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Reading fluency, the ability to read quickly and accurately, is a critical marker of successful reading and is notoriously difficult to improve in reading disabled populations. Despite its importance to functional literacy, fluency is a relatively under-studied aspect of reading, and the neural correlates of reading fluency are not well understood. Here, we review the literature of the neural correlates of reading fluency as well as rapid automatized naming (RAN), a task that is robustly related to reading fluency. In a qualitative review of the neuroimaging literature, we evaluated structural and functional MRI studies of reading fluency in readers from a range of skill levels. This was followed by a quantitative activation likelihood estimate (ALE) meta-analysis of fMRI studies of reading speed and RAN measures. We anticipated that reading speed, relative to untimed reading and reading-related tasks, would harness ventral reading pathways that are thought to enable the fast, visual recognition of words. The qualitative review showed that speeded reading taps the entire canonical reading network. The meta-analysis indicated a stronger role of the ventral reading pathway in rapid reading and rapid naming. Both reviews identified regions outside the canonical reading network that contribute to reading fluency, such as the bilateral insula and superior parietal lobule. We suggest that fluent reading engages both domain-specific reading pathways as well as domain-general regions that support overall task performance and discuss future avenues of research to expand our understanding of the neural bases of fluent reading.
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Autism spectrum disorder (ASD) is a neurodevelopmental condition frequently associated with structural cerebellar abnormalities. Whether cerebellar grey matter volumes (GMV) are linked to verbal impairments remains controversial. Here, the association between cerebellar GMV and verbal abilities in ASD was examined across the lifespan. Lobular segmentation of the cerebellum was performed on structural MRI scans from the ABIDE I dataset in male individuals with ASD (N=144, age: 8.5-64.0 years) and neurotypical controls (N=188; age: 8.0-56.2 years). Stepwise linear mixed effects modeling including group (ASD vs. neurotypical controls), lobule-wise GMV, and age was performed to identify cerebellar lobules which best predicted verbal abilities as measured by verbal IQ (VIQ). An age-specific association between VIQ and GMV of bilateral Crus II was found in ASD relative to neurotypical controls. In children with ASD, higher VIQ was associated with larger GMV of left Crus II but smaller GMV of right Crus II. By contrast, in adults with ASD, higher VIQ was associated with smaller GMV of left Crus II and larger GMV of right Crus II. These findings indicate that relative to the contralateral hemisphere, an initial reliance on the language-nonspecific left cerebellar hemisphere is offset by more typical right-lateralization in adulthood.
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Transtorno do Espectro Autista , Cerebelo , Substância Cinzenta , Imageamento por Ressonância Magnética , Humanos , Masculino , Transtorno do Espectro Autista/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Criança , Adulto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Comportamento Verbal/fisiologiaRESUMO
Cerebellar differences have long been documented in autism spectrum disorder (ASD), yet the extent to which such differences might impact language processing in ASD remains unknown. To investigate this, we recorded brain activity with magnetoencephalography (MEG) while ASD and age-matched typically developing (TD) children passively processed spoken meaningful English and meaningless Jabberwocky sentences. Using a novel source localization approach that allows higher resolution MEG source localization of cerebellar activity, we found that, unlike TD children, ASD children showed no difference between evoked responses to meaningful versus meaningless sentences in right cerebellar lobule VI. ASD children also had atypically weak functional connectivity in the meaningful versus meaningless speech condition between right cerebellar lobule VI and several left-hemisphere sensorimotor and language regions in later time windows. In contrast, ASD children had atypically strong functional connectivity for in the meaningful versus meaningless speech condition between right cerebellar lobule VI and primary auditory cortical areas in an earlier time window. The atypical functional connectivity patterns in ASD correlated with ASD severity and the ability to inhibit involuntary attention. These findings align with a model where cerebro-cerebellar speech processing mechanisms in ASD are impacted by aberrant stimulus-driven attention, which could result from atypical temporal information and predictions of auditory sensory events by right cerebellar lobule VI.
