Visuomotor Cerebellum in Human and Nonhuman Primates

In this paper, we will review the anatomical components of the visuomotor cerebellum in human and, where possible, in non-human primates and discuss their function in relation to those of extracerebellar visuomotor regions with which they are connected. The floccular lobe, the dorsal paraflocculus, the oculomotor vermis, the uvula?Cnodulus, and the ansiform lobule are more or less independent components of the visuomotor cerebellum that are involved in different corticocerebellar and/or brain stem olivocerebellar loops. The floccular lobe and the oculomotor vermis share different mossy fiber inputs from the brain stem; the dorsal paraflocculus and the ansiform lobule receive corticopontine mossy fibers from postrolandic visual areas and the frontal eye fields, respectively. Of the visuomotor functions of the cerebellum, the vestibulo-ocular reflex is controlled by the floccular lobe; saccadic eye movements are controlled by the oculomotor vermis and ansiform lobule, while control of smooth pursuit involves all these cerebellar visuomotor regions. Functional imaging studies in humans further emphasize cerebellar involvement in visual reflexive eye movements and are discussed.     

Brain areas activated by uncertain reward-based decision-making in healthy volunteers

Reward-based decision-making has been found to activate several brain areas, including the ven- trolateral prefronta~ lobe, orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mesolimbic dopaminergic system. In this study, we observed brain areas activated under three de- grees of uncertainty in a reward-based decision-making task （certain, risky, and ambiguous）. The tasks were presented using a brain function audiovisual stimulation system. We conducted brain scans of 15 healthy volunteers using a 3.0T magnetic resonance scanner. We used SPM8 to ana- lyze the location and intensity of activation during the reward-based decision-making task, with re- spect to the three conditions. We found that the orbitofrontal cortex was activated in the certain reward condition, while the prefrontal cortex, precentral gyrus, occipital visual cortex, inferior parietal lobe, cerebellar posterior lobe, middle temporal gyrus, inferior temporal gyrus, limbic lobe, and midbrain were activated during the ＇risk＇ condition. The prefrontal cortex, temporal pole, inferior temporal gyrus, occipital visual cortex, and cerebellar posterior lobe were activated during am- biguous decision-making. The ventrolateral prefrontal lobe, frontal pole of the prefrontal lobe, orbi- tofrontal cortex, precentral gyrus, inferior temporal gyrus, fusiform gyrus, supramarginal gyrus, infe- rior parietal Iobule, and cerebellar posterior lobe exhibited greater activation in the ＇risk＇ than in the ＇certain＇ condition （P 〈 0.05）. The frontal pole and dorsolateral region of the prefrontal lobe, as well as the cerebellar posterior lobe, showed significantly greater activation in the ＇ambiguous＇ condition compared to the ＇risk＇ condition （P 〈 0.05）. The prefrontal lobe, occipital lobe, parietal lobe, temporal lobe, limbic lobe, midbrain, and posterior lobe of the cerebellum were activated during deci- sion-making about uncertain rewards. Thus, we observed different levels and regions of activation for different types of reward processing during decision-making. Specifically, when the degree of reward uncertainty increased, the number of activated brain areas increased, including greater ac- tivation of brain areas associated with loss.     

Contribution of electrophysiological studies to cerebellar physiology

Electrical stimulation and the recording of electrical potentials have made important contributions to the classic formulations of cerebellar function. These electrical methods also have contributed to a re-appraisal, now underway, of the cerebellar role in the human brain. Beyond its accepted role in motor function, the cerebellum seems to contribute to some nonmotor functions. It is now known to communicate with the prefrontal cortex as well as with the motor cortex of the frontal lobe, and it seems to be involved in some prefrontal cognitive and language functions as well as in motor function. Investigations of cerebellar involvement in such functions are now being carried out, with encouraging results. If confirmed by further clinical evidence, this broader concept of cerebellar function would explain the mystery of why the most lateral parts of the cerebellum enlarged dramatically in the human brain, concomitantly with the enlargement of the cerebral association areas.     

