Auditory hemispheric asymmetry for actions and objects.

What is the function of auditory hemispheric asymmetry? We propose that the identification of sound sources relies on the asymmetric processing of two complementary and perceptually relevant acoustic invariants: actions and objects. In a large dataset of environmental sounds, we observed that temporal and spectral modulations display only weak covariation. We then synthesized auditory stimuli by simulating various actions (frictions) occurring on different objects (solid surfaces). Behaviorally, discrimination of actions relies on temporal modulations, while discrimination of objects relies on spectral modulations. Functional magnetic resonance imaging data showed that actions and objects are decoded in the left and right hemispheres, respectively, in bilateral superior temporal and left inferior frontal regions. This asymmetry reflects a generic differential processing-through differential neural sensitivity to temporal and spectral modulations present in environmental sounds-that supports the efficient categorization of actions and objects. These results support an ecologically valid framework of the functional role of auditory brain asymmetry.

Central nervous system regulation of diffuse glioma growth and invasion: from single unit physiology to circuit remodeling.

PURPOSE: Understanding the complex bidirectional interactions between neurons and glioma cells could help to identify new therapeutic targets. Herein, the techniques and application of novel neuroscience tools implemented to study the complex interactions between brain and malignant gliomas, their results, and the potential therapeutic opportunities were reviewed. METHODS: Literature search was performed on PubMed between 2001 and 2023 using the keywords "glioma", "glioblastoma", "circuit remodeling", "plasticity", "neuron networks" and "cortical networks". Studies including grade 2 to 4 gliomas, diffuse midline gliomas, and diffuse intrinsic pontine gliomas were considered. RESULTS: Glioma cells are connected through tumour microtubes and form a highly connected network within which pacemaker cells drive tumorigenesis. Unconnected cells have increased invasion capabilities. Glioma cells are also synaptically integrated within neural circuitry. Neurons promote tumour growth via paracrine and direct electrochemical mechanisms, including glutamatergic AMPA-receptors. Increased glutamate release in the tumor microenvironment and loss of peritumoral GABAergic inhibitory interneurons result in network hyperexcitability and secondary epilepsy. Functional imaging, local field potentials and subcortical mapping, performed in awake patients, have defined patterns of malignant circuit remodeling. Glioma-induced remodeling is frequent in language and even motor cortical networks, depending on tumour biological parameters, and influences functional outcomes. CONCLUSION: These data offer new insights into glioma tumorigenesis. Future work will be needed to understand how tumor intrinsic molecular drivers influence neuron-glioma interactions but also to integrate these results to design new therapeutic options for patients.

Time-restricted feeding can increase food-related impulsivity: a randomized controlled trial.

OBJECTIVES: Although an increasing number of studies show that time-restricted feeding may improve metabolic health, studies examining the behavioral effects of this eating pattern are limited. This study examined the effect of time-restricted feeding on impulsivity in adults. METHODS: Thirty adults aged 25-41 years participated in this randomized controlled trial. The intervention group followed time-restricted feeding for 4 weeks and there was no energy restriction in the intervention group (n = 15) or control group (n = 15). Impulsivity was assessed before and after the intervention with the Barratt Impulsiveness Scale and the Go/NoGo task. RESULTS: The compliance rate (the percentage of days when participants had a feeding time of ≤ 8 hours/day) of the intervention group to the time-restricted feeding pattern was 92.38 ± 4.24%. The Barratt Impulsiveness Scale-11 total score of the intervention group increased from 55.53 ± 6.37 to 59.47 ± 7.67 (p = 0.02). During the Go/NoGo task, an indicator of inhibitory control, the reaction time to food and non-food stimuli was significantly shortened in the intervention group (respectively; p = 0.009, p = 0.01). In the control group, no significant change was detected in impulsivity determined by the BIS-11 or Go/NoGo task. DISCUSSION: This study showed that although time-restricted feeding may reduce body weight, it can lead to increased impulsivity and impaired inhibitory control.Trial registration: ClinicalTrials.gov identifier: NCT04960969.

Anton, Balint, Charles Bonnet, and the Others: The ABC of Cerebral Visual Syndromes (A Historical Guide and an Update).

Cerebral visual impairments have been of great interest to neurologists, ophthalmologists, and neuroscientists. Complicated or partial varieties related to cortical blindness are discussed in this review. They are a fascinating alphabet of eponymic clinical syndromes, bordering neurology, ophthalmology, and even psychiatry. Recent functional imaging and experimental studies have contributed further knowledge of cognitive visual organization in addition to the classical lesion evidence.

