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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.

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ID: 895 8114 6322, Code: CNS
Previous events are available OnDemand on YouTube:  www.youtube.com/c/ClinicalNeuroanatomySeminars

Neuroccino 7th October 2024 - Covid-19, cortical thickness, and ageing
33:38
Clinical Neuroanatomy Seminars

Neuroccino 7th October 2024 - Covid-19, cortical thickness, and ageing

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.
Neuroccino 23rd September - developmental dyslexia
32:58
Clinical Neuroanatomy Seminars

Neuroccino 23rd September - developmental dyslexia

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.
Neuroccino 16th September 2024 - Semantic encoding at the single cell level
34:35
Clinical Neuroanatomy Seminars

Neuroccino 16th September 2024 - Semantic encoding at the single cell level

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.
Neuroccino 2nd September - New Digital Cerebellar Atlas
25:18
Clinical Neuroanatomy Seminars

Neuroccino 2nd September - New Digital Cerebellar Atlas

The Human Cerebellum: A Digital Anatomical Atlas at the Level of Individual Folia John G. Samuelsson, Jeremy D. Schmahmann, Martin Sereno, Bruce Rosen, Matti S. Hämäläinen doi: https://doi.org/10.1101/2024.08.27.610006 Scientific interest in the cerebellum has surged in the last few decades with an emerging consensus on a multifaceted functionality and intricate, but not yet fully understood, functional topography over the cerebellar cortex. To further refine this structure-function relationship and quantify its inter-subject variability, a high-resolution digital anatomical atlas is fundamental. Using a combination of manual labeling and image processing, we turned a recently published reconstruction of the human cerebellum, the first such reconstruction fine enough to resolve the individual folia, into a digital atlas with both surface and volumetric representations. Its unprecedented granularity (0.16 mm) and detailed expert labeling make the atlas usable as an anatomical ground truth, enabling new ways of analyzing and visualizing cerebellar data through its digital format. Paper link: https://www.biorxiv.org/content/10.1101/2024.08.27.610006v1 Sereno 2020: https://www.pnas.org/doi/full/10.1073/pnas.2002896117 Other YouTUBe talks on the cerebellum: 1. Fibre dissection of deep cerebellar nuclei and cerebellar peduncles - Nupur Pruthi https://www.youtube.com/watch?v=J1ck8bg7z3c&t=493s 2. Fiber dissection technique: dissection of the brainstem - Carlo Serra https://www.youtube.com/watch?v=GHFqiH2u9uk&t=6s
Neuroccino 26th August 2024 - Tractography from T1-weighted MRI: streamlines without diffusion MRI
32:09
Clinical Neuroanatomy Seminars

Neuroccino 26th August 2024 - Tractography from T1-weighted MRI: streamlines without diffusion MRI

Tractography from T1-weighted MRI: Empirically exploring the clinical viability of streamline propagation without diffusion MRI Paper link: https://doi.org/10.1162/imag_a_00259 Abstract: Over the last few decades, diffusion MRI (dMRI) streamline tractography has emerged as the dominant method for in vivo estimation of white matter (WM) pathways in the brain. One key limitation to this technique is that modern tractography implementations require high angular resolution diffusion imaging (HARDI). However, HARDI can be difficult to collect clinically, limiting the reach of tractography analyses to research cohorts and thus limiting many WM investigations to certain populations and pathologies. As such, a clinically viable tractography solution applicable to wider patient populations scanned as a part of routine care would be of key significance in broadening WM analyses to underfunded or rarer diseases and to the clinical setting. Such a solution would require the ability to perform arbitrary tractography analyses, use only clinical imaging for input, and be open source and widely accessible and implementable. Thus, here we evaluate our recently developed, containerized, and open-source, T1-weighted (T1w) MRI-based deep learning model for streamline propagation. We empirically assess its performance against traditional dMRI-based and established atlas-based approaches in a healthy young population, an aging one, and in those with epilepsy, depression, and brain cancer. In the healthy young population, we find slightly increased error compared to traditional tractography with the deep learning model that falls within the bounds attributable to dMRI variability and is considerably less than the atlas-based approach. Further, seeking to replicate previously published dMRI tractography effects in the remaining cohorts as an initial assessment of clinical viability, we find this model successfully does so in some key cases—particularly in applications that rely on long-range streamlines including those not captured by the atlas-based approach—but importantly not all. These results suggest a deep learning-based approach to tractography with T1w MRI demonstrates promise within the limitations of our definition of clinical viability and especially over atlas-based approaches but requires refinement and more robust consideration of out-of-distribution effects prior to widespread clinical use. We also find these results raise additional questions regarding the differences in image content between dMRI and T1w MRI and their relationship to tractography. Further investigation of these questions will improve the field’s understanding of which features of the brain influence measured tractography effects. diffusion MRI, T1-weighted MRI, streamline tractography, open-source software, white matter, convolutional recurrent neural networks, CoRNN, #Tractography from #T1-weighted #MRI: Empirically exploring the #clinical viability of streamline propagation without #diffusion MRI
Neuroccino 10th June 2024 - Language & Ageing
29:42
Clinical Neuroanatomy Seminars

