Come and join us! 
Monday mornings at 9:30 am Amsterdam time,
we discuss exciting new science from last week with colleagues,
students and everyone interested in the brain.
Previous events are available OnDemand on YouTube:  https://www.youtube.com/@CNSeminars

Synthetic Diffusion Tensor Imaging Maps Generated by 2D and 3D Probabilistic Diffusion Models: Evaluation and Applications Diffusion tensor imaging (DTI) is a key neuroimaging modality for assessing brain tissue microstructure, yet high-quality acquisitions are costly, time-intensive, and prone to artifacts. To address data scarcity and privacy concerns – and to augment the available data for training deep learning methods – synthetic DTI generation has gained interest. Specifically, denoising diffusion probabilistic models (DDPMs) have emerged as a promising approach due to their superior fidelity, diversity, controllability, and stability compared to generative adversarial networks (GANs) and variational autoencoders (VAEs). In this work, we evaluate the quality, fidelity and added value for downstream applications of synthetic DTI mean diffusivity (MD) maps generated by 2D slice-wise and 3D volume-wise DDPMs. We evaluate their computational efficiency and utility for data augmentation in two downstream tasks: sex classification and dementia classification using 2D and 3D convolutional neural networks (CNNs). Our findings show that 3D synthesis outperforms 2D slice-wise generation in downstream tasks. We present a benchmark analysis of synthetic diffusion-weighted imaging approaches, highlighting key trade-offs in image quality, diversity, efficiency, and downstream performance. Paper link: https://www.biorxiv.org/content/10.1101/2025.02.21.639511v1

Auditory and speech signals are undisputedly processed in both left and right hemispheres, but this bilateral allocation is likely unequal. The Asymmetric Sampling in Time (AST) hypothesis proposed a division of labor that has its neuroanatomical basis in the distribution of neuronal ensembles with differing temporal integration constants: left auditory areas house a larger proportion of ensembles with shorter temporal integration windows (tens of milliseconds), suited to process rapidly changing signals; right auditory areas host a larger proportion with longer time constants (∼150–300 ms), ideal for slowly changing signals. Here we evaluate the large body of findings that clarifies this relationship between auditory temporal structure and functional lateralization. In this reappraisal, we unpack whether this relationship is influenced by stimulus type (speech/nonspeech), stimulus temporal extent (long/short), task engagement (high/low), or (imaging) modality (hemodynamic/electrophysiology/behavior). We find that the right hemisphere displays a clear preference for slowly changing signals whereas the left-hemispheric preference for rapidly changing signals is highly dependent on the experimental design. We consider neuroanatomical properties potentially linked to functional lateralization, contextualize the results in an evolutionary perspective, and highlight future directions. Paper link: https://doi.org/10.1016/j.neubiorev.2025.106082

Electrophysiological signatures underlying variability in human memory consolidation We experience countless pieces of new information each day, but remembering them later depends on firmly instilling memory storage in the brain. Numerous studies have implicated non-rapid eye movement (NREM) sleep in consolidating memories via interactions between hippocampus and cortex. However, the temporal dynamics of this hippocampal-cortical communication and the concomitant neural oscillations during memory reactivations remains unclear. To address this issue, the present study used the procedure of targeted memory reactivation (TMR) following learning of object-location associations to selectively reactivate memories during human NREM sleep. Cortical pattern reactivation and hippocampal-cortical coupling were measured with intracranial EEG recordings in patients with epilepsy. We found that TMR produced variable amounts of memory enhancement across a set of object-location associations. Successful TMR increased hippocampal ripples and cortical spindles, apparent during two discrete sweeps of reactivation. The first reactivation sweep was accompanied by increased hippocampal-cortical communication and hippocampal ripple events coupled to local cortical activity (cortical ripples and high-frequency broadband activity). In contrast, hippocampal-cortical coupling decreased during the second sweep, while increased cortical spindle activity indicated continued cortical processing to achieve long-term storage. Taken together, our findings show how dynamic patterns of item-level reactivation and hippocampal-cortical communication support memory enhancement during NREM sleep. Paper link: https://www.nature.com/articles/s41467-025-57766-x#Abs1 Presenter: Dr Marcela Ovando-Tellez

At the heart of medicine lies physician–patient dialogue, where skillful history-taking enables effective diagnosis, management and enduring trust1,2. Artificial intelligence (AI) systems capable of diagnostic dialogue could increase accessibility and quality of care. However, approximating clinicians’ expertise is an outstanding challenge. Here we introduce AMIE (Articulate Medical Intelligence Explorer), a large language model (LLM)-based AI system optimized for diagnostic dialogue. AMIE uses a self-play-based3 simulated environment with automated feedback for scaling learning across disease conditions, specialties and contexts. We designed a framework for evaluating clinically meaningful axes of performance, including history-taking, diagnostic accuracy, management, communication skills and empathy. We compared AMIE’s performance to that of primary care physicians in a randomized, double-blind crossover study of text-based consultations with validated patient-actors similar to objective structured clinical examination4,5. The study included 159 case scenarios from providers in Canada, the United Kingdom and India, 20 primary care physicians compared to AMIE, and evaluations by specialist physicians and patient-actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 30 out of 32 axes according to the specialist physicians and 25 out of 26 axes according to the patient-actors. Our research has several limitations and should be interpreted with caution. Clinicians used synchronous text chat, which permits large-scale LLM–patient interactions, but this is unfamiliar in clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI. Paper link: https://www.nature.com/articles/s41586-025-08866-7

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