CONNECTing Concussion Care with Research Across Ontario.

Common data elements (CDEs) for concussion, as established by international bodies, are not being widely used in Ontario, resulting in significant variability in the data being assessed and collected across clinics. CDEs support standardization of care as well as large-scale data sharing for high impact research. A collaborative network - Concussion Ontario Network: Neuroinformatics to Enhance Clinical care and Translation (CONNECT) - comprised of health care professionals, researchers, members from advocacy groups, and patients was formed to establish and implement CDEs for concussion care and research. While the seeds have been planted and initial effectiveness demonstrated, future challenges exist.

The Glutamatergic Effects of Clinical Repetitive Transcranial Magnetic Stimulation in Depressed Populations: A Preliminary Meta-Analysis of Proton Magnetic Resonance Spectroscopy Studies.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) alleviates symptoms of major depressive disorder, but its neurobiological mechanisms remain to be fully understood. Growing evidence from proton magnetic resonance spectroscopy (1HMRS) studies suggests that rTMS alters excitatory and inhibitory neurometabolites. This preliminary meta-analysis aims to quantify current trends in the literature and identify future directions for the field. METHODS: Ten eligible studies that quantified Glutamate (Glu), Glu+Glutamine (Glx), or GABA before and after an rTMS intervention in depressed samples were sourced from PubMed, MEDLINE, PsychInfo, Google Scholar, and primary literature following PRISMA guidelines. Data were pooled using a random-effects model, Cohen's d effect sizes were calculated, and moderators, such as neurometabolite and 1HMRS sequence, were assessed. It was hypothesized that rTMS would increase cortical neurometabolites. RESULTS: Within-subjects data from 224 cases encompassing 31 neurometabolite effects (k) were analyzed. Active rTMS in clinical responders (n = 128; k = 22) nominally increased glutamatergic neurometabolites (d = 0.15 [95% CI: -0.01, 0.30], p = 0.06). No change was found in clinical nonresponders (p = 0.8) or sham rTMS participants (p = 0.4). A significant increase was identified in Glx (p = 0.01), but not Glu (p = 0.6). Importantly, effect size across conditions were associated with the number of rTMS pulses patients received (p = 0.05), suggesting dose dependence. CONCLUSIONS: Clinical rTMS is associated with a nominal, dose-dependent increase in glutamatergic neurometabolites, suggesting rTMS may induce Glu-dependent neuroplasticity and upregulate neurometabolism. More, larger scale studies adhering to established acquisition and reporting standards are needed to further elucidate the neurometabolic mechanisms of rTMS.

"Brain-IT": Exergame training with biofeedback breathing in neurocognitive disorders.

INTRODUCTION: The combination of exergame-based motor-cognitive training with resonance breathing guided by heart-rate variability biofeedback (HRV-BF) targets various relevant mechanisms of action to alleviate the pathological state in mild neurocognitive disorders (mNCD). METHODS: This randomized controlled trial (RCT) investigated the effectiveness of adding this novel intervention approach to usual care in mNCD. The individualized intervention was delivered via the "Brain-IT" training concept, which was iteratively co-designed, tested, and refined with patient and public involvement. RESULTS: We observed statistically significant effects with large effect sizes for global cognitive performance, immediate verbal recall, and delayed verbal recall in favor of the intervention group. Fifty-five percent of participants showed a clinically relevant improvement in response to training. DISCUSSION: Confirmatory RCTs are warranted to investigate whether the observed improvements in cognitive performance translate to affecting the rates of progression to or onset of dementia and test the implementation of the training in clinical practice. HIGHLIGHTS: We proposed a novel intervention approach for mild neurocognitive disorders. It combines exergame-based training with biofeedback-guided resonance breathing. Our results confirm the effectiveness of this approach. Fifty-five percent of participants showed a clinically relevant improvement in response to training.

FROM THE GATE TO THE GATEWAY: PSYCHOANALYTIC NAVIGATIONS ONLINE.