The human cerebro-cerebellar system: its computing, cognitive, and language skills.

In this review of the human cerebro-cerebellar system, the focus is on the possible contributions of the cerebellum to cognitive and language functions. The role of the cerebellum in these human functions has tended to be obscured by the traditional preoccupation with the motor functions of the cerebellum, which have been widely observed in other vertebrates as well. In the human brain, some phylogenetically new parts evolved and enlarged in the cerebellum, concomitantly with the enlargement of association areas in the cerebral cortex. Anatomical evidence and behavioral evidence combine to suggest that this enlarged cerebellum contributes not only to motor function but also to some sensory, cognitive, linguistic, and emotional aspects of behavior. The anatomical evidence derives from the modularity of the cerebellum, whose cortical nerve cells are organized into longitudinal micro-modules, which are arrayed perpendicular to the cortical surface and parallel to each other. The number of these micro-modules increased when the cerebellum enlarged, which enlarged the computing capabilities of the network. (From principles underlying the processing of information, it is known that when modules with modest processing capabilities are assembled in large numbers in parallel, the resulting network can achieve remarkably powerful computing capabilities.) Such cerebellar computing capabilities can be utilized in the different areas of the cerebral cortex to which the cerebellum sends signals. The cerebellar output connections convey signals through the thalamus to the cerebral cortex in segregated channels of communication, which preserve the modularity of the cerebellum. Through these channels, modules in the lateral cerebellum can send signals to new cognitive and language areas of the cerebral cortex, such as Broca's area in the prefrontal cortex. The anatomy of the human cerebro-cerebellar system therefore suggests that the cerebellum can contribute to the learning not only of motor skills but also of some cognitive and language skills. Supporting this anatomical evidence is the mounting behavioral evidence, obtained both in normal brains and in clinical studies, which indicates that the lateral cerebellum is indeed involved in some cognitive and language functions.     

Relationship between prefrontal and limbic cortex: a comparative anatomical review

Certain cortical areas of the frontal lobe which are included in the limbic system on functional grounds and by virtue of their hypothalamic and amygdaloid connections must also be considered part of the prefrontal cortex if the latter is defined as the projection field of the mediodorsal thalamic nucleus (MD). This ambiguity has resulted in general confusion regarding the anatomical organization of these areas. The present review attempts to clarify these issues by briefly discussing the historical development of the concepts of limbic and prefrontal cortex, then reviewing comparative data on cytoarchitectural structure and afferent connections among several orders of mammals. It is shown that in all cases the entire cerebral cortex can be divided into concentric rings of allocortex, mesocortex and isocortex. The cortical projections of MD and the amygdala overlap primarily in the mesocortical regions which constitute limbic cortex, and the MD projection field extends further to include the granular isocortex of the frontal lobe. This close correspondence between cytoarchitectonic structure and afferent connections in different groups of mammals suggests that these anatomical features are fundamental aspects of cortical organization and that they be used to re-orient terminology such as limbic cortex and prefrontal cortex, as well as guide our understanding of the functional roles played by these cortical areas.     

Bridging the gap between functional and anatomical features of cortico‐cerebellar circuits using meta‐analytic connectivity modeling

Theories positing that the cerebellum contributes to cognitive as well as motor control are driven by two sources of information: (1) studies highlighting connections between the cerebellum and both prefrontal and motor territories, (2) functional neuroimaging studies demonstrating cerebellar activations evoked during the performance of both cognitive and motor tasks. However, almost no studies to date have combined these two sources of information and investigated cortico‐cerebellar connectivity during task performance. Through the use of a novel neuroimaging tool (Meta‐Analytic Connectivity Modelling) we demonstrate for the first time that cortico‐cerebellar connectivity patterns seen in anatomical studies and resting fMRI are also present during task performance. Consistent with human and nonhuman primate anatomical studies cerebellar lobules Crus I and II were significantly coactivated with prefrontal and parietal cortices during task performance, whilst lobules HV, HVI, HVIIb, and HVIII were significantly coactivated with the pre‐ and postcentral gyrus. An analysis of the behavioral domains showed that these circuits were driven by distinct tasks. Prefrontal‐parietal‐cerebellar circuits were more active during cognitive and emotion tasks whilst motor‐cerebellar circuits were more active during action execution tasks. These results highlight the separation of prefrontal and motor cortico‐cerebellar loops during task performance, and further demonstrate that activity within these circuits relates to distinct functions. Hum Brain Mapp 35:3152–3169, 2014. © 2013 Wiley Periodicals, Inc.     

