Utilizing connectome fingerprinting functional MRI models for motor activity prediction in presurgical planning: A feasibility study.

Presurgical planning prior to brain tumor resection is critical for the preservation of neurologic function post-operatively. Neurosurgeons increasingly use advanced brain mapping techniques pre- and intra-operatively to delineate brain regions which are "eloquent" and should be spared during resection. Functional MRI (fMRI) has emerged as a commonly used non-invasive modality for individual patient mapping of critical cortical regions such as motor, language, and visual cortices. To map motor function, patients are scanned using fMRI while they perform various motor tasks to identify brain networks critical for motor performance, but it may be difficult for some patients to perform tasks in the scanner due to pre-existing deficits. Connectome fingerprinting (CF) is a machine-learning approach that learns associations between resting-state functional networks of a brain region and the activations in the region for specific tasks; once a CF model is constructed, individualized predictions of task activation can be generated from resting-state data. Here we utilized CF to train models on high-quality data from 208 subjects in the Human Connectome Project (HCP) and used this to predict task activations in our cohort of healthy control subjects (n = 15) and presurgical patients (n = 16) using resting-state fMRI (rs-fMRI) data. The prediction quality was validated with task fMRI data in the healthy controls and patients. We found that the task predictions for motor areas are on par with actual task activations in most healthy subjects (model accuracy around 90%-100% of task stability) and some patients suggesting the CF models can be reliably substituted where task data is either not possible to collect or hard for subjects to perform. We were also able to make robust predictions in cases in which there were no task-related activations elicited. The findings demonstrate the utility of the CF approach for predicting activations in out-of-sample subjects, across sites and scanners, and in patient populations. This work supports the feasibility of the application of CF models to presurgical planning, while also revealing challenges to be addressed in future developments. PRACTITIONER POINTS: Precision motor network prediction using connectome fingerprinting. Carefully trained models' performance limited by stability of task-fMRI data. Successful cross-scanner predictions and motor network mapping in patients with tumor.

Predicting an individual's cerebellar activity from functional connectivity fingerprints.

The cerebellum is gaining scientific attention as a key neural substrate of cognitive function; however, individual differences in the cerebellar organization have not yet been well studied. Individual differences in functional brain organization can be closely tied to individual differences in brain connectivity. 'Connectome Fingerprinting' is a modeling approach that predicts an individual's brain activity from their connectome. Here, we extend 'Connectome Fingerprinting' (CF) to the cerebellum. We examined functional MRI data from 160 subjects (98 females) of the Human Connectome Project young adult dataset. For each of seven cognitive task paradigms, we constructed CF models from task activation maps and resting-state cortico-cerebellar functional connectomes, using a set of training subjects. For each model, we then predicted task activation in novel individual subjects, using their resting-state functional connectomes. In each cognitive paradigm, the CF models predicted individual subject cerebellar activity patterns with significantly greater precision than did predictions from the group average task activation. Examination of the CF models revealed that the cortico-cerebellar connections that carried the most information were those made with the non-motor portions of the cerebral cortex. These results demonstrate that the fine-scale functional connectivity between the cerebral cortex and cerebellum carries important information about individual differences in cerebellar functional organization. Additionally, CF modeling may be useful in the examination of patients with cerebellar dysfunction, since model predictions require only resting-state fMRI data which is more easily obtained than task fMRI.

Functional network reconfiguration supporting memory-guided attention.

Studies have identified several brain regions whose activations facilitate attentional deployment via long-term memories. We analyzed task-based functional connectivity at the network and node-specific level to characterize large-scale communication between brain regions underlying long-term memory guided attention. We predicted default mode, cognitive control, and dorsal attention subnetworks would contribute differentially to long-term memory guided attention, such that network-level connectivity would shift based on attentional demands, requiring contribution of memory-specific nodes within default mode and cognitive control subnetworks. We expected that these nodes would increase connectivity with one another and with dorsal attention subnetworks during long-term memory guided attention. Additionally, we hypothesized connectivity between cognitive control and dorsal attention subnetworks facilitating external attentional demands. Our results identified both network-based and node-specific interactions that facilitate different components of LTM-guided attention, suggesting a crucial role across the posterior precuneus and restrosplenial cortex, acting independently from the divisions of default mode and cognitive control subnetworks. We found a gradient of precuneus connectivity, with dorsal precuneus connecting to cognitive control and dorsal attention regions, and ventral precuneus connecting across all subnetworks. Additionally, retrosplenial cortex showed increased connectivity across subnetworks. We suggest that connectivity from dorsal posterior midline regions is critical for the integration of external information with internal memory that facilitates long-term memory guided attention.

