Komm und mach mit! 

Jeden Montagmorgen um 9:30 Uhr Pariser Zeit diskutieren wir mit Kollegen, Studenten und allen, die sich für das Gehirn interessieren, über spannende neue wissenschaftliche Erkenntnisse der letzten Woche.

Verbinden Sie sich live über Zoom:VERKNÜPFUNG
ID: 895 8114 6322, Code: CNS

Frühere Veranstaltungen sind OnDemand auf YouTube verfügbar:  www.youtube.com/c/ClinicalNeuroanatomySeminars

Promoting Open Discussions of Scientific Failure within the Annual Society for Neuroscience Conference The annual Society for Neuroscience (SfN) meeting is a bonanza of scientific achievement: famous keynote speakers, beautiful scientific results, and award ceremonies. This focus is exciting and invigorating but glosses over the many failures, mistakes, and rejections that typically lead to scientific success. Our goal has been to create a space within the annual SfN meeting for open conversation about scientific failure and, by doing so, increase transparency, resilience, and mental well-being within our community. In this article, we share the materials that we have used at SfN during the past 4 years (2021–2024) to promote discussions of scientific failure, including formal storytelling, individual and interactive games, and confessionals. For each activity, we provide the rationale and practical guidance regarding logistics and usage. We hope this will aid scientists interested in adapting the activities for their own communities or local events. We end with a call for scientific institutions to commit to providing space for open discussions of failure within their educational programs and conferences. Paper link: https://www.eneuro.org/content/12/3/ENEURO.0524-24.2024

Paper link: https://direct.mit.edu/nol/article/5/3/676/114495/The-Contributions-of-the-Cerebellar-Peduncles-and Abstract Fluent speech production is a complex task that spans multiple processes, from conceptual framing and lexical access, through phonological encoding, to articulatory control. For the most part, imaging studies portraying the neural correlates of speech fluency tend to examine clinical populations sustaining speech impairments and focus on either lexical access or articulatory control, but not both. Here, we evaluated the contribution of the cerebellar peduncles to speech fluency by measuring the different components of the process in a sample of 45 neurotypical adults. Participants underwent an unstructured interview to assess their natural speaking rate and articulation rate, and completed timed semantic and phonemic fluency tasks to assess their verbal fluency. Diffusion magnetic resonance imaging with probabilistic tractography was used to segment the bilateral cerebellar peduncles (CPs) and frontal aslant tract (FAT), previously associated with speech production in clinical populations. Our results demonstrate distinct patterns of white matter associations with different fluency components. Specifically, verbal fluency is associated with the right superior CP, whereas speaking rate is associated with the right middle CP and bilateral FAT. No association is found with articulation rate in these pathways, in contrast to previous findings in persons who stutter. Our findings support the contribution of the cerebellum to aspects of speech production that go beyond articulatory control, such as lexical access, pragmatic or syntactic generation. Further, we demonstrate that distinct cerebellar pathways dissociate different components of speech fluency in neurotypical speakers. cerebellum, DTI, probabilistic tractography, speaking rate, speech production, white matter

Cell-based therapies hold great promise for brain repair after stroke. While accumulating evidence confirms the preclinical and clinical benefits of cell therapies, the underlying mechanisms by which they promote brain repair remain unclear. Here, we briefly review endogenous mechanisms of brain repair after ischaemic stroke and then focus on how different stem and progenitor cell sources can promote brain repair. Specifically, we examine how transplanted cell grafts contribute to improved functional recovery either through direct cell replacement or by stimulating endogenous repair pathways. Additionally, we discuss recently implemented preclinical refinement methods, such as preconditioning, microcarriers, genetic safety switches and universal (immune evasive) cell transplants, as well as the therapeutic potential of these pharmacologic and genetic manipulations to further enhance the efficacy and safety of cell therapies. By gaining a deeper understanding of post-ischaemic repair mechanisms, prospective clinical trials may be further refined to advance post-stroke cell therapy to the clinic. paper link: https://academic.oup.com/brain/article/147/10/3286/7698450

