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![Activations projected onto the dentate nuclei showing examples of force related effects surviving a threshold of T-value 2, for illustration purposes (significant results are indicated using white arrows in the figure). In the effect maps, right is right (ipsilateral) and all activations are projected on axial sections (white numbers indicate z-coordinate). R: rostral; C: caudal; V: ventral; D: dorsal. [Color figure can be viewed at wileyonlinelibrary.com]](publication/314091630/figure/fig5/AS:533127857491974@1504118994395/Activations-projected-onto-the-dentate-nuclei-showing-examples-of-force-related-effects.png)
Activations projected onto the dentate nuclei showing examples of force related effects surviving a threshold of T-value 2, for illustration purposes (significant results are indicated using white arrows in the figure). In the effect maps, right is right (ipsilateral) and all activations are projected on axial sections (white numbers indicate z-coordinate). R: rostral; C: caudal; V: ventral; D: dorsal. [Color figure can be viewed at wileyonlinelibrary.com]
Source publication
The relationship between the BOLD response and an applied force was quantified in the cerebellum using a power grip task. To investigate whether the cerebellum responds in an on/off way to motor demands or contributes to motor responses in a parametric fashion, similarly to the cortex, five grip force levels were investigated under visual feedback....
Context in source publication
Context 1
... we found that the right DN showed a main effect of movement (e.g., 0th order, Fig. 4) as well as higher order non-linear effects (Fig. 5). For example, during the main effect of movement, all the ipsilateral subdivisions of the DN were involved-with more exten- sive involvements of the DRDN and DCDN (i.e., more dorsal DN involvements). The contralateral DN was also involved-with activations mainly localized in the ...
Citations
... Located in each cerebellar hemisphere and farthest from the cerebellar midline, the DN is the largest cerebellar nucleus [1]. The DN participates in both motor and non-motor functions, contributing to sensorimotor processes and higher cerebellar functions [2], [3]. ...
As the largest human cerebellar nucleus, the dentate nucleus (DN) functions significantly in the communication between the cerebellum and the rest of the brain. Structural connectivity-based parcellation has the potential to reveal the topography of the DN and enable the study of its subregions. In this paper, we investigate a deep nonnegative matrix factorization clustering method (DNMFC) for parcellation of the human DN based on its structural connectivity using diffusion MRI tractography. We propose to describe the connectivity of the DN using a set of curated tractography fiber clusters within the cerebellum. Experiments are conducted on the diffusion MRI data of 50 healthy adults from the Human Connectome Project. In comparison with state-of-the-art clustering methods, DN parcellations resulting from DNMFC show better quality and consistency of parcels across subjects.
... A possible NVC region specificity was recently suggested by the evidence of different BOLD responses in the cerebellar cortex during the execution of intensity-graded grip force motor task in humans, with the most substantial effects appearing in vermis lobule V and hemisphere lobule VI [24,25], but it is unclear whether these differences simply reflect different cortical inputs or local NVC factors. Moreover, reports of non-linear BOLD response alterations due to pathology such as multiple sclerosis make understanding NVC factors very important for explaining the mechanisms of disease [26,27]. ...
Neurovascular coupling (NVC) is the process associating local cerebral blood flow (CBF) to neuronal activity (NA). Although NVC provides the basis for the blood oxygen level dependent (BOLD) effect used in functional MRI (fMRI), the relationship between NVC and NA is still unclear. Since recent studies reported cerebellar non-linearities in BOLD signals during motor tasks execution, we investigated the NVC/NA relationship using a range of input frequencies in acute mouse cerebellar slices of vermis and hemisphere. The capillary diameter increased in response to mossy fiber activation in the 6–300 Hz range, with a marked inflection around 50 Hz (vermis) and 100 Hz (hemisphere). The corresponding NA was recorded using high-density multi-electrode arrays and correlated to capillary dynamics through a computational model dissecting the main components of granular layer activity. Here, NVC is known to involve a balance between the NMDAR-NO pathway driving vasodilation and the mGluRs-20HETE pathway driving vasoconstriction. Simulations showed that the NMDAR-mediated component of NA was sufficient to explain the time course of the capillary dilation but not its non-linear frequency dependence, suggesting that the mGluRs-20HETE pathway plays a role at intermediate frequencies. These parallel control pathways imply a vasodilation–vasoconstriction competition hypothesis that could adapt local hemodynamics at the microscale bearing implications for fMRI signals interpretation.