Extended Frontal Networks for Visual and Auditory Working Memory.

Working memory (WM) supports the persistent representation of transient sensory information. Visual and auditory stimuli place different demands on WM and recruit different brain networks. Separate auditory- and visual-biased WM networks extend into the frontal lobes, but several challenges confront attempts to parcellate human frontal cortex, including fine-grained organization and between-subject variability. Here, we use differential intrinsic functional connectivity from 2 visual-biased and 2 auditory-biased frontal structures to identify additional candidate sensory-biased regions in frontal cortex. We then examine direct contrasts of task functional magnetic resonance imaging during visual versus auditory 2-back WM to validate those candidate regions. Three visual-biased and 5 auditory-biased regions are robustly activated bilaterally in the frontal lobes of individual subjects (N = 14, 7 women). These regions exhibit a sensory preference during passive exposure to task stimuli, and that preference is stronger during WM. Hierarchical clustering analysis of intrinsic connectivity among novel and previously identified bilateral sensory-biased regions confirms that they functionally segregate into visual and auditory networks, even though the networks are anatomically interdigitated. We also observe that the frontotemporal auditory WM network is highly selective and exhibits strong functional connectivity to structures serving non-WM functions, while the frontoparietal visual WM network hierarchically merges into the multiple-demand cognitive system.

Neural correlates associated with impaired global motion perception in cerebral visual impairment (CVI).

Cerebral visual impairment (CVI) is associated with a wide range of visual perceptual deficits including global motion processing. However, the underlying neurophysiological basis for these impairments remain poorly understood. We investigated global motion processing abilities in individuals with CVI compared to neurotypical controls using a combined behavioral and multi-modal neuroimaging approach. We found that CVI participants had a significantly higher mean motion coherence threshold (determined using a random dot kinematogram pattern simulating optic flow motion) compared to controls. Using functional magnetic resonance imaging (fMRI), we investigated activation response profiles in functionally defined early (i.e. primary visual cortex; area V1) and higher order (i.e. middle temporal cortex; area hMT+) stages of motion processing. In area V1, responses to increasing motion coherence were similar in both groups. However, in the CVI group, activation in area hMT+ was significantly reduced compared to controls, and consistent with a surround facilitation (rather than suppression) response profile. White matter tract reconstruction obtained from high angular resolution diffusion imaging (HARDI) revealed evidence of increased mean, axial, and radial diffusivities within cortico-cortical (i.e. V1-hMT+), but not thalamo-hMT+ connections. Overall, our results suggest that global motion processing deficits in CVI may be associated with impaired signal integration and segregation mechanisms, as well as white matter integrity at the level of area hMT+.

Individual Subject Approaches to Mapping Sensory-Biased and Multiple-Demand Regions in Human Frontal Cortex.

Sensory modality, widely accepted as a key factor in the functional organization of posterior cortical areas, also shapes the organization of human frontal lobes. 'Deep imaging,' or the practice of collecting a sizable amount of data on individual subjects, offers significant advantages in revealing fine-scale aspects of functional organization of the human brain. Here, we review deep imaging approaches to mapping multiple sensory-biased and multiple-demand regions within human lateral frontal cortex. In addition, we discuss how deep imaging methods can be transferred to large public data sets to further extend functional mapping at the group level. We also review how 'connectome fingerprinting' approaches, combined with deep imaging, can be used to localize fine-grained functional organization in individual subjects using resting-state data. Finally, we summarize current 'best practices' for deep imaging.

Attention and Default Mode Network Assessments of Meditation Experience during Active Cognition and Rest.