The shift towards remote or online therapy was compelled by the Pandemic. Many colleagues, who neither had practice using this modality, nor had ever considered it as a possibility, ultimately adopted it. This experience brought with it a substantial expansion of online therapy beyond that moment of emergency. It opened up new prospects of intervention, but at the same time it required a greater measure of reflection in order to understand how to inhabit this new therapy space. Setting aside provisory, intermittent, or emergency situations, which temporarily transfer therapy into a "field of tents" (Bolognini, 2021), the author proposes to consider how online psychotherapy redefines an important element of the psychoanalytic setting-the issue of the space. This is no longer the therapist's place of work, envisaged and organized by him/her/them, fixed in time, and contrived only to welcome the therapeutic relationship-one of the crucial aspects of the external setting, which together with the temporal dimension, fulfills the therapy ritual. Assuming the framework to be essential to the psychoanalytic process, this paper will focus on the methodology of online therapy. The author will describe the contributions of the neurosciences, to provide a deeper understanding of the distinctive characteristics of sharing in an online vs. an offline space. Online therapy should be assessed for its distinguishing qualities within a complete theoretical, technical, and clinical reflection specific to each case. Proceeding as if it were a mere relocation of an in-person analysis would enhance the seductiveness of a therapy that is easily accessible with any laptop anywhere, anytime, and in which one could mistake an online connection for a deep connection.

The origins of film, psychology and the neurosciences.

The invention of film technologies in France at the end of the 19th century inspired neurologists and associated professionals to engage with this new medium to demonstrate their theories of the brain, the nervous system, and the mind. Beginning with the origins of cinema in Paris, this article explores how film technologies were used at La Salpêtrière, and beyond, to visualise internal mental processes, and to support the burgeoning sciences of the mind. This film-making became increasingly sophisticated by the late 1910s and early 1920s, creating innovative ways to present psychological experiences on film. This article focuses on films produced by Albert Londe, Vincenzo Neri, Gheorghe Marinescu, and Jean Comandon. It argues that these polymaths created new filming techniques that built complexity into the visual articulation of psychological concepts. Their films were essential to shaping early debates in neurology, psychology, and the observational sciences during this critical period in the establishment of the modern sciences of the self.

Connecting Women in Neurosciences: A networking project to sustain mutual empowerment in young, female clinical neuroscientists.

Simultaneously acquiring broad clinical knowledge and scientific expertise is a major challenge for young clinical scientists. Female researchers may face additional hurdles in their career, for example, due to unconscious bias. We aimed to address clinical, research, and gender-related challenges among young female clinical neuroscientists. We implemented a peer-led networking group dedicated to increasing clinical and scientific knowledge, improve soft skills, and encourage exchange between fellow residents. In monthly meetings, two participants hold short presentations on a clinical topic or scientific method, followed by a discussion and feedback to the presenter. Afterwards, participants network and discuss challenges they face in their daily experience. Nine neurology residents at a Swiss University Hospital with ≤3 years of training participated in the Connecting Women in Neurosciences project from August 2020 to June 2021. In a qualitative evaluation, participants reported they felt empowered by these meetings and profited from their new network. We identified several challenges in combining clinical and research activities, some of which participants perceived to be gender-related. In addition to women-only meetings, we will promote events addressing all interested researchers. Peer-to-peer networking is an easy and low-budget intervention to encourage female residents to engage in research activities, profit from each other's expertise, and promote interdisciplinary teamwork. It can provide a protected environment to discuss and overcome in particular gender-related challenges. We encourage young colleagues to regularly engage in structured networking activities with their local peers.

Clinical application of magnetic resonance elastography in pediatric neurological disorders.

Magnetic resonance elastography is a relatively new, rapidly evolving quantitative magnetic resonance imaging technique which can be used for mapping the viscoelastic mechanical properties of soft tissues. MR elastography measurements are akin to manual palpation but with the advantages of both being quantitative and being useful for regions which are not available for palpation, such as the human brain. MR elastography is noninvasive, well tolerated, and complements standard radiological and histopathological studies by providing in vivo measurements that reflect tissue microstructural integrity. While brain MR elastography studies in adults are becoming frequent, published studies on the utility of MR elastography in children are sparse. In this review, we have summarized the major scientific principles and recent clinical applications of brain MR elastography in diagnostic neuroscience and discuss avenues for impact in assessing the pediatric brain.

Challenges With the Use of Digital Sham: Systematic Review and Recommendations.

