首页 > 最新文献

Brain communications最新文献

英文 中文
JAK4D, a first-in-class thyrotropin-releasing hormone analogue, reverses scopolamine-induced memory deficits. JAK4D是一种一流的促甲状腺激素释放激素类似物,可以逆转东莨菪碱引起的记忆缺陷。
IF 4.5 Q1 CLINICAL NEUROLOGY Pub Date : 2026-01-16 eCollection Date: 2026-01-01 DOI: 10.1093/braincomms/fcag006
Roisin McMackin, Smita Price, Gillian R Slator, Orla Hardiman, Julie A Kelly

There is a pressing unmet clinical and health economic need for effective drugs to treat cognitive impairment that occurs in neurodegenerative diseases. JAK4D is a first-in-class thyrotropin releasing hormone (TRH) analogue that overcomes the pharmacological limitations of thyrotropin releasing hormone and enables delivery of the long-recognized multifactorial neurotherapeutic actions of thyrotropin releasing hormone without inducing endocrine side effects. JAK4D is demonstrated to be neuroprotective and significantly reduce excitotoxic-induced hippocampal-dependent memory deficits in rat. In the present study, we used the scopolamine challenge test coupled with the novel object recognition test to evaluate the effect of JAK4D on scopolamine-induced recognition memory deficits in the male, Lister-Hooded rat. Scopolamine administration has been shown by others to mimic cholinergic and brain network disruption in neurodegenerative diseases. Although the scopolamine challenge test does not fully replicate the pathophysiology of neurodegenerative disease, such as Alzheimer's disease, it is a well-recognized acute pharmacological model for assessing the ability of pharmacological interventions to counteract memory deficits relevant to neurodegenerative diseases. In this model of cholinergic dysfunction, we also assessed the effects of thyrotropin releasing hormone, taltirelin (a degradation-stabilized thyrotropin releasing hormone analogue) and the acetylcholinesterase inhibitor, donepezil, as a positive reference compound. The discrimination (d2) index was used as the primary measure to assess the effect of treatment on scopolamine-induced performance deficit in the novel object recognition test. d2 is a standard well-recognized measure of discrimination between a novel and familiar object in the novel object recognition test, which advantageously takes into account individual differences in exploration levels. Across all investigations, JAK4D (1 mg/kg i.p.) significantly reversed scopolamine-induced recognition memory impairment (P = 0.0274, P = 0.0002, P < 0.0001). The degree of reversal of scopolamine-induced memory deficits by JAK4D (1 mg/kg i.p.) was indistinguishable from that observed for donepezil (0.1 mg/kg p.o.) (P = 0.026). Subcutaneously administered JAK4D (0.3-10.0 mg/kg) also significantly reversed this deficit (P = 0.0432-0.0021). Furthermore, similar pro-cognitive effects were exerted by thyrotropin releasing hormone (5 mg/kg i.p., P = 0.0055) and taltirelin (10 mg/kg p.o., P = 0.0002). Together, these results underscore the relevance of the central thyrotropin releasing hormone signalling system for the treatment of memory impairment. Data from the current study provide further evidence in support of the potential of JAK4D as a novel therapeutic for cognitive deficits in neurodegenerative diseases.