Meditation experience has previously been shown to improve performance on behavioral assessments of attention, but the neural bases of this improvement are unknown. Two prominent, strongly competing networks exist in the human cortex: a dorsal attention network, that is activated during focused attention, and a default mode network, that is suppressed during attentionally demanding tasks. Prior studies suggest that strong anti-correlations between these networks indicate good brain health. In addition, a third network, a ventral attention network, serves as a "circuit-breaker" that transiently disrupts and redirects focused attention to permit salient stimuli to capture attention. Here, we used functional magnetic resonance imaging to contrast cortical network activation between experienced focused attention Vipassana meditators and matched controls. Participants performed two attention tasks during scanning: a sustained attention task and an attention-capture task. Meditators demonstrated increased magnitude of differential activation in the dorsal attention vs. default mode network in a sustained attention task, relative to controls. In contrast, there were no evident attention network differences between meditators and controls in an attentional reorienting paradigm. A resting state functional connectivity analysis revealed a greater magnitude of anticorrelation between dorsal attention and default mode networks in the meditators as compared to both our local control group and a n = 168 Human Connectome Project dataset. These results demonstrate, with both task- and rest-based fMRI data, increased stability in sustained attention processes without an associated attentional capture cost in meditators. Task and resting-state results, which revealed stronger anticorrelations between dorsal attention and default mode networks in experienced mediators than in controls, are consistent with a brain health benefit of long-term meditation practice.

Towards Neuroscience of the Everyday World (NEW) using functional Near-Infrared Spectroscopy.

Functional Near-Infrared Spectroscopy (fNIRS) assesses human brain activity by noninvasively measuring changes of cerebral hemoglobin concentrations caused by modulation of neuronal activity. Recent progress in signal processing and advances in system design, such as miniaturization, wearability and system sensitivity, have strengthened fNIRS as a viable and cost-effective complement to functional Magnetic Resonance Imaging (fMRI), expanding the repertoire of experimental studies that can be performed by the neuroscience community. The availability of fNIRS and Electroencephalography (EEG) for routine, increasingly unconstrained, and mobile brain imaging is leading towards a new domain that we term "Neuroscience of the Everyday World" (NEW). In this light, we review recent advances in hardware, study design and signal processing, and discuss challenges and future directions towards achieving NEW.

Stimulus-Specific Visual Working Memory Representations in Human Cerebellar Lobule VIIb/VIIIa.

fMRI research has revealed that cerebellar lobule VIIb/VIIIa exhibits load-dependent activity that increases with the number of items held in visual working memory (VWM). However, it remains unclear whether these cerebellar responses reflect processes specific to VWM or more general visual attentional mechanisms. To investigate this question, we examined whether cerebellar activity during the delay period of a VWM task is selective for stimuli held in working memory. A sample of male and female human subjects performed a VWM continuous report task in which they were retroactively cued to remember the direction of motion of moving dot stimuli. Cerebellar lobule VIIb/VIIIa delay-period activation accurately decoded the direction of the remembered stimulus, as did frontal and parietal regions of the dorsal attention network. Arguing against a motor explanation, no other cerebellar area exhibited stimulus specificity, including the oculomotor vermis, a key area associated with eye movement control. Finer-scale analysis revealed that the medial portion of lobule VIIb and to a lesser degree the lateral most portion of lobules VIIb and VIIIa, which exhibit robust resting state connectivity with frontal and parietal regions of the dorsal attention network, encoded the identity of the remembered stimulus, while intermediate portions of lobule VIIb/VIIIa did not. These findings of stimulus-specific coding of VWM within lobule VIIb/VIIIa indicate for the first time that the distributed network responsible for the encoding and maintenance of mnemonic representations extends to the cerebellum.SIGNIFICANCE STATEMENT There is considerable debate concerning where in the brain the contents of visual working memory (VWM) are stored. To date, this literature has primarily focused on the role of regions located within cerebral cortex. There is growing evidence for cerebellar involvement in higher-order cognitive functions including working memory. While the cerebellum has been previously shown to be recruited by VWM paradigms, it is unclear whether any portion of cerebellum actively encodes and maintains mnemonic representations. The present study demonstrates that cerebellar lobule VIIb/VIIIa activity patterns are selective for remembered stimuli and that this selectivity persists in the absence of perceptual input. These findings provide novel evidence for the participation of cerebellar structures in the persistent storage of visual information.

Gradients of functional organization in posterior parietal cortex revealed by visual attention, visual short-term memory, and intrinsic functional connectivity.

