Bilateral Simultaneous Magnetic Resonance-Guided Focused Ultrasound Pallidotomy for Life-Threatening Status Dystonicus.

BACKGROUND: Invasive treatments like radiofrequency stereotactic lesioning or deep brain stimulation of the globus pallidus internus can resolve drug-resistant status dystonicus (SD). However, these open procedures are not always feasible in patients with SD. OBJECTIVE: The aim was to report the safety and efficacy of simultaneous asleep bilateral transcranial magnetic resonance-guided focused ultrasound (MRgFUS) pallidotomy for life-threatening SD. METHODS: We performed bilateral simultaneous MRgFUS pallidotomy under general anesthesia in 2 young patients with pantothenate kinase-associated neurodegeneration and GNAO1 encephalopathy. Both patients had medically refractory SD and severe comorbidities contraindicating open surgery. RESULTS: SD resolved at 4 and 12 days after MRgFUS, respectively. Adverse events (intraoperative hypothermia and postoperative facial paralysis) were mild and transient. CONCLUSION: Bilateral simultaneous MRgFUS pallidotomy under general anesthesia is safe and may be a valid alternative therapeutic option for fragile patients. Further studies are needed to assess long-term efficacy of the procedure. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Distinct neural signatures of pulvinar in C9orf72 amyotrophic lateral sclerosis mutation carriers and noncarriers.

BACKGROUND AND PURPOSE: Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia-amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high-order thalamic nucleus and timekeeper for large-scale cortical networks, has been hypothesized to be involved in C9orf72-related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS C9orf72 mutation carriers and noncarriers and how underlying functional connectivity changes affect this region. METHODS: We studied 19 ALS C9orf72 mutation carriers (ALSC9+) accurately matched with wild-type ALS (ALSC9-) and ALS mimic (ALSmimic) patients using structural and resting-state functional magnetic resonance imaging data. Pulvinar volume was computed using automatic segmentation. Seed-to-voxel functional connectivity analyses were performed using seeds from a pulvinar functional parcellation. RESULTS: Pulvinar structural integrity had high discriminative values for ALSC9+ patients compared to ALSmimic (area under the curve [AUC] = 0.86) and ALSC9- (AUC = 0.77) patients, yielding a volume cutpoint of approximately 0.23%. Compared to ALSmimic, ALSC9- showed increased anterior, inferior, and lateral pulvinar connections with bilateral occipital-temporal-parietal regions, whereas ALSC9+ showed no differences. ALSC9+ patients when compared to ALSC9- patients showed reduced pulvinar-occipital connectivity for anterior and inferior pulvinar seeds. CONCLUSIONS: Pulvinar volume could be a differential biomarker closely related to the C9orf72 mutation. A pulvinar-cortical circuit dysfunction might play a critical role in disease progression and development, in both the genetic phenotype and ALS wild-type patients.

Increased interhemispheric functional connectivity after right anodal tDCS in chronic non-fluent aphasia: preliminary findings.

Introduction: Anodal transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost and environment-friendly brain neuromodulation technique that increases cortical excitability. In post-stroke aphasia, the role of the right hemisphere in language recovery remains debated. In this preliminary study, we aimed to investigate the efficacy of excitatory tDCS on the right hemisphere in chronic aphasic patients. Methods: We applied anodal tDCS to the right homologous region of Broca's area in four chronic aphasic patients while performing a one-month naming rehabilitation treatment. Longitudinal data on language assessment and naming performance were collected. Resting-state fMRI images were acquired before and after treatment to measure changes in functional connectivity. Results: Results showed enhanced positive functional connectivity of the right Broca homologous with the left middle frontal and middle temporal gyri. Every patient showed improvements in language functions, but no major changes in naming performance. Conclusion: These preliminary findings suggest that tDCS applied over the unaffected hemisphere may result in longitudinal inter-hemispheric functional neuroplastic changes that could specifically improve language recovery and could potentially be included in therapeutic neurorehabilitative plans.

On the brain struggles to recognize basic facial emotions with face masks: an fMRI study.

