RESUMO
Both cortical and cerebellar developmental differences have been implicated in attention-deficit/hyperactivity disorder (ADHD). Recently accumulating neuroimaging studies have highlighted hierarchies as a fundamental principle of brain organization, suggesting the importance of assessing hierarchy abnormalities in ADHD. A novel gradient-based resting-state functional connectivity analysis was applied to investigate the cerebro-cerebellar disturbed hierarchy in children and adolescents with ADHD. We found that the interaction of functional gradient between diagnosis and age was concentrated in default mode network (DMN) and visual network (VN). At the same time, we also found that the opposite gradient changes of DMN and VN caused the compression of the cortical main gradient in ADHD patients, implicating the co-occurrence of both low- (visual processing) and high-order (self-related thought) cognitive dysfunction manifesting in abnormal cerebro-cerebellar organizational hierarchy in ADHD. Our study provides a neurobiological framework to better understand the co-occurrence and interaction of both low-level and high-level functional abnormalities in the cortex and cerebellum in ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Cerebelo , Córtex Cerebral , Conectoma , Imageamento por Ressonância Magnética , Rede Nervosa , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Adolescente , Criança , Masculino , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Feminino , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologiaRESUMO
Psychiatric symptoms are common in neurodevelopmental movement disorders, including some types of dystonia. However, research has mainly focused on motor manifestations and underlying circuits. Myoclonus-dystonia is a rare and homogeneous neurodevelopmental condition serving as an illustrative paradigm of childhood-onset dystonias, associated with psychiatric symptoms. Here, we assessed the prevalence of psychiatric disorders and the severity of depressive symptoms in patients with myoclonus-dystonia and healthy volunteers (HV). Using resting-state functional neuroimaging, we compared the effective connectivity within and among non-motor and motor brain networks between patients and HV. We further explored the hierarchical organization of these networks and examined the relationship between their connectivity and the depressive symptoms. Comparing 19 patients to 25 HV, we found a higher prevalence of anxiety disorders and more depressive symptoms in the patient group. Patients exhibited abnormal modulation of the cerebellum on the cerebral cortex in the sensorimotor, dorsal attention, salience, and default mode networks. Moreover, the salience network activity was directed by the cerebellum in patients and was related to depressive symptoms. Altogether, our findings highlight the role of the cerebellar drive on both motor and non-motor cortical areas in this disorder, suggesting cerebellar involvement in the complex phenotype of such neurodevelopmental movement disorders.
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Cerebelo , Córtex Cerebral , Distúrbios Distônicos , Humanos , Masculino , Feminino , Cerebelo/fisiopatologia , Cerebelo/diagnóstico por imagem , Distúrbios Distônicos/fisiopatologia , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Adulto , Fenótipo , Depressão/fisiopatologia , Adulto Jovem , Imageamento por Ressonância Magnética , Adolescente , Transtornos do Neurodesenvolvimento/fisiopatologiaRESUMO
INTRODUCTION: The cerebellar response has been studied for years with different models of alteration of other brain structures to understand its complex functioning and its relationship with the rest of the body. Studies in patients with Parkinson's disease (PD) showed that the cerebellar function is modified by deficit of the basal ganglia; which supports the hypothesis that both structures are related anatomically and functionally. METHODS: In our study, the ventrolateral striatum (VLS) of the basal ganglia was altered by an electrolytic lesion, in order to produce a similar jaw frequency of jaw tremor movements presented in parkinsonism, thereafter we analyzed the effect of the lesion on the expression of multiunit activity (MUA) of the cerebellum. RESULTS: We found cerebellar activation during mandibular movements and increment during oral jaw tremor movements. In addition, the amplitude of baseline MUA registered in animals with alteration of the VLS decreased with respect to the intact group. CONCLUSIONS: Accordingly, we conclude that cerebellar changes in MUA may be due to a decrease in the cerebellar inflectional or as a possible compensatory function between cerebellum and basal ganglia.
Assuntos
Gânglios da Base , Cerebelo , Transtornos Parkinsonianos , Cerebelo/fisiopatologia , Gânglios da Base/fisiopatologia , Animais , Transtornos Parkinsonianos/fisiopatologia , Modelos Animais de Doenças , Masculino , Tremor/fisiopatologiaRESUMO
BACKGROUND: The pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls. METHODS: To that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM. RESULTS: We found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine. CONCLUSIONS: A distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology.
