Functional Integration of the Subregions of the Primary Motor Cortex: The Impact of Handedness and Hemispheric Lateralization.

OBJECTIVE: Cytoarchitectonic mapping has revealed distinct subregions within Broadmann area 4 (BA 4) - BA 4a and BA 4p - with varying functional roles across tasks. We investigate their functional connectivity using resting-state functional magnetic resonance imaging (rsfMRI) to explore bilateral differences and the impact of handedness on connectivity within major brain networks. METHODS: This retrospective study involved 54 left- and right-handed subjects. We employed regions-to-regions-network rsfMRI analysis to examine the Cytoarchitectonic mapping of BA 4a and BA 4p functional connectivity with eight major brain networks. RESULTS: Our findings reveal differential connectivity patterns in both right-handed and left-handed subjects: Both right-handed subjects' BA 4a and BA 4p subregions exhibit connections to sensorimotor, dorsal attention, frontoparietal, and anterior cerebellar networks. Notably, BA 4a shows unique connectivity to the posterior cerebellum, lateral visual networks, and select salience regions. Similar connectivity patterns are observed in left-handed subjects, with BA 4a linked to sensorimotor, dorsal attention, frontoparietal, and anterior cerebellar networks. However, BA 4a in left-handed subjects shows distinct connectivity only to the posterior cerebellum. In both groups, the right portion of BA 4 demonstrates heightened connectivity compared to the left portion within each subregion. CONCLUSION: Our study uncovers complex patterns of functional connectivity within BA 4a and BA 4p, influenced by handedness. These findings emphasize the importance of considering hemisphere-specific and handedness-related factors in functional connectivity analyses, with potential implications for understanding brain organization in health and neurodegenerative diseases.

Beyond boundaries: investigating shared and divergent connectivity in the pre-/postcentral gyri and supplementary motor area.

OBJECTIVE: This study aimed to comprehensively investigate the functional connectivity of key brain regions involved in motor and sensory functions, namely the precentral gyrus, postcentral gyrus and supplementary motor area (SMA). Using advanced MRI, the objective was to understand the neurophysiological integrative characterizations of these regions by examining their connectivity with eight distinct functional brain networks. The goal was to uncover their roles beyond conventional motor and sensory functions, contributing to a more holistic understanding of brain functioning. METHODS: The study involved 198 healthy volunteers, with the primary methodology being functional connectivity analysis using advanced MRI techniques. The bilateral precentral gyrus, postcentral gyrus and SMA served as seed regions, and their connectivity with eight distinct brain regional functional networks was investigated. This approach allowed for the exploration of synchronized activity between these critical brain areas, shedding light on their integrated functioning and relationships with other brain networks. RESULTS: The study revealed a nuanced landscape of functional connectivity for the precentral gyrus, postcentral gyrus and SMA with the main functional brain networks. Despite their high functional connectedness, these regions displayed diverse functional integrations with other networks, particularly in the salience, visual, cerebellar and language networks. Specific data and statistical significance were not provided in the abstract, but the results suggested unique and distinct roles for each brain area in sophisticated cognitive tasks beyond their conventional motor and sensory functions. CONCLUSION: The study emphasized the multifaceted roles of the precentral gyrus, postcentral gyrus and SMA. Beyond their crucial involvement in motor and sensory functions, these regions exhibited varied functional integrations with different brain networks. The observed disparities, especially in the salience, visual, cerebellar and language networks, indicated a nuanced and specialized involvement of these regions in diverse cognitive functions. The study underscores the importance of considering the broader neurophysiological landscape to comprehend the intricate roles of these brain areas, contributing to ongoing efforts in unraveling the complexities of brain function.

Gender and cytoarchitecture differences: Functional connectivity of the hippocampal sub-regions.