Visual attention and visual working memory tasks recruit a common network of lateral frontal cortical (LFC) and posterior parietal cortical (PPC) regions. Here, we examine finer-scale organization of this frontoparietal network. Three LFC regions recruited by visual cognition tasks, superior precentral sulcus (sPCS), inferior precentral sulcus (iPCS), and mid inferior frontal sulcus (midIFS) exhibit differential patterns of resting-state functional connectivity to PPC. A broad dorsomedial to ventrolateral gradient is observed, with sPCS connectivity dominating in the dorsomedial PPC band, iPCS dominating in the middle band, and midIFS dominating in the ventrolateral band. These connectivity-defined subregions of PPC capture differential task activation between a pair of visual attention and working memory tasks. The relative functional connectivity of sPCS and iPCS also varies along the rostral-caudal axis of the retinotopic regions of PPC. iPCS connectivity is relatively stronger near the IPS0/IPS1 and IPS2/IPS3 borders, especially on the lateral portions of these borders, which each preferentially encode central visual field representations. In contrast, sPCS connectivity is relatively stronger elsewhere in retinotopic IPS regions which preferentially encode peripheral visual field representations. These findings reveal fine-scale gradients in functional connectivity within the frontoparietal visual network that capture a high-degree of specificity in PPC functional organization.

Cortico-cerebellar networks for visual attention and working memory.

Cerebellar cortex, which is cytoarchitectonically homogenous, can be functionally differentiated by connectivity differences across the cerebral cortex. The cerebral cortical dorsal attention network exhibits strong, selective connectivity with a set of cerebellar circuits, including lobule VIIb/VIIIa. Recent findings demonstrate that lobule VIIb/VIIIa exhibits functional properties characteristic of the cortical dorsal attention network: task-specific activation; working memory load-dependent responses; and the representation of visuospatial location. Moreover, functional cortico-cerebellar subnetworks exhibit topographic specialization for different aspects of visual attentional processing. Thus, cerebellar lobule VIIb/VIIIa, rather than simply supporting motor functions, appears to be an integral part of the brain's visual attentional circuitry. More generally, these findings suggest that parallel cortico-cerebellar networks may play highly specific functional roles in a broad range of cognitive processes.

Predicting an individual's dorsal attention network activity from functional connectivity fingerprints.

The cortical dorsal attention network (DAN) is a set of parietal and frontal regions that support a wide variety of attentionally demanding tasks. Whereas attentional deployment reliably drives DAN activity across subjects, there is a large degree of variation in the activation pattern in individual subjects. We hypothesize that a subject's own idiosyncratic pattern of cortical DAN activity can be predicted from that subject's own unique pattern of functional connectivity. By modeling task activation as a function of whole brain connectivity patterns, we are able to define the connectivity fingerprints for the frontal and parietal DAN, and use it to predict a subject's characteristic DAN activation pattern with high accuracy. These predictions outperform the standard group-average benchmark and predict a subject's own activation pattern above and beyond predictions from another subject's connectivity pattern. Thus an individual's distinctive connectivity pattern accounts for substantial variance in DAN functional responses. Last, we show that the set of connections that predict cortical DAN responses, the frontal and parietal DAN connectivity fingerprints, is predominantly composed of other coactive regions, including regions outside of the DAN including occipital and temporal visual cortices. These connectivity fingerprints represent defining computational characteristics of the DAN, delineating which voxels are or are not capable of exerting top-down attentional bias to other regions of the brain. NEW & NOTEWORTHY The dorsal attention network (DAN) is a set of regions in frontoparietal cortex that reliably activate during attentional tasks. We designed computational models that predict the degree of an individual's DAN activation using their resting-state connectivity pattern alone. This uncovered the connectivity fingerprints of the DAN, which define it so well that we can predict how a voxel will respond to an attentional task given only its pattern of connectivity, with outstanding accuracy.

Identification of Visual Attentional Regions of the Temporoparietal Junction in Individual Subjects using a Vivid, Novel Oddball Paradigm.

