Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas

Altmetric: 2More detail Article | OPEN Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas Fulvia Palesi, Andrea De Rinaldis, Gloria Castellazzi, Fernando Calamante, Nils Muhlert, Declan Chard, J. Donald Tournier, Giovanni Magenes, Egidio D’Angelo & Claudia A. M. Gandini Wheeler-Kingshott Scientific Reports 7, Article number: 12841 (2017) doi:10.1038/s41598-017-13079-8 Download Citation BrainNeuroscience Received: 11 May 2017 Accepted: 18 September 2017 Published online: 09 October 2017 Abstract Cerebellar involvement in cognition, as well as in sensorimotor control, is increasingly recognized and is thought to depend on connections with the cerebral cortex. Anatomical investigations in animals and post-mortem humans have established that cerebro-cerebellar connections are contralateral to each other and include the cerebello-thalamo-cortical (CTC) and cortico-ponto-cerebellar (CPC) pathways. CTC and CPC characterization in humans in vivo is still challenging. Here advanced tractography was combined with quantitative indices to compare CPC to CTC pathways in healthy subjects. Differently to previous studies, our findings reveal that cerebellar cognitive areas are reached by the largest proportion of the reconstructed CPC, supporting the hypothesis that a CTC-CPC loop provides a substrate for cerebro-cerebellar communication during cognitive processing. Amongst the cerebral areas identified using in vivo tractography, in addition to the cerebral motor cortex, major portions of CPC streamlines leave the prefrontal and temporal cortices. These findings are useful since provide MRI-based indications of possible subtending connectivity and, if confirmed, they are going to be a milestone for instructing computational models of brain function. These results, together with further multi-modal investigations, are warranted to provide important cues on how the cerebro-cerebellar loops operate and on how pathologies involving cerebro-cerebellar connectivity are generated

Development of brain structures following perinatal cerebral lesions suggests the involvement of the cerebellum in the working memory network

openCrossed cerebro-cerebellar diaschisis in very preterm born individuals, following perinatal cerebral lesions, reveals functional connectivity between some cerebral areas involved in working memory (WM) and yet undefined cerebellar regions: this may support the role of the latter in the WM network. The cerebellum has long been associated with motor control and coordination. In the last two decades, researchers have studied its involvement in a broad range of cognitive functions, such as visuospatial attention and WM. In this overview, I define the brain regions activated by the WM network and their development in term- and very preterm- infants compared, according to the most recent studies. These findings could contribute to support the involvement of the cerebellum in non-motor functions, specifically in WM.Crossed cerebro-cerebellar diaschisis in very preterm born individuals, following perinatal cerebral lesions, reveals functional connectivity between some cerebral areas involved in working memory (WM) and yet undefined cerebellar regions: this may support the role of the latter in the WM network. The cerebellum has long been associated with motor control and coordination. In the last two decades, researchers have studied its involvement in a broad range of cognitive functions, such as visuospatial attention and WM. In this overview, I define the brain regions activated by the WM network and their development in term- and very preterm- infants compared, according to the most recent studies. These findings could contribute to support the involvement of the cerebellum in non-motor functions, specifically in WM

Towards a systems-level view of cerebellar function::the interplay between cerebellum, basal ganglia and cortex

Contains fulltext : 170319.pdf (Publisher’s version ) (Open Access)Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field