Introduction: The hippocampus plays a significant role in learning, memory encoding, and spatial navigation. Typically, the hippocampus is investigated as a whole region of interest. However, recent work has developed fully detailed atlases based on cytoarchitecture properties of brain regions, and the hippocampus has been sub-divided into seven sub-areas that have structural differences in terms of distinct numbers of cells, neurons, and other structural and chemical properties. Moreover, gender differences are of increasing concern in neuroscience research. Several neuroscience studies have found structural and functional variations between the brain regions of females and males, and the hippocampus is one of these regions. Aim: The aim of this study to explore whether the cytoarchitecturally distinct sub-regions of the hippocampus have varying patterns of functional connectivity with different networks of the brain and how these functional connections differ in terms of gender differences. Method: This study investigated 200 healthy participants using seed-based resting-state functional magnetic resonance imaging (rsfMRI). The primary aim of this study was to explore the resting connectivity and gender distinctions associated with specific sub-regions of the hippocampus and their relationship with major functional brain networks. Results: The findings revealed that the majority of the seven hippocampal sub-regions displayed functional connections with key brain networks, and distinct patterns of functional connectivity were observed between the hippocampal sub-regions and various functional networks within the brain. Notably, the default and visual networks exhibited the most consistent functional connections. Additionally, gender-based analysis highlighted evident functional resemblances and disparities, particularly concerning the anterior section of the hippocampus. Conclusion: This study highlighted the functional connectivity patterns and involvement of the hippocampal sub-regions in major brain functional networks, indicating that the hippocampus should be investigated as a region of multiple distinct functions and should always be examined as sub-regions of interest. The results also revealed clear gender differences in functional connectivity.

B-mode ultrasound characteristics of carotid plaques in symptomatic and asymptomatic patients with low-grade stenosis.

Carotid plaque features assessed using B-mode ultrasound can be useful for the prediction of cerebrovascular symptoms. Therefore, the aim of this retrospective study was to determine the ability of ultrasound B-mode imaging to differentiate between carotid plaques causing less than 50% stenosis in symptomatic and asymptomatic patients. A dataset of 1,593 patients with carotid disease who underwent carotid ultrasound between 2016 and 2021 was evaluated retrospectively between January and April of 2022. A total of 107 carotid plaques from 35 symptomatic and 52 asymptomatic patients causing low-grade stenosis on B-mode images were included in the analysis. Chi-square, independent t-test and Mann-Whitney U test were used to compare the variables. There was a significant association between hypertension and the presence of cerebrovascular symptoms (p = 0.01). Predominantly hypoechoic and hyperechoic carotid plaque were significantly associated with the presence and absence of cerebrovascular symptoms, respectively (predominantly hypoechoic: p = 0.01; predominantly hyperechoic: p = 0.02). Surface irregularity was significantly associated with the presence of cerebrovascular symptoms (p = 0.02). There is was a significant difference in the carotid plaque length and area between the symptomatic and asymptomatic patients (plaque length: symptomatic median 9 mm, interquartile range [IQR] 6 mm; asymptomatic median 6 mm, IQR 4.5 mm, p = 0.01; plaque area: symptomatic median 24 mm, IQR 30 mm; asymptomatic median 14 mm, IQR 17 mm, p = 0.01); however, this difference was not significant for plaque thickness (p = 0.55), or common carotid artery intima-media thickness (p = 0.7). Our findings indicate that hypertension patients with predominantly hypoechoic carotid plaques and plaques with an irregular surface are associated with the presence of cerebrovascular symptoms. In addition, the carotid plaques in symptomatic patients were longer and larger compared to asymptomatic patients.

The Cerebellum's Orchestra: Understanding the Functional Connectivity of Its Lobes and Deep Nuclei in Coordination and Integration of Brain Networks.

The cerebellum, a crucial brain region, significantly contributes to various brain functions. Although it occupies a small portion of the brain, it houses nearly half of the neurons in the nervous system. Previously thought to be solely involved in motor activities, the cerebellum has since been found to play a role in cognitive, sensory, and associative functions. To further elucidate the intricate neurophysiological characteristics of the cerebellum, we investigated the functional connectivity of cerebellar lobules and deep nuclei with 8 major functional brain networks in 198 healthy subjects. Our findings revealed both similarities and differences in the functional connectivity of key cerebellar lobules and nuclei. Despite robust functional connectivity among these lobules, our results demonstrated that they exhibit heterogeneous functional integration with different functional networks. For instance, lobules 4, 5, 6, and 8 were linked to sensorimotor networks, while lobules 1, 2, and 7 were associated with higher-order, non-motor, and complex functional networks. Notably, our study uncovered a lack of functional connectivity in lobule 3, strong connections between lobules 4 and 5 with the default mode networks, and connections between lobules 6 and 8 with the salience, dorsal attention, and visual networks. Additionally, we found that cerebellar nuclei, particularly the dentate cerebellar nuclei, were connected to sensorimotor, salience, language, and default-mode networks. This study provides valuable insights into the diverse functional roles of the cerebellum in cognitive processing.