对于治疗神经退行性疾病中发生的认知障碍的有效药物,存在着迫切的临床和卫生经济需求。JAK4D是一种一流的促甲状腺激素释放激素(TRH)类似物,克服了促甲状腺激素释放激素的药理学限制,使促甲状腺激素释放激素的多因素神经治疗作用得以实现,而不会引起内分泌副作用。JAK4D被证明具有神经保护作用,可显著减少大鼠兴奋性毒性诱导的海马依赖性记忆缺陷。在本研究中,我们采用东莨菪碱激发试验结合新型物体识别试验来评估JAK4D对东莨菪碱诱导的雄性李斯特兜头大鼠识别记忆缺陷的影响。其他研究表明,东莨菪碱管理可以模拟神经退行性疾病中的胆碱能和脑网络破坏。虽然东莨菪碱激发试验不能完全复制神经退行性疾病(如阿尔茨海默病)的病理生理学,但它是一个公认的急性药理学模型,用于评估药物干预抵消与神经退行性疾病相关的记忆缺陷的能力。在这个胆碱能功能障碍模型中,我们还评估了促甲状腺激素释放激素他替雷林(一种降解稳定的促甲状腺激素释放激素类似物)和乙酰胆碱酯酶抑制剂多奈哌齐作为阳性对照化合物的作用。以区分(d2)指数为主要指标,评价治疗对东莨菪碱诱导的新目标识别成绩缺陷的影响。D2是在新物体识别测试中区分新物体和熟悉物体的标准的公认的度量,它有利地考虑了探索水平的个体差异。在所有研究中,JAK4D (1 mg/kg i.p)显著逆转东莨菪碱诱导的识别记忆障碍(P = 0.0274, P = 0.0002, P < 0.0001)。JAK4D (1 mg/kg i.p)对东莨菪碱诱导的记忆缺陷的逆转程度与多奈哌齐(0.1 mg/kg i.p)的逆转程度没有区别。(p = 0.026)。皮下注射JAK4D (0.3-10.0 mg/kg)也显著逆转了这种缺陷(P = 0.0432-0.0021)。此外,促甲状腺激素释放激素(5 mg/kg i.p., P = 0.0055)和他替雷林(10 mg/kg i.p., P = 0.0002)也有类似的促认知作用。总之,这些结果强调了中枢促甲状腺激素释放激素信号系统与治疗记忆障碍的相关性。当前研究的数据进一步证明了JAK4D作为神经退行性疾病认知缺陷的新疗法的潜力。
{"title":"JAK4D, a first-in-class thyrotropin-releasing hormone analogue, reverses scopolamine-induced memory deficits.","authors":"Roisin McMackin, Smita Price, Gillian R Slator, Orla Hardiman, Julie A Kelly","doi":"10.1093/braincomms/fcag006","DOIUrl":"10.1093/braincomms/fcag006","url":null,"abstract":"<p><p>There is a pressing unmet clinical and health economic need for effective drugs to treat cognitive impairment that occurs in neurodegenerative diseases. JAK4D is a first-in-class thyrotropin releasing hormone (TRH) analogue that overcomes the pharmacological limitations of thyrotropin releasing hormone and enables delivery of the long-recognized multifactorial neurotherapeutic actions of thyrotropin releasing hormone without inducing endocrine side effects. JAK4D is demonstrated to be neuroprotective and significantly reduce excitotoxic-induced hippocampal-dependent memory deficits in rat. In the present study, we used the scopolamine challenge test coupled with the novel object recognition test to evaluate the effect of JAK4D on scopolamine-induced recognition memory deficits in the male, Lister-Hooded rat. Scopolamine administration has been shown by others to mimic cholinergic and brain network disruption in neurodegenerative diseases. Although the scopolamine challenge test does not fully replicate the pathophysiology of neurodegenerative disease, such as Alzheimer's disease, it is a well-recognized acute pharmacological model for assessing the ability of pharmacological interventions to counteract memory deficits relevant to neurodegenerative diseases. In this model of cholinergic dysfunction, we also assessed the effects of thyrotropin releasing hormone, taltirelin (a degradation-stabilized thyrotropin releasing hormone analogue) and the acetylcholinesterase inhibitor, donepezil, as a positive reference compound. The discrimination (d2) index was used as the primary measure to assess the effect of treatment on scopolamine-induced performance deficit in the novel object recognition test. d2 is a standard well-recognized measure of discrimination between a novel and familiar object in the novel object recognition test, which advantageously takes into account individual differences in exploration levels. Across all investigations, JAK4D (1 mg/kg i.p.) significantly reversed scopolamine-induced recognition memory impairment (<i>P</i> = 0.0274, <i>P</i> = 0.0002, <i>P</i> < 0.0001). The degree of reversal of scopolamine-induced memory deficits by JAK4D (1 mg/kg i.p.) was indistinguishable from that observed for donepezil (0.1 mg/kg p.o.) (<i>P</i> = 0.026). Subcutaneously administered JAK4D (0.3-10.0 mg/kg) also significantly reversed this deficit (<i>P</i> = 0.0432-0.0021). Furthermore, similar pro-cognitive effects were exerted by thyrotropin releasing hormone (5 mg/kg i.p., <i>P</i> = 0.0055) and taltirelin (10 mg/kg p.o., <i>P</i> = 0.0002). Together, these results underscore the relevance of the central thyrotropin releasing hormone signalling system for the treatment of memory impairment. Data from the current study provide further evidence in support of the potential of JAK4D as a novel therapeutic for cognitive deficits in neurodegenerative diseases.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 1","pages":"fcag006"},"PeriodicalIF":4.5,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12848665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088460","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}
引用次数: 0
Optical coherence tomography angiography reveals insights into complementary vascular and neurodegenerative mechanisms in multiple sclerosis. 光学相干断层扫描血管造影揭示了在多发性硬化症互补血管和神经退行性机制的见解。
IF 4.5 Q1 CLINICAL NEUROLOGY Pub Date : 2026-01-10 eCollection Date: 2026-01-01 DOI: 10.1093/braincomms/fcag007
Charmaine Hiu-Ying Yam, Danuta M Sampson, Andreia Marques Elias, Jed Wingrove, Baris Kanber, Ronja Christensen, Pryanka Sood, Riccardo Nistri, Anna He, Alyssa A Toorop, Elena Panella, Dimitrios Champsas, Suraya Mohamud, Weaam Hamed, Ferran Prados Carrasco, Frederik Barkhof, Ahmed T Toosy, Olga Ciccarelli
<p><p>Optical coherence tomography angiography quantifies retinal microvasculature biomarkers, offering insights into neurovascular mechanisms underlying brain damage in multiple sclerosis. This study evaluated these potential mechanisms of neurodegeneration by examining associations between optical coherence tomography and optical coherence tomography angiography metrics, brain volumes and clinical outcomes in people with multiple sclerosis. This cross-sectional study included multiple sclerosis patients from a prospective cohort. Participants underwent optical coherence tomography/optical coherence tomography angiography, vision and clinical assessments and brain MRI. Age- and sex-matched controls underwent optical coherence tomography/optical coherence tomography angiography. The OCTA Vascular Analyser toolbox was used to derive metrics that reflect superficial plexus retinal vessel density (vessel area density, vessel length density) and network complexity. Differences in optical coherence tomography angiography and optical coherence tomography (peripapillary retinal nerve fibre layer and macular ganglion cell-inner plexiform layer) metrics between controls and patient eyes and associations with brain volumes and visual outcomes were analysed using linear-mixed models, adjusted for age, sex, disease duration and optic neuritis. Vision outcome models were compared using Akaike Information Criterion. The study included 323 multiple sclerosis patients (603 eyes; 98 with prior optic neuritis) and 80 controls (147 eyes), with 267 patients undergoing brain MRI. Patients exhibited reduced vessel area density and vessel length density and thinner peripapillary retinal nerve fibre layer and macular ganglion cell-inner plexiform layer in non-optic neuritis eyes compared with controls. Optic neuritis eyes showed deviations compared with non-optic neuritis eyes. In patients, reductions in optical coherence tomography angiography and optical coherence tomography metrics were associated with smaller volumes of the primary visual cortex (calcarine cortex and occipital pole) and thalamus but reduced vessel area density/vessel length density correlated predominantly with smaller higher-order visual processing region volumes, such as the cuneus (vessel area density: β = 0.36, vessel length density: β = 0.070), inferior occipital (vessel area density: β = 0.28, vessel length density: β = 0.057) and occipital fusiform gyrus (vessel area density: β = 0.51, vessel length density: β = 0.094) (all <i>P</i> < 0.01). In contrast, peripapillary retinal nerve fibre layer thinning was associated with smaller white matter (β = 0.10, <i>P</i> = 0.008) and optic chiasm volumes (β = 293.30, <i>P</i> < 0.0001). Reduced vessel densities were more strongly associated with worse high-contrast visual acuity and colour vision than macular ganglion cell-inner plexiform layer and peripapillary retinal nerve fibre layer. Retinal microvasculature abnormalities were associated with reg
光学相干断层扫描血管造影量化视网膜微血管生物标志物,为多发性硬化症脑损伤的神经血管机制提供见解。本研究通过检查多发性硬化症患者的光学相干断层扫描和光学相干断层扫描血管造影指标、脑容量和临床结果之间的关系,评估了这些神经变性的潜在机制。这项横断面研究包括来自前瞻性队列的多发性硬化症患者。参与者接受了光学相干断层扫描/光学相干断层扫描血管造影、视觉和临床评估以及脑MRI。年龄和性别匹配的对照组接受光学相干断层扫描/光学相干断层扫描血管造影。使用OCTA血管分析仪工具箱得出反映浅丛视网膜血管密度(血管面积密度、血管长度密度)和网络复杂性的指标。使用线性混合模型,根据年龄、性别、疾病持续时间和视神经炎进行调整,分析了对照组和患者眼睛之间光学相干断层扫描血管造影和光学相干断层扫描(乳头周围视网膜神经纤维层和黄斑神经节细胞-内丛状层)指标的差异以及与脑容量和视觉结果的关联。视觉结果模型采用赤池信息标准进行比较。该研究包括323名多发性硬化症患者(603只眼睛,98名既往视神经炎患者)和80名对照组(147只眼睛),其中267名患者接受了脑部MRI。与对照组相比,非视神经炎患者的血管面积密度和血管长度密度降低,乳头周围视网膜神经纤维层和黄斑神经节细胞-内丛状层变薄。视神经炎眼与非视神经炎眼相比有明显的偏差。在患者中,光学相干断层扫描血管造影和光学相干断层扫描测量的减少与初级视觉皮层(胼胝体皮层和枕极)和丘脑的体积变小有关,但血管面积密度/血管长度密度的减少主要与高阶视觉处理区域的体积变小相关,如楔叶(血管面积密度:β = 0.36,血管长度密度:β = 0.070),枕下(血管面积密度:β = 0.070)。β = 0.28,血管长度密度:β = 0.057)和枕梭状回(血管面积密度:β = 0.51,血管长度密度:β = 0.094)(均P < 0.01)。相比之下,乳头周围视网膜神经纤维层变薄与白质变小(β = 0.10, P = 0.008)和视交叉体积变小(β = 293.30, P < 0.0001)有关。与黄斑神经节细胞-内丛状层和乳头周围视网膜神经纤维层相比,血管密度降低与高对比视力和色觉差的相关性更强。视网膜微血管异常与高阶视觉处理区的区域性灰质萎缩有关。我们推测,脑灌注不足——以及视网膜灌注不足——可能与区域特异性神经退行性变有机制关系。相反,乳头状周围视网膜神经纤维层变薄可能反映更广泛的神经退行性过程,包括沃勒氏变性和白质连接中断。临床表现为对比敏感度和色觉受损。这些发现强调了光学相干断层扫描血管造影作为光学相干断层扫描探测视觉通路完整性的补充生物标志物的潜力,强调了其在评估早期多发性硬化症的神经血管病理和进展方面的前景。
{"title":"Optical coherence tomography angiography reveals insights into complementary vascular and neurodegenerative mechanisms in multiple sclerosis.","authors":"Charmaine Hiu-Ying Yam, Danuta M Sampson, Andreia Marques Elias, Jed Wingrove, Baris Kanber, Ronja Christensen, Pryanka Sood, Riccardo Nistri, Anna He, Alyssa A Toorop, Elena Panella, Dimitrios Champsas, Suraya Mohamud, Weaam Hamed, Ferran Prados Carrasco, Frederik Barkhof, Ahmed T Toosy, Olga Ciccarelli","doi":"10.1093/braincomms/fcag007","DOIUrl":"https://doi.org/10.1093/braincomms/fcag007","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Optical coherence tomography angiography quantifies retinal microvasculature biomarkers, offering insights into neurovascular mechanisms underlying brain damage in multiple sclerosis. This study evaluated these potential mechanisms of neurodegeneration by examining associations between optical coherence tomography and optical coherence tomography angiography metrics, brain volumes and clinical outcomes in people with multiple sclerosis. This cross-sectional study included multiple sclerosis patients from a prospective cohort. Participants underwent optical coherence tomography/optical coherence tomography angiography, vision and clinical assessments and brain MRI. Age- and sex-matched controls underwent optical coherence tomography/optical coherence tomography angiography. The OCTA Vascular Analyser toolbox was used to derive metrics that reflect superficial plexus retinal vessel density (vessel area density, vessel length density) and network complexity. Differences in optical coherence tomography angiography and optical coherence tomography (peripapillary retinal nerve fibre layer and macular ganglion cell-inner plexiform layer) metrics between controls and patient eyes and associations with brain volumes and visual outcomes were analysed using linear-mixed models, adjusted for age, sex, disease duration and optic neuritis. Vision outcome models were compared using Akaike Information Criterion. The study included 323 multiple sclerosis patients (603 eyes; 98 with prior optic neuritis) and 80 controls (147 eyes), with 267 patients undergoing brain MRI. Patients exhibited reduced vessel area density and vessel length density and thinner peripapillary retinal nerve fibre layer and macular ganglion cell-inner plexiform layer in non-optic neuritis eyes compared with controls. Optic neuritis eyes showed deviations compared with non-optic neuritis eyes. In patients, reductions in optical coherence tomography angiography and optical coherence tomography metrics were associated with smaller volumes of the primary visual cortex (calcarine cortex and occipital pole) and thalamus but reduced vessel area density/vessel length density correlated predominantly with smaller higher-order visual processing region volumes, such as the cuneus (vessel area density: β = 0.36, vessel length density: β = 0.070), inferior occipital (vessel area density: β = 0.28, vessel length density: β = 0.057) and occipital fusiform gyrus (vessel area density: β = 0.51, vessel length density: β = 0.094) (all &lt;i&gt;P&lt;/i&gt; &lt; 0.01). In contrast, peripapillary retinal nerve fibre layer thinning was associated with smaller white matter (β = 0.10, &lt;i&gt;P&lt;/i&gt; = 0.008) and optic chiasm volumes (β = 293.30, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001). Reduced vessel densities were more strongly associated with worse high-contrast visual acuity and colour vision than macular ganglion cell-inner plexiform layer and peripapillary retinal nerve fibre layer. Retinal microvasculature abnormalities were associated with reg","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 1","pages":"fcag007"},"PeriodicalIF":4.5,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12835921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095228","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}
引用次数: 0
Investigation of the rimegepant effect on cerebral and extracerebral arteries during migraine attacks: a longitudinal magnetic resonance angiography study. 偏头痛发作时脑和脑外动脉的巨大影响的研究:纵向磁共振血管造影研究。
IF 4.5 Q1 CLINICAL NEUROLOGY Pub Date : 2026-01-09 eCollection Date: 2026-01-01 DOI: 10.1093/braincomms/fcag004
Basit Ali Chaudhry, Samaira Younis, Hassan Al-Mashat, Emil Gozalov, Tariq Mohammad Amin, Patrick J H de Koning, Henrik Bo Wiberg Larsson, Faisal Mohammad Amin