Paper link: https://pmc.ncbi.nlm.nih.gov/articles/PMC10570710 Neural evidence for procedural automatization during cognitive development: Intraparietal response to changes in very-small addition problem-size increases with age Cognitive development is often thought to depend on qualitative changes in problem-solving strategies, with early developing algorithmic procedures (e.g., counting when adding numbers) considered being replaced by retrieval of associations (e.g., between operands and answers of addition problems) in adults. However, algorithmic procedures might also become automatized with practice. In a large cross-sectional fMRI study from age 8 to adulthood (n = 128), we evaluate this hypothesis by measuring neural changes associated with age-related reductions in a behavioral hallmark of mental addition, the problem-size effect (an increase in solving time as problem sum increases). We found that age-related decreases in problem-size effect were paralleled by age-related increases of activity in a region of the intraparietal sulcus that already supported the problem-size effect in 8- to 9-year-olds, at an age the effect is at least partly due to explicit counting. This developmental effect, which was also observed in the basal ganglia and prefrontal cortex, was restricted to problems with operands ≤ 4. These findings are consistent with a model positing that very-small arithmetic problems–and not larger problems–might rely on an automatization of counting procedures rather than a shift towards retrieval, and suggest a neural automatization of procedural knowledge during cognitive development. Keywords: Development, Arithmetic, Procedure, Problem-size effect, FMRI

Adaptive deep brain stimulation (aDBS) is an emerging advancement in DBS technology; however, local field potential (LFP) signal rate detection sufficient for aDBS algorithms and the methods to set-up aDBS have yet to be defined. Here we summarize sensing data and aDBS programming steps associated with the ongoing Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) pivotal trial (NCT04547712). Sixty-eight patients were enrolled with either subthalamic nucleus or globus pallidus internus DBS leads connected to a Medtronic PerceptTM PC neurostimulator. During the enrollment and screening procedures, a LFP (8–30 Hz, ≥1.2 µVp) control signal was identified by clinicians in 84.8% of patients on medication (65% bilateral signal), and in 92% of patients off medication (78% bilateral signal). The ADAPT-PD trial sensing data indicate a high LFP signal presence in both on and off medication states of these patients, with bilateral signal in the majority, regardless of PD phenotype. Paper link: https://www.nature.com/articles/s41531-024-00772-5

Conducting Research with Highly Portable MRI in Community Settings: A Practical Guide to Navigating Ethical Issues and ELSI Checklist Highly portable and accessible MRI technology will allow researchers to conduct field-based MRI research in community settings. Previous guidance for researchers working with fixed MRI does not address the novel ethical, legal, and societal issues (ELSI) of portable MRI (pMRI). Our interdisciplinary Working Group (WG) previously identified 15 core ELSI challenges associated with pMRI research and recommended solutions. In this article, we distill those detailed recommendations into a Portable MRI Research ELSI Checklist that offers practical operational guidance for researchers contemplating using this technology. Paper link: https://www.cambridge.org/core/journals/journal-of-law-medicine-and-ethics/article/conducting-research-with-highly-portable-mri-in-community-settings-a-practical-guide-to-navigating-ethical-issues-and-elsi-checklist/0C7A788A41C1FA0D85E96CE27352C591 Octoberfest mobile scanning: https://www.nejm.org/doi/full/10.1056/NEJMc2306490

Human intraparietal sulcal morphology relates to individual differences in language and memory performance The sulco-gyral pattern is a qualitative feature of the cortical anatomy that is determined in utero, stable throughout lifespan and linked to brain function. The intraparietal sulcus (IPS) is a nodal associative brain area, but the relation between its morphology and cognition is largely unknown. By labelling the left and right IPS of 390 healthy participants into two patterns, according to the presence or absence of a sulcus interruption, here we demonstrate a strong association between the morphology of the right IPS and performance on memory and language tasks. We interpret the results as a morphological advantage of a sulcus interruption, probably due to the underlying white matter organization. The right-hemisphere specificity of this effect emphasizes the neurodevelopmental and plastic role of sulcus morphology in cognition prior to lateralisation processes. The results highlight a promising area of investigation on the relationship between cognitive performance, sulco-gyral pattern and white matter bundles. Paper link: https://www.nature.com/articles/s42003-024-06175-9