... Two further observations are worth mentioning and highlighting. SPL 7PC and SPL 7A were the two subregions found to be positively connected to the anterior cerebellum, which is known to be involved in motorrelated functions [40][41][42][43][44][45][46]. This suggests that these two sub-regions could have a direct role in organising the pathways and functional involvements of the anterior cerebellum. ...
Objectives
Traditionally, the superior parietal lobule (SPL) is usually investigated as one region of interest, particularly in functional magnetic resonance imaging (fMRI) studies. However, cytoarchitectonic analysis has shown that the SPL has a complex, heterogeneous topology that comprises more than seven sub-regions. Since previous studies have shown how the SPL is significantly involved in different neurological functions—such as visuomotor, cognitive, sensory, higher order, working memory and attention—this study aims to investigate whether these cytoarchitecturally different sub-regions have different functional connectivity to different functional brain networks.
Methods
This study examined 198 healthy subjects using resting-state fMRI and investigated the functional connectivity of seven sub-regions of the SPL to eight regional functional networks.
Results
The findings showed that most of the seven sub-regions were functionally connected to these targeted networks and that there are differences between these sub-regions and their functional connectivity patterns. The most consistent functional connectivity was observed with the visual and attention networks. There were also clear functional differences between Brodmann area (BA) 5 and BA7. BA5, with its three sub-regions, had strong functional connectivity to both the sensorimotor and salience networks.
Conclusion
These findings have enhanced our understanding of the functional organisations of the complexity of the SPL and its varied topology and also provide clear evidence of the functional patterns and involvements of the SPL in major brain functions.
... Boynton et al. (1996) demonstrated the linearity of BOLD signal increments in an earlier study, showing that the BOLD signal increment to long visual stimulus could be predicted by the summation of the BOLD signal increment to shorter visual stimulus and its temporally shifted copy or copies (Boynton et al., 1996). While the linearity of BOLD signal increments to long stimuli has been confirmed (Birn et al., 2001;Soltysik et al., 2004), several studies reported non-linearity for BOLD signal increments to transient stimuli (Savoy et al., 1995;Konishi et al., 1996;Friston et al., 1998;Robson et al., 1998;Vazquez and Noll, 1998;Birn et al., 2001;Soltysik et al., 2004;Wager et al., 2005;Thompson et al., 2014;Alahmadi et al., 2017). Specifically, the predictions made by BOLD signal increments to transient stimuli tended to overestimate the BOLD signal increments to longer stimuli. ...
The linearity of BOLD responses is a fundamental presumption in most analysis procedures for BOLD fMRI studies. Previous studies have examined the linearity of BOLD signal increments, but less is known about the linearity of BOLD signal decrements. The present study assessed the linearity of both BOLD signal increments and decrements in the human primary visual cortex using a contrast adaptation paradigm. Results showed that both BOLD signal increments and decrements kept linearity to long stimuli (e.g., 3 s, 6 s), yet, deviated from linearity to transient stimuli (e.g., 1 s). Furthermore, a voxel-wise analysis showed that the deviation patterns were different for BOLD signal increments and decrements: while the BOLD signal increments demonstrated a consistent overestimation pattern, the patterns for BOLD signal decrements varied from overestimation to underestimation. Our results suggested that corrections to deviations from linearity of transient responses should consider the different effects of BOLD signal increments and decrements.
... Moreover, reports of non-linear BOLD response alterations due to pathology such as multiple sclerosis make understanding NVC factors very important for explaining the mechanisms of disease 26,27 . ...