Migraine is a leading cause of disability worldwide, and triptans, the most widely used acute treatment, act through vasoconstriction and are contraindicated in patients with vascular disease. Rimegepant, a calcitonin gene-related peptide receptor antagonist, is proposed as a non-vasoconstrictive alternative, but its direct vascular effects during spontaneous migraine attacks have not been examined. This was a prospective, longitudinal study conducted at a single academic imaging centre between 12 January 2024 and 10 June 2025. Eighteen women aged 18-40 years with menstrually related migraine without aura were enrolled. Fifteen participants completed high-resolution 3 T magnetic resonance angiography during a spontaneous migraine attack before, and at 30 and 60 min after, administration of a single 75 mg oral dose of rimegepant. The primary outcome was change in arterial circumference of the cerebral artery and meningeal artery. Circumference was measured in millimetre and compared using paired samples t-tests. No significant vasoconstriction was observed in either artery following rimegepant administration. Cerebral artery circumference remained stable (baseline 8.13 ± 0.93 mm; 30 min 8.02 ± 0.84 mm, P = 0.404; 60 min 8.15 ± 0.90 mm, P = 0.918). Meningeal artery circumference showed no significant change (baseline 4.30 ± 0.83 mm; 30 min 4.47 ± 0.68 mm, P = 0.084; 60 min 4.35 ± 0.78 mm, P = 0.688). Rimegepant did not induce measurable constriction of cerebral or meningeal arteries during spontaneous migraine attacks. These findings support its vascular safety and indicate that effective migraine relief with calcitonin gene-related peptide receptor antagonists does not depend on vasoconstriction, in contrast to triptan therapy.