The cerebellum mediates conflict resolution

Regions within the frontal and parietal cortex have been implicated as important neural correlates for cognitive control during conflict resolution. Despite the extensive reciprocal connectivity between the cerebellum and these putatively critical cortical areas, a role for the cerebellum in conflict resolution has never been identified. We used a task-switching paradigm that separates processes related to task-set switching and the management of response conflict independent of motor processing. Eleven patients with chronic, focal lesions to the cerebellum and 11 healthy controls were compared. Patients were slower and less accurate in conditions involving conflict resolution. In the absence of response conflict, however, tasks-witching abilities were not impaired in our patients. The cerebellum may play an important role in coordinating with other areas of cortex to modulate active response states. These results are the first demonstration of impaired conflict resolution following cerebellar lesions in the presence of an intact prefrontal cortex.     

The Functional Organization of Working Memory Processes Within Human Lateral Frontal Cortex: The Contribution of Functional Neuroimaging

Recent functional neuroimaging studies have provided a wealth of new information about the likely organization of working memory processes within the human lateral frontal cprtex. This article seeks to evaluate the results of these studies in the context of two contrasting theoretical models of lateral frontal-lobe function, developed through lesion and electrophysiological recording work in non-human primates (Goldman-Rakic, 1994, 1995; Petrides, 1994, 1995). Both models focus on a broadly similar distinction between anatomically and cytoarchitectonically distinct dorsolateral and ventrolateral frontal cortical areas, but differ in the precise functions ascribed to those regions. Following a review of the relevant anatomical data, the origins of these two theoretical positions are considered in some detail and the main predictions arising from each are identified. Recent functional neuroimaging studies of working memory processes are then critically reviewed in order to assess the extent to which they support either, or both, sets of predictions. The results of this meta-analysis suggest that lateral regions of the frontal lobe are not functionally organized according to stimulus modality, as has been widely assumed, but that specific regions within the dorsolateral or ventrolateral frontal cortex make identical functional contributions to both spatial and non-spatial working memory.     

Redes neurales atencionales en enfermedades neurodegenerativas: evidencias anatómico-funcionales empleando el Attention Network Test

IntroductionUnderstanding alterations to brain anatomy and cognitive function associated with neurodegenerative diseases remains a challenge for neuroscience today. In experimental neuroscience, several computerised tests have been developed to contribute to our understanding of neural networks involved in cognition. The Attention Network Test (ANT) enables us to measure the activity of 3 attentional networks (alertness, orienting, and executive function).ObjectivesThe main aim of this review is to describe all the anatomical and functional alterations found in diverse neurological diseases using the ANT.Material and methodsWe collected studies published since 2010 in the PubMed database that employed the ANT in different neurological diseases. Thirty-two articles were obtained, addressing multiple sclerosis, epilepsy, and Parkinson's disease, among other disorders.ConclusionsSome of the anatomical structures proposed in the 3 attentional networks model were confirmed. The most relevant structures in the alertness network are the prefrontal cortex, parietal region, thalamus, and cerebellum. The thalamus is also relevant in the orienting network, together with posterior parietal regions. The executive network does not depend exclusively on the prefrontal cortex and anterior cingulate cortex, but also involves such subcortical structures as the basal ganglia and cerebellum and their projections towards the entire cortex.     

