evaluate if causative genetic variants could predict seizure response to the ketogenic diet. A cohort study of 226 children with refractory epilepsy and classic ketogenic diet treatment for at least 3 months (76.9% of the 294 who started) was performed. The median age at diet start was 5.1 years (range 0.1-17.8), 118 were girls and 108 boys. They had previous trials of a median of 6.0 anti-seizure medications (range 0-12) and intellectual disability was found in 87%. Seizure response (≥50% reduction) was found in 138/226 patients (61.1%) at 3 months, 121 (53.5%) at 6 months, 107 (47.3%) at 1 year and in 80 (37.0%) at 2 years follow-up of ketogenic diet. Age of epilepsy onset was lower and combined epilepsy type less common in responders compared to non-responders but no differences were found for specific seizure types, ketogenic ratio or beta-hydroxybutyric acid blood levels. A causative pathogenic/likely pathogenic variant was detected in 107/153 = 69.9% in 48 different genes. Next generation sequencing was used in 91/226 (40%) cases with a diagnostic yield of 58.2% (53/91). In comparison with cases without a revealed genetic aetiology, patients with a causative genetic variant had less atonic seizures and epileptic spasms and a better seizure response with 17.3% seizure free and 25% with >90% seizure reduction at 2-year follow-up. Causative variants in <i>SLC2A1</i>, <i>SCN1A</i>, <i>STXBP1</i> and <i>PAFAH1B1</i> showed significant diet response (<i>P</i> < 0.05) and good efficacy was also associated with <i>DEPDC5</i>, <i>GLDC</i>, <i>KCNT1</i>, <i>PDHA1</i>, <i>SLC25A12</i> and <i>TSC1</i>. Causative variants in <i>COL4A1</i> and <i>DYNC1H1</i> were among genes linked to a lack of response. To our knowledge not described previously, we report a good ketogenic diet response related to causative variants in <i>CSNK2A1</i>, <i>FARS2</i>, <i>GABRB3</i>, <i>GRIN1</i>, <i>KCNA2</i>, <i>KCTD3</i>, <i>STX1B</i> and <i>SLC16A2</i> but a lack of response for causative variants in <i>CLN5</i>, <i>GLI3</i>, <i>MACF1</i>, <i>MAGEL2</i>, <i>NANS</i>, <i>NEMO/IKBKG</i>, <i>RORB</i>, <i>SLC17A5</i> and <i>UFSP2.</i> After grouping of genes into functional groups, causative variants in transporter genes had the best response (<i>P</i> = 0.009) and variants in other membrane-related proteins (ion channels and neurotransmitter receptors) also showed good efficacy. However, the gene group related to cell structural integrity and/or homeostasis had the worst diet response (<i>P</i> = 0.00006). In conclusion, our results support that causative genetic variants may be used as prognostic markers of ketogenic diet response, constituting an example in the expanding area of precision medicine.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf134"},"PeriodicalIF":4.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045031","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":"Neurophysiological signatures of ageing: compensatory and compromised neural mechanisms.","authors":"Kamalini G Ranasinghe, Kiwamu Kudo, Kaitlin Casaletto, Julio C Rojas-Martinez, Faatimah Syed, Keith Vossel, Bruce L Miller, Gil D Rabinovici, Joel H Kramer, Katherine P Rankin, Srikantan S Nagarajan","doi":"10.1093/braincomms/fcaf131","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf131","url":null,"abstract":"<p><p>Spatiotemporal patterns of neural oscillations change with ageing, even in the cognitively unimpaired individual. Whether these neurophysiological changes represent ageing-related vulnerabilities or mechanisms that support cognitive resilience remains largely unknown. In this study, we used magnetoencephalography imaging to examine age-related changes of resting-state whole-brain neurophysiology in a well-characterized cohort of cognitively unimpaired individuals (<i>n</i> = 70; age range 52-87 years). We quantified spatial patterns of age-related changes in band-limited spectral power within delta-theta (2-7 Hz), alpha (8-12 Hz) and beta (13-30 Hz) bands and the spectral aperiodic slope (15-50 Hz), and examined how spectral changes are associated with cognitive abilities in healthy ageing. In a subset of individuals (<i>n</i> = 40) who were evaluated with a uniform battery of cognitive tests, using a partial least square regression approach, we examined the associations between age-related spectral changes and cognitive performance. We found that, with advancing age, delta-theta and beta spectral power reduces, while alpha spectral power increases. A periodic slope also showed reductions with ageing. Better cognitive scores were positively correlated