偏头痛是世界范围内致残的主要原因,而曲坦类药物是最广泛使用的急性治疗药物,通过血管收缩起作用,是血管疾病患者的禁忌症。Rimegepant是一种降钙素基因相关肽受体拮抗剂,被认为是一种非血管收缩的替代药物,但其在自发性偏头痛发作期间对血管的直接影响尚未得到证实。这是一项前瞻性纵向研究,于2024年1月12日至2025年6月10日在一个学术成像中心进行。18名年龄在18-40岁之间的无先兆偏头痛患者被纳入研究。15名参与者在自发性偏头痛发作前、发作后30分钟和60分钟分别完成了高分辨率的3t磁共振血管造影。主要观察指标是脑动脉和脑膜动脉的动脉周长变化。周长以毫米为单位测量,并使用配对样本t检验进行比较。大剂量给药后两支动脉均未见明显血管收缩。脑动脉周长保持稳定(基线8.13±0.93 mm; 30分钟8.02±0.84 mm, P = 0.404; 60分钟8.15±0.90 mm, P = 0.918)。脑膜动脉周长无明显变化(基线4.30±0.83 mm; 30分钟4.47±0.68 mm, P = 0.084; 60分钟4.35±0.78 mm, P = 0.688)。自发性偏头痛发作时,利美吉坦没有引起可测量的脑或脑膜动脉收缩。这些发现支持其血管安全性,并表明与曲坦治疗相比,降钙素基因相关肽受体拮抗剂有效缓解偏头痛不依赖于血管收缩。
{"title":"Investigation of the rimegepant effect on cerebral and extracerebral arteries during migraine attacks: a longitudinal magnetic resonance angiography study.","authors":"Basit Ali Chaudhry, Samaira Younis, Hassan Al-Mashat, Emil Gozalov, Tariq Mohammad Amin, Patrick J H de Koning, Henrik Bo Wiberg Larsson, Faisal Mohammad Amin","doi":"10.1093/braincomms/fcag004","DOIUrl":"10.1093/braincomms/fcag004","url":null,"abstract":"<p><p>Migraine is a leading cause of disability worldwide, and triptans, the most widely used acute treatment, act through vasoconstriction and are contraindicated in patients with vascular disease. Rimegepant, a calcitonin gene-related peptide receptor antagonist, is proposed as a non-vasoconstrictive alternative, but its direct vascular effects during spontaneous migraine attacks have not been examined. This was a prospective, longitudinal study conducted at a single academic imaging centre between 12 January 2024 and 10 June 2025. Eighteen women aged 18-40 years with menstrually related migraine without aura were enrolled. Fifteen participants completed high-resolution 3 T magnetic resonance angiography during a spontaneous migraine attack before, and at 30 and 60 min after, administration of a single 75 mg oral dose of rimegepant. The primary outcome was change in arterial circumference of the cerebral artery and meningeal artery. Circumference was measured in millimetre and compared using paired samples <i>t</i>-tests. No significant vasoconstriction was observed in either artery following rimegepant administration. Cerebral artery circumference remained stable (baseline 8.13 ± 0.93 mm; 30 min 8.02 ± 0.84 mm, <i>P</i> = 0.404; 60 min 8.15 ± 0.90 mm, <i>P</i> = 0.918). Meningeal artery circumference showed no significant change (baseline 4.30 ± 0.83 mm; 30 min 4.47 ± 0.68 mm, <i>P</i> = 0.084; 60 min 4.35 ± 0.78 mm, <i>P</i> = 0.688). Rimegepant did not induce measurable constriction of cerebral or meningeal arteries during spontaneous migraine attacks. These findings support its vascular safety and indicate that effective migraine relief with calcitonin gene-related peptide receptor antagonists does not depend on vasoconstriction, in contrast to triptan therapy.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 1","pages":"fcag004"},"PeriodicalIF":4.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031985","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}
引用次数: 0
Peer review: a collective commitment to knowledge and excellence. 同行评议:对知识和卓越的集体承诺。
IF 4.5 Q1 CLINICAL NEUROLOGY Pub Date : 2026-01-09 eCollection Date: 2026-01-01 DOI: 10.1093/braincomms/fcaf498
David Belin, Tara L Spires-Jones

Our editors discuss the importance of fair and constructive peer review while extending thanks to all those who have contributed their expertise in reviewing manuscripts for Brain Communications.

我们的编辑讨论了公平和建设性同行评议的重要性,同时向所有为《脑通讯》审稿贡献专业知识的人表示感谢。
{"title":"Peer review: a collective commitment to knowledge and excellence.","authors":"David Belin, Tara L Spires-Jones","doi":"10.1093/braincomms/fcaf498","DOIUrl":"10.1093/braincomms/fcaf498","url":null,"abstract":"<p><p>Our editors discuss the importance of fair and constructive peer review while extending thanks to all those who have contributed their expertise in reviewing manuscripts for <i>Brain Communications.</i></p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 1","pages":"fcaf498"},"PeriodicalIF":4.5,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12784156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954334","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}
引用次数: 0
Clinical and genetic determinants of survival in amyotrophic lateral sclerosis patients from North India. 北印度肌萎缩侧索硬化症患者生存的临床和遗传决定因素。
IF 4.5 Q1 CLINICAL NEUROLOGY Pub Date : 2026-01-08 eCollection Date: 2026-01-01 DOI: 10.1093/braincomms/fcag003
Shiffali Khurana, Mandaville Gourie-Devi, Yuvraj Vats, Sagar Verma, Nirmal Kumar Ganguly, Parul Chugh, Ankkita Sharma, Laxmi Khanna, Uma Dhawan, Vibha Taneja

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, with significant clinical and genetic variability. While the role of genetic factors is well-established in ALS pathogenesis, their impact on survival outcomes remains poorly understood, particularly in the Indian population. We performed whole-exome sequencing in 159 ALS patients from North India (familial = 2, sporadic = 157). Clinical parameters, including age at onset, site of onset, sex, family history and survival, were recorded. Males exhibited shorter survival than females, but did not achieve statistical significance (median: 48 versus 60 years, P = 0.05). Bulbar-onset patients developed ALS at a significantly older age (mean: 59.7 versus 54 years, P = 0.007) and experienced poorer survival outcomes than spinal-onset patients (median: 48 versus 60 months, P = 0.03). A small subset of ALS patients (6.3%, n = 10) had very long survival duration of more than 10 years. We identified 102 genetic variants in 92 ALS patients, of which 45 variants were novel. According to American College of Medical Genetics and Genomics guidelines, 13.5% of total variants were pathogenic, 19.8% were likely pathogenic, and 66.7% were variants of uncertain significance. The presence of genetic variations was significantly associated with delayed onset (mean: 53.4 versus 57.1 years, P = 0.049) and diminished life expectancy (median: 48 versus 60 months, P = 0.029). Variations in more than one gene were detected in 16.7% of the patients, supporting the theory of oligogenic basis for ALS. After adjusting for age at onset, increased risk of mortality was associated with males [hazard ratio = 1.740, 95% confidence interval (CI) = 1.105-2.740] and rare genetic variations (hazard ratio = 1.533, 95% CI = 1.001-2.350). Furthermore, bulbar onset (hazard ratio = 1.75, 95% CI = 1.11-2.75) was found to be a negative prognostic factor for survival. Our study provides valuable insights into the genetic complexity and its impact on clinical outcomes in ALS patients of North Indian origin.