Cognitive control of vocalizations in the primate ventrolateral-dorsomedial frontal (VLF-DMF) brain network

This review centers on the neural mechanisms underlying the primate cognitive control of vocalizations, i.e. the capacity to regulate vocal productions in a goal-directed manner. In both human and non-human primates (NHPs), two main frontal brain regions are associated with top-down vocal control: a ventrolateral frontal region (VLF), comprising the ventrolateral prefrontal cortex and ventral premotor region; and a dorsomedial frontal region (DMF), comprising the mid-cingulate cortex, pre-supplementary and supplementary motor areas. These regions are cytoarchitectonically comparable across humans and NHPs and could serve generic functions in primate vocal control. Here, we first summarize the key anatomical properties of VLF and DMF regions as well as their involvements in the motor and cognitive control of vocalizations in both humans and NHPs. Finally, in light of the reviewed evidence, we discuss the existence of a primate VLF-DMF network and its generic functions in the cognitive control of vocalizations. We further suggest how this network and its functions may have changed across primate evolution to enable modern human speech.     

Commentary on “The Cerebellar System and What it Signifies from a Biological Perspective: A Communication by Christofredo Jakob (1866–1956) Before the Society of Neurology and Psychiatry of Buenos Aires,December 1938”

This commentary highlights a “cerebellar classic” by a pioneer of neurobiology, Christfried Jakob. Jakob discussed the connectivity between the cerebellum and mesencephalic, diencephalic, and telencephalic structures in an evolutionary, developmental, and histophysiological perspective. He proposed three evolutionary morphofunctional stages, the archicerebellar, paleocerebellar, and neocerebellar; he attributed the reduced cerebellospinal connections in humans, compared to other primates, to the perfection of the rubrolenticular and thalamocortical systems and the intense ascending pathways to the red nucleus in exchange for the more elementary descending efferent pathways. Jakob hypothesized the convergence of cerebellar pathways in associative cortical regions, insisting on the intimate collaboration of the cerebellum with the frontal lobe. The extensive lines of communication between regions throughout the association cortex substantiate Jakob’s intuition and begin to outline the mechanisms for substantial cerebellar involvement in functions beyond the purely motor domain. Atop a foundation of anatomical and phylogenetic mastery, Jakob conceived ideas that were noteworthy, timely, and have much relevance to our current thinking on cerebellar structure and function.     

Hemispheric dissociation of visual-pattern processing and visual rotation

We aimed at investigating whether on-line and delayed visual pattern processing activated different areas in human prefrontal and parietal cortex. For this purpose we measured the regional cerebral blood flow (rCBF) during simultaneous and successive visual matrix processing in 10 right-handed subjects. Delayed matching to sample activated predominantly left hemispheric ventrolateral prefrontal cortex, Broca's area and parts of the parietal cortex. In contrast, visuospatial matrix rotation showed activation of the right dorsolateral prefrontal cortex and parietal lobe. The present results suggest a hemispheric dissociation of fronto-parietal circuits with a left dominance for visual pattern processing like storage and a right dominance for visuospatial processing.     

反社会人格障碍男性青年大脑白质异常改变： 证据来自于基于体素脑形态测量学的DARTEL分析

SPM8 DARTEL工具包对3D脑结构成像数据对男性青年反社会人格障碍者和正常组的大脑白质结构进行基于体素的形态学分析（VBM）。结果显示,与正常对照者比较,反社会人格障碍者主要表现为双侧前额叶、右岛叶、中央前回,左右颞上回、右中央后回、右侧顶下小叶、右侧楔前叶、右枕中叶、右海马旁回及双侧扣带回等多个脑区白质体积密度增加,左颞中叶、右小脑的白质体积密度减小。相关分析显示,额内侧回的白质体积密度增加与反社会行为的评分(PDQ)有正相关。提示反社会人格障碍者存在多个脑区的白质形态学明显异常,这些异常可能与其反社会行为有关。     

What can atypical language hemispheric specialization tell us about cognitive functions?