Introduction: The COVID-19 pandemic impacted public health and our lifestyles, leading to new social adaptations such as quarantine, social distancing, and facial masks. Face masks, covering extended facial zones, hamper our ability to extract relevant socio-emotional information from others' faces. In this fMRI study, we investigated how face masks interfere with facial emotion recognition, focusing on brain responses and connectivity patterns as a function of the presence of a face mask. Methods: A total of 25 healthy participants (13F; mean age: 32.64 ± 7.24y; mean education: 18.28 ± 1.31y) were included. Participants underwent task-related fMRI during the presentation of images of faces expressing basic emotions (joy or fear versus neutral expression). Half of the faces were covered by a face mask. Subjects had to recognize the facial emotion (masked or unmasked). FMRI whole-brain and regions-of-interest analyses were performed, as well as psychophysiological interaction analysis (PPI). Results: Subjects recognized better and faster emotions on unmasked faces. FMRI analyses showed that masked faces induced a stronger activation of a right occipito-temporal cluster, including the fusiform gyrus and the occipital face area bilaterally. The same activation pattern was found for the neutral masked > neutral unmasked contrast. PPI analyses of the masked > unmasked contrast showed, in the right occipital face area, a stronger correlation with the left superior frontal gyrus, left precentral gyrus, left superior parietal lobe, and the right supramarginal gyrus. Discussion: Our study showed how our brain differentially struggles to recognize face-masked basic emotions, implementing more neural resources to correctly categorize those incomplete facial expressions.

Involvement of the ipsilateral-to-the-pain anterior-superior hypothalamic subunit in chronic cluster headache.

BACKGROUND: Despite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a limited understanding of the hypothalamic areas involved, impede a comprehensive interpretation of its involvement in this condition. METHODS: We used an automated algorithm to extract hypothalamic subunit volumes from 105 cluster headache patients (57 chronic and 48 episodic) and 59 healthy individuals; after correcting the measures for the respective intracranial volumes, we performed the relevant comparisons employing logist regression models. Only for subunits that emerged as abnormal, we calculated their correlation with the years of illness and the number of headache attacks per day, and the effects of lithium treatment. As a post-hoc approach, using the 7 T resting-state fMRI dataset from the Human Connectome Project, we investigated whether the observed abnormal subunit, comprising the paraventricular nucleus and preoptic area, shows robust functional connectivity with the mesocorticolimbic system, which is known to be modulated by oxytocin neurons in the paraventricular nucleus and that is is abnormal in chronic cluster headache patients. RESULTS: Patients with chronic (but not episodic) cluster headache, compared to control participants, present an increased volume of the anterior-superior hypothalamic subunit ipsilateral to the pain, which, remarkably, also correlates significantly with the number of daily attacks. The post-hoc approach showed that this hypothalamic area presents robust functional connectivity with the mesocorticolimbic system under physiological conditions. No evidence of the effects of lithium treatment on this abnormal subunit was found. CONCLUSIONS: We identified the ipsilateral-to-the-pain antero-superior subunit, where the paraventricular nucleus and preoptic area are located, as the key hypothalamic region of the pathophysiology of chronic cluster headache. The significant correlation between the volume of this area and the number of daily attacks crucially reinforces this interpretation. The well-known roles of the paraventricular nucleus in coordinating autonomic and neuroendocrine flow in stress adaptation and modulation of trigeminovascular mechanisms offer important insights into the understanding of the pathophysiology of cluster headache.

Resting-state fMRI functional connectome of C9orf72 mutation status.

OBJECTIVE: The resting-state functional connectome has not been extensively investigated in amyotrophic lateral sclerosis (ALS) spectrum disease, in particular in relationship with patients' genetic status. METHODS: Here we studied the network-to-network connectivity of 19 ALS patients carrying the C9orf72 hexanucleotide repeat expansion (C9orf72+), 19 ALS patients not affected by C9orf72 mutation (C9orf72-), and 19 ALS-mimic patients (ALSm) well-matched for demographic and clinical variables. RESULTS: When compared with ALSm, we observed greater connectivity of the default mode and frontoparietal networks with the visual network for C9orf72+ patients (P = 0.001). Moreover, the whole-connectome showed greater node degree (P < 0.001), while sensorimotor cortices resulted isolated in C9orf72+. INTERPRETATION: Our results suggest a crucial involvement of extra-motor functions in ALS spectrum disease. In particular, alterations of the visual cortex may have a pathogenic role in C9orf72-related ALS. The prominent feature of these patients would be increased visual system connectivity with the networks responsible of the functional balance between internal and external attention.