with delta-theta reductions and alpha power increases associated with ageing, suggesting that these may represent compensatory neural mechanisms. Beta power reductions and spectral aperiodic slope changes, in contrast, correlated negatively with higher cognitive scores, suggesting that these may represent compromised neural mechanisms of ageing. Our findings highlighted that the neurophysiological changes that occur during later decades of life were distinct from the previously known lifespan changes. This study demonstrates the trajectories of neurophysiological changes in cognitive ageing explicitly relating to conserved and impaired neural mechanisms with important implications for identifying specific spectral changes in neurodegenerative processes in the context of ageing.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf131"},"PeriodicalIF":4.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046385","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 small vessel disease among rural-dwelling Chinese older adults: prevalence, distribution, and associated factors.","authors":"Huisi Zhang, Chunyan Li, Jiafeng Wang, Mingqing Zhao, Ziwei Chen, Qianqian Xie, Tao Gong, Tingting Hou, Yongxiang Wang, Lin Cong, Lenore J Launer, Lin Song, Yifeng Du, Chengxuan Qiu","doi":"10.1093/braincomms/fcaf136","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf136","url":null,"abstract":"<p><p>Epidemiological characteristics of cerebral small vessel disease (cSVD) in the general population, especially among rural older adults, are poorly defined. Here, we reported the prevalence, distribution, and associated factors of cSVD in a rural-dwelling older population in China. This population-based cross-sectional study included 1272 older adults (age ≥60 years; mean age 69.43 years; 58.57% women) who underwent structural brain MRI scans (3.0T) in 2018-2020. MRI markers of cSVD were assessed following the Standards for Reporting Vascular Changes on Neuroimaging-1 criteria. We performed descriptive and regression analyses. The overall prevalence was 20.31% for cerebral microbleeds (CMBs), 26.87% for lacunes, 60.06% for basal ganglia perivascular spaces (PVS), 76.31% for centrum semiovale PVS, 95.74% for deep white matter hyperintensities (WMHs), and 94.17% for periventricular WMHs. The prevalence increased with advancing age for all cSVD markers, except PVS in the centrum semiovale. The prevalence of moderate-to-severe deep WMHs was higher in women than in men (<i>P</i> = 0.005). Older age and hypertension were associated with increased likelihoods of all cSVD markers. A higher body mass index was linked to more WMHs. Coronary heart disease (CHD) was associated with WMHs, CMBs, and lacunes. Our study suggests that cSVD, especially WMHs and PVS, was highly prevalent among rural Chinese older adults. Older age, hypertension, and CHD are associated with distinct cSVD. Future prospective cohort studies are warranted to determine incidence and major risk factors of cSVD, which could facilitate preventive interventions to reduce the burden of cSVD in resource-limited settings.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf136"},"PeriodicalIF":4.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047230","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":"Co-activation of interictal epileptiform discharges localizes seizure onset zone and fluctuates with brain state.","authors":"Samuel B Tomlinson, Benjamin C Kennedy, Eric D Marsh","doi":"10.1093/braincomms/fcaf127","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf127","url":null,"abstract":"<p><p>Seizures are increasingly understood as emergent phenomena of complex, pathophysiologic networks. Interictal spikes are ubiquitous markers of paroxysmal synchronization in the epileptic brain and have been shown to co-activate between brain regions with millisecond-scale latencies, suggesting that they can spread through distributed networks of functionally inter-connected neuronal populations. In this study, we examined the relationship between interictal spike co-activation, seizure localization and resting-state EEG activity in children with medically refractory epilepsy. Twenty paediatric patients (mean age: 10.6 years) undergoing invasive EEG investigation with subdural electrodes were examined. Automated techniques were used to extract time-varying interictal spike co-activation networks from full-duration interictal recordings (mean: 108.6 h/patient). Networks were clustered into discrete node communities based on the conditional probability of spike co-activation. Patterns of