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Transtorno do Espectro Autista , Criança , Humanos , Transtorno do Espectro Autista/diagnóstico por imagem , Magnetoencefalografia , Cerebelo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Mapeamento EncefálicoRESUMO
Disorders of reading (developmental dyslexia) and attention (ADHD) have a high rate of comorbidity (25-40%), yet little is known about the neural underpinnings of this phenomenon. The current study investigated the shared and unique neural correlates of reading and attention in 330 typically developing children ages 8-18 from the Philadelphia Neurodevelopmental Cohort. Multiple regression analyses were used to identify regions of the brain where grey matter (GM) volume was associated with reading or attention scores (p < 0.001, cluster FDR p < 0.05). Better attention scores correlated with increased GM in the precuneus and higher reading scores were associated with greater thalamic GM. An exploratory conjunction analysis (p < 0.05, k > 239) found that GM in the caudate and precuneus correlated with both reading and attention scores. These results are consistent with a recent meta-analysis which identified GM reductions in the caudate in both dyslexia and ADHD and reveal potential shared neural correlates of reading and attention.
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Transtorno do Deficit de Atenção com Hiperatividade , Dislexia , Criança , Humanos , Adolescente , Substância Cinzenta/diagnóstico por imagem , Leitura , Imageamento por Ressonância Magnética/métodos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Dislexia/diagnóstico por imagemRESUMO
Social interactions involve processes ranging from face recognition to understanding others' intentions. To guide appropriate behavior in a given context, social interactions rely on accurately predicting the outcomes of one's actions and the thoughts of others. Because social interactions are inherently dynamic, these predictions must be continuously adapted. The neural correlates of social processing have largely focused on emotion, mentalizing, and reward networks, without integration of systems involved in prediction. The cerebellum forms predictive models to calibrate movements and adapt them to changing situations, and cerebellar predictive modeling is thought to extend to nonmotor behaviors. Primary cerebellar dysfunction can produce social deficits, and atypical cerebellar structure and function are reported in autism, which is characterized by social communication challenges and atypical predictive processing. We examine the evidence that cerebellar-mediated predictions and adaptation play important roles in social processes and argue that disruptions in these processes contribute to autism.
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Doenças Cerebelares , Cerebelo , Emoções , Humanos , Comportamento Social , Meio SocialRESUMO
BACKGROUND: Aphasia is a common, debilitating consequence of stroke, and speech therapy is often inadequate to achieve a satisfactory outcome. Neuromodulation techniques have emerged as a potential augmentative treatment for improving aphasia outcomes. Most studies have targeted the cerebrum, but there are theoretical and practical reasons that stimulation over the cerebral hemispheres might not be ideal. On the other hand, the right cerebellum is functionally and anatomically linked to major language areas in the left hemisphere, making it a promising alternative target site for stimulation. OBJECTIVE: To provide preliminary effect sizes for the ability of a short course of anodal transcranial direct current stimulation (tDCS) targeted over the right cerebellum to enhance language processing in individuals with chronic poststroke aphasia. METHOD: Ten individuals received five sessions of open-label anodal tDCS targeting the right cerebellum. The effects of the tDCS were compared with the effects of sham tDCS on 14 controls from a previous clinical trial. In total, 24 individuals with chronic poststroke aphasia participated in the study. Behavioral testing was conducted before treatment, immediately following treatment, and at the 3-month follow-up. RESULTS: Cerebellar tDCS did not significantly enhance language processing measured either immediately following treatment or at the 3-month follow-up. The effect sizes of tDCS over sham treatment were generally nil or small, except for the mean length of utterance on the picture description task, for which medium to large effects were observed. CONCLUSION: These results may provide guidance for investigators who are planning larger trials of tDCS for individuals with chronic poststroke aphasia.