The Temporoparietal Junction (TPJ) of the cerebral cortex is a functionally heterogeneous region that also exhibits substantial anatomical variability across individuals. As a result, the precise functional organization of TPJ remains controversial. One or more regions within TPJ support visual attention processes, but the "attention TPJ" is difficult to functionally observe in individual subjects, and thus is typically identified by averaging across a large group of subjects. However, group-averaging also blurs localization and can obscure functional organization. Here, we develop and test an individual-subject approach to identifying attentional TPJ. This paradigm employs novel oddball images with a strong visual drive to produce robust TPJ responses in individuals. Vivid, novel oddballs drive responses in two TPJ regions bilaterally, a posterior region centered in posterior Superior Temporal Sulcus (TPJSTS) and an anterior region in ventral Supramarginal Gyrus (TPJSMG). Although an attentional reorienting task fails to drive TPJ activation in individuals, group analysis of the attentional reorienting contrast reveals recruitment of right TPJSTS, but not right TPJSMG. Similarly, right TPJSTS, as identified in individual subjects by the vivid, novel oddball contrast, is activated by attentional reorienting, but right TPJSMG is not. These findings advance an individual-subject based approach to understanding the functional organization of TPJ.

Topographic Cortico-cerebellar Networks Revealed by Visual Attention and Working Memory.

Substantial portions of the cerebellum appear to support non-motor functions; however, previous investigations of cerebellar involvement in cognition have revealed only a coarse degree of specificity. Although somatotopic maps have been observed within cerebellum, similar precision within cortico-cerebellar networks supporting non-motor functions has not previously been reported. Here, we find that human cerebellar lobule VIIb/VIIIa differentially codes key aspects of visuospatial cognition. Ipsilateral visuospatial representations were observed during both a visual working memory and an attentionally demanding visual receptive field-mapping fMRI task paradigm. Moreover, within lobule VIIb/VIIIa, we observed a functional dissociation between spatial coding and visual working memory processing. Visuospatial representations were found in the dorsomedial portion of lobule VIIb/VIIIa, and load-dependent visual working memory processing was shifted ventrolaterally. A similar functional gradient for spatial versus load processing was found in posterior parietal cortex. This cerebral cortical organization was well predicted by functional connectivity with spatial and load regions of cerebellar lobule VIIb/VIIIa. Collectively, our findings indicate that recruitment by visuospatial attentional functions within cerebellar lobule VIIb/VIIIa is highly specific. Furthermore, the topographic arrangement of these functions is mirrored in frontal and parietal cortex. These findings motivate a closer examination of cortico-cerebellar functional specialization across a broad range of cognitive domains.

Prediction of individualized task activation in sensory modality-selective frontal cortex with 'connectome fingerprinting'.

The human cerebral cortex is estimated to comprise 200-300 distinct functional regions per hemisphere. Identification of the precise anatomical location of an individual's unique set of functional regions is a challenge for neuroscience that has broad scientific and clinical utility. Recent studies have demonstrated the existence of four interleaved regions in lateral frontal cortex (LFC) that are part of broader visual attention and auditory attention networks (Michalka et al., 2015; Noyce et al., 2017; Tobyne et al., 2017). Due to a large degree of inter-subject anatomical variability, identification of these regions depends critically on within-subject analyses. Here, we demonstrate that, for both sexes, an individual's unique pattern of resting-state functional connectivity can accurately identify their specific pattern of visual- and auditory-selective working memory and attention task activation in lateral frontal cortex (LFC) using "connectome fingerprinting." Building on prior techniques (Saygin et al., 2011; Osher et al., 2016; Tavor et al., 2016; Smittenaar et al., 2017; Wang et al., 2017; Parker Jones et al., 2017), we demonstrate here that connectome fingerprint predictions are far more accurate than group-average predictions and match the accuracy of within-subject task-based functional localization, while requiring less data. These findings are robust across brain parcellations and are improved with penalized regression methods. Because resting-state data can be easily and rapidly collected, these results have broad implications for both clinical and research investigations of frontal lobe function. Our findings also provide a set of recommendations for future research.

Visual Short-Term Memory Activity in Parietal Lobe Reflects Cognitive Processes beyond Attentional Selection.