Assuntos
Cerebelo , Conectoma , Imageamento por Ressonância Magnética , Transtornos de Enxaqueca , Humanos , Feminino , Adulto , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Cerebelo/patologia , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/fisiopatologia , Transtornos de Enxaqueca/patologia , Adulto Jovem , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors, with childhood trauma recognized as a contributing factor to its pathophysiology. This study aimed to delineate brain functional aberrations in OCD patients and explore the association between these abnormalities and childhood trauma, to gain insights into the neural underpinnings of OCD. Forty-eight drug-naive OCD patients and forty-two healthy controls (HC) underwent resting-state functional magnetic resonance imaging and clinical assessments, including the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Childhood Trauma Questionnaire-Short Form (CTQ-SF). Compared to HCs, OCD patients exhibited significantly decreased amplitude of low-frequency fluctuations (ALFF) in the right cerebellum, decreased regional homogeneity (ReHo) in the right cerebellum and right superior occipital lobes (FWE-corrected p < 0.05), which negatively correlated with Y-BOCS scores (p < 0.05). Furthermore, cerebellar ALFF negatively correlated with the CTQ emotional abuse subscale (r = - 0.514, p < 0.01). Mediation analysis revealed that cerebellar ALFF mediated the relationship between CTQ-emotional abuse and Y-BOCS (good model fit: R2 = 0.231, MSE = 14.311, F = 5.721, p < 0.01; direct effect, c' = 0.153, indirect effect, a*b = 0.191). Findings indicated abnormal spontaneous and regional cerebellar activity in OCD, suggesting childhood trauma impacts OCD symptoms through cerebellar neural remodeling, highlighting its importance for clinical treatment selection.
Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Masculino , Feminino , Adulto , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Cerebelo/fisiopatologia , Cerebelo/diagnóstico por imagem , Mapeamento Encefálico , Adulto Jovem , Estudos de Casos e ControlesRESUMO
In this randomized, double-blind, sham-controlled trial of Cerebellar Stimulation for Aphasia Rehabilitation (CeSAR), we will determine the effectiveness of cathodal tDCS (transcranial direct current stimulation) to the right cerebellum for the treatment of chronic aphasia (>6 months post stroke). We will test the hypothesis that cerebellar tDCS in combination with an evidenced-based anomia treatment (semantic feature analysis, SFA) will be associated with greater improvement in naming untrained pictures (as measured by the change in Philadelphia Picture Naming Test), 1-week post-treatment, compared to sham plus SFA. We will also evaluate the effects of cerebellar tDCS on naming trained items as well as the effects on functional communication, content, efficiency, and word-retrieval of picture description, and quality of life. Finally, we will identify imaging and linguistic biomarkers to determine the characteristics of stroke patients that benefit from cerebellar tDCS and SFA treatment. We expect to enroll 60 participants over five years. Participants will receive 15, 25-minute sessions of cerebellar tDCS (3-5 sessions per week) or sham tDCS combined with 1 hour of SFA treatment. Participants will be evaluated prior to the start of treatment, one-week post-treatment, 1-, 3-, and 6-months post-treatment on primary and secondary outcome variables. The long-term aim of this study is to provide the basis for a Phase III randomized controlled trial of cerebellar tDCS vs sham with concurrent language therapy for treatment of chronic aphasia. Trial registration: The trial is registered with ClinicalTrials.gov NCT05093673.