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Afasia , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Adulto , Idoso , Afasia/etiologia , Afasia/terapia , Cerebelo , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapiaRESUMO
The human cerebellum contributes to both motor and non-motor processes. Within the cerebellum, different subregions support sensorimotor and broader cognitive functions, due to regional patterns in anatomical connectivity with the cerebral cortex and spinal and vestibular systems. We evaluated the effects of transcranial direct current stimulation (tDCS) targeting different cerebellar regions on language task performance and whole-brain functional activation patterns. Functional MRI data were acquired while 43 healthy young adults (15 males, 28 females; 23.3⯱â¯3.0â¯years) performed a sentence completion task before and after 20â¯min of 1.5â¯mA anodal tDCS. Participants received tDCS targeting either the anterior sensorimotor cerebellum (nâ¯=â¯11; 3â¯cm right of inion, over lobule V); the right posterolateral cerebellum (nâ¯=â¯18; 1â¯cm down and 4â¯cm right of inion, over lobule VII); or sham tDCS (nâ¯=â¯14). TDCS targeting the right posterolateral cerebellum improved task accuracy relative to the sham condition (pâ¯=â¯0.04) and increased activation in left frontal and temporal cortices relevant to task performance (post-tDCSâ¯>â¯pre-tDCS; T 3.17, FDR pâ¯<â¯0.05 cluster correction). The regions of increased BOLD signal after right posterolateral cerebellar tDCS fell within the network showing functional connectivity with right cerebellar lobule VII, suggesting specific modulation of this network. In contrast, tDCS targeting the sensorimotor cerebellum did not impact task performance and increased BOLD signal only in one cluster extending into the precentral gyrus. These findings indicate that sensorimotor and cognitive functional cerebellar subregions differentially impact behavioral task performance and task-relevant activation patterns, further contributing to our understanding of the cerebellar modulation of motor and non-motor functions.
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Estimulação Transcraniana por Corrente Contínua , Encéfalo , Cerebelo , Cognição , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
Cerebellar dysfunction has been demonstrated in autism spectrum disorders (ASDs); however, the circuits underlying cerebellar contributions to ASD-relevant behaviors remain unknown. In this study, we demonstrated functional connectivity between the cerebellum and the medial prefrontal cortex (mPFC) in mice; showed that the mPFC mediates cerebellum-regulated social and repetitive/inflexible behaviors; and showed disruptions in connectivity between these regions in multiple mouse models of ASD-linked genes and in individuals with ASD. We delineated a circuit from cerebellar cortical areas Right crus 1 (Rcrus1) and posterior vermis through the cerebellar nuclei and ventromedial thalamus and culminating in the mPFC. Modulation of this circuit induced social deficits and repetitive behaviors, whereas activation of Purkinje cells (PCs) in Rcrus1 and posterior vermis improved social preference impairments and repetitive/inflexible behaviors, respectively, in male PC-Tsc1 mutant mice. These data raise the possibility that these circuits might provide neuromodulatory targets for the treatment of ASD.
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Transtorno do Espectro Autista/fisiopatologia , Cerebelo/fisiopatologia , Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Animais , Masculino , Camundongos , Camundongos MutantesRESUMO
The traditional view on the cerebellum is that it controls motor behavior. Although recent work has revealed that the cerebellum supports also nonmotor functions such as cognition and affect, only during the last 5 years it has become evident that the cerebellum also plays an important social role. This role is evident in social cognition based on interpreting goal-directed actions through the movements of individuals (social "mirroring") which is very close to its original role in motor learning, as well as in social understanding of other individuals' mental state, such as their intentions, beliefs, past behaviors, future aspirations, and personality traits (social "mentalizing"). Most of this mentalizing role is supported by the posterior cerebellum (e.g., Crus I and II). The most dominant hypothesis is that the cerebellum assists in learning and understanding social action sequences, and so facilitates social cognition by supporting optimal predictions about imminent or future social interaction and cooperation. This consensus paper brings together experts from different fields to discuss recent efforts in understanding the role of the cerebellum in social cognition, and the understanding of social behaviors and mental states by others, its effect on clinical impairments such as cerebellar ataxia and autism spectrum disorder, and how the cerebellum can become a potential target for noninvasive brain stimulation as a therapeutic intervention. We report on the most recent empirical findings and techniques for understanding and manipulating cerebellar circuits in humans. Cerebellar circuitry appears now as a key structure to elucidate social interactions.