Visual short-term memory (VSTM) and attention are distinct yet interrelated processes. While both require selection of information across the visual field, memory additionally requires the maintenance of information across time and distraction. VSTM recruits areas within human (male and female) dorsal and ventral parietal cortex that are also implicated in spatial selection; therefore, it is important to determine whether overlapping activation might reflect shared attentional demands. Here, identical stimuli and controlled sustained attention across both tasks were used to ask whether fMRI signal amplitude, functional connectivity, and contralateral visual field bias reflect memory-specific task demands. While attention and VSTM activated similar cortical areas, BOLD amplitude and functional connectivity in parietal cortex differentiated the two tasks. Relative to attention, VSTM increased BOLD amplitude in dorsal parietal cortex and decreased BOLD amplitude in the angular gyrus. Additionally, the tasks differentially modulated parietal functional connectivity. Contrasting VSTM and attention, intraparietal sulcus (IPS) 1-2 were more strongly connected with anterior frontoparietal areas and more weakly connected with posterior regions. This divergence between tasks demonstrates that parietal activation reflects memory-specific functions and consequently modulates functional connectivity across the cortex. In contrast, both tasks demonstrated hemispheric asymmetries for spatial processing, exhibiting a stronger contralateral visual field bias in the left versus the right hemisphere across tasks, suggesting that asymmetries are characteristic of a shared selection process in IPS. These results demonstrate that parietal activity and patterns of functional connectivity distinguish VSTM from more general attention processes, establishing a central role of the parietal cortex in maintaining visual information.SIGNIFICANCE STATEMENT Visual short-term memory (VSTM) and attention are distinct yet interrelated processes. Cognitive mechanisms and neural activity underlying these tasks show a large degree of overlap. To examine whether activity within the posterior parietal cortex (PPC) reflects object maintenance across distraction or sustained attention per se, it is necessary to control for attentional demands inherent in VSTM tasks. We demonstrate that activity in PPC reflects VSTM demands even after controlling for attention; remembering items across distraction modulates relationships between parietal and other areas differently than during periods of sustained attention. Our study fills a gap in the literature by directly comparing and controlling for overlap between visual attention and VSTM tasks.

Cortical and Subcortical Contributions to Long-Term Memory-Guided Visuospatial Attention.

Long-term memory (LTM) helps to efficiently direct and deploy the scarce resources of the attentional system; however, the neural substrates that support LTM-guidance of visual attention are not well understood. Here, we present results from fMRI experiments that demonstrate that cortical and subcortical regions of a network defined by resting-state functional connectivity are selectively recruited for LTM-guided attention, relative to a similarly demanding stimulus-guided attention paradigm that lacks memory retrieval and relative to a memory retrieval paradigm that lacks covert deployment of attention. Memory-guided visuospatial attention recruited posterior callosal sulcus, posterior precuneus, and lateral intraparietal sulcus bilaterally. Additionally, 3 subcortical regions defined by intrinsic functional connectivity were recruited: the caudate head, mediodorsal thalamus, and cerebellar lobule VI/Crus I. Although the broad resting-state network to which these nodes belong has been referred to as a cognitive control network, the posterior cortical regions activated in the present study are not typically identified with supporting standard cognitive control tasks. We propose that these regions form a Memory-Attention Network that is recruited for processes that integrate mnemonic and stimulus-based representations to guide attention. These findings may have important implications for understanding the mechanisms by which memory retrieval influences attentional deployment.

Sensory-biased attention networks in human lateral frontal cortex revealed by intrinsic functional connectivity.

Human frontal cortex is commonly described as being insensitive to sensory modality, however several recent studies cast doubt on this view. Our laboratory previously reported two visual-biased attention regions interleaved with two auditory-biased attention regions, bilaterally, within lateral frontal cortex. These regions selectively formed functional networks with posterior visual-biased and auditory-biased attention regions. Here, we conducted a series of functional connectivity analyses to validate and expand this analysis to 469 subjects from the Human Connectome Project (HCP). Functional connectivity analyses replicated the original findings and revealed a novel hemispheric connectivity bias. We also subdivided lateral frontal cortex into 21 thin-slice ROIs and observed bilateral patterns of spatially alternating visual-biased and auditory-biased attention network connectivity. Finally, we performed a correlation difference analysis that revealed five additional bilateral lateral frontal regions differentially connected to either the visual-biased or auditory-biased attention networks. These findings leverage the HCP dataset to demonstrate that sensory-biased attention networks may have widespread influence in lateral frontal cortical organization.

Sensory-Biased and Multiple-Demand Processing in Human Lateral Frontal Cortex.