Assuntos
Afasia , Cerebelo , Estimulação Transcraniana por Corrente Contínua , Humanos , Afasia/reabilitação , Afasia/terapia , Afasia/etiologia , Método Duplo-Cego , Estimulação Transcraniana por Corrente Contínua/métodos , Cerebelo/fisiopatologia , Masculino , Feminino , Reabilitação do Acidente Vascular Cerebral/métodos , Pessoa de Meia-Idade , Qualidade de Vida , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Adulto , Resultado do Tratamento , IdosoRESUMO
Hyperactivity in children with attention-deficit/hyperactivity disorder (ADHD) leads to restlessness and impulse-control impairments. Nevertheless, the relation between ADHD symptoms and brain regions interactions remains unclear. We focused on dynamic causal modeling to study the effective connectivity in a fully connected network comprised of four regions of the default mode network (DMN) (linked to response control behaviors) and four other regions with previously-reported structural alterations due to ADHD. Then, via the parametric empirical Bayes analysis, the most significant connections, with the highest correlation to the covariates ADHD/control, age, and sex were extracted. Our results demonstrated a positive correlation between ADHD and effective connectivity between the right cerebellum and three DMN nodes (intrinsically inhibitory connections). Therefore, an increase in the effective connectivity leads to more inhibition imposition from the right cerebellum to DMN that reduces this network activation. The lower DMN activity makes leaving the resting-state easier, which may be involved in the restlessness symptom. Furthermore, our results indicated a negative correlation between age and these connections. We showed that the difference between the average of effective connectivities of ADHD and control groups in the age-range of 7-11 years disappeared after 14 years-old. Therefore, aging tends to alleviate ADHD-specific symptoms.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Cerebelo , Rede de Modo Padrão , Hipocampo , Imageamento por Ressonância Magnética , Vias Neurais , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Masculino , Criança , Feminino , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia , Córtex Visual/diagnóstico por imagem , Córtex Visual/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Conectoma/métodosRESUMO
AIM: Cerebello-cortical functional dysconnectivity plays a key role in the pathology of schizophrenia (SZ). We aimed to investigate the changes in cerebello-cortical directional connectivity in patients with SZ. METHODS: A total of 180 drug-naïve patients with first-episode SZ (54 reassessed after 1 year of treatment) and 166 healthy controls (HCs) were included. Resting-state functional magnetic resonance imaging was used to perform Granger causal analysis, in which each of the nine cerebellar functional systems was defined as a seed. The observed effective connectivity (EC) alterations at baseline were further assessed at follow-up and were associated with changes in psychotic symptom. RESULTS: We observed increased bottom-up EC in first-episode SZ from the cerebellum to the cerebrum (e.g. from the cerebellar attention and cingulo-opercular systems to the bilateral angular gyri, and from the cerebellar cingulo-opercular system to the right inferior frontal gyrus). In contrast, decreased top-down EC in the first-episode SZ was mainly from the cerebrum to the cerebellum (e.g. from the right inferior temporal gyrus, left middle temporal gyrus, left putamen, and right angular gyrus to the cerebellar language system). After 1 year of antipsychotic treatment, information projections from the cerebrum to the cerebellum were partly restored and positively related to symptom remission. CONCLUSION: These findings suggest that decreased top-down EC during the acute phase of SZ may be a state-dependent alteration related to symptoms and medication. However, increased bottom-up EC may reflect a persistent pathological trait.
Assuntos
Antipsicóticos , Cerebelo , Conectoma , Imageamento por Ressonância Magnética , Esquizofrenia , Humanos , Esquizofrenia/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Masculino , Adulto , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Feminino , Antipsicóticos/farmacologia , Antipsicóticos/administração & dosagem , Adulto Jovem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , SeguimentosRESUMO
The role of cerebellar-cerebral functional connectivity (CC-FC) in obsessive-compulsive disorder (OCD), its trajectory post-pharmacotherapy, and its potential as a prognostic biomarker and genetic mechanism remain uncertain. To address these gaps, this study included 37 drug-naive OCD patients and 37 healthy controls (HCs). Participants underwent baseline functional magnetic resonance imaging (fMRI), followed by four weeks of paroxetine treatment for patients with OCD, and another fMRI scan post-treatment. We examined seed-based CC-FC differences between the patients and HCs, and pre- and post-treatment patients. Support vector regression (SVR) based on CC-FC was performed to predict treatment response. Correlation analysis explored associations between CC-FC and clinical features, as well as gene profiles. Compared to HCs, drug-naive OCD patients exhibited reduced CC-FC in executive, affective-limbic, and sensorimotor networks, with specific genetic profiles associated with altered CC-FC. Gene enrichment analyses highlighted the involvement of these genes in various biological processes, molecular functions, and pathways. Post-treatment, the patients showed partial clinical improvement and partial restoration of the previously decreased CC-FC. Abnormal CC-FC at baseline correlated negatively with compulsions severity and social functional impairment, while changes in CC-FC correlated with cognitive function changes post-treatment. CC-FC emerged as a potential predictor of symptom severity in patients following paroxetine treatment. This longitudinal resting-state fMRI study underscores the crucial role of CC-FC in the neuropsychological mechanisms of OCD and its pharmacological treatment. Transcriptome-neuroimaging spatial correlation analyses provide insight into the neurobiological mechanisms underlying OCD pathology. Furthermore, SVR analyses hold promise for advancing precision medicine approaches in treating patients with OCD.