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Cerebelo/diagnóstico por imagem , Cerebelo/fisiologia , Consenso , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Cognição Social , Mapeamento Encefálico/métodos , Humanos , Mentalização/fisiologia , Desempenho Psicomotor/fisiologia , Comportamento SocialRESUMO
Quantitative magnetic resonance imaging (MRI) investigations of brain anatomy in children and young adults with Down syndrome (DS) are limited, with no diffusion tensor imaging (DTI) studies covering that age range. We used DTI-driven tensor based morphometry (DTBM), a novel technique that extracts morphometric information from diffusion data, to investigate brain anatomy in 15 participants with DS and 15 age- and sex-matched typically developing (TD) controls, ages 6-24 years (mean age ~17 years). DTBM revealed marked hypoplasia of cerebellar afferent systems in DS, including fronto-pontine (middle cerebellar peduncle) and olivo-cerebellar (inferior cerebellar peduncle) connections. Prominent gray matter hypoplasia was observed in medial frontal regions, the inferior olives, and the cerebellum. Very few abnormalities were detected by classical diffusion MRI metrics, such as fractional anisotropy and mean diffusivity. Our results highlight the potential importance of cerebro-cerebellar networks in the clinical manifestations of DS and suggest a role for DTBM in the investigation of other brain disorders involving white matter hypoplasia or atrophy.
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Antropometria/métodos , Cerebelo/anormalidades , Cerebelo/patologia , Imagem de Tensor de Difusão/métodos , Síndrome de Down/patologia , Adolescente , Adulto , Anisotropia , Atrofia , Cerebelo/anatomia & histologia , Cerebelo/diagnóstico por imagem , Criança , Síndrome de Down/diagnóstico por imagem , Feminino , Humanos , Masculino , Substância Branca/patologia , Adulto JovemRESUMO
Sporadically advocated over the last two centuries, a cerebellar role in cognition and affect has been rigorously established in the past few decades. In the clinical domain, such progress is epitomized by the "cerebellar cognitive affective syndrome" ("CCAS") or "Schmahmann syndrome." Introduced in the late 1990s, CCAS reflects a constellation of cerebellar-induced sequelae, comprising deficits in executive function, visuospatial cognition, emotion-affect, and language, over and above speech. The CCAS thus offers excellent grounds to investigate the functional topography of the cerebellum, and, ultimately, illustrate the precise mechanisms by which the cerebellum modulates cognition and affect. The primary objective of this task force paper is thus to stimulate further research in this area. After providing an up-to-date overview of the fundamental findings on cerebellar neurocognition, the paper substantiates the concept of CCAS with recent evidence from different scientific angles, promotes awareness of the CCAS as a clinical entity, and examines our current insight into the therapeutic options available. The paper finally identifies topics of divergence and outstanding questions for further research.
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Comitês Consultivos , Doenças Cerebelares/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Transtornos do Humor/diagnóstico por imagem , Doenças Cerebelares/epidemiologia , Doenças Cerebelares/psicologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Humanos , Transtornos do Humor/epidemiologia , Transtornos do Humor/psicologia , SíndromeRESUMO
BACKGROUND: Dyslexia and Attention-deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders (estimates of 25-40% bidirectional comorbidity). Previous work has identified strong genetic and cognitive overlap between the disorders, but neural overlap is relatively unexplored. This study is a systematic meta-analysis of existing voxel-based morphometry studies to determine whether there is any overlap in the gray matter correlates of both disorders. METHODS: We conducted anatomic likelihood estimate (ALE) meta-analyses of voxel-based morphometry studies in which individuals with dyslexia (15 studies; 417 cases, 416 controls) or ADHD (22 studies; 898 cases, 763 controls) were compared to typically developing controls. We generated ALE maps for dyslexia vs. controls and ADHD vs. controls using more conservative (p < .001, k = 50) and more lenient (p < .005, k = 50) thresholds. To determine the overlap of gray matter correlates of dyslexia and ADHD, we examined the statistical conjunction between the ALE maps for dyslexia vs. controls and ADHD vs. controls (false discovery rate [FDR] p < .05, k = 50, 5000 permutations). RESULTS: Results showed largely distinct gray matter differences associated with dyslexia and ADHD. There was no evidence of statistically significant gray matter overlap at our conservative threshold, and only one region of overlap in the right caudate at our more lenient threshold. Reduced gray matter in the right caudate may be relevant to shared cognitive correlates in executive functioning and/or procedural learning. The more general finding of largely distinct regional differences in gray matter between dyslexia and ADHD suggests that other neuroimaging modalities may be more sensitive to overlapping neural correlates, and that current neuroimaging recruitment approaches may be hindering progress toward uncovering neural systems associated with comorbidity. CONCLUSIONS: The current study is the first to meta-analyze overlap between gray matter differences in dyslexia and ADHD, which is a critical step toward constructing a multi-level understanding of this comorbidity that spans the genetic, neural, and cognitive levels of analysis.