regional and distributed interictal spike synchrony were investigated over time in relation to variables such as temporal proximity to nearest seizure and background oscillatory coherence. We demonstrate that the irritative neocortex comprises a network of semi-independent, highly cohesive communities with stereotyped local spike propagation patterns. Distributed coupling of spikes between communities was driven by outflow from the seizure onset zone and fluctuated over time in association with inter-regional coherence and temporal proximity to seizures. These results elucidate network dynamics facilitating pathologic hypersynchrony across the epileptic neocortex and further highlight the complex relationship between interictal epileptiform discharges and seizures.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf127"},"PeriodicalIF":4.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060853","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":"Alpha-synuclein aggregation induces prominent cellular lipid changes as revealed by Raman spectroscopy and machine learning analysis.","authors":"Nathan P Coles, Suzan Elsheikh, Agathe Quesnel, Lucy Butler, Ojodomo Achadu, Meez Islam, Karunakaran Kalesh, Annalisa Occhipinti, Claudio Angione, Jon Marles-Wright, David J Koss, Alan J Thomas, Tiago F Outeiro, Panagiota S Filippou, Ahmad A Khundakar","doi":"10.1093/braincomms/fcaf133","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf133","url":null,"abstract":"<p><p>The aggregation of α-synuclein is a central neuropathological hallmark in neurodegenerative disorders known as Lewy body diseases, including Parkinson's disease and dementia with Lewy bodies. In the aggregation process, α-synuclein transitions from its native disordered/α-helical form to a β-sheet-rich structure, forming oligomers and protofibrils that accumulate into Lewy bodies, in a process that is thought to underlie neurodegeneration. Lipids are thought to play a critical role in this process by facilitating α-synuclein aggregation and contributing to cell toxicity, possibly through ceramide production. This study aimed to investigate biochemical changes associated with α-synuclein aggregation, focusing on lipid changes, using Raman spectroscopy coupled with machine learning. HEK293, Neuro2a and SH-SY5Y expressing increased levels of α-synuclein were treated with sonicated α-synuclein pre-formed fibrils, to model seeded aggregation. Raman spectroscopy, complemented by an in-house lipid spectral library, was used to monitor the aggregation process and its effects on cellular viability over 14 days. We detected α-synuclein aggregation by assessing β-sheet peaks at 1045 cm⁻¹, in cells treated with α-synuclein pre-formed fibrils, using machine learning (principal component analysis and uniform manifold approximation and projection) analysis based on Raman spectral features. Changes in lipid profiles, and especially sphingolipids, including a decrease in sphingomyelin and increase in ceramides, were observed, consistent with oxidative stress and apoptosis. Altogether, our study informs on biochemical alterations that can be considered for the design of therapeutic strategies for Parkinson's disease and related synucleinopathies.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf133"},"PeriodicalIF":4.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065393","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 lobe dysfunction for comorbid depressive symptoms in postherpetic neuralgia patients.","authors":"Ying Wu, Chao Wang, Wei Qian, Lieju Wang, Lina Yu, Minming Zhang, Min Yan","doi":"10.1093/braincomms/fcaf132","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf132","url":null,"abstract":"<p><p>Depression often occurs concurrently with postherpetic neuralgia (PHN), yet the neural mechanism underlying pain-depression comorbidity remains poorly understood. For this observational study, we recruited 17 depressed PHN patients, 19 non-depressed PHN patients, and 34 healthy controls (HCs) for resting-state functional MRI scans. We firstly investigated the differences in fractional amplitude of low-frequency fluctuation and regional homogeneity values among the three groups to identify a characteristic brain signal of pain-depression comorbidity. Abnormal voxel-wised functional connectivity was then compared across groups and correlated with clinical variables in each group. One-way analysis of covariance results revealed the fractional amplitude of low-frequency fluctuation values differences in the right temporal lobe (TL) and its voxel-wised connectivity with the inferior frontal gyrus (IFG) among three groups. Furthermore, the TL-IFG connectivity was positively associated with the positive emotional scores and life quality scores among depressed PHN patients, but not non-depressed PHN patients and HCs. In summary, these findings highlighted the TL dysfunction in pain-depression comorbidity among PHN population and may offer heuristic cues for central therapeutic targets that could disrupt the pain-depression vicious circle.