Recent studies have made substantial progress in understanding the interactions between cognitive functions, from language to cognitive control, attention, and memory. However, dissociating these functions has been hampered by the close proximity of regions involved, as in the case in the prefrontal and parietal cortex. In this article, we review a series of studies that investigated the relationship between language and other cognitive functions in an alternative way –– by examining their functional(co-)lateralization. We argue that research on the hemispheric lateralization of language and its link with handedness can offer an appropriate startingpoint to shed light on the relationships between different functions. Besides functional interactions, anatomical asymmetries in non-human primates and those underlying language in humans can provide unique information about cortical organization. Finally, some open questions and criteria are raised for an ideal theoretical model of the cortex based on hemispheric specialization.     

Broca’s region: linking human brain functional connectivity data and non‐human primate tracing anatomy studies

Brodmann areas 6, 44 and 45 in the ventrolateral frontal cortex of the left hemisphere of the human brain constitute the anterior language production zone. The anatomical connectivity of these areas with parietal and temporal cortical regions was recently examined in an autoradiographic tract‐tracing study in the macaque monkey. Studies suggest strong correspondence between human resting state functional connectivity (RSFC) based on functional magnetic resonance imaging data and experimentally demonstrated anatomical connections in non‐human primates. Accordingly, we hypothesized that areas 6, 44 and 45 of the human brain would exhibit patterns of RSFC consistent with patterns of anatomical connectivity observed in the macaque. In a primary analysis, we examined the RSFC associated with regions‐of‐interest placed in ventrolateral frontal areas 6, 44 and 45, on the basis of local sulcal and gyral anatomy. We validated the results of the primary hypothesis‐driven analysis with a data‐driven partitioning of ventrolateral frontal cortex into regions exhibiting distinct RSFC patterns, using a spectral clustering algorithm. The RSFC of ventrolateral frontal areas 6, 44 and 45 was consistent with patterns of anatomical connectivity shown in the macaque. We observed a striking dissociation between RSFC for the ventral part of area 6 that is involved in orofacial motor control and RSFC associated with Broca’s region (areas 44 and 45). These findings indicate rich and differential RSFC patterns for the ventrolateral frontal areas controlling language production, consistent with known anatomical connectivity in the macaque brain, and suggest conservation of connectivity during the evolution of the primate brain.     

The Cerebellum and Cognition: Evidence from Functional Imaging Studies

Evidence for a role of the human cerebellum in cognitive functions comes from anatomical, clinical and neuroimaging data. Functional neuroimaging reveals cerebellar activation during a variety of cognitive tasks, including language, visual?Cspatial, executive, and working memory processes. It is important to note that overt movement is not a prerequisite for cerebellar activation: the cerebellum is engaged during conditions which either control for motor output or do not involve motor responses. Resting-state functional connectivity data reveal that, in addition to networks underlying motor control, the cerebellum is part of ??cognitive?? networks with prefrontal and parietal association cortices. Consistent with these findings, regional differences in activation patterns within the cerebellum are evident depending on the task demands, suggesting that the cerebellum can be broadly divided into functional regions based on the patterns of anatomical connectivity between different regions of the cerebellum and sensorimotor and association areas of the cerebral cortex. However, the distinct contribution of the cerebellum to cognitive tasks is not clear. Here, the functional neuroimaging evidence for cerebellar involvement in cognitive functions is reviewed and related to hypotheses as to why the cerebellum is active during such tasks. Identifying the precise role of the cerebellum in cognition??as well as the mechanism by which the cerebellum modulates performance during a wide range of tasks??remains a challenge for future investigations.     