Functional connectivity of sub-cortical brain regions: disparities and similarities.

Sub-cortical grey matter structures, such as the putamen, pallidum, caudate, thalamus, amygdala and hippocampus, play substantial roles in both simple and complex brain functions, including regulation of pleasure and emotions; control of movements; learning; decision-making; language development; and sensory, cognitive, social and other higher-order functions. Most of these regions act as information hubs for the nervous system, relaying and controlling the flow of information to various portions of the brain. To further understand the complex neurophysiological characteristics of sub-cortical areas, the aim of this study was to investigate the functional integrations of six sub-cortical areas to different major functional brain networks. One hundred ninety-eight healthy individuals were examined using resting-state functional MRI. The seeds identified in this study were six sub-cortical deep grey matter regions, namely putamen, pallidum, caudate, thalamus, amygdala and hippocampus. The analysis indicated that the link between the sub-cortical regions and some functional brain networks was similar in some aspects, but there were disparities in the mechanism underlying such a link and in the existence of functional connections between these regions and networks. Despite the substantial functional connectivity linkages between the sub-cortical regions, discrepancies were still noted. On the basis of the connections to the majority of the major brain networks, this study demonstrated the essential functional roles and involvements of the sub-cortical regions. This finding is consistent with an earlier report that revealed a substantial role of the sub-cortical regions in several brain functions.

The Experience of Using Online Education in a Radiological Academic Department During the Pandemic of Corona Virus COVID-19.

Purpose: In response to the coronavirus (COVID-19) pandemic, most educational institutions transitioned to online delivery because of the urgent need to avoid spreading the virus. For this study, the emergency transformation to 100% online education in a diagnostic radiology department was evaluated based on student experience and performance. Methods: One hundred and thirty four radiology students participated in this study. Reflecting on the department's shift to online education, students rated their experience: their general opinions about courses, preferences for online education, their evaluation of the procedures of the implemented plans, and their evaluation of academic components such as exams, lectures, assignments, teamwork, interaction, and compensating for the loss of practical learning. Results: The results indicate that the students appreciated the online emergency plan. Overall, they preferred online education compared to traditional classes, especially with regard to lectures, exams, teamwork, and interaction. Students agreed that some courses can be delivered online effectively, such as physics and research courses, while others should not. In general, this study demonstrates that radiology courses can be effectively delivered using online distance methods, and this should be a compulsory part of instruction in the future. Conclusion: This study describes the effects of moving to online education in the field of radiology on both practical and theoretical learning outcomes.

Blood Oxygenation Level-Dependent Response to Multiple Grip Forces in Multiple Sclerosis: Going Beyond the Main Effect of Movement in Brodmann Area 4a and 4p.

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.

Investigating the sub-regions of the superior parietal cortex using functional magnetic resonance imaging connectivity.

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.

Mind the gap: from neurons to networks to outcomes in multiple sclerosis.

MRI studies have provided valuable insights into the structure and function of neural networks, particularly in health and in classical neurodegenerative conditions such as Alzheimer disease. However, such work is also highly relevant in other diseases of the CNS, including multiple sclerosis (MS). In this Review, we consider the effects of MS pathology on brain networks, as assessed using MRI, and how these changes to brain networks translate into clinical impairments. We also discuss how this knowledge can inform the targeting of MS treatments and the potential future directions for research in this area. Studying MS is challenging as its pathology involves neurodegenerative and focal inflammatory elements, both of which could disrupt neural networks. The disruption of white matter tracts in MS is reflected in changes in network efficiency, an increasingly random grey matter network topology, relative cortical disconnection, and both increases and decreases in connectivity centred around hubs such as the thalamus and the default mode network. The results of initial longitudinal studies suggest that these changes evolve rather than simply increase over time and are linked with clinical features. Studies have also identified a potential role for treatments that functionally modify neural networks as opposed to altering their structure.