肌萎缩性侧索硬化症(ALS)是一种以进行性运动神经元变性为特征的致死性神经退行性疾病,具有显著的临床和遗传变异性。虽然遗传因素在ALS发病机制中的作用已经确立,但它们对生存结果的影响仍然知之甚少,特别是在印度人群中。我们对来自北印度的159例ALS患者(家族性= 2,散发性= 157)进行了全外显子组测序。临床参数包括发病年龄、发病部位、性别、家族史和生存率。男性的生存期短于女性,但无统计学意义(中位数:48年vs 60年,P = 0.05)。球茎起病患者发生ALS的年龄明显大于脊髓起病患者(平均:59.7岁vs 54岁,P = 0.007),且生存期较脊髓起病患者差(中位:48个月vs 60个月,P = 0.03)。一小部分ALS患者(6.3%,n = 10)的生存期非常长,超过10年。我们在92例ALS患者中鉴定出102种遗传变异,其中45种是新发现的。根据美国医学遗传学和基因组学学院的指南,13.5%的变异是致病的,19.8%是可能致病的,66.7%是意义不确定的变异。遗传变异的存在与延迟发病(平均:53.4年对57.1年,P = 0.049)和预期寿命缩短(中位数:48个月对60个月,P = 0.029)显著相关。在16.7%的患者中检测到一个以上基因的变异,支持ALS的寡基因基础理论。在调整发病年龄后,死亡风险增加与男性[风险比= 1.740,95%可信区间(CI) = 1.105-2.740]和罕见遗传变异(风险比= 1.533,95% CI = 1.001-2.350)相关。此外,发现球部发病(风险比= 1.75,95% CI = 1.11-2.75)是生存的一个负面预后因素。我们的研究为北印度裔ALS患者的遗传复杂性及其对临床结果的影响提供了有价值的见解。
{"title":"Clinical and genetic determinants of survival in amyotrophic lateral sclerosis patients from North India.","authors":"Shiffali Khurana, Mandaville Gourie-Devi, Yuvraj Vats, Sagar Verma, Nirmal Kumar Ganguly, Parul Chugh, Ankkita Sharma, Laxmi Khanna, Uma Dhawan, Vibha Taneja","doi":"10.1093/braincomms/fcag003","DOIUrl":"10.1093/braincomms/fcag003","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, with significant clinical and genetic variability. While the role of genetic factors is well-established in ALS pathogenesis, their impact on survival outcomes remains poorly understood, particularly in the Indian population. We performed whole-exome sequencing in 159 ALS patients from North India (familial = 2, sporadic = 157). Clinical parameters, including age at onset, site of onset, sex, family history and survival, were recorded. Males exhibited shorter survival than females, but did not achieve statistical significance (median: 48 versus 60 years, <i>P</i> = 0.05). Bulbar-onset patients developed ALS at a significantly older age (mean: 59.7 versus 54 years, <i>P</i> = 0.007) and experienced poorer survival outcomes than spinal-onset patients (median: 48 versus 60 months, <i>P</i> = 0.03). A small subset of ALS patients (6.3%, <i>n</i> = 10) had very long survival duration of more than 10 years. We identified 102 genetic variants in 92 ALS patients, of which 45 variants were novel. According to American College of Medical Genetics and Genomics guidelines, 13.5% of total variants were pathogenic, 19.8% were likely pathogenic, and 66.7% were variants of uncertain significance. The presence of genetic variations was significantly associated with delayed onset (mean: 53.4 versus 57.1 years, <i>P</i> = 0.049) and diminished life expectancy (median: 48 versus 60 months, <i>P</i> = 0.029). Variations in more than one gene were detected in 16.7% of the patients, supporting the theory of oligogenic basis for ALS. After adjusting for age at onset, increased risk of mortality was associated with males [hazard ratio = 1.740, 95% confidence interval (CI) = 1.105-2.740] and rare genetic variations (hazard ratio = 1.533, 95% CI = 1.001-2.350). Furthermore, bulbar onset (hazard ratio = 1.75, 95% CI = 1.11-2.75) was found to be a negative prognostic factor for survival. Our study provides valuable insights into the genetic complexity and its impact on clinical outcomes in ALS patients of North Indian origin.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 1","pages":"fcag003"},"PeriodicalIF":4.5,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12822497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032052","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}
引用次数: 0
Relational personhood: the missing link for evaluating clinical impact of brain-computer interfaces. 关系人格:评估脑机接口临床影响的缺失环节。
IF 4.5 Q1 CLINICAL NEUROLOGY Pub Date : 2026-01-08 eCollection Date: 2026-01-01 DOI: 10.1093/braincomms/fcaf470
Bouke van Balen, Nick F Ramsey, Mariska J Vansteensel
{"title":"Relational personhood: the missing link for evaluating clinical impact of brain-computer interfaces.","authors":"Bouke van Balen, Nick F Ramsey, Mariska J Vansteensel","doi":"10.1093/braincomms/fcaf470","DOIUrl":"10.1093/braincomms/fcaf470","url":null,"abstract":"","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 1","pages":"fcaf470"},"PeriodicalIF":4.5,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12781884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954326","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}
引用次数: 0
The Functional Neurological Disorder special collection in Brain Communications: bringing FND into the mainstream. 脑通讯中的功能性神经障碍特辑:将FND纳入主流。
IF 4.5 Q1 CLINICAL NEUROLOGY Pub Date : 2026-01-08 eCollection Date: 2026-01-01 DOI: 10.1093/braincomms/fcaf481
Jon Stone

Our Guest Editor, Jon Stone, introduces a special collection of articles focusing on functional neurological disorder.

我们的客座编辑乔恩·斯通介绍了一组特别的关于功能性神经障碍的文章。
{"title":"The Functional Neurological Disorder special collection in <i>Brain Communications</i>: bringing FND into the mainstream.","authors":"Jon Stone","doi":"10.1093/braincomms/fcaf481","DOIUrl":"10.1093/braincomms/fcaf481","url":null,"abstract":"<p><p>Our Guest Editor, Jon Stone, introduces a special collection of articles focusing on functional neurological disorder.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 1","pages":"fcaf481"},"PeriodicalIF":4.5,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12781867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954354","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}
引用次数: 0
Diffusion tensor imaging along the perivascular space and disease progression in people with multiple sclerosis: a 5-year longitudinal MRI study. 多发性硬化症患者血管周围弥散张量成像与疾病进展:一项5年纵向MRI研究
IF 4.5 Q1 CLINICAL NEUROLOGY Pub Date : 2026-01-08 eCollection Date: 2026-01-01 DOI: 10.1093/braincomms/fcag002
Ashley Tranquille, Robert Zivadinov, Bianca Weinstock-Guttman, Svetlana P Eckert, David Hojnacki, Michael G Dwyer, Niels Bergsland

Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS) was originally proposed to quantify glymphatic functioning. Although a direct interpretation is now questioned, cross-sectional studies show associations with disability in people with multiple sclerosis (pwMS). Regardless, serial DTI-ALPS studies are largely lacking in MS. In a longitudinal study, we investigated DTI-ALPS with respect to confirmed disability progression (CDP) and progression independent of relapse activity (PIRA) in people with relapsing-remitting MS (pwRRMS) and progressive MS (pwPMS). This study included 72 pwRRMS, 27 pwPMS, and 23 healthy controls (HC) imaged with 3T MRI and again after 5 years. The DTI-ALPS index was calculated using an automated pipeline using template-defined regions of interest (ROIs) in the superior longitudinal fasciculus and superior corona radiata. Areas corresponding to T2 hyperintensities were removed to avoid the influence of overt pathology. CDP and PIRA were assessed after 5 years and in 64 pwRRMS/17 pwPMS after 10 years. Comparisons between those with and without follow-up CDP or PIRA were assessed using analysis of covariance and repeated including normal appearing white matter (NAWM) mean diffusivity (MD) as an additional covariate. Multivariable binary logistic regression was used to explore whether DTI-ALPS offers independent value beyond general disease burden. Although significantly lower in pwMS compared with HCs (1.347 ± 0.178 versus 1.437 ± 0.132, P = 0.034, partial η 2 = 0.021), the difference was no longer so after controlling for NAWM MD (P = 0.094, partial η 2 = 0.024). DTI-ALPS decreases over 5 years were similar between HC and pwMS (P = 0.188, partial η 2 = 0.021). In pwRRMS, baseline DTI-ALPS was lower in those who developed CDP or PIRA at 5- and 10 years of follow-up (all P ≤ 0.019, partial η 2 > 0.080, except for PIRA at 5 years, P = 0.051, partial η 2 = 0.055). When controlling for NAWM MD, results were in line with original findings. Baseline T2-LV was the only retained imaging predictor of CDP and PIRA over 5 years while only baseline DTI-ALPS was selected for in 10 year models. No associations were found in the pwPMS group. Changes in DTI-ALPS over 5 years did not relate to CDP nor PIRA in neither group. In conclusion, although DTI-ALPS values were not significantly different compared with HCs after considering NAWM MD, decreased baseline DTI-ALPS is associated with disability progression in pwRRMS. The lack of associations in pwPMS suggests that DTI-ALPS may be less informative with more advanced disease.

沿着血管周围空间的弥散张量图像分析(DTI-ALPS)最初被提出用于量化淋巴功能。虽然直接解释现在受到质疑,但横断面研究显示与多发性硬化症(pwMS)患者的残疾有关。在一项纵向研究中,我们调查了DTI-ALPS在复发-缓解型MS (pwRRMS)和进展型MS (pwPMS)患者中确认的残疾进展(CDP)和独立于复发活动的进展(PIRA)方面的影响。本研究包括72名pwRRMS, 27名pwPMS和23名健康对照(HC), 5年后再次进行3T MRI成像。DTI-ALPS指数是使用自动管道计算的,使用模板定义的感兴趣区域(roi)在上纵束和上辐射冠。切除T2高信号区以避免明显病理影响。5年后评估CDP和PIRA, 64名pwRRMS/17名pwPMS在10年后评估CDP和PIRA。采用协方差分析和重复分析,包括正常出现白质(NAWM)平均扩散率(MD)作为附加协变量,对有无随访CDP或PIRA的患者进行比较。采用多变量二元逻辑回归探讨DTI-ALPS是否具有一般疾病负担之外的独立价值。虽然pwMS与hc相比显著降低(1.347±0.178 vs 1.437±0.132,P = 0.034,偏η 2 = 0.021),但在控制NAWM MD后,差异不再存在(P = 0.094,偏η 2 = 0.024)。DTI-ALPS在5年内的下降在HC和pwMS之间相似(P = 0.188,偏η 2 = 0.021)。在pwRRMS中,5年和10年随访时发生CDP或PIRA的患者的基线DTI-ALPS较低(P≤0.019,偏η 2 > 0.080,除了5年随访时发生PIRA, P = 0.051,偏η 2 = 0.055)。当控制NAWM MD时,结果与原始发现一致。基线T2-LV是5年内唯一保留的CDP和PIRA的影像学预测指标,而在10年模型中仅选择基线DTI-ALPS。pwPMS组无相关性。两组患者5年内DTI-ALPS的变化与CDP和PIRA无关。综上所述,尽管在考虑NAWM MD后,DTI-ALPS值与hc相比没有显著差异,但基线DTI-ALPS的降低与pwRRMS的残疾进展有关。在pwPMS中缺乏相关性表明DTI-ALPS对晚期疾病的信息可能较少。
{"title":"Diffusion tensor imaging along the perivascular space and disease progression in people with multiple sclerosis: a 5-year longitudinal MRI study.","authors":"Ashley Tranquille, Robert Zivadinov, Bianca Weinstock-Guttman, Svetlana P Eckert, David Hojnacki, Michael G Dwyer, Niels Bergsland","doi":"10.1093/braincomms/fcag002","DOIUrl":"10.1093/braincomms/fcag002","url":null,"abstract":"<p><p>Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS) was originally proposed to quantify glymphatic functioning. Although a direct interpretation is now questioned, cross-sectional studies show associations with disability in people with multiple sclerosis (pwMS). Regardless, serial DTI-ALPS studies are largely lacking in MS. In a longitudinal study, we investigated DTI-ALPS with respect to confirmed disability progression (CDP) and progression independent of relapse activity (PIRA) in people with relapsing-remitting MS (pwRRMS) and progressive MS (pwPMS). This study included 72 pwRRMS, 27 pwPMS, and 23 healthy controls (HC) imaged with 3T MRI and again after 5 years. The DTI-ALPS index was calculated using an automated pipeline using template-defined regions of interest (ROIs) in the superior longitudinal fasciculus and superior corona radiata. Areas corresponding to T2 hyperintensities were removed to avoid the influence of overt pathology. CDP and PIRA were assessed after 5 years and in 64 pwRRMS/17 pwPMS after 10 years. Comparisons between those with and without follow-up CDP or PIRA were assessed using analysis of covariance and repeated including normal appearing white matter (NAWM) mean diffusivity (MD) as an additional covariate. Multivariable binary logistic regression was used to explore whether DTI-ALPS offers independent value beyond general disease burden. Although significantly lower in pwMS compared with HCs (1.347 ± 0.178 versus 1.437 ± 0.132, <i>P</i> = 0.034, partial <i>η</i> <sup>2</sup> = 0.021), the difference was no longer so after controlling for NAWM MD (<i>P</i> = 0.094, partial <i>η</i> <sup>2</sup> = 0.024). DTI-ALPS decreases over 5 years were similar between HC and pwMS (<i>P</i> = 0.188, partial <i>η</i> <sup>2</sup> = 0.021). In pwRRMS, baseline DTI-ALPS was lower in those who developed CDP or PIRA at 5- and 10 years of follow-up (all <i>P</i> ≤ 0.019, partial <i>η</i> <sup>2</sup> > 0.080, except for PIRA at 5 years, <i>P</i> = 0.051, partial <i>η</i> <sup>2</sup> = 0.055). When controlling for NAWM MD, results were in line with original findings. Baseline T2-LV was the only retained imaging predictor of CDP and PIRA over 5 years while only baseline DTI-ALPS was selected for in 10 year models. No associations were found in the pwPMS group. Changes in DTI-ALPS over 5 years did not relate to CDP nor PIRA in neither group. In conclusion, although DTI-ALPS values were not significantly different compared with HCs after considering NAWM MD, decreased baseline DTI-ALPS is associated with disability progression in pwRRMS. The lack of associations in pwPMS suggests that DTI-ALPS may be less informative with more advanced disease.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 1","pages":"fcag002"},"PeriodicalIF":4.5,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032015","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}
引用次数: 0
Compensatory hallucinogenesis across three neuropsychiatric disorders: a Bayesian account. 三种神经精神疾病的代偿性幻觉发生:贝叶斯解释。
IF 4.5 Q1 CLINICAL NEUROLOGY Pub Date : 2026-01-07 eCollection Date: 2026-01-01 DOI: 10.1093/braincomms/fcag001
Raina Vin, Jordan Galbraith, Rashina Seabury, Hae Young Yi, Gabriela Hernández-Busot, Lucas Oland, Boris Epie, Anne Trainer, Carolyn Fredericks, Albert R Powers