BACKGROUND: Digital therapeutics (DTx) are software-based products that prevent, manage, or treat a medical condition and are delivered through a smartphone app, web application, or wearable device. Clinical trials assessing DTx pose challenges, foremost among which is designing appropriate digital shams (or digital placebos), which should ideally mimic DTx (in terms of design, components, and duration of treatment) while omitting the active principle or component. OBJECTIVE: The objective of our review was to understand how digital shams are being used in clinical research on DTx in neuroscience, which is the most common therapy area for DTx. METHODS: We conducted a systematic literature review of DTx in neuroscience (including neurodevelopmental, neurodegenerative, and psychiatric disorders) with a focus on controlled clinical trials involving digital shams. Studies were identified from trial registries (ClinicalTrials.gov, the European Union Clinical Trials Register, and Trial Trove) and through structured searches in MEDLINE and Embase (both via the Embase website) and were limited to articles in English published from 2010 onward. These were supplemented by keyword-based searches in PubMed, Google, and Google Scholar and bibliographic searches. Studies assessing DTx in neuroscience (including neurodevelopmental, neurodegenerative, and psychiatric disorders) were included. Details related to the publication, DTx, comparator, patient population, and outcomes were extracted and analyzed. RESULTS: Our search criteria identified 461 neuroscience studies involving 213 unique DTx. Most DTx were extended reality based (86/213, 40.4%) or mobile device based (56/213, 26.3%); 313 were comparative, of which 68 (21.7%) used shams. The most common therapeutic areas assessed in these studies were stroke (42/213, 19.7%), depression (32/213, 15%), and anxiety (24/213, 11.3%). The most common treatments were cognitive behavioral therapy or behavioral therapy (67/213, 32.4%), physical rehabilitation (60/213, 28.2%), and cognitive training (41/213, 19.2%). We identified the following important issues related to the use of digital shams in neuroscience: shams were not validated before use in studies, they varied widely in design (from being nearly identical to the DTx to using different software programs altogether), and the level of patient engagement or satisfaction with the sham and the impact of the sham on study outcomes were infrequently reported. CONCLUSIONS: Digital shams are critical for the clinical development of DTx in neuroscience. Given the importance of sham controls in evaluating DTx efficacy, we provide recommendations on the key information that should be reported in a well-designed DTx trial and propose an algorithm to allow the correct interpretation of DTx study results. Sham-controlled studies should be routinely used in DTx trials-in early-phase studies-to help identify DTx active components and-in late-phase studies-to confirm the efficacy of DTx. The use of shams early in development will ensure that the appropriate sham control is used in later confirmatory trials.

Mortality Following Diagnosis of Nontraumatic Intracerebral Hemorrhage Within an Integrated "Hub-and-Spoke" Neuroscience Care Model: Is Spoke Presentation Noninferior to Hub Presentation?

BACKGROUND: Practice guidelines recommend that patients with intracerebral hemorrhage (ICH) be treated in units with acute neuroscience care experience. However, most hospitals in the United States lack this degree of specialization. We sought to examine outcome differences for patients with nontraumatic ICH presenting to centers with and without advanced neuroscience care specialization. METHODS: This was a retrospective study of adult patients presenting with nontraumatic ICH between 1/1/2011 and 9/30/2020 across 21 medical centers within Kaiser Permanente Northern California, an integrated care system that employs a "hub-and-spoke" model of neuroscience care in which two centers service as neuroscience "hubs" and the remaining 19 centers service as referral "spokes." Patients presenting to spokes can receive remote consultation (including image review) by neurosurgical or neurointensive care specialists located at hubs. The primary outcome was 90-day mortality. We used hierarchical logistic regression, adjusting for ICH score components, comorbidities, and demographics, to test a hypothesis that initial presentation to a spoke medical center was noninferior to hub presentation [defined as an odds ratio (OR) with an upper 95% confidence interval (CI) limit of 1.24 or less]. RESULTS: A total of 6978 patients were included, with 6170 (88%) initially presenting to spoke medical centers. The unadjusted 90-day mortality for patients initially presenting to spoke versus hub medical centers was 32.2% and 32.7%, respectively. In adjusted analysis, presentation to a spoke medical center was neither noninferior nor inferior for 90-day mortality risk (OR 1.21, 95% CI 0.84-1.74). Sensitivity analysis excluding patients admitted to general wards or lacking continuous health plan insurance during the follow-up period trended closer to a noninferior result (OR 0.99, 95% CI 0.69-1.44). CONCLUSIONS: Within an integrated "hub-and-spoke" neuroscience care model, the risk of 90-day mortality following initial presentation with nontraumatic ICH to a spoke medical center was not conclusively noninferior compared with initial presentation to a hub medical center. However, there was also no indication that care for selected patients with nontraumatic ICH within medical centers lacking advanced neuroscience specialization resulted in significantly inferior outcomes. This finding may support the safety and efficiency of a "hub-and-spoke" care model for patients with nontraumatic ICH, although additional investigations are warranted.