Efficacy of mindfulness added to treatment as usual in patients with chronic migraine and medication overuse headache: a phase-III single-blind randomized-controlled trial (the MIND-CM study).

BACKGROUND: Mindfulness gained considerable attention for migraine management, but RCTs are lacking. We aimed to assess the efficacy of a six-sessions mindfulness-based treatment added to treatment as usual (TaU) in patients with Chronic Migraine (CM) and Medication Overuse Headache (MOH) on headache frequency, medication intake, quality of life, disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. METHODS: In this Phase-III single-blind RCT carried out in a specialty Italian headache center, 177 patients with CM and MOH were randomized 1:1 to either TaU (withdrawal from overused drugs, education on proper medication use and lifestyle issues, and tailored prophylaxis) or mindfulness-based intervention added to TaU (TaU + MIND). The mindfulness-based intervention consisted of six group session of mindfulness practice and 7-10 min daily self-practice. The primary endpoint was the achievement of ≥ 50% headache frequency reduction at 12 months compared to baseline, and was analyzed on an intention-to-treat principle using Pearson's Chi-Squared test. Secondary endpoints included medication intake, quality of life (QoL), disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. The secondary endpoints were analyzed using per-protocol linear mixed models. RESULTS: Out of the 177 participants 89 were randomized to TaU and 88 to TaU + MIND. Patients in the TaU + MIND group outperformed those in TaU for the primary endpoint (78.4% vs. 48.3%; p < 0.0001), and showed superior improvement in headache frequency, QoL and disability, headache impact, loss of productive time, medication intake, and in total, indirect and direct healthcare costs. CONCLUSIONS: A mindfulness-based treatment composed of six-week session and 7-10 min daily self-practice added on to TaU is superior to TaU alone for the treatment of patients with CM and MOH. TRIAL REGISTRATION: MIND-CM was registered on clinicaltrials.gov (NCT03671681) on14/09/2018.

C9orf72 ALS mutation carriers show extensive cortical and subcortical damage compared to matched wild-type ALS patients.

OBJECTIVE: C9orf72 mutation carriers with different neurological phenotypes show cortical and subcortical atrophy in multiple different brain regions, even in pre-symptomatic phases. Despite there is a substantial amount of knowledge, small sample sizes, clinical heterogeneity, as well as different choices of image analysis may hide anatomical abnormalities that are unique to amyotrophic lateral sclerosis (ALS) patients with this genotype or that are indicative of the C9orf72-specific trait overlain in fronto-temporal dementia patients. METHODS: Brain structural and resting state functional magnetic imaging was obtained in 24 C9orf72 positive (ALSC9+) ALS patients paired for burden disease with 24 C9orf72 negative (ALSC9-) ALS patients. A comprehensive structural evaluation of cortical thickness and subcortical volumes between ALSC9+ and ALSC9- patients was performed while a region of interest (ROI)-ROI analysis of functional connectivity was implemented to assess functional alterations among abnormal cortical and subcortical regions. Results were corrected for multiple comparisons. RESULTS: Compared to ALSC9- patients, ALSC9+ patients exhibited extensive disease-specific patterns of thalamo-cortico-striatal atrophy, supported by functional alterations of the identified abnormal regions. Cortical thinning was most pronounced in posterior areas and extended to frontal regions. Bilateral atrophy of the mediodorsal and pulvinar nuclei was observed, emphasizing a focal rather than global thalamus atrophy. Volume loss in a large portion of bilateral caudate and left putamen was reported. The marked reduction of functional connectivity observed between the left posterior thalamus and almost all the atrophic cortical regions support the central role of the thalamus in the pathogenic mechanism of C9orf72-mediated disease. CONCLUSIONS: These findings constitute a coherent and robust picture of ALS patients with C9orf72-mediated disease, unveiling a specific structural and functional characterization of thalamo-cortico-striatal circuit alteration. Our study introduces new evidence in the characterization of the pathogenic mechanisms of C9orf72 mutation.