Paper link: https://www.eneuro.org/content/11/5/ENEURO.0408-23.2024 Abstract Singing-based treatments of aphasia can improve language outcomes, but the neural benefits of group-based singing in aphasia are unknown. Here, we set out to determine the structural neuroplasticity changes underpinning group-based singing-induced treatment effects in chronic aphasia. Twenty-eight patients with at least mild nonfluent poststroke aphasia were randomized into two groups that received a 4-month multicomponent singing intervention (singing group) or standard care (control group). High-resolution T1 images and multishell diffusion-weighted MRI data were collected in two time points (baseline/5 months). Structural gray matter (GM) and white matter (WM) neuroplasticity changes were assessed using language network region of interest-based voxel-based morphometry (VBM) and quantitative anisotropy-based connectometry, and their associations to improved language outcomes (Western Aphasia Battery Naming and Repetition) were evaluated. Connectometry analyses showed that the singing group enhanced structural WM connectivity in the left arcuate fasciculus (AF) and corpus callosum as well as in the frontal aslant tract (FAT), superior longitudinal fasciculus, and corticostriatal tract bilaterally compared with the control group. Moreover, in VBM, the singing group showed GM volume increase in the left inferior frontal cortex (Brodmann area 44) compared with the control group. The neuroplasticity effects in the left BA44, AF, and FAT correlated with improved naming abilities after the intervention. These findings suggest that in the poststroke aphasia group, singing can bring about structural neuroplasticity changes in left frontal language areas and in bilateral language pathways, which underpin treatment-induced improvement in speech production.

Paper link https://academic.oup.com/brain/article/146/3/1212/6661441?login=false Abstract There are currently no non-invasive imaging methods available for astrogliosis assessment or mapping in the central nervous system despite its essential role in the response to many disease states, such as infarcts, neurodegenerative conditions, traumatic brain injury and infection. Multidimensional MRI is an increasingly employed imaging modality that maximizes the amount of encoded chemical and microstructural information by probing relaxation (T1 and T2) and diffusion mechanisms simultaneously. Here, we harness the exquisite sensitivity of this imagining modality to derive a signature of astrogliosis and disentangle it from normative brain at the individual level using machine learning. We investigated ex vivo cerebral cortical tissue specimens derived from seven subjects who sustained blast-induced injuries, which resulted in scar-border forming astrogliosis without being accompanied by other types of neuropathological abnormality, and from seven control brain donors. By performing a combined post-mortem radiology and histopathology correlation study we found that astrogliosis induces microstructural and chemical changes that are robustly detected with multidimensional MRI, and which can be attributed to astrogliosis because no axonal damage, demyelination or tauopathy were histologically observed in any of the cases in the study. Importantly, we showed that no one-dimensional T1, T2 or diffusion MRI measurement can disentangle the microscopic alterations caused by this neuropathology. Based on these findings, we developed a within-subject anomaly detection procedure that generates MRI-based astrogliosis biomarker maps ex vivo, which were significantly and strongly correlated with co-registered histological images of increased glial fibrillary acidic protein deposition. Our findings elucidate the underpinning of MRI signal response from astrogliosis, and the demonstrated high spatial sensitivity and specificity in detecting reactive astrocytes at the individual level, and if reproduced in vivo, will significantly impact neuroimaging studies of injury, disease, repair and aging, in which astrogliosis has so far been an invisible process radiologically.

Paper link: https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awae343/7916407 Abstract Although both central and peripheral inflammation have been observed consistently in depression, the relationship between the two remains obscure. Extra-axial immune cells may play a role in mediating the connection between central and peripheral immunity. This study investigates the potential roles of calvarial bone marrow and parameningeal spaces in mediating interactions between central and peripheral immunity in depression. PET was used to measure regional TSPO expression in the skull and parameninges as a marker of inflammatory activity. This measure was correlated with brain TSPO expression and peripheral cytokine concentrations in a cohort enriched for heightened peripheral and central immunity comprising 51 individuals with depression and 25 healthy controls. The findings reveal a complex relationship between regional skull TSPO expression and both peripheral and central immunity. Facial and parietal skull bone TSPO expression showed significant associations with both peripheral and central immunity. TSPO expression in the confluence of sinuses was also linked to both central and peripheral immune markers. Group-dependent elevations in TSPO expression within the occipital skull bone marrow were also found to be significantly associated with central inflammation. Significant associations between immune activity within the skull, parameninges, parenchyma and periphery highlight the role of the skull bone marrow and venous sinuses as pivotal sites for peripheral and central immune interactions.