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf132"},"PeriodicalIF":4.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052042","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":"Sleep abnormalities are associated with greater cognitive deficits and disease activity in Huntington's disease: a 12-year polysomnographic study.","authors":"Zanna J Voysey, Anna O G Goodman, Lorraine Rogers, Jonathan A Holbrook, Alpar S Lazar, Roger A Barker","doi":"10.1093/braincomms/fcaf126","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf126","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Increasing evidence suggests that the sleep pathology associated with neurodegenerative diseases can in turn exacerbate both the cognitive deficits and underlying pathobiology of these conditions. Treating sleep may therefore bear significant, even disease-modifying, potential for these conditions, but how best and when to do so remains undetermined. Huntington's disease, by virtue of being an autosomal dominant neurodegenerative disease presenting in mid-life, presents a key 'model' condition through which to advance this field. To date, however, there has been no clinical longitudinal study of sleep abnormalities in Huntington's disease and no robust interrogation of their association with disease onset, cognitive deficits and markers of disease activity. Here, we present the first such study. Huntington's disease gene carriers (&lt;i&gt;n&lt;/i&gt; = 28) and age- and sex-matched controls (&lt;i&gt;n&lt;/i&gt; = 21) were studied at baseline and 10- and 12-year follow-up. All Huntington's disease gene carriers were premanifest at baseline and were stratified at follow-up into 'prodromal/manifest' versus 'premanifest' groups. Objective sleep abnormalities were assessed through two-night inpatient polysomnography and 2-week domiciliary actigraphy, and their association was explored against Montreal Cognitive Assessment, Trail A/B task, Symbol Digit Modalities Task (SDMT), Hopkins Verbal Learning Task (HVLT) and Montgomery-Asberg Depression Rating Scale (MADRS) scores, plus serum neurofilament light levels. Statistical analysis incorporated cross-sectional ANOVA, longitudinal repeated measures linear models and regressions adjusted for multiple confounders including disease stage. Fifteen Huntington's disease gene carriers phenoconverted to prodromal/early manifest Huntington's disease by study completion. At follow-up, these gene carriers showed more frequent sleep stage changes (&lt;i&gt;P&lt;/i&gt; ≤ 0.001, η&lt;sub&gt;p&lt;/sub&gt; &lt;sup&gt;2&lt;/sup&gt; = 0.62) and higher levels of sleep maintenance insomnia (defined by wake after sleep onset, &lt;i&gt;P&lt;/i&gt; = 0.002, η&lt;sub&gt;p&lt;/sub&gt; &lt;sup&gt;2&lt;/sup&gt; = 0.52). The latter finding was corroborated by nocturnal motor activity patterns on follow-up actigraphy (&lt;i&gt;P&lt;/i&gt; = 0.004, η&lt;sub&gt;p&lt;/sub&gt; &lt;sup&gt;2&lt;/sup&gt; = 0.32). Greater sleep maintenance insomnia was associated with greater cognitive deficits (Trail A &lt;i&gt;P&lt;/i&gt; ≤ 0.001, &lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 0.78; SDMT &lt;i&gt;P&lt;/i&gt; = 0.008, &lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 0.63; Trail B &lt;i&gt;P&lt;/i&gt; = 0.013, &lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 0.60) and higher levels of neurofilament light (&lt;i&gt;P&lt;/i&gt; = 0.015, &lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 0.39). Longitudinal modelling suggested that sleep stage instability accrues from the early premanifest phase, whereas sleep maintenance insomnia emerges closer to phenoconversion. Baseline sleep stage instability was able to discriminate those who phenoconverted within the study period from those who remained premanifest (area under curve = 0.81, &lt;i&gt;P&lt;/i&gt; = 0.024). These results demonstrate that the key sleep abnormalities of ","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 2","pages":"fcaf126"},"PeriodicalIF":4.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065394","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}