Virtual student-led neuroscience conferencing: a UK multicentre prospective study investigating delegate outcomes and delivery mode.

BACKGROUND: Clinical neuroscience training programmes are becoming increasingly competitive to enter. UK university neuroscience societies act as a local environment for students to develop their career interests and provide portfolio building opportunities through hosting events such as annual conferences. Recently there has been a transition to more of these events being held online yet the impact of this, if any, remains unclear. This prospective study aimed to identify the impact of student-led neuroscience conferences on delegates and examine attitudes towards an online delivery approach. METHODS: Multi-centre prospective survey study using pre-conference, post-conference, and 6-month post-conference online questionnaires distributed at 6 virtual student-led neuroscience conferences in 2021. The questionnaires had five-domains: demographics, career aspirations, academic skillsets, an educational manipulation check (EMC) and mode of delivery preference. RESULTS: Nine hundred twenty-four surveys were completed across 559 conference attendances. 79.9% of delegates were medical students. Interest in a neuroscience career (p < 0.001), preparedness to undertake research (p < 0.001) and presentation (p < 0.001), as well as EMC scores (p < 0.001) increased immediately post conference. Most participants at 6 months post-attendance had completed an academic project (71.9%) or presentation (50.9%), although 88.8% were lost to follow up. Online format was preferred (65%) with reasons including elimination of travel and access to home facilities whilst lack of face-to-face interaction and engagement were recognised limitations. CONCLUSION: UK student-led online neuroscience conferences play a role in developing knowledge and may facilitate career interest, academic skillset and longer term portfolio building. A hybrid virtual and in-person experience would offer an ideal solution to future conferencing, providing options promoting engagement and interactivity whilst advocating sustainability, accessibility and widening participation.

[Understanding functional neurological disorders: From biological markers to pathophysiological models]. / Étiopathogénie des troubles neurologiques fonctionnels : marqueurs biologiques et modèles théoriques.

OBJECTIVES: Functional neurological disorders have witnessed intense research activity in the fields of structural and functional neuroimaging for more than twenty years. Thus, we propose a synthesis of recent research findings and etiological hypotheses that have been proposed so far. This work should help clinicians to better understand the nature of the mechanisms involved, but also help patients to increase their knowledge about the biological features underlying their functional symptoms. METHODS: We carried out a narrative review of international publications dealing with neuroimaging and biology of functional neurological disorders, from 1997 to 2023. RESULTS: Several brain networks underlie functional neurological symptoms. These networks play a role in the management of cognitive resources, in attentional control, emotion regulation, in agency and in the processing of interoceptive signals. The mechanisms of the stress response are also associated with the symptoms. The biopsychosocial model helps to better understand predisposing, precipitating, and perpetuating factors involved. The functional neurological phenotype results from the interaction between: i) a specific pre-existing vulnerability resulting from biological background and epigenetic modifications, and ii) exposure to stress factors, according to the stress-diathesis model. This interaction causes emotional disturbances including hypervigilance, lack of integration of sensations and affects, and emotional dysregulation. These characteristics in turn impact the cognitive, motor and affective control processes related with the functional neurological symptoms. CONCLUSIONS: A better knowledge of the biopsychosocial determinants of brain network dysfunctions is necessary. Understanding them would help developing targeted treatments, but is also critical for patients care.

[Mother brain: Bayesian theory of maternal interoception during pregnancy and postpartum]. / Cerveau maternel : Théorie bayésienne de l'intéroception maternelle pendant la grossesse et le postpartum.

The perinatal period, including pregnancy and postpartum, causes major morphological, endocrinal, and thermal transitions in women. As the fetus grows, abdominal muscle fibers stretch, internal organs such as the bladder or colon move, and the uterine anatomy changes. Many of these changes involve interoception, the perception of internal body signals such as muscle and visceral sensations. Despite the importance of these interoceptive signals, few studies have explored perinatal interoception. We propose an innovative theory of maternal interoception based on recent findings in neuroscience. We show that interoceptive signals processing during pregnancy is crucial for understanding perinatal phenomenology and psychopathology, such as maternal perception of fetal movements, maternal-infant bonding, denial of pregnancy, phantom fetal movements after childbirth, pseudocyesis or even puerperal delusion. Knowing the importance of these interoceptive mechanisms, clinicians in obstetrics, gynecology and mental health should be particularly vigilant to maternal interoception during the perinatal period.