Cingulate cortex morphology impacts on neurofunctional activity and behavioral performance in interference tasks.

Inhibitory control is the capacity to withhold or suppress a thought or action intentionally. The anterior Midcingulate Cortex (aMCC) participates in response inhibition, a proxy measure of inhibitory control. Recent research suggests that response inhibition is modulated by individual variability in the aMCC sulcal morphology. However, no study has investigated if this phenomenon is associated with neurofunctional differences during a task. In this study, 42 participants performed an Attention Network Task and a Numerical Stroop task in an MRI scanner. We investigated differences in brain activity and response inhibition efficiency between individuals with symmetric and asymmetric aMCC sulcal patterns. The results showed that aMCC morphological variability is partly associated with inhibitory control, and revealed greater activation in individuals with symmetric patterns during the Stroop task. Our findings provide novel insights into the functional correlates of the relationship between aMCC morphology and executive abilities.

Investigating sexual dimorphism in human brain structure by combining multiple indexes of brain morphology and source-based morphometry.

Computational morphometry of magnetic resonance images represents a powerful tool for studying macroscopic differences in human brains. In the present study (N participants = 829), we combined different techniques and measures of brain morphology to investigate one of the most compelling topics in neuroscience: sexual dimorphism in human brain structure. When accounting for overall larger male brains, results showed limited sex differences in gray matter volume (GMV) and surface area. On the other hand, we found larger differences in cortical thickness, favoring both males and females, arguably as a result of region-specific differences. We also observed higher values of fractal dimension, a measure of cortical complexity, for males versus females across the four lobes. In addition, we applied source-based morphometry, an alternative method for measuring GMV based on the independent component analysis. Analyses on independent components revealed higher GMV in fronto-parietal regions, thalamus and caudate nucleus for females, and in cerebellar- temporal cortices and putamen for males, a pattern that is largely consistent with previous findings.

A multimodal imaging approach to foreign accent syndrome. A case report.

This article describes a case of Foreign accent syndrome (FAS) in an Italian woman who developed a Canadian-like foreign accent without brain damage (functional FAS). The patient underwent an in-depth neuroimaging and (neuro)psychological evaluation. Language networks in the frontotemporal-parietal areas were typically activated bilaterally through fMRI and MEG assessments based on task-based data. Resting-state fMRI showed preserved connectivity between language areas. An obsessive-compulsive personality profile and mild anxiety were found, suggesting psychological and psychiatric factors may be relevant. Accordingly with our findings, multimodal imaging is beneficial to understand FAS neurological and functional etiologies.

The bilingual structural connectome: Dual-language experiential factors modulate distinct cerebral networks.

Bilingualism is a natural laboratory for studying whether the brain's structural connectome is influenced by different aspects of language experience. However, evidence on how distinct components of bilingual experience may contribute to structural brain adaptations is mixed. The lack of consistency, however, may depend, at least in part, on methodological choices in data acquisition and processing. Herein, we adopted the Network Neuroscience framework to investigate how individual differences in second language (L2) exposure, proficiency, and age of acquisition (AoA) - measured as continuous between-subject variables - relate to whole-brain structural organization. We observed that L2 exposure modulated the connectivity of two networks of regions subserving language comprehension and production. L2 proficiency was associated with enhanced connectivity within a rostro-caudal network, which supports language selection and word learning. Moreover, L2 AoA and exposure affected inter-hemispheric communication between control-related regions. These findings expand mechanistic knowledge about particular environmental factors associated with specific variation in brain structure.

Evidence for the Concreteness of Abstract Language: A Meta-Analysis of Neuroimaging Studies.