On the scent of human olfactory orbitofrontal cortex: Meta-analysis and comparison to non-human primates

It is widely accepted that the orbitofrontal cortex (OFC) represents the main neocortical target of primary olfactory cortex. In non-human primates, the olfactory neocortex is situated along the basal surface of the caudal frontal lobes, encompassing agranular and dysgranular OFC medially and agranular insula laterally, where this latter structure wraps onto the posterior orbital surface. Direct afferent inputs arrive from most primary olfactory areas, including piriform cortex, amygdala, and entorhinal cortex, in the absence of an obligatory thalamic relay. While such findings are almost exclusively derived from animal data, recent cytoarchitectonic studies indicate a close anatomical correspondence between non-human primate and human OFC. Given this cross-species conservation of structure, it has generally been presumed that the olfactory projection area in human OFC occupies the same posterior portions of OFC as seen in non-human primates. This review questions this assumption by providing a critical survey of the localization of primate and human olfactory neocortex. Based on a meta-analysis of human functional neuroimaging studies, the region of human OFC showing the greatest olfactory responsivity appears substantially rostral and in a different cytoarchitectural area than the orbital olfactory regions as defined in the monkey. While this anatomical discrepancy may principally arise from methodological differences across species, these results have implications for the interpretation of prior human lesion and neuroimaging studies and suggest constraints upon functional extrapolations from animal data.     

Implications of animal object memory research for human amnesia

Damage to structures in the human medial temporal lobe causes severe memory impairment. Animal object recognition tests gained prominence from attempts to model ‘global’ human medial temporal lobe amnesia, such as that observed in patient HM. These tasks, such as delayed nonmatching-to-sample and spontaneous object recognition, for assessing object memory in non-human primates and rodents have proved invaluable as animal models of specific aspects of human declarative memory processes. This paper reviews research in non-human primates and rats using object recognition memory tasks to assess the neurobiological bases of amnesia. A survey of this research reveals several important implications for our understanding of the anatomical basis of memory and the medial temporal lobe amnesic syndrome. First, research with monkeys and rats reveals that the contributions of medial temporal lobe structures such as the hippocampus and perirhinal cortex to memory processes are dissociable, with particular structures contributing to specific tasks on the basis of the specific type of information that a structure is optimized to process. Second, the literature suggests that cognitive tasks requiring integration of different types of information, such as in the case of complex, multimodal declarative memory, will recruit structures of the medial temporal lobe in an interactive manner. The heterogeneity of function within the medial temporal lobe, as well as the multimodal and complex nature of human declarative memory, implies that animal tests of object recognition memory, once believed to be comprehensive models for the study of human global amnesia, model just one important facet of human declarative memory. Finally, in light of the research reviewed here, it is apparent that the specific nature of amnesia observed in an individual with medial temporal lobe damage will depend on the particular medial temporal lobe regions affected and their specific representational capacities.     

Who comes first? The role of the prefrontal and parietal cortex in cognitive control

Cognitive control processes enable us to adjust our behavior to changing environmental demands. Although neuropsychological studies suggest that the critical cortical region for cognitive control is the prefrontal cortex, neuro-imaging studies have emphasized the interplay of prefrontal and parietal cortices. This raises the fundamental question about the different contributions of prefrontal and parietal areas in cognitive control. It was assumed that the prefrontal cortex biases processing in posterior brain regions. This assumption leads to the hypothesis that neural activity in the prefrontal cortex should precede parietal activity in cognitive control. The present study tested this assumption by combining results from functional magnetic resonance imaging (fMRI) providing high spatial resolution and event-related potentials (ERPs) to gain high temporal resolution. We collected ERP data using a modified task-switching paradigm. In this paradigm, a situation where the same task was indicated by two different cues was compared with a situation where two cues indicated different tasks. Only the latter condition required updating of the task set. Task-set updating was associated with a midline negative ERP deflection peaking around 470 msec. We placed dipoles in regions activated in a previous fMRI study that used the same paradigm (left inferior frontal junction, right inferior frontal gyrus, right parietal cortex) and fitted their directions and magnitudes to the ERP effect. The frontal dipoles contributed to the ERP effect earlier than the parietal dipole, providing support for the view that the prefrontal cortex is involved in updating of general task representations and biases relevant stimulus-response associations in the parietal cortex.