Human brain networks of auditory attention and working memory

This thesis examines brain networks involved in auditory attention and auditory working memory using measures of task performance, brain activity, and neuroanatomical connectivity. Auditory orienting and maintenance of attention were compared with visual orienting and maintenance of attention, and top-down controlled attention was compared to bottom-up triggered attention in audition. Moreover, the effects of cognitive load on performance and brain activity were studied using an auditory working memory task. Corbetta and Shulman s (2002) model of visual attention suggests that what is known as the dorsal attention system (intraparietal sulcus/superior parietal lobule, IPS/SPL and frontal eye field, FEF) is involved in the control of top-down controlled attention, whereas what is known as the ventral attention system (temporo-parietal junction, TPJ and areas of the inferior/middle frontal gyrus, IFG/MFG) is involved in bottom-up triggered attention. The present results show that top-down controlled auditory attention also activates IPS/SPL and FEF. Furthermore, in audition, TPJ and IFG/MFG were activated not only by bottom-up triggered attention, but also by top-down controlled attention. In addition, the posterior cerebellum and thalamus were activated by top-down controlled attention shifts and the ventromedial prefrontal cortex (VMPFC) was activated by to-be-ignored, but attention-catching salient changes in auditory input streams. VMPFC may be involved in the evaluation of environmental events causing the bottom-up triggered engagement of attention. Auditory working memory activated a brain network that largely overlapped with the one activated by top-down controlled attention. The present results also provide further evidence of the role of the cerebellum in cognitive processing: During auditory working memory tasks, both activity in the posterior cerebellum (the crus I/II) and reaction speed increased when the cognitive load increased. Based on the present results and earlier theories on the role of the cerebellum in cognitive processing, the function of the posterior cerebellum in cognitive tasks may be related to the optimization of response speed.Tässä väitöskirjatutkimuksessa tutkittiin kuulotarkkaavaisuuteen ja kuulonvaraiseen työmuistiin liittyviä aivoverkostoja mittaamalla tehtäväsuoriutumista, aivojen aktivaatiota ja aivoalueiden välisiä anatomisia yhteyksiä. Ääniin kohdistuvan tarkkaavaisuuden suuntaamista ja ylläpitoa verrattiin kuviin kohdistuvan tarkkaavaisuuden suuntaamiseen ja ylläpitoon, sekä ääniin tavoitteellisesti kohdistettua tarkkaavaisuutta verrattiin niihin tahattomasti kohdistuvaan tarkkaavaisuuteen. Lisäksi tutkittiin kognitiivisen kuormituksen vaikutuksia tehtäväsuoriutumiseen ja aivojen aktivaatioon kuulonvaraisessa työmuistitehtävässä. Corbettan ja Shulmanin (2002) mallin mukaan niin sanottu dorsaalinen tarkkaavaisuusjärjestelmä (päälaen- ja otsalohkon yläosien taaemmat alueet) säätelee tavoitteellista, ylhäältä alaspäin kontrolloitua näkötarkkaavaisuutta, kun taas niin sanottu ventraalinen tarkkaavaisuusjärjestelmä (päälaenlohkon alaosan ja etuotsalohkon sivun alaosan taaemmat alueet) osallistuu näkökohteiden alhaalta ylöspäin käynnistämään tarkkaavaisuuteen. Osoitimme, että myös tavoitteellinen kuulotarkkaavaisuuden suuntaaminen aktivoi samoja päälaenlohkon ja etuotsalohkon yläosien taaempia alueita kun näkötarkkaavaisuuden suuntaaminen. Kuulojärjestelmässä päälaenlohkon alaosan ja etuotsalohkon sivun taaempien alaosan alueiden aktivaation kasvu ei sen sijaan liittynyt vain äänten käynnistämään tahattomaan tarkkaavaisuuteen, vaan myös tavoitteelliseen kuulotarkkaavaisuuden suuntaamiseen. Lisäksi tavoitteelliseen tarkkaavaisuuden suuntaamiseen liittyi myös pikkuaivojen takaosan ja talamuksen aktivaation kasvu, ja etuotsalohkon sisäpinnan alaosa puolestaan aktivoitui ei-tarkkailtavien äänten joukossa esiintyneiden muita hieman voimakkaampien äänten vaikutuksesta. Tämä etuotsalohkojen sisäpinnan alue saattaa osallistua tarkkaavaisuuden puoleensa vetävien äänien merkityksen arviointiin. Tulokset osoittivat myös, että kuulonvaraisen työmuistitehtävä aktivoi pääosin samoja aivoalueita kuin tavoitteellinen tarkkaavaisuuden suuntaaminen. Kun työmuistitehtävän aikana esiintyvä pikkuaivojen taka-osan aktivaatio kasvoi, koehenkilöiden reaktioajat lyhenivät. Näiden tulosten ja aiempien teorioiden perusteella tämä pikkuaivojen alue saattaa osallistua reaktionopeuden optimointiin kognitiivisessa tehtävässä