Effects of different smoothing on global and regional resting functional connectivity.

PURPOSE: Spatial smoothing is an essential pre-processing step in the process of analysing functional magnetic resonance imaging (fMRI) data, both during an experimental task or during resting-state fMRI (rsfMRI). The main benefit of this spatial smoothing step is to artificially increase the signal-to-noise ratio of the fMRI signal. Previous fMRI studies have investigated the impact of spatial smoothing on task fMRI data, while rsfMRI studies usually apply the same analytical process used for the task data. However, this study investigates changes in different rsfMRI analyses, such as ROI-to-ROI, seed-to-voxels and ICA analyses. METHODS: Nineteen healthy volunteers were scanned using rsfMRI with three applied smoothing kernels: 0 mm, 4 mm and 8 mm. Appropriate statistical comparisons were made. RESULTS: The findings showed that spatial smoothing has a greater effect on rsfMRI data when analysed using seed-to-voxel-based analysis. The effect was less pronounced when analysing data using ROI-ROI or ICA analyses. The results demonstrated that even when analysing the data without the application of spatial smoothing, the results were significant compared with data analysed using a typical smoothing kernel. However, data analysed with lower-smoothing kernels produced greater negative correlations, particularly with the ICA analysis. CONCLUSION: The results suggest that a medium smoothing kernel (around 4 mm) may be preferable, as it is comparable with the 8 mm kernel in all of the analyses performed. It is also recommended that the researchers consider analysing the data using two different smoothing kernels, as this will help to confirm the significance of the results and avoid overestimating the findings.

Functional network analysis of the sub-regions of the primary motor cortex during rest.

The cytoarchitectonic properties of the primary motor cortex have shown two distinct sub-regions: Anterior Broadmann area 4 (BA4a) and Posterior Broadmann area 4 (BA4p). Some previous studies have suggested that these two sub-regions are functionally different and showed that in few fMRI experiments, these sub-regions may have different roles in brain functions. Resting-state fMRI (rsfMRI) is advanced technique that allows investigating in detail the functional connectivity and provides a greater understanding of the physiological behavior of different brain regions. In this study, 198 healthy subjects were examined using a region-based rsfMRI analysis to investigate whether BA4a and BA4p have similar or different connections to other brain networks. The finding shows that indeed these two sub-regions have distinct connectivity to different brain networks. BA4a has a greater connection to motor-related areas while BA4p has connections to nonmotor-related areas (such as sensory, attentional, and higher order regions), suggesting that these two sub-regions should be considered as two separate regions of interests.

I See Your Effort: Force-Related BOLD Effects in an Extended Action Execution-Observation Network Involving the Cerebellum.

Action observation (AO) is crucial for motor planning, imitation learning, and social interaction, but it is not clear whether and how an action execution-observation network (AEON) processes the effort of others engaged in performing actions. In this functional magnetic resonance imaging (fMRI) study, we used a "squeeze ball" task involving different grip forces to investigate whether AEON activation showed similar patterns when executing the task or observing others performing it. Both in action execution, AE (subjects performed the visuomotor task) and action observation, AO (subjects watched a video of the task being performed by someone else), the fMRI signal was detected in cerebral and cerebellar regions. These responses showed various relationships with force mapping onto specific areas of the sensorimotor and cognitive systems. Conjunction analysis of AE and AO was repeated for the "0th" order and linear and nonlinear responses, and revealed multiple AEON nodes remapping the detection of actions, and also effort, of another person onto the observer's own cerebrocerebellar system. This result implies that the AEON exploits the cerebellum, which is known to process sensorimotor predictions and simulations, performing an internal assessment of forces and integrating information into high-level schemes, providing a crucial substrate for action imitation.

Cerebellar lobules and dentate nuclei mirror cortical force-related-BOLD responses: Beyond all (linear) expectations.