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Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Núcleo Caudado/diagnóstico por imagem , Comorbidade , Dislexia/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Neuroimagem , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Dislexia/epidemiologia , HumanosRESUMO
Cerebellar neuroscience has undergone a paradigm shift. The theories of the universal cerebellar transform and dysmetria of thought and the principles of organization of cerebral cortical connections, together with neuroanatomical, brain imaging, and clinical observations, have recontextualized the cerebellum as a critical node in the distributed neural circuits subserving behavior. The framework for cerebellar cognition stems from the identification of three cognitive representations in the posterior lobe, which are interconnected with cerebral association areas and distinct from the primary and secondary cerebellar sensorimotor representations linked with the spinal cord and cerebral motor areas. Lesions of the anterior lobe primary sensorimotor representations produce dysmetria of movement, the cerebellar motor syndrome. Lesions of the posterior lobe cognitive-emotional cerebellum produce dysmetria of thought and emotion, the cerebellar cognitive affective/Schmahmann syndrome. The notion that the cerebellum modulates thought and emotion in the same way that it modulates motor control advances the understanding of the mechanisms of cognition and opens new therapeutic opportunities in behavioral neurology and neuropsychiatry.
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Encéfalo/fisiologia , Cognição/fisiologia , Emoções/fisiologia , Neurociências , Animais , Encéfalo/patologia , Ataxia Cerebelar/fisiopatologia , Doenças Cerebelares/fisiopatologia , Humanos , Neurociências/métodosRESUMO
Accumulating evidence points to a critical role for the human cerebellum in both motor and nonmotor behaviors. A core tenet of this new understanding of cerebellar function is the existence of functional subregions within the cerebellum that differentially support motor, cognitive, and affective behaviors. This cerebellar functional topography - based on converging evidence from neuroanatomic, neuroimaging, and clinical studies - is evident in both adult and pediatric populations. The sensorimotor homunculi in the anterior lobe and lobule VIII established in early tract tracing and electrophysiologic studies are evident in both task-based and resting-state human functional imaging studies. In patients, damage to the anterior cerebellum, extending into medial lobule VI, is associated with the cerebellar motor syndrome. The cerebellar posterior lobe, including vermal and hemispheric regions of lobules VI and VII, is reciprocally interconnected with cerebral association and paralimbic cortices. Resting-state and task-based neuroimaging studies show functional activation patterns in these regions during higher-level cognitive tasks, and lesions of the posterior cerebellum lead to the cerebellar cognitive affective/Schmahmann syndrome with its characteristic intellectual and emotional impairments. The existence of cerebellar connectional and functional topography provides the critical anatomic substrate for a cerebellar role in both motor and nonmotor functions. It also establishes a framework for interpreting cerebellar activation patterns, cognitive and behavioral outcomes following cerebellar damage, and the cerebellar structural and functional differences reported in a range of neurodevelopmental and neuropsychiatric disorders.
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Mapeamento Encefálico , Cerebelo/anatomia & histologia , Cerebelo/fisiologia , Animais , Cerebelo/diagnóstico por imagem , Cognição , Humanos , Rede Nervosa/citologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , NeuroimagemRESUMO
In the version of this article initially published, the Simons Foundation was missing from the list of sources of support to P.T.T. in the Acknowledgments. The error has been corrected in the HTML and PDF versions of the article.