Emerging evidence suggests that hallucinations may arise because of an over-reliance on prior knowledge during perception. While best established in psychosis-spectrum illness, data also support the presence of this abnormality in other hallucination-prone neuropsychiatric illnesses that vary in their association with disruption of sensory circuits. In this piece, we ask whether an over-weighting of expectations may be conceived of as a compensatory response to degraded incoming sensory information. We make the case that visual hallucinogenesis across a wide array of neuropsychiatric disorders can be captured within a common Bayesian computational framework, as a compensatory response to sensory signal disruptions at different levels of the visual processing hierarchy. We focus on three specific disorders (Charles Bonnet syndrome, dementia with Lewy Bodies and psychosis) with prominent visual hallucinations and highlight the fact that these disorders describe a spectrum of visual impairment where the overtness and localization of the visual processing disruption is reflected in the characteristics of the emergent visual hallucinations. We examine how discrete sensory disruptions in Charles Bonnet syndrome translate to hallucinations via known circuits, and then how different disruptions in dementia with Lewy Bodies and Schizophrenia may lead to hallucinations with distinct phenomenology, comorbidities and circuit involvement. Finally, we appeal to emerging computational theories to unite these observations under a common conceptual umbrella. Taken together, this work presents a means of understanding how sensory disruptions could interact with other aspects of cognitive and neural architecture to produce hallucinations across neuropsychiatric disease. It is our hope that this framework will help in efforts to identify pathophysiologically distinct patient subgroups and new pharmacological and circuit-based interventions.