Neuroccino 10th June 2024 - Language & Ageing

Hemispheric dissociations in regions supporting auditory sentence comprehension in older adults Paper link: https://www.sciencedirect.com/science/article/pii/S2589958922000238?via%3Dihub Abstract We investigated how the aging brain copes with acoustic and syntactic challenges during spoken language comprehension. Thirty-eight healthy adults aged 54 – 80 years (M = 66 years) participated in an fMRI experiment wherein listeners indicated the gender of an agent in short spoken sentences that varied in syntactic complexity (object-relative vs subject-relative center-embedded clause structures) and acoustic richness (high vs low spectral detail, but all intelligible). We found widespread activity throughout a bilateral frontotemporal network during successful sentence comprehension. Consistent with prior reports, bilateral inferior frontal gyrus and left posterior superior temporal gyrus were more active in response to object-relative sentences than to subject-relative sentences. Moreover, several regions were significantly correlated with individual differences in task performance: Activity in right frontoparietal cortex and left cerebellum (Crus I & II) showed a negative correlation with overall comprehension. By contrast, left frontotemporal areas and right cerebellum (Lobule VII) showed a negative correlation with accuracy specifically for syntactically complex sentences. In addition, laterality analyses confirmed a lack of hemispheric lateralization in activity evoked by sentence stimuli in older adults. Importantly, we found different hemispheric roles, with a left-lateralized core language network supporting syntactic operations, and right-hemisphere regions coming into play to aid in general cognitive demands during spoken sentence processing. Together our findings support the view that high levels of language comprehension in older adults are maintained by a close interplay between a core left hemisphere language network and additional neural resources in the contralateral hemisphere.
Neuroccino 27th May 2024 - Responses to emotional linguistic stimuli predict brain injury outcome
24:44
Clinical Neuroanatomy Seminars

Neuroccino 27th May 2024 - Responses to emotional linguistic stimuli predict brain injury outcome

Autonomic responses to emotional linguistic stimuli and amplitude of low-frequency fluctuations predict outcome after severe brain injury An accurate prognosis on the outcome of brain-injured patients with disorders of consciousness (DOC) remains a significant challenge, especially in the acute stage. In this study, we applied a multiple-technique approach to provide accurate predictions on functional outcome after 6 months in 15 acute DOC patients. Electrophysiological correlates of implicit cognitive processing of verbal stimuli and data-driven voxel-wise resting-state fMRI signals, such as the fractional amplitude of low-frequency fluctuations (fALFF), were employed. Event-related electrodermal activity, an index of autonomic activation, was recorded in response to emotional words and pseudo-words at baseline (T0). On the same day, patients also underwent a resting-state fMRI scan. Six months later (T1), patients were classified as outcome-negative and outcome-positive using a standard functional outcome scale. We then revisited the baseline measures to test their predictive power for the functional outcome measured at T1. We found that only outcome-positive patients had an earlier, higher autonomic response for words compared to pseudo-words, a pattern similar to that of healthy awake controls. Furthermore, DOC patients showed reduced fALFF in the posterior cingulate cortex (PCC), a brain region that contributes to autonomic regulation and awareness. The event-related electrodermal marker of residual cognitive functioning was found to have a significant correlation with residual local neuronal activity in the PCC. We propose that a residual autonomic response to cognitively salient stimuli, together with a preserved resting-state activity in the PCC, can provide a useful prognostic index in acute DOC. Paperlink: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397392/
Neuroccino 29th April 2024 - White matter and cortical gray matter morphology across the lifespan
35:02
Clinical Neuroanatomy Seminars

Neuroccino 29th April 2024 - White matter and cortical gray matter morphology across the lifespan

Abstract Characterizing how, when and where the human brain changes across the lifespan is fundamental to our understanding of developmental processes of childhood and adolescence, degenerative processes of aging, and divergence from normal patterns in disease and disorders. We aimed to provide detailed descriptions of white matter pathways across the lifespan by thoroughly characterizing white matter microstructure, white matter macrostructure, and morphology of the cortex associated with white matter pathways. We analyzed 4 large, high-quality, publicly-available datasets comprising 2789 total imaging sessions, and participants ranging from 0 to 100 years old, using advanced tractography and diffusion modeling. We first find that all microstructural, macrostructural, and cortical features of white matter bundles show unique lifespan trajectories, with rates and timing of development and degradation that vary across pathways - describing differences between types of pathways and locations in the brain, and developmental milestones of maturation of each feature. Second, we show cross-sectional relationships between different features that may help elucidate biological changes occurring during different stages of the lifespan. Third, we show unique trajectories of age-associations across features. Finally, we find that age associations during development are strongly related to those during aging. Overall, this study reports normative data for several features of white matter pathways of the human brain that will be useful for studying normal and abnormal white matter development and degeneration. Paper link: https://pubmed.ncbi.nlm.nih.gov/37808645/
Neuroccino 18th March 2024 - Causation in Neuroscience
35:09
Clinical Neuroanatomy Seminars