Structural and connectivity parameters reveal spared connectivity in young patients with non-progressive compared to slow-progressive cerebellar ataxia

INTRODUCTION: Within Pediatric Cerebellar Ataxias (PCAs), patients with non-progressive ataxia (NonP) surprisingly show postural motor behavior comparable to that of healthy controls, differently to slow-progressive ataxia patients (SlowP). This difference may depend on the building of compensatory strategies of the intact areas in NonP brain network. METHODS: Eleven PCAs patients were recruited: five with NonP and six with SlowP. We assessed volumetric and axonal bundles alterations with a multimodal approach to investigate whether eventual spared connectivity between basal ganglia and cerebellum explains the different postural motor behavior of NonP and SlowP patients. RESULTS: Cerebellar lobules were smaller in SlowP patients. NonP patients showed a lower number of streamlines in the cerebello-thalamo-cortical tracts but a generalized higher integrity of white matter tracts connecting the cortex and the basal ganglia with the cerebellum. DISCUSSION: This work reveals that the axonal bundles connecting the cerebellum with basal ganglia and cortex demonstrate a higher integrity in NonP patients. This evidence highlights the importance of the cerebellum-basal ganglia connectivity to explain the different postural motor behavior of NonP and SlowP patients and support the possible compensatory role of basal ganglia in patients with stable cerebellar malformation

Structural Loop Between the Cerebellum and the Superior Temporal Sulcus: Evidence from Diffusion Tensor Imaging

The cerebellum is believed to play an essential role in a variety of motor and cognitive functions through reciprocal interaction with the cerebral cortex. Recent findings suggest that cerebellar involvement in the network specialized for visual body motion processing may be mediated through interaction with the right superior temporal sulcus (STS). Yet, the underlying pattern of structural connectivity between the STS and the cerebellum remains unidentified. In the present work, diffusion tensor imaging analysis on seeds derived from functional magnetic resonance imaging during a task on point-light biological motion perception uncovers a structural pathway between the right posterior STS and the left cerebellar lobule Crus I. The findings suggest existence of a structural loop underpinning bidirectional communication between the STS and cerebellum. This connection might also be of potential value for other visual social abilitie

Cerebellar gray matter and lobular volumes correlate with core autism symptoms

AbstractNeuroanatomical differences in the cerebellum are among the most consistent findings in autism spectrum disorder (ASD), but little is known about the relationship between cerebellar dysfunction and core ASD symptoms. The newly-emerging existence of cerebellar sensorimotor and cognitive subregions provides a new framework for interpreting the functional significance of cerebellar findings in ASD. Here we use two complementary analyses — whole-brain voxel-based morphometry (VBM) and the SUIT cerebellar atlas — to investigate cerebellar regional gray matter (GM) and volumetric lobular measurements in 35 children with ASD and 35 typically-developing (TD) children (mean age 10.4 ± 1.6 years; range 8–13 years). To examine the relationships between cerebellar structure and core ASD symptoms, correlations were calculated between scores on the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI) and the VBM and volumetric data. Both VBM and the SUIT analyses revealed reduced GM in ASD children in cerebellar lobule VII (Crus I/II). The degree of regional and lobular gray matter reductions in different cerebellar subregions correlated with the severity of symptoms in social interaction, communication, and repetitive behaviors. Structural differences and behavioral correlations converged on right cerebellar Crus I/II, a region which shows structural and functional connectivity with fronto-parietal and default mode networks. These results emphasize the importance of the location within the cerebellum to the potential functional impact of structural differences in ASD, and suggest that GM differences in cerebellar right Crus I/II are associated with the core ASD profile