Neurovascular coupling (NVC) is the process associating local cerebral blood flow (CBF) to neuronal activity (NA). Although NVC provides the basis for the blood-oxygen-level-dependent (BOLD) effect used in functional MRI (fMRI), the relationship between NVC and NA is still unclear. Since recent studies reported cerebellar non-linearities in BOLD signals during motor tasks execution, we investigated the NVC/NA relationship using a range of input frequencies in acute mouse cerebellar slices of vermis and hemisphere. The capillary diameter increased in response to mossy fiber activation in the 6-300Hz range, with a marked inflection around 50Hz (vermis) and 100Hz (hemisphere). The corresponding NA was recorded using high-density multi-electrode arrays and correlated to capillary dynamics through a computational model dissecting the main components of granular layer activity. Here, NVC is known to involve a balance between the NMDAR-NO pathway driving vasodilation and the mGluRs-20HETE pathway driving vasoconstriction. Simulations showed that the NMDAR-mediated component of NA was sufficient to explain the time-course of the capillary dilation but not its non-linear frequency-dependence, suggesting that the mGluRs-20HETE pathway plays a role at intermediate frequencies. These parallel control pathways imply a vasodilation-vasoconstriction competition hypothesis that could adapt local hemodynamics at the microscale bearing implications for fMRI signals interpretation.
... Most of the efferent cerebellar connections towards the cerebral cortex synapse in the DN then convey in the superior cerebellar peduncle and pass through the contralateral red nucleus to end in the thalamus (Voogd & Ruigrok, 2012). Commonly, the DNs are known to be involved in sensorimotor processes but recent functional imaging investigations have revealed that they play a role also in non-motor functions (Alahmadi et al., 2017;Bharti et al., 2020;Habas, Guillevin, & Abanou, 2011;Zhang et al., 2015). This finding is in line with the recent understanding that the cerebellum is connected to cognitive and associative cortical areas, as supported by either tract-tracing techniques (Kelly & Strick, 2003;Middleton & Strick, 1994;Schmahmann & Caplan, 2006;Schmahmann & Pandya, 1995;Strick, Dum, & Fiez, 2009a) or diffusion MRI tractography studies of the cerebro-cerebellar loop (Kim, Im, Kim, & Park, 2019;Palesi et al., 2015Palesi et al., , 2016Palesi et al., , 2017. ...
Deep gray matter nuclei are the synaptic relays, responsible to route signals between specific brain areas. Dentate nuclei (DNs) represent the main output channel of the cerebellum and yet are often unexplored especially in humans. We developed a multimodal MRI approach to identify DNs topography on the basis of their connectivity as well as their microstructural features. Based on results, we defined DN parcellations deputed to motor and to higher-order functions in humans in vivo. Whole-brain probabilistic tractography was performed on 25 healthy subjects from the Human Connectome Project to infer DN parcellations based on their connectivity with either the cerebral or the cerebellar cortex, in turn. A third DN atlas was created inputting microstructural diffusion-derived metrics in an unsupervised fuzzy c-means classification algorithm. All analyses were performed in native space, with probability atlas maps generated in standard space. Cerebellar lobule-specific connectivity identified one motor parcellation, accounting for about 30% of the DN volume, and two non-motor parcellations, one cognitive and one sensory, which occupied the remaining volume. The other two approaches provided overlapping results in terms of geometrical distribution with those identified with cerebellar lobule-specific connectivity, although with some differences in volumes. A gender effect was observed with respect to motor areas and higher-order function representations. This is the first study that indicates that more than half of the DN volumes is involved in non-motor functions and that connectivity-based and microstructure-based atlases provide complementary information. These results represent a step-ahead for the interpretation of pathological conditions involving cerebro-cerebellar circuits.
... Magnetic resonance imaging (MRI) functional studies have shown that in healthy volunteers, the blood oxygen leveldependent (BOLD) signal response is modulated by attention (Binkofski et al., 2002) and imagined forces (Sharma et al., 2008) in BA 4p, while BA 4a responds to motor control (Alahmadi et al., 2016). In other words, BA 4a is predominantly related to execution, whereas BA 4p is predominantly related to higherorder cognitive tasks (Binkofski et al., 2002;Sharma et al., 2008;Alahmadi et al., 2015bAlahmadi et al., , 2016Alahmadi et al., , 2017Alahmadi, 2020). ...