Assuntos
Cerebelo , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo , Paroxetina , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Masculino , Adulto , Feminino , Estudos Longitudinais , Paroxetina/farmacologia , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Adulto Jovem , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Conectoma , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologiaRESUMO
Cognitive functioning is a crucial aspect in schizophrenia (SZ), and when altered it has devastating effects on patients' quality of life and treatment outcomes. Several studies suggested that they could result from altered communication between the cortex and cerebellum. However, the neural correlates underlying these impairments have not been identified. In this study, we investigated resting state functional connectivity (rsFC) in SZ patients, by considering the interactions between cortical networks supporting cognition and cerebellum. In addition, we investigated the relationship between SZ patients' rsFC and their symptoms. We used fMRI data from 74 SZ patients and 74 matched healthy controls (HC) downloaded from the publicly available database SchizConnect. We implemented a seed-based connectivity approach to identify altered functional connections between specific cortical networks and cerebellum. We considered ten commonly studied resting state networks, whose functioning encompasses specific cognitive functions, and the cerebellum, whose involvement in supporting cognition has been recently identified. We then explored the relationship between altered rsFC values and Positive and Negative Syndrome Scale (PANSS) scores. The SZ group showed increased connectivity values compared with HC group for cortical networks involved in attentive processes, which were also linked to PANSS items describing attention and language-related processing. We also showed decreased connectivity between cerebellar regions, and increased connectivity between them and attentive networks, suggesting the contribution of cerebellum to attentive and affective deficits. In conclusion, our findings highlighted the link between negative symptoms in SZ and altered connectivity within the cerebellum and between the same and cortical networks supporting cognition.
Assuntos
Cerebelo , Conectoma , Imageamento por Ressonância Magnética , Rede Nervosa , Esquizofrenia , Humanos , Esquizofrenia/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Cerebelo/fisiopatologia , Cerebelo/diagnóstico por imagem , Masculino , Adulto , Feminino , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Pessoa de Meia-Idade , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico por imagemRESUMO
The cerebellum has been involved in social abilities and autism. Given that the cerebellum is connected to the cortex via the cerebello-thalamo-cortical loop, the connectivity between the cerebellum and cortical regions involved in social interactions, that is, the right temporo-parietal junction (rTPJ) has been studied in individuals with autism, who suffer from prototypical deficits in social abilities. However, existing studies with small samples of categorical, case-control comparisons have yielded inconsistent results due to the inherent heterogeneity of autism, suggesting that investigating how clinical dimensions are related to cerebellar-rTPJ functional connectivity might be more relevant. Therefore, our objective was to study the functional connectivity between the cerebellum and rTPJ, focusing on its association with social abilities from a dimensional perspective in a transdiagnostic sample. We analyzed structural magnetic resonance imaging (MRI) and functional MRI (fMRI) scans obtained during naturalistic films watching from a large transdiagnostic dataset, the Healthy Brain Network (HBN), and examined the association between cerebellum-rTPJ functional connectivity and social abilities measured with the social responsiveness scale (SRS). We conducted univariate seed-to-voxel analysis, multivariate canonical correlation analysis (CCA), and predictive support vector regression (SVR). We included 1404 subjects in the structural analysis (age: 10.516 ± 3.034, range: 5.822-21.820, 506 females) and 414 subjects in the functional analysis (age: 11.260 ± 3.318 years, range: 6.020-21.820, 161 females). Our CCA model revealed a significant association between cerebellum-rTPJ functional connectivity, full-scale IQ (FSIQ) and SRS scores. However, this effect was primarily driven by FSIQ as suggested by SVR and univariate seed-to-voxel analysis. We also demonstrated the specificity of the rTPJ and the influence of structural anatomy in this association. Our results suggest that there is a complex relationship between cerebellum-rTPJ connectivity, social performance and IQ. This relationship is specific to the cerebellum-rTPJ connectivity, and is largely related to structural anatomy in these two regions. PRACTITIONER POINTS: We analyzed cerebellum-right temporoparietal junction (rTPJ) connectivity in a pediatric transdiagnostic sample. We found a complex relationship between cerebellum and rTPJ connectivity, social performance and IQ. Cerebellum and rTPJ functional connectivity is related to structural anatomy in these two regions.