The neural mechanisms subserving the processing of abstract concepts remain largely debated. Even within the embodiment theoretical framework, most authors suggest that abstract concepts are coded in a linguistic propositional format, although they do not completely deny the role of sensorimotor and emotional experiences in coding it. To our knowledge, only one recent proposal puts forward that the processing of concrete and abstract concepts relies on the same mechanisms, with the only difference being in the complexity of the underlying experiences. In this paper, we performed a meta-analysis using the Activation Likelihood Estimates (ALE) method on 33 functional neuroimaging studies that considered activations related to abstract and concrete concepts. The results suggest that (1) concrete and abstract concepts share the recruitment of the temporo-fronto-parietal circuits normally involved in the interactions with the physical world, (2) processing concrete concepts recruits fronto-parietal areas better than abstract concepts, and (3) abstract concepts recruit Broca's region more strongly than concrete ones. Based on anatomical and physiological evidence, Broca's region is not only a linguistic region mainly devoted to speech production, but it is endowed with complex motor representations of different biological effectors. Hence, we propose that the stronger recruitment of this region for abstract concepts is expression of the complex sensorimotor experiences underlying it, rather than evidence of a purely linguistic format of its processing.

Sulcal Pattern Variability and Dorsal Anterior Cingulate Cortex Functional Connectivity Across Adult Age.

Background: The dorsal anterior cingulate cortex (dACC) is a key network hub for cognitive control and environmental adaptation. Previous studies have shown that task-based functional activity in this area is constrained by individual differences in sulcal pattern, a morphologic feature of cortex anatomy determined during fetal life and stable throughout development. Methods: By using anatomical magnetic resonance imaging and seed-based resting-state functional connectivity (rsFC), we explored the influence of sulcal pattern variability on the functional architecture of the dACC in a sample of healthy adults aged 20-80 years (n = 173). Results: Overall, rsFC was associated with individual differences in sulcal pattern. Furthermore, rsFC was modulated by the age-sulcal pattern interaction. Conclusion: Our results suggest a relationship between brain structure and function that partly traces back to early stages of brain development. The modulation of rsFC by the age-sulcal pattern interaction indicates that the effects of sulcal pattern variability on the functional architecture of the dACC may change over adulthood, with potential repercussions for brain network efficiency and cognitive function in aging.

Bilingualism as a gradient measure modulates functional connectivity of language and control networks.

There is currently no agreement on which factor modulates most effectively and enduringly brain plasticity in bilingual individuals. Grouping heterogeneous linguistic profiles under a dichotomous condition (bilingualism versus monolingualism) may obscure critical aspects of language experience underlying neural changes, thus leading to variable and often conflicting findings. In the present study, we overcome these limitations by analyzing the individual and joint contribution of L2 AoA, proficiency and usage - all measured as continuous variables - on the resting-state functional connectivity of the brain networks mediating the specific demands of bilingual language processing: the language network and the executive control network. Our results indicate that bilingual experience - defined as a continuous and multifaceted phenomenon - impacts brain plasticity by modulating the functional connectivity both within and between language and control networks. Each experience-related factor considered played a role in changing the connectivity of these regions. Moreover, the effect of AoA was modulated by proficiency and usage. These findings shed new light on the importance of modeling bilingualism as a gradient measure rather than an all-or-none phenomenon.

Bilingual language processing: A meta-analysis of functional neuroimaging studies.

Notwithstanding rising interest, a coherent picture of the brain's representation of two languages has not yet been achieved. In the present meta-analysis we analysed a large number of functional neuroimaging studies focusing on language processing in bilinguals. We used activation likelihood estimation (ALE) to enucleate activation areas involved in bilingual processing and control of different types of linguistic knowledge - lexico-semantics, grammar, phonology - in L1 and L2. Results show that surprisingly, compared to L2, lexico-semantic processing in L1 involves a widespread system of cortico-subcortical regions, especially when L2 is acquired later in life. By contrast, L2 processing recruits regions exceeding the L1 semantic network and relating to executive control processes. Only few regions displayed selective activation for grammar and phonology. Analyses of language switching highlight a functional overlap between domain-general and bilingual language control networks. Collectively, our findings point to a shared neural network for L1 and L2 with few differences depending on the linguistic level. The emerging picture identifies under-investigated issues, offering clear directions for future research.

The relationship between bilingual experience and gyrification in adulthood: A cross-sectional surface-based morphometry study.