... The design comprised five GF targets [20,30,40,50, and 60% of subjects' maximum voluntary contraction (MVC)] interleaved with rest intervals, each repeated randomly 15 times. This paradigm has been validated previously in studies of healthy volunteers (Alahmadi et al., 2015b(Alahmadi et al., , 2016(Alahmadi et al., , 2017Casiraghi et al., 2019). ...
... is complex and region specific. In previous studies of healthy volunteers, we have demonstrated the complexity of BOLD signals as a function of GF in different motor, submotor, associative, and cerebellar areas (Alahmadi et al., 2015b(Alahmadi et al., , 2016(Alahmadi et al., , 2017Casiraghi et al., 2019). These were seen as well in action observation and execution networks (Casiraghi et al., 2019). ...
This study highlights the importance of looking beyond the main effect of movement to study alterations in functional response in the presence of central nervous system pathologies such as multiple sclerosis (MS). Data show that MS selectively affects regional BOLD (blood oxygenation level dependent) responses to variable grip forces (GF). It is known that the anterior and posterior BA 4 areas (BA 4a and BA 4p) are anatomically and functionally distinct. It has also been shown in healthy volunteers that there are linear (first order, typical of BA 4a) and nonlinear (second to fourth order, typical of BA 4p) BOLD responses to different levels of GF applied during a dynamic motor paradigm. After modeling the BOLD response with a polynomial expansion of the applied GFs, the particular case of BA 4a and BA 4p were investigated in healthy volunteers (HV) and MS subjects. The main effect of movement (zeroth order) analysis showed that the BOLD signal is greater in MS compared with healthy volunteers within both BA 4 subregions. At higher order, BOLD-GF responses were similar in BA 4a but showed a marked alteration in BA 4p of MS subjects, with those with greatest disability showing the greatest deviations from the healthy response profile. Therefore, the different behaviors in HV and MS could only be uncovered through a polynomial analysis looking beyond the main effect of movement into the two BA 4 subregions. Future studies will investigate the source of this pathophysiology, combining the present fMRI paradigm with blood perfusion and nonlinear neuronal response analysis.
... The dentate nuclei (DNs), the largest of the four pairs of cerebellar nuclei, are highly convoluted clusters of neurons embedded in the WM of the cerebellum (Sultan et al., 2010). The DNs play a role in cognitive, affective, and motor domains of behavior and are part of anatomical circuits linking the cerebellar cortex, thalamus, cerebral cortex, and basal ganglia (Alahmadi et al., 2017;Bernard et al., 2014;Bostan et al., 2010;Dum and Strick, 2003;Habas, 2010;Hoshi et al., 2005;Kuper et al., 2011). Tract-tracing studies demonstrate DN anatomical connectivity to motor cortical areas (BA 4,6) and nonmotor cognitive areas such as medial, dorsolateral, and orbital prefrontal cortices (Dum and Strick, 2003). ...
... Importantly, the dorsal and ventral aspects of the DN are functionally distinct. The dorsal DN contributes to motor processes, while the ventral DN contributes to nonmotor processes (Alahmadi et al., 2017;Bernard et al., 2014;Dum and Strick, 2003). Diffusion tensor imaging studies have confirmed this functional topography of the DN, with connectivity between the dorsal DN and motor aspects of the cerebellum (lobules IV, V, and VI) and between the ventral DN and nonmotor aspects of the cerebellum (Crus I/II) (Steele et al., 2017). ...
Cerebellar abnormalities are commonly reported in autism spectrum disorder (ASD). Dentate nuclei (DN) is a key structure in the anatomical circuits linking the cerebellum to the extracerebellum. Previous resting-state functional connectivity (RsFc) analyses reported DN abnormalities in high-functioning ASD (HF-ASD). This study examined the RsFc of the DN in young adults with HF-ASD compared to healthy controls (HC) with the aim to expand upon previous findings of DN in a dataset using advanced imaging acquisition methods that optimize spatiotemporal resolution and statistical power. Additional seed-to-voxel analyses were carried out using motor and non-motor DN coordinates reported in previous studies as seeds. We report abnormal dentato-cerebral and dentato-cerebellar functional connectivity in ASD. Our results expand and in part replicate previous descriptions of DN RsFc abnormalities in this disorder, and reveal correlations between DN-cerebral RsFc and ASD symptom severity.