Assuntos
Cerebelo , Imageamento por Ressonância Magnética , Humanos , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Cerebelo/patologia , Masculino , Feminino , Adulto Jovem , Adulto , Conectoma/métodos , Habilidades Sociais , Adolescente , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagemRESUMO
Parkinson's disease (PD) is characterized by decreased dopamine in the basal ganglia that causes excessive tonic inhibition of the thalamus. This excessive inhibition seems to explain inhibitory motor symptoms in PD, but the source of tremor remains unclear. This paper investigates how neural inhibition may change the closed-loop characteristics of the human motor control system to determine how this established pathophysiology could produce tremor. The rate-coding model of neural signals suggests increased inhibition decreases signal amplitude, which could create a mismatch between the closed-loop dynamics and the internal models that overcome proprioceptive feedback delays. This paper aims to identify a candidate model structure with decreased-amplitude-induced tremor in PD that also agrees with previously recorded movements of healthy and cerebellar patients. The optimal feedback control theory of human motor control forms the basis of the model. Key additional elements include gating of undesired movements via the basal ganglia-thalamus-motor cortex circuit and the treatment of the efferent copy of the control input as a measurement in the state estimator. Simulations confirm the model's ability to capture tremor in PD and also demonstrate how disease progression could affect tremor and other motor symptoms, providing insight into the existence of tremor and non-tremor phenotypes. Altogether, the physiological underpinnings of the model structure and the agreement of model predictions with clinical observations provides support for the hypothesis that unstable feedback produces parkinsonian tremor. Consequently, these results also support the associated framework for the neuroanatomy of human motor control.
Assuntos
Gânglios da Base , Simulação por Computador , Doença de Parkinson , Tremor , Humanos , Tremor/fisiopatologia , Tremor/etiologia , Gânglios da Base/fisiopatologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Modelos Neurológicos , Córtex Motor/fisiopatologia , Tálamo/fisiopatologia , Algoritmos , Retroalimentação Fisiológica , Cerebelo/fisiopatologia , Movimento/fisiologiaRESUMO
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that often persists into adulthood. Underlying alterations in brain connectivity have been identified but some relevant connections, such as the middle, superior, and inferior cerebellar peduncles (MCP, SCP, and ICP, respectively), have remained largely unexplored; thus, we sought to investigate whether the cerebellar peduncles contribute to ADHD pathophysiology among adults. METHODS: We applied diffusion-weighted spherical deconvolution tractography to dissect the cerebellar peduncles of male adults with ADHD (including those who did or did not respond to methylphenidate, based on at least 30% symptom improvement at 2 months) and controls. We investigated differences in tract metrics between controls and the whole ADHD sample and between controls and treatment-response groups using sensitivity analyses. Finally, we analyzed the association between the tract metrics and cliniconeuropsychological profiles. RESULTS: We included 60 participants with ADHD (including 42 treatment responders and 18 nonresponders) and 20 control participants. In the whole ADHD sample, MCP fractional anisotropy (FA; t 78 = 3.24, p = 0.002) and hindrance modulated orientational anisotropy (HMOA; t 78 = 3.01, p = 0.004) were reduced, and radial diffusivity (RD) in the right ICP was increased (t 78 = -2.84, p = 0.006), compared with controls. Although case-control differences in MCP FA and HMOA, which reflect white-matter microstructural organization, were driven by both treatment response groups, only responders significantly differed from controls in right ICP RD, which relates to myelination (t 60 = 3.14, p = 0.003). Hindrance modulated orientational anisotropy of the MCP was significantly positively associated with hyperactivity measures. LIMITATIONS: This study included only male adults with ADHD. Further research needs to investigate potential sex- and development-related differences. CONCLUSION: These results support the role of the cerebellar networks, especially of the MCP, in adult ADHD pathophysiology and should encourage further investigation. CLINICAL TRIAL REGISTRATION: NCT03709940.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Cerebelo , Imagem de Tensor de Difusão , Metilfenidato , Adulto , Humanos , Masculino , Adulto Jovem , Anisotropia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Estudos de Casos e Controles , Estimulantes do Sistema Nervoso Central , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Cerebelo/fisiopatologia , Metilfenidato/uso terapêutico , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/patologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