Paper link: https://www.bmj.com/content/387/bmj-2024-081948 Objective To evaluate the cognitive abilities of the leading large language models and identify their susceptibility to cognitive impairment, using the Montreal Cognitive Assessment (MoCA) and additional tests. Design Cross sectional analysis. Setting Online interaction with large language models via text based prompts. Participants Publicly available large language models, or “chatbots”: ChatGPT versions 4 and 4o (developed by OpenAI), Claude 3.5 “Sonnet” (developed by Anthropic), and Gemini versions 1 and 1.5 (developed by Alphabet). Assessments The MoCA test (version 8.1) was administered to the leading large language models with instructions identical to those given to human patients. Scoring followed official guidelines and was evaluated by a practising neurologist. Additional assessments included the Navon figure, cookie theft picture, Poppelreuter figure, and Stroop test. Main outcome measures MoCA scores, performance in visuospatial/executive tasks, and Stroop test results. Results ChatGPT 4o achieved the highest score on the MoCA test (26/30), followed by ChatGPT 4 and Claude (25/30), with Gemini 1.0 scoring lowest (16/30). All large language models showed poor performance in visuospatial/executive tasks. Gemini models failed at the delayed recall task. Only ChatGPT 4o succeeded in the incongruent stage of the Stroop test. Conclusions With the exception of ChatGPT 4o, almost all large language models subjected to the MoCA test showed signs of mild cognitive impairment. Moreover, as in humans, age is a key determinant of cognitive decline: “older” chatbots, like older patients, tend to perform worse on the MoCA test. These findings challenge the assumption that artificial intelligence will soon replace human doctors, as the cognitive impairment evident in leading chatbots may affect their reliability in medical diagnostics and undermine patients’ confidence.

paper link: https://www.nature.com/articles/s41592-024-02472-7 In vivo imaging of the human brain with the Iseult 11.7-T MRI scanner The understanding of the human brain is one of the main scientific challenges of the twenty-first century. In the early 2000s, the French Atomic Energy Commission launched a program to conceive and build a human magnetic resonance imaging scanner operating at 11.7 T. We have now acquired human brain images in vivo at such a magnetic field. We deployed parallel transmission tools to mitigate the radiofrequency field inhomogeneity problem and tame the specific absorption rate. The safety of human imaging at such high field strength was demonstrated using physiological, vestibular, behavioral and genotoxicity measurements on the imaged volunteers. Our technology yields T2 and T2*-weighted images reaching mesoscale resolutions within short acquisition times and with a high signal and contrast-to-noise ratio.

Paper link: https://www.nature.com/articles/s41593-024-01787-0

Paper link: https://www.nature.com/articles/s41562-024-02046-9 Scientific discoveries often hinge on synthesizing decades of research, a task that potentially outstrips human information processing capacities. Large language models (LLMs) offer a solution. LLMs trained on the vast scientific literature could potentially integrate noisy yet interrelated findings to forecast novel results better than human experts. Here, to evaluate this possibility, we created BrainBench, a forward-looking benchmark for predicting neuroscience results. We find that LLMs surpass experts in predicting experimental outcomes. BrainGPT, an LLM we tuned on the neuroscience literature, performed better yet. Like human experts, when LLMs indicated high confidence in their predictions, their responses were more likely to be correct, which presages a future where LLMs assist humans in making discoveries. Our approach is not neuroscience specific and is transferable to other knowledge-intensive endeavours.