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Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit. Atypical RCrusI-inferior parietal lobule structural connectivity was also evident in the Purkinje neuron (PN) TscI ASD mouse model. Additionally, chemogenetically mediated inhibition of RCrusI PN activity in mice was sufficient to generate ASD-related social, repetitive, and restricted behaviors, while stimulation of RCrusI PNs rescued social impairment in the PN TscI ASD mouse model. Together, these studies reveal important roles for RCrusI in ASD-related behaviors. Further, the rescue of social behaviors in an ASD mouse model suggests that investigation of the therapeutic potential of cerebellar neuromodulation in ASD may be warranted.
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Transtorno do Espectro Autista/patologia , Transtorno do Espectro Autista/psicologia , Cerebelo/patologia , Animais , Comportamento Animal , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos , Vias Neurais/fisiopatologia , Células de Purkinje , Descanso , Olfato , Comportamento Social , Adulto JovemRESUMO
There is growing evidence that the cerebellum is involved in cognition and cognitive development, yet little is known about the developmental relationship between cerebellar structure and cognitive subdomains in children. We used voxel-based morphometry to assess the relationship between cerebellar grey matter (GM) and language, reading, working memory, executive function, and processing speed in 110 individuals aged 8-17 years from the Pediatric Imaging, Neurocognition, and Genetics (PING) Study. Further, we examined the effect of age on the relationships between cerebellar GM and cognition. Higher scores on vocabulary, reading, working memory, and set-shifting were associated with increased GM in the posterior cerebellum (lobules VI-IX), in regions which are typically engaged during cognitive tasks in healthy adults. For reading, working memory, and processing speed, the relationship between cerebellar GM and cognitive performance changed with age in specific cerebellar subregions. As in adults, posterior lobe cerebellar GM was associated with cognitive performance in a pediatric population, and this relationship mirrored the known developmental trajectory of posterior cerebellar GM. These findings provide further evidence that specific regions of the cerebellum support cognition and cognitive development, and suggest that the strength of this relationship depends on developmental stage.
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Cerebelo/anatomia & histologia , Cognição/fisiologia , Função Executiva/fisiologia , Substância Cinzenta/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Criança , Feminino , Humanos , MasculinoRESUMO
It has been proposed that the cerebellum acquires internal models of mental processes that enable prediction, allowing for the optimization of behavior. In language, semantic prediction speeds speech production and comprehension. Right cerebellar lobules VI and VII (including Crus I/II) are engaged during a variety of language processes and are functionally connected with cerebral cortical language networks. Further, right posterolateral cerebellar neuromodulation modifies behavior during predictive language processing. These data are consistent with a role for the cerebellum in semantic processing and semantic prediction. We combined transcranial direct current stimulation (tDCS) and fMRI to assess the behavioral and neural consequences of cerebellar tDCS during a sentence completion task. Task-based and resting-state fMRI data were acquired in healthy human adults (n = 32; µ = 23.1 years) both before and after 20 min of 1.5 mA anodal (n = 18) or sham (n = 14) tDCS applied to the right posterolateral cerebellum. In the sentence completion task, the first four words of the sentence modulated the predictability of the final target word. In some sentences, the preceding context strongly predicted the target word, whereas other sentences were nonpredictive. Completion of predictive sentences increased activation in right Crus I/II of the cerebellum. Relative to sham tDCS, anodal tDCS increased activation in right Crus I/II during semantic prediction and enhanced resting-state functional connectivity between hubs of the reading/language networks. These results are consistent with a role for the right posterolateral cerebellum beyond motor aspects of language, and suggest that cerebellar internal models of linguistic stimuli support semantic prediction.SIGNIFICANCE STATEMENT Cerebellar involvement in language tasks and language networks is now well established, yet the specific cerebellar contribution to language processing remains unclear. It is thought that the cerebellum acquires internal models of mental processes that enable prediction, allowing for the optimization of behavior. Here we combined neuroimaging and neuromodulation to provide evidence that the cerebellum is specifically involved in semantic prediction during sentence processing. We found that activation within right Crus I/II was enhanced when semantic predictions were made, and we show that modulation of this region with transcranial direct current stimulation alters both activation patterns and functional connectivity within whole-brain language networks. For the first time, these data show that cerebellar neuromodulation impacts activation patterns specifically during predictive language processing.