Background: The basal ganglia-thalamocortical (BGTC) and cerebello-thalamocortical (CTC) networks are implicated in tremor genesis; however, exact contributions across disorders have not been studied. Objective: Evaluate the structural connectivity of BGTC and CTC in tremor-dominant Parkinson's disease (TDPD) and essential tremor plus (ETP) with the aid of probabilistic tractography and graph theory analysis. Methods: Structural connectomes of the BGTC and CTC were generated by probabilistic tractography for TDPD (n = 25), ETP (ET with rest tremor, n = 25), and healthy control (HC, n = 22). The Brain Connectivity Toolbox was used for computing standard topological graph measures of segregation, integration, and centrality. Tremor severity was ascertained using the Fahn-Tolosa-Marin tremor rating scale (FTMRS). Results: There was no difference in total FTMRS scores. Compared with HC, TDPD had a lower global efficiency and characteristic path length. Abnormality in segregation, integration, and centrality of bilateral putamen, globus pallidus externa (GPe), and GP interna (GPi), with reduction of centrality of right caudate and cerebellar lobule 8, was observed. ETP showed reduction in segregation and integration of right GPe and GPi, ventrolateral posterior nucleus, and centrality of right putamen, compared with HC. Differences between TDPD and ETP were a reduction of strength of the right putamen, and lower clustering coefficient, local efficiency, and strength of the left GPi in TDPD. Conclusions: Contrary to expectations, TDPD and ETP may not be significantly different with regard to tremor pathogenesis, with definite overlaps. There may be fundamental similarities in network disruption across different tremor disorders with the same tremor activation patterns, along with disease-specific changes.
Assuntos
Imagem de Tensor de Difusão , Tremor Essencial , Vias Neurais , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/fisiopatologia , Tremor Essencial/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Imagem de Tensor de Difusão/métodos , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Conectoma/métodos , Tremor/diagnóstico por imagem , Tremor/fisiopatologia , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Cerebelo/patologia , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologiaRESUMO
Neuroimaging studies on healthy subjects described the causal effective connectivity of cerebellar-cerebral social mentalizing networks, revealing the presence of closed-loops. These studies estimated effective connectivity by applying Dynamic Causal Modeling on task-related fMRI data of healthy subjects performing mentalizing tasks. Thus far, few studies have applied Dynamic Causal Modeling to resting-state fMRI (rsfMRI) data to test the effective connectivity within the cerebellar-cerebral mentalizing network in the absence of experimental manipulations, and no study applied Dynamic Causal Modeling on fMRI data of patients with cerebellar disorders typically showing social cognition deficits. Thus, in this research we applied spectral Dynamic Causal Modeling, to rsfMRI data of 13 patients affected by spinocerebellar ataxia type 2 (SCA2) and of 23 matched healthy subjects. Specifically, effective connectivity was tested between acknowledged mentalizing regions of interest: bilateral cerebellar Crus II, dorsal and ventral medial prefrontal cortex, bilateral temporo-parietal junctions and precuneus. SCA2 and healthy subjects shared some similarities in cerebellar-cerebral mentalizing effective connectivity at rest, confirming the presence of closed-loops between cerebellar and cerebral mentalizing regions in both groups. However, relative to healthy subjects, SCA2 patients showed effective connectivity variations mostly in cerebellar-cerebral closed loops, namely weakened inhibitory connectivity from the cerebellum to the cerebral cortex, but stronger inhibitory connectivity from the cerebral cortex to the cerebellum. The present study demonstrated that effective connectivity changes affect a function-specific mentalizing network in SCA2 patients, allowing to deepen the direction and strength of the causal effective connectivity mechanisms driven by the cerebellar damage associated with SCA2.
Assuntos
Imageamento por Ressonância Magnética , Ataxias Espinocerebelares , Humanos , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Ataxias Espinocerebelares/fisiopatologia , Ataxias Espinocerebelares/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Descanso/fisiologia , Teoria da Mente/fisiologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Mentalização/fisiologia , Mapeamento Encefálico/métodos , Cerebelo/fisiopatologia , Cerebelo/diagnóstico por imagem , IdosoRESUMO
PURPOSE: To investigate dynamic functional connectivity (dFC) within the cerebellar-whole brain network and dynamic topological properties of the cerebellar network in obstructive sleep apnea (OSA) patients. METHODS: Sixty male patients and 60 male healthy controls were included. The sliding window method examined the fluctuations in cerebellum-whole brain dFC and connection strength in OSA. Furthermore, graph theory metrics evaluated the dynamic topological properties of the cerebellar network. Additionally, hidden Markov modeling validated the robustness of the dFC. The correlations between the abovementioned measures and clinical assessments were assessed. RESULTS: Two dynamic network states were characterized. State 2 exhibited a heightened frequency, longer fractional occupancy, and greater mean dwell time in OSA. The cerebellar networks and cerebrocerebellar dFC alterations were mainly located in the default mode network, frontoparietal network, somatomotor network, right cerebellar CrusI/II, and other networks. Global properties indicated aberrant cerebellar topology in OSA. Dynamic properties were correlated with clinical indicators primarily on emotion, cognition, and sleep. CONCLUSION: Abnormal dFC in male OSA may indicate an imbalance between the integration and segregation of brain networks, concurrent with global topological alterations. Abnormal default mode network interactions with high-order and low-level cognitive networks, disrupting their coordination, may impair the regulation of cognitive, emotional, and sleep functions in OSA.