Neuroimaging evidence suggests that bilingualism may act as a source of neural plasticity. However, prior work has mostly focused on bilingualism-induced alterations in gray matter volume and white matter tract microstructure, with additional effects related to other neurostructural indices that might have remained undetected. The degree of cortical folding or gyrification is a morphometric parameter which provides information about changes on the brain's surface during development, aging and disease. We used Surface-based Morphometry (SBM) to investigate the contribution of bilingual experience to gyrification from early adulthood to old age in a sample of bilinguals and monolingual controls. Despite widespread cortical folding reductions for all participants with increasing age, preserved gyrification exclusive to bilinguals was detected in the right cingulate and entorhinal cortices, regions vulnerable with normal and pathological brain aging. Our results provide novel insights on experience-related cortical reshaping and bilingualism-induced cortical plasticity in adulthood.

Are you really cursing? Neural processing of taboo words in native and foreign language.

The use of socially opprobrious words (taboo words) is a cross-cultural phenomenon occurring between individuals from almost all social extractions. The neurocognitive correlates of using taboo words in the native language (L1) as compared to their use in a second (L2) language are largely unknown. We used fMRI to investigate the processing of taboo and non-taboo stimuli in monolinguals (Experiment 1) and highly proficient bilinguals (Experiment 2) engaged in lexical decision tasks. We report that for L1 socio-pragmatic knowledge is automatically conveyed and taboo words are processed with less effort than non-taboo words. For L2 the processing of taboo words is more effortful and engages additional structures (anterior cingulate cortex, insula) involved in social-norm representation and evaluation. Our results contribute to understand the interface between language and social-norm processing indicating that lexical processing is affected by socio-pragmatic knowledge, but only when the speaker has a contextual use of the language.

ACC Sulcal Patterns and Their Modulation on Cognitive Control Efficiency Across Lifespan: A Neuroanatomical Study on Bilinguals and Monolinguals.

The anterior cingulate cortex (ACC) is a key structure implicated in the regulation of cognitive control (CC). Previous studies suggest that variability in the ACC sulcal pattern-a neurodevelopmental marker unaffected by maturation or plasticity after birth-is associated with intersubject differences in CC performance. Here, we investigated whether bilingual experience modulates the effects of ACC sulcal variability on CC performance across the lifespan. Using structural MRI, we first established the distribution of the ACC sulcal patterns in a large sample of healthy individuals (N = 270) differing on gender and ethnicity. Second, a participants' subsample (N = 157) was selected to test whether CC performance was differentially affected by ACC sulcation in bilinguals and monolinguals across age. A prevalent leftward asymmetry unaffected by gender or ethnicity was reported. Sulcal variability in the ACC predicted CC performance differently in bilinguals and monolinguals, with a reversed pattern of structure-function relationship: asymmetrical versus symmetrical ACC sulcal patterns were associated with a performance advantage in monolinguals and a performance detriment to bilinguals and vice versa. Altogether, these findings provide novel insights on the dynamic interplay between early neurodevelopment, environmental background and cognitive efficiency across age.

Neuroplasticity across the lifespan and aging effects in bilinguals and monolinguals.

Evidence that bilingualism protects against age-related neurocognitive decline is mixed. One relatively consistent finding is that bilingual seniors have greater grey matter volume (GMV) in regions implicated in executive control (EC) and language processing. Here, we compare the neuroplastic effects of bilingual experience on the EC network of young and aging populations directly, and for the first time we evaluate the extent to which such effects may predict executive control performance across age. We used GMV as an index of neural reserve and response time (RT) performance on the Flanker task for measuring EC efficiency. In the presence of age-related widespread GM deterioration, bilinguals had greater GMV than monolinguals in key regions of interest across age. Moreover, whereas EC performance in monolingual seniors was strictly related to GMV, this was not observed for bilingual seniors or younger participants in either group. Interactions between expected effects-of-age and language group on the relationships between GMV and RT suggested that bilingualism affords differential benefits across the lifespan. In younger participants, greater GMV offered no behavioral benefit on EC performance, whilst it did for seniors. It thus appears that age-related cognitive decline following GMV loss in the EC network is delayed in bilinguals.