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Cerebelo/fisiologia , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiologia , Tempo de Reação/fisiologia , Semântica , Estimulação Transcraniana por Corrente Contínua/métodos , Adolescente , Adulto , Cerebelo/diagnóstico por imagem , Feminino , Previsões , Humanos , Masculino , Rede Nervosa/diagnóstico por imagem , Estimulação Luminosa/métodos , Distribuição Aleatória , Método Simples-Cego , Adulto JovemRESUMO
Cerebellar lesions can cause motor deficits and/or the cerebellar cognitive affective syndrome (CCAS; Schmahmann's syndrome). We used voxel-based lesion-symptom mapping to test the hypothesis that the cerebellar motor syndrome results from anterior lobe damage whereas lesions in the posterolateral cerebellum produce the CCAS. Eighteen patients with isolated cerebellar stroke (13 males, 5 females; 20-66 years old) were evaluated using measures of ataxia and neurocognitive ability. Patients showed a wide range of motor and cognitive performance, from normal to severely impaired; individual deficits varied according to lesion location within the cerebellum. Patients with damage to cerebellar lobules III-VI had worse ataxia scores: as predicted, the cerebellar motor syndrome resulted from lesions involving the anterior cerebellum. Poorer performance on fine motor tasks was associated primarily with strokes affecting the anterior lobe extending into lobule VI, with right-handed finger tapping and peg-placement associated with damage to the right cerebellum, and left-handed finger tapping associated with left cerebellar damage. Patients with the CCAS in the absence of cerebellar motor syndrome had damage to posterior lobe regions, with lesions leading to significantly poorer scores on language (e.g. right Crus I and II extending through IX), spatial (bilateral Crus I, Crus II, and right lobule VIII), and executive function measures (lobules VII-VIII). These data reveal clinically significant functional regions underpinning movement and cognition in the cerebellum, with a broad anterior-posterior distinction. Motor and cognitive outcomes following cerebellar damage appear to reflect the disruption of different cerebro-cerebellar motor and cognitive loops.
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Doenças Cerebelares/patologia , Doenças Cerebelares/fisiopatologia , Doenças Cerebelares/psicologia , Acidente Vascular Cerebral/complicações , Adulto , Afeto , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Ataxia Cerebelar/etiologia , Ataxia Cerebelar/patologia , Ataxia Cerebelar/fisiopatologia , Ataxia Cerebelar/psicologia , Doenças Cerebelares/etiologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Função Executiva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Transtornos Motores/etiologia , Transtornos Motores/patologia , Testes Neuropsicológicos , Acidente Vascular Cerebral/patologia , Adulto JovemRESUMO
Early language delay (ELD) is one of the earliest indicators of autism spectrum disorder (ASD), and predicts later cognitive and behavioral outcomes. We aimed to determine the neural correlates of ELD in autism, and examine the relationships between gray matter (GM), age of first word/phrase, and core ASD symptoms. We used voxel-based morphometry to examine whole-brain differences in GM in 8-13 year old children with autism (n = 13 ELD; n = 22 non-ELD) and 35 age-matched typically developing (TD) children. Multiple regression analyses examined the relationships between GM, age of first word/phrase, and autism diagnostic observation schedule (ADOS) scores. Composite age of first word/phrase negatively correlated with GM throughout the cerebellum. Both ASD groups (ELD and non-ELD) had reduced GM in right cerebellar Crus I/II when compared to TD children. Left cerebellar Crus I/II was the only region in the brain that differentiated ELD and non-ELD children, with ELD children showing reduced GM relative to both non-ELD and TD groups. Group×score interactions converged in left Crus I/II, such that the non-ELD group showed poorer ADOS scores with increasing GM, whereas the ELD group showed poorer ADOS scores as GM decreased. Reduced GM in right cerebellar Crus I/I was related ASD diagnosis, while children with ELD showed additional reduced GM in left Crus I/II. These findings highlight the importance of specific cerebellar networks in both ASD and early language development, and suggest that bilateral disruption in cerebellar regions that interconnect with fronto-parietal networks could impact language acquisition in ASD. Autism Res 2016, 9: 1191-1204. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.