Assuntos
Cerebelo , Rede Nervosa , Apneia Obstrutiva do Sono , Humanos , Masculino , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Pessoa de Meia-Idade , Adulto , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Imageamento por Ressonância Magnética , Conectoma , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagemRESUMO
BACKGROUND: The application of cerebellar transcranial magnetic stimulation (TMS) in stroke patients has received increasing attention due to its neuromodulation mechanisms. However, studies on the effect and safety of cerebellar TMS to improve balance capacity and activity of daily living (ADL) for stroke patients are limited. This systematic review and meta-analysis aimed to investigate the effect and safety of cerebellar TMS on balance capacity and ADL in stroke patients. METHOD: A systematic search of seven electronic databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang and Chinese Scientific Journal) were conducted from their inception to October 20, 2023. The randomized controlled trials (RCTs) of cerebellar TMS on balance capacity and/or ADL in stroke patients were enrolled. The quality of included studies were assessed by Physiotherapy Evidence Database (PEDro) scale. RESULTS: A total of 13 studies involving 542 participants were eligible. The pooled results from 8 studies with 357 participants showed that cerebellar TMS could significantly improve the post-intervention Berg balance scale (BBS) score (MD = 4.24, 95%CI = 2.19 to 6.29, P < 0.00001; heterogeneity, I2 = 74%, P = 0.0003). The pooled results from 4 studies with 173 participants showed that cerebellar TMS could significantly improve the post-intervention Time Up and Go (TUG) (MD=-1.51, 95%CI=-2.8 to -0.22, P = 0.02; heterogeneity, I2 = 0%, P = 0.41). The pooled results from 6 studies with 280 participants showed that cerebellar TMS could significantly improve the post-intervention ADL (MD = 7.75, 95%CI = 4.33 to 11.17, P < 0.00001; heterogeneity, I2 = 56%, P = 0.04). The subgroup analysis showed that cerebellar TMS could improve BBS post-intervention and ADL post-intervention for both subacute and chronic stage stroke patients. Cerebellar high frequency TMS could improve BBS post-intervention and ADL post-intervention. Cerebellar TMS could still improve BBS post-intervention and ADL post-intervention despite of different cerebellar TMS sessions (less and more than 10 TMS sessions), different total cerebellar TMS pulse per week (less and more than 4500 pulse/week), and different cerebellar TMS modes (repetitive TMS and Theta Burst Stimulation). None of the studies reported severe adverse events except mild side effects in three studies. CONCLUSIONS: Cerebellar TMS is an effective and safe technique for improving balance capacity and ADL in stroke patients. Further larger-sample, higher-quality, and longer follow-up RCTs are needed to explore the more reliable evidence of cerebellar TMS in the balance capacity and ADL, and clarify potential mechanisms.
Assuntos
Atividades Cotidianas , Cerebelo , Equilíbrio Postural , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Equilíbrio Postural/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Cerebelo/fisiologia , Cerebelo/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
The role of the cerebellum in amnestic mild cognitive impairment (aMCI), typically a prodromal stage of Alzheimer's disease, is not fully understood. We studied the lobule-specific cerebello-cerebral connectivity in 15 cognitively normal and 16 aMCI using resting-state functional MRI. Our analysis revealed weaker connectivity between the cognitive cerebellar lobules and parietal lobe in aMCI. However, stronger connectivity was observed in the cognitive cerebellar lobules with certain brain regions, including the precuneus cortex, posterior cingulate gyrus, and caudate nucleus in participants with worse cognition. Leveraging these measurable changes in cerebello-parietal functional networks in aMCI could offer avenues for future therapeutic interventions.