Biclustering fMRI time series: a comparative study.

BACKGROUND: The effectiveness of biclustering, simultaneous clustering of rows and columns in a data matrix, was shown in gene expression data analysis. Several researchers recognize its potentialities in other research areas. Nevertheless, the last two decades have witnessed the development of a significant number of biclustering algorithms targeting gene expression data analysis and a lack of consistent studies exploring the capacities of biclustering outside this traditional application domain. RESULTS: This work evaluates the potential use of biclustering in fMRI time series data, targeting the Region × Time dimensions by comparing seven state-in-the-art biclustering and three traditional clustering algorithms on artificial and real data. It further proposes a methodology for biclustering evaluation beyond gene expression data analysis. The results discuss the use of different search strategies in both artificial and real fMRI time series showed the superiority of exhaustive biclustering approaches, obtaining the most homogeneous biclusters. However, their high computational costs are a challenge, and further work is needed for the efficient use of biclustering in fMRI data analysis. CONCLUSIONS: This work pinpoints avenues for the use of biclustering in spatio-temporal data analysis, in particular neurosciences applications. The proposed evaluation methodology showed evidence of the effectiveness of biclustering in finding local patterns in fMRI time series data. Further work is needed regarding scalability to promote the application in real scenarios.

The cluster depth tests: Toward point-wise strong control of the family-wise error rate in massively univariate tests with application to M/EEG.

The cluster mass test has been widely used for massively univariate tests in M/EEG, fMRI and, recently, pupillometry analysis. It is a powerful method for detecting effects while controlling weakly the family-wise error rate (FWER), although its correct interpretation can only be performed at the cluster level without any point-wise conclusion. It implies that the discoveries of a cluster mass test cannot be precisely localized in time or in space. We propose a new multiple comparisons procedure, the cluster depth tests, that both controls the FWER while allowing an interpretation at the time point level. We show the conditions for a strong control of the FWER, and a simulation study shows that the cluster depth tests achieve large power and guarantee the FWER even in the presence of physiologically plausible effects. By having an interpretation at the time point/voxel level, the cluster depth tests make it possible to take full advantage of the high temporal resolution of EEG recording and give a precise timing of the start and end of the significant effects.

Comment on the article "Spatially-extended nucleation-aggregation-fragmentation models for the dynamics of prion-like neurodegenerative protein-spreading in the brain and its connectome 486 (2020) 110102".

Considering the reaction schemes (20) and (21) in Fornari et al. (2020), the fragmentation terms Fi (Eq. (22) in Fornari et al. (2020)) are not correct. Thus, the fragmentation terms Fi (Eq. (12) in Fornari et al. (2020)) are also incorrect when the reaction schemes (10) and (11) in Fornari et al. (2020) are taken into account. Here, the correct equations will be presented.

Defining the phenotypical spectrum associated with variants in TUBB2A.

BACKGROUND: Variants in genes belonging to the tubulin superfamily account for a heterogeneous spectrum of brain malformations referred to as tubulinopathies. Variants in TUBB2A have been reported in 10 patients with a broad spectrum of brain imaging features, ranging from a normal cortex to polymicrogyria, while one patient has been reported with progressive atrophy of the cerebellar vermis. METHODS: In order to further refine the phenotypical spectrum associated with TUBB2A, clinical and imaging features of 12 patients with pathogenic TUBB2A variants, recruited via the international network of the authors, were reviewed. RESULTS: We report 12 patients with eight novel and one recurrent variants spread throughout the TUBB2A gene but encoding for amino acids clustering at the protein surface. Eleven patients (91.7%) developed seizures in early life. All patients suffered from intellectual disability, and 11 patients had severe motor developmental delay, with 4 patients (36.4 %) being non-ambulatory. The cerebral cortex was normal in five individuals and showed dysgyria of variable severity in seven patients. Associated brain malformations were less frequent in TUBB2A patients compared with other tubulinopathies. None of the patients had progressive cerebellar atrophy. CONCLUSION: The imaging phenotype associated with pathogenic variants in TUBB2A is highly variable, ranging from a normal cortex to extensive dysgyria with associated brain malformations. For recurrent variants, no clear genotype-phenotype correlations could be established, suggesting the role of additional modifiers.