... Previous studies have repeatedly found that the cerebellum plays an important role in motor learning and acquisition of new skills [2][3][4][5][6]. Recently, the results from task-state neuroimaging and intrinsic functional connectivity (FC) studies demonstrated that different subregions of cerebellum have different functions in motor learning or skill learning, e.g., hemispheric IV-V and VIII associated with sensorimotor processing [7][8][9][10][11]; hemispheric VI involved in motor coordination [12][13]; vermal VI-IX responsible for eye movement control [10,[14][15][16]. ...
... The voxel-wise FC analysis was then conducted to characterize functional integration. Based on the literatures [7][8][9][10][11][12][13][14][15][16], the cerebellar sub-regions associated with sensorimotor processing (i.e., hemispheric IV-V and VIII), motor coordination (i.e., hemispheric VI) and eye movement (i.e., vermal VI-IX) were defined as regions of interest (ROIs) used to perform ALFF analysis and voxel-wise FC. ...
... The hemispheric VI in the cerebellum has been demonstrated to be involved in motor coordination in complex movements, such as visually-guided movements [13] and sequential movements [12]. For example, in the study by Alahmadi et al. [13], bilateral cerebellar hemispheric VI was activated, when participants were asked to complete a complex grip task with their right hand according to a visual cue defining the target force. ...
... Previous studies have repeatedly found that the cerebellum plays an important role in motor learning and acquisition of new skills [2][3][4][5][6]. Recently, the results from task-state neuroimaging and intrinsic functional connectivity (FC) studies demonstrated that different subregions of cerebellum have different functions in motor learning or skill learning, e.g., hemispheric IV-V and VIII associated with sensorimotor processing [7][8][9][10][11]; hemispheric VI involved in motor coordination [12][13]; vermal VI-IX responsible for eye movement control [10,[14][15][16]. ...
... The voxel-wise FC analysis was then conducted to characterize functional integration. Based on the literatures [7][8][9][10][11][12][13][14][15][16], the cerebellar sub-regions associated with sensorimotor processing (i.e., hemispheric IV-V and VIII), motor coordination (i.e., hemispheric VI) and eye movement (i.e., vermal VI-IX) were defined as regions of interest (ROIs) used to perform ALFF analysis and voxel-wise FC. ...
... The hemispheric VI in the cerebellum has been demonstrated to be involved in motor coordination in complex movements, such as visually-guided movements [13] and sequential movements [12]. For example, in the study by Alahmadi et al. [13], bilateral cerebellar hemispheric VI was activated, when participants were asked to complete a complex grip task with their right hand according to a visual cue defining the target force. ...
Previous studies have shown that sport experts are different from novices in functions and structures of the cerebellar sub-regions and the functional connectivity (FC) associated with the cerebellum, suggesting the role of the cerebellum on motor skill learning (MSL). However, the manipulation of individuals with different motor skills fails to exclude the effects of innate talents. In addition, individuals with higher motor skills often start with the MSL in their young ages. It is still unclear whether the effects regarding the cerebellum would be shown at one’s adult age. The present study was to directly alter individuals’ motor skills to investigate whether MSL (taking learning to play badminton as an example) in adulthood influences resting-state activity in the cerebellum. To this end, young adults without ball training experience were recruited as participants and were assigned randomly into the experimental group and the control group. Participants in the experimental group were asked to attend a badminton training course for 12 weeks, while the control group did not regularly attend any ball sports during this period. Resting-state functional magnetic resonance imaging (fMRI) was recorded before and after the training. Results showed that compared to the control group, the experimental group had smaller amplitude of low-frequency fluctuation (ALFF) in right cerebellar hemispheric VI and left VIII after training. For the experimental group, right hemispheric VIII had a stronger FC with left hemispheric IV-V, cerebellar vermal IX, left middle cingulate gyrus and right hippocampus after training. Taken together, these findings suggested that MSL, at least learning to play badminton in adulthood, reduces resting-state activity in different sub-regions in the cerebellum but increases FC between sub-regions of the cerebellum as well as between sub-regions of the cerebellum and cerebral cortices (e.g., middle cingulate cortex and hippocampus).