DEVELOPMENT OF A CEREBELLAR MEAN FIELD MODEL: THE THEORETICAL FRAMEWORK, THE IMPLEMENTATION AND THE FIRST APPLICATION

Brain modeling constantly evolves to improve the accuracy of the simulated brain dynamics with the ambitious aim to build a digital twin of the brain. Specific models tuned on brain regions specific features empower the brain simulations introducing bottom-up physiology properties into data-driven simulators. Despite the cerebellum contains 80 % of the neurons and is deeply involved in a wide range of functions, from sensorimotor to cognitive ones, a specific cerebellar model is still missing. Furthermore, its quasi-crystalline multi-layer circuitry deeply differs from the cerebral cortical one, therefore is hard to imagine a unique general model suitable for the realistic simulation of both cerebellar and cerebral cortex. The present thesis tackles the challenge of developing a specific model for the cerebellum. Specifically, multi-neuron multi-layer mean field (MF) model of the cerebellar network, including Granule Cells, Golgi Cells, Molecular Layer Interneurons, and Purkinje Cells, was implemented, and validated against experimental data and the corresponding spiking neural network microcircuit model. The cerebellar MF model was built using a system of interdependent equations, where the single neuronal populations and topological parameters were captured by neuron-specific inter- dependent Transfer Functions. The model time resolution was optimized using Local Field Potentials recorded experimentally with high-density multielectrode array from acute mouse cerebellar slices. The present MF model satisfactorily captured the average discharge of different microcircuit neuronal populations in response to various input patterns and was able to predict the changes in Purkinje Cells firing patterns occurring in specific behavioral conditions: cortical plasticity mapping, which drives learning in associative tasks, and Molecular Layer Interneurons feed-forward inhibition, which controls Purkinje Cells activity patterns. The cerebellar multi-layer MF model thus provides a computationally efficient tool that will allow to investigate the causal relationship between microscopic neuronal properties and ensemble brain activity in health and pathological conditions. Furthermore, preliminary attempts to simulate a pathological cerebellum were done in the perspective of introducing our multi-layer cerebellar MF model in whole-brain simulators to realize patient-specific treatments, moving ahead towards personalized medicine. Two preliminary works assessed the relevant impact of the cerebellum on whole-brain dynamics and its role in modulating complex responses in causal connected cerebral regions, confirming that a specific model is required to further investigate the cerebellum-on- cerebrum influence. The framework presented in this thesis allows to develop a multi-layer MF model depicting the features of a specific brain region (e.g., cerebellum, basal ganglia), in order to define a general strategy to build up a pool of biology grounded MF models for computationally feasible simulations. Interconnected bottom-up MF models integrated in large-scale simulators would capture specific features of different brain regions, while the applications of a virtual brain would have a substantial impact on the reality ranging from the characterization of neurobiological processes, subject-specific preoperative plans, and development of neuro-prosthetic devices

How the Cerebellum and Cerebral Cortex Collaborate to Compose Fractal Patterns Underlying Transpersonal Experience

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Collaboration of Cerebello-Rubral and Cerebello-Striatal Loops in a Motor Preparation Task

International audienceIn this study, we used fMRI to identify brain regions associated with concentration (sustained attention) during a motor preparation task. In comparison with a non-concentration task, increased activities were observed (P < 0.05, FWEcorrected P values) in cerebellar lobules VI and VII, motor cortex, pre-supplementary motor area (pre-SMA), thalamus, red nucleus (RN), and caudate nucleus (CN). Moreover, analysis of effective connectivity inter-areal (psychophysiological interactions) showed that during preparation, concentration-related brain activity increase was dependent on Cerebellothalamo-pre-SMA-RN and Pre-SMA-CN-thalamo-M1 loops. We postulate that, while pre-SMA common to both loops is specifically involved in the movement preparation and readiness for voluntary movement through the striatum, the cerebellar lobule VI in conjunction with RN, likely through a cerebellar-rubro-olivary-cerebellar loop, might be implicated in concentration-related optimization of upcoming motor performances