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. Functional MRI data were acquired in 13 healthy volunteers and their responses were analyzed using a cerebellum-optimized pipeline. This allowed us to evaluate, within the cerebellum, voxelwise linear and non-linear associations between cerebellar activations and forces. We showed extensive non-linear activations (with a parametric design), covering the anterior and posterior lobes of the cerebellum with a BOLD-force relationship that is region-dependent. Linear responses were mainly located in the anterior lobe, similarly to the cortex, where linear responses are localized in M1. Complex responses were localized in the posterior lobe, reflecting its key role in attention and executive processing, required during visually guided movement. Given the highly organized responses in the cerebellar cortex, a key question is whether deep cerebellar nuclei show similar parametric effects. We found positive correlations with force in the ipsilateral dentate nucleus and negative correlations on the contralateral side, suggesting a somatotopic organization of the dentate nucleus in line with cerebellar and cortical areas. Our results confirm that there is cerebellar organization involving all grey matter structures that reflect functional segregation in the cortex, where cerebellar lobules and dentate nuclei contribute to complex motor tasks with different BOLD response profiles in relation to the forces. Hum Brain Mapp 38:2566-2579, 2017. © 2017 Wiley Periodicals, Inc.

Complex motor task associated with non-linear BOLD responses in cerebro-cortical areas and cerebellum.

UNLABELLED: Previous studies have used fMRI to address the relationship between grip force (GF) applied to an object and BOLD response. However, whilst the majority of these studies showed a linear relationship between GF and neural activity in the contralateral M1 and ipsilateral cerebellum, animal studies have suggested the presence of non-linear components in the GF-neural activity relationship. Here, we present a methodology for assessing non-linearities in the BOLD response to different GF levels, within primary motor as well as sensory and cognitive areas and the cerebellum. To be sensitive to complex forms, we designed a feasible grip task with five GF targets using an event-related visually guided paradigm and studied a cohort of 13 healthy volunteers. Polynomial functions of increasing order were fitted to the data. MAJOR FINDINGS: (1) activated motor areas irrespective of GF; (2) positive higher-order responses in and outside M1, involving premotor, sensory and visual areas and cerebellum; (3) negative correlations with GF, predominantly involving the visual domain. Overall, our results suggest that there are physiologically consistent behaviour patterns in cerebral and cerebellar cortices; for example, we observed the presence of a second-order effect in sensorimotor areas, consistent with an optimum metabolic response at intermediate GF levels, while higher-order behaviour was found in associative and cognitive areas. At higher GF levels, sensory-related cortical areas showed reduced activation, interpretable as a redistribution of the neural activity for more demanding tasks. These results have the potential of opening new avenues for investigating pathological mechanisms of neurological diseases.

Differential involvement of cortical and cerebellar areas using dominant and nondominant hands: An FMRI study.

Motor fMRI studies, comparing dominant (DH) and nondominant (NDH) hand activations have reported mixed findings, especially for the extent of ipsilateral (IL) activations and their relationship with task complexity. To date, no study has directly compared DH and NDH activations using an event-related visually guided dynamic power-grip paradigm with parametric (three) forces (GF) in healthy right-handed subjects. We implemented a hierarchical statistical approach aimed to: (i) identify the main effect networks engaged when using either hand; (ii) characterise DH/NDH responses at different GFs; (iii) assess contralateral (CL)/IL-specific and hemisphere-specific activations. Beyond confirming previously reported results, this study demonstrated that increasing GF has an effect on motor response that is contextualised also by the use of DH or NDH. Linear analysis revealed increased activations in sensorimotor areas, with additional increased recruitments of subcortical and cerebellar areas when using the NDH. When looking at CL/IL-specific activations, CL sensorimotor areas and IL cerebellum were activated with both hands. When performing the task with the NDH, several areas were also recruited including the CL cerebellum. Finally, there were hand-side-independent activations of nonmotor-specific areas in the right and left hemispheres, with the right hemisphere being involved more extensively in sensori-motor integration through associative areas while the left hemisphere showing greater activation at higher GF. This study shows that the functional networks subtending DH/NDH power-grip visuomotor functions are qualitatively and quantitatively distinct and this should be taken into consideration when performing fMRI studies, particularly when planning interventions in patients with specific impairments.