The functionality of much of human lateral frontal cortex (LFC) has been characterized as "multiple demand" (MD) as these regions appear to support a broad range of cognitive tasks. In contrast to this domain-general account, recent evidence indicates that portions of LFC are consistently selective for sensory modality. Michalka et al. (2015) reported two bilateral regions that are biased for visual attention, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), interleaved with two bilateral regions that are biased for auditory attention, transverse gyrus intersecting precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS). In the present study, we use fMRI to examine both the multiple-demand and sensory-bias hypotheses within caudal portions of human LFC (both men and women participated). Using visual and auditory 2-back tasks, we replicate the finding of two bilateral visual-biased and two bilateral auditory-biased LFC regions, corresponding to sPCS and iPCS and to tgPCS and cIFS, and demonstrate high within-subject reliability of these regions over time and across tasks. In addition, we assess MD responsiveness using BOLD signal recruitment and multi-task activation indices. In both, we find that the two visual-biased regions, sPCS and iPCS, exhibit stronger MD responsiveness than do the auditory-biased LFC regions, tgPCS and cIFS; however, neither reaches the degree of MD responsiveness exhibited by dorsal anterior cingulate/presupplemental motor area or by anterior insula. These results reconcile two competing views of LFC by demonstrating the coexistence of sensory specialization and MD functionality, especially in visual-biased LFC structures.SIGNIFICANCE STATEMENT Lateral frontal cortex (LFC) is known to play a number of critical roles in supporting human cognition; however, the functional organization of LFC remains controversial. The "multiple demand" (MD) hypothesis suggests that LFC regions provide domain-general support for cognition. Recent evidence challenges the MD view by demonstrating that a preference for sensory modality, vision or audition, defines four discrete LFC regions. Here, the sensory-biased LFC results are reproduced using a new task, and MD responsiveness of these regions is tested. The two visual-biased regions exhibit MD behavior, whereas the auditory-biased regions have no more than weak MD responses. These findings help to reconcile two competing views of LFC functional organization.

Functional Evidence for a Cerebellar Node of the Dorsal Attention Network.

UNLABELLED: The "dorsal attention network" or "frontoparietal network" refers to a network of cortical regions that support sustained attention and working memory. Recent work has demonstrated that cortical nodes of the dorsal attention network possess intrinsic functional connections with a region in ventral cerebellum, in the vicinity of lobules VII/VIII. Here, we performed a series of task-based and resting-state fMRI experiments to investigate cerebellar participation in the dorsal attention network in humans. We observed that visual working memory and visual attention tasks robustly recruit cerebellar lobules VIIb and VIIIa, in addition to canonical cortical dorsal attention network regions. Across the cerebellum, resting-state functional connectivity with the cortical dorsal attention network strongly predicted the level of activation produced by attention and working memory tasks. Critically, cerebellar voxels that were most strongly connected with the dorsal attention network selectively exhibited load-dependent activity, a hallmark of the neural structures that support visual working memory. Finally, we examined intrinsic functional connectivity between task-responsive portions of cerebellar lobules VIIb/VIIIa and cortex. Cerebellum-to-cortex functional connectivity strongly predicted the pattern of cortical activation during task performance. Moreover, resting-state connectivity patterns revealed that cerebellar lobules VIIb/VIIIa group with cortical nodes of the dorsal attention network. This evidence leads us to conclude that the conceptualization of the dorsal attention network should be expanded to include cerebellar lobules VIIb/VIIIa. SIGNIFICANCE STATEMENT: The functional participation of cerebellar structures in nonmotor cortical networks remains poorly understood and is highly understudied, despite the fact that the cerebellum possesses many more neurons than the cerebral cortex. Although visual attention paradigms have been reported to activate cerebellum, many researchers have largely dismissed the possibility of a cerebellar contribution to attention in favor of a motor explanation, namely, eye movements. The present study demonstrates that a cerebellar subdivision (mainly lobules VIIb/VIIIa), which exhibits strong intrinsic functional connectivity with the cortical dorsal attention network, also closely mirrors a myriad of cortical dorsal attention network responses to visual attention and working memory tasks. This evidence strongly supports a reconceptualization of the dorsal attention network to include cerebellar lobules VIIb/VIIIa.