Paper link: https://www.nature.com/articles/s41559-021-01391-6 The study of audition in fossil hominins is of great interest given its relationship with intraspecific vocal communication. While the auditory capacities have been studied in early hominins and in the Middle Pleistocene Sima de los Huesos hominins, less is known about the hearing abilities of the Neanderthals. Here, we provide a detailed approach to their auditory capacities. Relying on computerized tomography scans and a comprehensive model from the field of auditory bioengineering, we have established sound power transmission through the outer and middle ear and calculated the occupied bandwidth in Neanderthals. The occupied bandwidth is directly related to the efficiency of the vocal communication system of a species. Our results show that the occupied bandwidth of Neanderthals was greater than the Sima de los Huesos hominins and similar to extant humans, implying that Neanderthals evolved the auditory capacities to support a vocal communication system as efficient as modern human speech.

Paper link: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002492 Stuttering occurs in early childhood during a dynamic phase of brain and behavioral development. The latest studies examining children at ages close to this critical developmental period have identified early brain alterations that are most likely linked to stuttering, while spontaneous recovery appears related to increased inter-area connectivity. By contrast, therapy-driven improvement in adults is associated with a functional reorganization within and beyond the speech network. The etiology of stuttering, however, remains enigmatic. This Unsolved Mystery highlights critical questions and points to neuroimaging findings that could inspire future research to uncover how genetics, interacting neural hierarchies, social context, and reward circuitry contribute to the many facets of stuttering.

Paper link: https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(24)00038-3/fulltext Background Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed.

The two-network framework of number processing: a step towards a better understanding of the neural origins of developmental dyscalculia Developmental dyscalculia is a specific learning disorder that persists over lifetime and can have an enormous impact on personal, health-related, and professional aspects of life. Despite its central importance, the origin both at the cognitive and neural level is not yet well understood. Several classification schemas of dyscalculia have been proposed, sometimes together with an associated deficit at the neural level. However, these explanations are (a) not providing an exhaustive framework that is at levels with the observed complexity of developmental dyscalculia at the behavioral level and (b) are largely mono-causal approaches focusing on gray matter deficits. We suggest that number processing is instead the result of context-dependent interaction of two anatomically largely separate, distributed but overlapping networks that function/cooperate in a closely integrated fashion. The proposed two-network framework (TNF) is the result of a series of studies in adults on the neural correlates underlying magnitude processing and arithmetic fact retrieval, which comprised neurofunctional imaging of various numerical tasks, the application of probabilistic fiber tracking to obtain well-defined connections, and the validation and modification of these results using disconnectome mapping in acute stroke patients. Emerged from data in adults, it represents the endpoint of the acquisition and use of mathematical competencies in adults. Yet, we argue that its main characteristics should already emerge earlier during development. Based on this TNF, we develop a classification schema of phenomenological subtypes and their underlying neural origin that we evaluate against existing propositions and the available empirical data. Paper link: https://link.springer.com/article/10.1007/s00702-022-02580-8

Paper link: https://academic.oup.com/brain/article/147/10/3286/7698450

Paper link: https://www.pnas.org/doi/10.1073/pnas.2403200121 Significance We report that the lockdown measures enacted during the COVID-19 pandemic resulted in unusually accelerated brain maturation in adolescents and that this accelerated maturation was much more pronounced in females than in males. These findings indicate greater vulnerability of the female brain, as compared to the male brain, to the lifestyle changes resulting from the pandemic lockdowns. They additionally provide a potential neurophysiological mechanism for alterations in adolescent mental health and other behaviors associated with the lockdowns. Since accelerated brain maturation has been associated with increased risk for the development of neuropsychiatric and behavioral disorders, these findings highlight the importance of providing ongoing monitoring and support to individuals who were adolescents during the COVID-19 pandemic. Abstract Adolescence is a period of substantial social–emotional development, accompanied by dramatic changes to brain structure and function. Social isolation due to lockdowns that were imposed because of the COVID-19 pandemic had a detrimental impact on adolescent mental health, with the mental health of females more affected than males. We assessed the impact of the COVID-19 pandemic lockdowns on adolescent brain structure with a focus on sex differences. We collected MRI structural data longitudinally from adolescents prior to and after the pandemic lockdowns. The pre-COVID data were used to create a normative model of cortical thickness change with age during typical adolescent development. Cortical thickness values in the post-COVID data were compared to this normative model. The analysis revealed accelerated cortical thinning in the post-COVID brain, which was more widespread throughout the brain and greater in magnitude in females than in males. When measured in terms of equivalent years of development, the mean acceleration was found to be 4.2 y in females and 1.4 y in males. Accelerated brain maturation as a result of chronic stress or adversity during development has been well documented. These findings suggest that the lifestyle disruptions associated with the COVID-19 pandemic lockdowns caused changes in brain biology and had a more severe impact on the female than the male brain.