Neuroccino 18th March 2024 - Causation in Neuroscience

Causation in neuroscience: keeping mechanism meaningful A fundamental goal of research in neuroscience is to uncover the causal structure of the brain. This focus on causation makes sense, because causal information can provide explanations of brain function and identify reliable targets with which to understand cognitive function and prevent or change neurological conditions and psychiatric disorders. In this research, one of the most frequently used causal concepts is ‘mechanism’ — this is seen in the literature and language of the field, in grant and funding inquiries that specify what research is supported, and in journal guidelines on which contributions are considered for publication. In these contexts, mechanisms are commonly tied to expressions of the main aims of the field and cited as the ‘fundamental’, ‘foundational’ and/or ‘basic’ unit for understanding the brain. Despite its common usage and perceived importance, mechanism is used in different ways that are rarely distinguished. Given that this concept is defined in different ways throughout the field — and that there is often no clarification of which definition is intended — there remains a marked ambiguity about the fundamental goals, orientation and principles of the field. Here we provide an overview of causation and mechanism from the perspectives of neuroscience and philosophy of science, in order to address these challenges. Paper link: https://www.nature.com/articles/s41583-023-00778-7 #review
Neuroccino 11th March 20204 - Parkinson disease severity determined by cortical compensation decline
43:34
Clinical Neuroanatomy Seminars

Neuroccino 11th March 20204 - Parkinson disease severity determined by cortical compensation decline

Paper link: https://pubmed.ncbi.nlm.nih.gov/37757883/ Dopaminergic dysfunction in the basal ganglia, particularly in the posterior putamen, is often viewed as the primary pathological mechanism behind motor slowing (i.e. bradykinesia) in Parkinson's disease. However, striatal dopamine loss fails to account for interindividual differences in motor phenotype and rate of decline, implying that the expression of motor symptoms depends on additional mechanisms, some of which may be compensatory in nature. Building on observations of increased motor-related activity in the parieto-premotor cortex of Parkinson patients, we tested the hypothesis that interindividual differences in clinical severity are determined by compensatory cortical mechanisms and not just by basal ganglia dysfunction. Using functional MRI, we measured variability in motor- and selection-related brain activity during a visuomotor task in 353 patients with Parkinson's disease (≤5 years disease duration) and 60 healthy controls. In this task, we manipulated action selection demand by varying the number of possible actions that individuals could choose from. Clinical variability was characterized in two ways. First, patients were categorized into three previously validated, discrete clinical subtypes that are hypothesized to reflect distinct routes of α-synuclein propagation: diffuse-malignant (n = 42), intermediate (n = 128) or mild motor-predominant (n = 150). Second, we used the scores of bradykinesia severity and cognitive performance across the entire sample as continuous measures. Patients showed motor slowing (longer response times) and reduced motor-related activity in the basal ganglia compared with controls. However, basal ganglia activity did not differ between clinical subtypes and was not associated with clinical scores. This indicates a limited role for striatal dysfunction in shaping interindividual differences in clinical severity. Consistent with our hypothesis, we observed enhanced action selection-related activity in the parieto-premotor cortex of patients with a mild-motor predominant subtype, both compared to patients with a diffuse-malignant subtype and controls. Furthermore, increased parieto-premotor activity was related to lower bradykinesia severity and better cognitive performance, which points to a compensatory role. We conclude that parieto-premotor compensation, rather than basal ganglia dysfunction, shapes interindividual variability in symptom severity in Parkinson's disease. Future interventions may focus on maintaining and enhancing compensatory cortical mechanisms, rather than only attempting to normalize basal ganglia dysfunction.
Neuroccino February 19th - Dice coefficient
39:59
Clinical Neuroanatomy Seminars

Neuroccino February 19th - Dice coefficient

Paper link: https://arxiv.org/abs/2206.01653 Try their tool: https://metrics-reloaded.dkfz.de/ Abstract: Increasing evidence shows that flaws in machine learning (ML) algorithm validation are an underestimated global problem. Particularly in automatic biomedical image analysis, chosen performance metrics often do not reflect the domain interest, thus failing to adequately measure scientific progress and hindering translation of ML techniques into practice. To overcome this, our large international expert consortium created Metrics Reloaded, a comprehensive framework guiding researchers in the problem-aware selection of metrics. Following the convergence of ML methodology across application domains, Metrics Reloaded fosters the convergence of validation methodology. The framework was developed in a multi-stage Delphi process and is based on the novel concept of a problem fingerprint - a structured representation of the given problem that captures all aspects that are relevant for metric selection, from the domain interest to the properties of the target structure(s), data set and algorithm output. Based on the problem fingerprint, users are guided through the process of choosing and applying appropriate validation metrics while being made aware of potential pitfalls. Metrics Reloaded targets image analysis problems that can be interpreted as a classification task at image, object or pixel level, namely image-level classification, object detection, semantic segmentation, and instance segmentation tasks. To improve the user experience, we implemented the framework in the Metrics Reloaded online tool, which also provides a point of access to explore weaknesses, strengths and specific recommendations for the most common validation metrics. The broad applicability of our framework across domains is demonstrated by an instantiation for various biological and medical image analysis use cases. Just published din @Nature Methods
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