越来越多的证据表明,幻觉可能是由于在感知过程中过度依赖先验知识而产生的。虽然在精神病谱系疾病中得到了最好的证实,但数据也支持在其他容易产生幻觉的神经精神疾病中存在这种异常,这些疾病与感觉回路的破坏有不同的联系。在这篇文章中,我们询问是否期望的过度加权可以被认为是对退化的传入感官信息的补偿性反应。我们认为,在一个共同的贝叶斯计算框架内,可以捕获各种神经精神疾病的视觉幻觉发生,作为对视觉处理层次不同层次的感觉信号中断的代偿反应。我们关注三种特殊的疾病(Charles Bonnet综合征、路易体痴呆和精神病),这些疾病有明显的视觉幻觉,并强调这些疾病描述了一系列视觉障碍,其中视觉处理中断的显性和局部化反映在突发性视觉幻觉的特征中。我们研究了查尔斯·邦纳综合征中离散的感觉中断如何通过已知的回路转化为幻觉,然后研究了路易体痴呆和精神分裂症中不同的感觉中断如何导致具有不同现象学、合并症和回路参与的幻觉。最后,我们呼吁新兴的计算理论将这些观察结果统一在一个共同的概念伞下。综上所述,这项工作提供了一种理解感觉中断如何与认知和神经结构的其他方面相互作用,从而在神经精神疾病中产生幻觉的方法。这是我们的希望,这一框架将有助于努力确定病理生理不同的患者亚组和新的药理学和基于电路的干预措施。
{"title":"Compensatory hallucinogenesis across three neuropsychiatric disorders: a Bayesian account.","authors":"Raina Vin, Jordan Galbraith, Rashina Seabury, Hae Young Yi, Gabriela Hernández-Busot, Lucas Oland, Boris Epie, Anne Trainer, Carolyn Fredericks, Albert R Powers","doi":"10.1093/braincomms/fcag001","DOIUrl":"https://doi.org/10.1093/braincomms/fcag001","url":null,"abstract":"<p><p>Emerging evidence suggests that hallucinations may arise because of an over-reliance on prior knowledge during perception. While best established in psychosis-spectrum illness, data also support the presence of this abnormality in other hallucination-prone neuropsychiatric illnesses that vary in their association with disruption of sensory circuits. In this piece, we ask whether an over-weighting of expectations may be conceived of as a compensatory response to degraded incoming sensory information. We make the case that visual hallucinogenesis across a wide array of neuropsychiatric disorders can be captured within a common Bayesian computational framework, as a compensatory response to sensory signal disruptions at different levels of the visual processing hierarchy. We focus on three specific disorders (Charles Bonnet syndrome, dementia with Lewy Bodies and psychosis) with prominent visual hallucinations and highlight the fact that these disorders describe a spectrum of visual impairment where the overtness and localization of the visual processing disruption is reflected in the characteristics of the emergent visual hallucinations. We examine how discrete sensory disruptions in Charles Bonnet syndrome translate to hallucinations via known circuits, and then how different disruptions in dementia with Lewy Bodies and Schizophrenia may lead to hallucinations with distinct phenomenology, comorbidities and circuit involvement. Finally, we appeal to emerging computational theories to unite these observations under a common conceptual umbrella. Taken together, this work presents a means of understanding how sensory disruptions could interact with other aspects of cognitive and neural architecture to produce hallucinations across neuropsychiatric disease. It is our hope that this framework will help in efforts to identify pathophysiologically distinct patient subgroups and new pharmacological and circuit-based interventions.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 1","pages":"fcag001"},"PeriodicalIF":4.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12835829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095179","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}
引用次数: 0
Attenuated heartbeat-evoked potentials in functional neurological disorder. 功能性神经障碍的心电诱发电位减弱。
IF 4.5 Q1 CLINICAL NEUROLOGY Pub Date : 2026-01-03 eCollection Date: 2026-01-01 DOI: 10.1093/braincomms/fcaf503
Natascha Stoffel, Michaël Mouthon, Hang Yang, Laure von der Weid, Cristina Concetti, Olaf Blanke, Selma Aybek
<p><p>The pathophysiology of functional neurological disorders (FND) has been discussed to include dysfunctions in interoception, the modality about perceiving and processing internal bodily signals. However, findings on abnormal interoception in FND have been inconsistent and mainly limited to measures of accuracy and self-report. Interoceptive neuronal markers have only been investigated in specific symptoms, and interoceptive attentional modulation has been completely overlooked. In a cohort of patients with mixed FND (<i>N</i> = 44) and sex- and age-matched healthy controls (<i>N</i> = 48), we set out to assess first, interoceptive accuracy with an adapted version of the heartbeat counting task; secondly, interoceptive self-report with two different questionnaires (Multidimensional Assessment of Interoceptive Awareness and Interoceptive Accuracy Scale) and thirdly, neuronal trait markers under attention modulation by measuring heartbeat-evoked potentials, the neurophysiological signal related to the heartbeat. We searched for group differences (FND versus controls) across two attentional conditions, by asking participants to either focus on their heartbeat (i.e. interoceptive condition) or an external sound (i.e. exteroceptive control condition). Cardiac covariates (heart rate and heartrate variability or normalized electrocardiac amplitude) were included in the analysis as control. Patients with FND scored lower in both interoceptive self-report questionnaires (<i>P</i> < 0.020), reported higher difficulty concerning the focus towards their heartbeat (<i>P</i> = 0.004), while no significant difference was found in interoceptive accuracy using the heartbeat counting task (<i>P</i> = 0.060). Global field analyses revealed short intervals of a group-by-condition interaction in global field power (285-298 ms) and topographical differences (310-321 ms) confirming that patients with FND have lower overall activity and frontal deactivation during the interoceptive condition. Preselected electrodes for a targeted analysis of the heartbeat-evoked potential based on earlier work revealed a medium effect size attenuation at the frontal-lateralized F8 electrode at 250-595 ms following R-peak for patients with FND (<i>P</i> = 0.028), surviving correction for cardiac covariates. Exploratory analyses further identified an earlier difference at F1 (185-210 ms post-R-peak) in FND patients for interoceptive attention (<i>P</i> = 0.001), also surviving covariate control. While behavioural interoceptive accuracy was marginally preserved, these findings indicate overall altered interoceptive processing in FND, characterized by reduced self-report and difficulty to focus on cardiac signals, along with attenuated neural processes, especially in frontal-lateralized regions that further depend on attentional mechanisms. By identifying objective neural markers of interoceptive dysfunction in FND, this study highlights the involvement of interoception in a multidimens
功能性神经障碍(FND)的病理生理学包括内感受功能障碍,即身体内部信号的感知和处理方式。然而,关于FND异常内感受的研究结果并不一致,主要局限于准确性和自我报告的测量。内感觉神经元标记物仅在特定症状中被研究,而内感觉注意力调节已完全被忽视。在混合FND患者(N = 44)和性别和年龄匹配的健康对照(N = 48)的队列中,我们首先开始评估内感受性准确性,采用了一种改编版本的心跳计数任务;第二,用两种不同的问卷(《内感受意识多维度评估》和《内感受准确性量表》)进行内感受自我报告;第三,通过测量与心跳相关的神经生理信号——心跳诱发电位,观察注意调节下的神经元特征标记。我们通过要求参与者关注他们的心跳(即内感受性条件)或外部声音(即外感受性控制条件)来寻找两种注意力条件下的组差异(FND与对照组)。心脏协变量(心率和心率变异性或归一化心电振幅)被纳入分析作为对照。FND患者在两份内感受性自我报告问卷中得分均较低(P < 0.020),在关注心跳方面的难度较高(P = 0.004),而使用心跳计数任务的内感受性准确性无显著差异(P = 0.060)。整体视野分析显示,在整体视野功率(285-298 ms)和地形差异(310-321 ms)中,组间条件相互作用的间隔较短,证实了FND患者在内感受性条件下整体活动和额叶失活较低。预先选择的电极在早期工作的基础上对心跳诱发电位进行了针对性分析,结果显示,FND患者在r峰后250-595 ms时,额侧F8电极的效应大小呈中等衰减(P = 0.028),对心脏协变量进行了校正。探索性分析进一步确定了FND患者在F1 (r -峰后185-210 ms)的早期差异(P = 0.001),以及存活的共变量控制。虽然行为内感受的准确性略有保留,但这些发现表明,FND的内感受加工总体上发生了变化,其特征是自我报告减少,难以关注心脏信号,同时神经过程减弱,特别是在进一步依赖于注意机制的额侧区域。通过识别FND中内感受功能障碍的客观神经标记,本研究强调了内感受参与包括注意力相关性在内的多维评估。
{"title":"Attenuated heartbeat-evoked potentials in functional neurological disorder.","authors":"Natascha Stoffel, Michaël Mouthon, Hang Yang, Laure von der Weid, Cristina Concetti, Olaf Blanke, Selma Aybek","doi":"10.1093/braincomms/fcaf503","DOIUrl":"10.1093/braincomms/fcaf503","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The pathophysiology of functional neurological disorders (FND) has been discussed to include dysfunctions in interoception, the modality about perceiving and processing internal bodily signals. However, findings on abnormal interoception in FND have been inconsistent and mainly limited to measures of accuracy and self-report. Interoceptive neuronal markers have only been investigated in specific symptoms, and interoceptive attentional modulation has been completely overlooked. In a cohort of patients with mixed FND (&lt;i&gt;N&lt;/i&gt; = 44) and sex- and age-matched healthy controls (&lt;i&gt;N&lt;/i&gt; = 48), we set out to assess first, interoceptive accuracy with an adapted version of the heartbeat counting task; secondly, interoceptive self-report with two different questionnaires (Multidimensional Assessment of Interoceptive Awareness and Interoceptive Accuracy Scale) and thirdly, neuronal trait markers under attention modulation by measuring heartbeat-evoked potentials, the neurophysiological signal related to the heartbeat. We searched for group differences (FND versus controls) across two attentional conditions, by asking participants to either focus on their heartbeat (i.e. interoceptive condition) or an external sound (i.e. exteroceptive control condition). Cardiac covariates (heart rate and heartrate variability or normalized electrocardiac amplitude) were included in the analysis as control. Patients with FND scored lower in both interoceptive self-report questionnaires (&lt;i&gt;P&lt;/i&gt; &lt; 0.020), reported higher difficulty concerning the focus towards their heartbeat (&lt;i&gt;P&lt;/i&gt; = 0.004), while no significant difference was found in interoceptive accuracy using the heartbeat counting task (&lt;i&gt;P&lt;/i&gt; = 0.060). Global field analyses revealed short intervals of a group-by-condition interaction in global field power (285-298 ms) and topographical differences (310-321 ms) confirming that patients with FND have lower overall activity and frontal deactivation during the interoceptive condition. Preselected electrodes for a targeted analysis of the heartbeat-evoked potential based on earlier work revealed a medium effect size attenuation at the frontal-lateralized F8 electrode at 250-595 ms following R-peak for patients with FND (&lt;i&gt;P&lt;/i&gt; = 0.028), surviving correction for cardiac covariates. Exploratory analyses further identified an earlier difference at F1 (185-210 ms post-R-peak) in FND patients for interoceptive attention (&lt;i&gt;P&lt;/i&gt; = 0.001), also surviving covariate control. While behavioural interoceptive accuracy was marginally preserved, these findings indicate overall altered interoceptive processing in FND, characterized by reduced self-report and difficulty to focus on cardiac signals, along with attenuated neural processes, especially in frontal-lateralized regions that further depend on attentional mechanisms. By identifying objective neural markers of interoceptive dysfunction in FND, this study highlights the involvement of interoception in a multidimens","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"8 1","pages":"fcaf503"},"PeriodicalIF":4.5,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12810052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000273","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}
引用次数: 0
期刊
Brain communications
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1