Paper link: https://www.mpi.nl/publications/item2287091/recherches-cliniques-propres-demontrer-que-la-perte-de-la-parole Bouillaud, J. (1825). Recherches cliniques propres à démontrer que la perte de la parole correspond à la lésion des lobules antérieures du cerveau, et à confirmer l’opinion de M. Gall sur le siège de l’organe du language articulé. Archives Généralede Médecine, 3, 25-45.

Paper link: https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awae235/7729174?login=false Developmental dyslexia (DD) is one of the most common learning disorders, affecting millions of children and adults worldwide. To date, scientific research has attempted to explain DD primarily based on pathophysiological alterations in the cerebral cortex. In contrast, several decades ago, pioneering research on five post-mortem human brains suggested that a core characteristic of DD might be morphological alterations in a specific subdivision of the visual thalamus—the magnocellular lateral geniculate nucleus (M-LGN). However, due to considerable technical challenges in investigating LGN subdivisions non-invasively in humans, this finding was never confirmed in vivo, and its relevance for DD pathology remained highly controversial. Here, we leveraged recent advances in high resolution MRI at high field strength (7 T) to investigate the M-LGN in DD in vivo. Using a case-control design, we acquired data from a large sample of young adults with DD (n = 26; age 28 ± 7 years; 13 females) and matched control participants (n = 28; age 27 ± 6 years; 15 females). Each participant completed a comprehensive diagnostic behavioural test battery and participated in two MRI sessions, including three functional MRI experiments and one structural MRI acquisition. We measured blood oxygen level-dependent responses and longitudinal relaxation rates to compare both groups on LGN subdivision function and myelination. Based on previous research, we hypothesized that the M-LGN is altered in DD and that these alterations are associated with a key DD diagnostic score, i.e. rapid letter and number naming. The results showed aberrant responses of the M-LGN in DD compared to controls, which was reflected in a different functional lateralization of this subdivision between groups. These alterations were associated with rapid letter and number naming performance, specifically in male DD. We also found lateralization differences in the longitudinal relaxation rates of the M-LGN in DD relative to controls. Conversely, the other main subdivision of the LGN, the parvocellular LGN (P-LGN), showed comparable blood oxygen level-dependent responses and longitudinal relaxation rates between groups. The present study is the first to unequivocally show that M-LGN alterations are a hallmark of DD, affecting both the function and microstructure of this subdivision. It further provides a first functional interpretation of M-LGN alterations and a basis for a better understanding of sex-specific differences in DD with implications for prospective diagnostic and treatment strategies.

Paper link: https://www.nature.com/articles/s41586-024-07643-2 Abstract From sequences of speech sounds1,2 or letters3, humans can extract rich and nuanced meaning through language. This capacity is essential for human communication. Yet, despite a growing understanding of the brain areas that support linguistic and semantic processing4,5,6,7,8,9,10,11,12, the derivation of linguistic meaning in neural tissue at the cellular level and over the timescale of action potentials remains largely unknown. Here we recorded from single cells in the left language-dominant prefrontal cortex as participants listened to semantically diverse sentences and naturalistic stories. By tracking their activities during natural speech processing, we discover a fine-scale cortical representation of semantic information by individual neurons. These neurons responded selectively to specific word meanings and reliably distinguished words from nonwords. Moreover, rather than responding to the words as fixed memory representations, their activities were highly dynamic, reflecting the words’ meanings based on their specific sentence contexts and independent of their phonetic form. Collectively, we show how these cell ensembles accurately predicted the broad semantic categories of the words as they were heard in real time during speech and how they tracked the sentences in which they appeared. We also show how they encoded the hierarchical structure of these meaning representations and how these representations mapped onto the cell population. Together, these findings reveal a finely detailed cortical organization of semantic representations at the neuron scale in humans and begin to illuminate the cellular-level processing of meaning during language comprehension.