Case studies in neuroscience: reversible signatures of edema following electric and piezoelectric craniotomy drilling in macaques.

In vivo electrophysiology requires direct access to brain tissue, necessitating the development and refinement of surgical procedures and techniques that promote the health and well-being of animal subjects. Here, we report a series of findings noted on structural magnetic resonance imaging (MRI) scans in monkeys with MRI-compatible implants following small craniotomies that provide access for intracranial electrophysiology. We found distinct brain regions exhibiting hyperintensities in T2-weighted scans that were prominent underneath the sites at which craniotomies had been performed. We interpreted these hyperintensities as edema of the neural tissue and found that they were predominantly present following electric and piezoelectric drilling, but not when manual, hand-operated drills were used. Furthermore, the anomalies subsided within 2-3 wk following surgery. Our report highlights the utility of MRI-compatible implants that promote clinical examination of the animal's brain, sometimes revealing findings that may go unnoticed when incompatible implants are used. We show replicable differences in outcome when using electric versus mechanical devices, both ubiquitous in the field. If electric drills are used, our report cautions against electrophysiological recordings from tissue directly underneath the craniotomy for the first 2-3 wk following the procedure due to putative edema.NEW & NOTEWORTHY Close examination of structural MRI in eight nonhuman primates following craniotomy surgeries for intracranial electrophysiology highlights a prevalence of hyperintensities on T2-weighted scans following surgeries conducted using electric and piezoelectric drills, but not when using mechanical, hand-operated drills. We interpret these anomalies as edema of neural tissue that resolved 2-3 wk postsurgery. This finding is especially of interest as electrophysiological recordings from compromised tissue may directly influence the integrity of collected data immediately following surgery.

A causal role for the pulvinar in coordinating task-independent cortico-cortical interactions.

The pulvinar is the largest nucleus in the primate thalamus and has topographically organized connections with multiple cortical areas, thereby forming extensive cortico-pulvino-cortical input-output loops. Neurophysiological studies have suggested a role for these transthalamic pathways in regulating information transmission between cortical areas. However, evidence for a causal role of the pulvinar in regulating cortico-cortical interactions is sparse and it is not known whether pulvinar's influences on cortical networks are task-dependent or, alternatively, reflect more basic large-scale network properties that maintain functional connectivity across networks regardless of active task demands. In the current study, under passive viewing conditions, we conducted simultaneous electrophysiological recordings from ventral (area V4) and dorsal (lateral intraparietal area [LIP]) nodes of macaque visual system, while reversibly inactivating the dorsal part of the lateral pulvinar (dPL), which shares common anatomical connectivity with V4 and LIP, to probe a causal role of the pulvinar. Our results show a significant reduction in local field potential phase coherence between LIP and V4 in low frequencies (4-15 Hz) following muscimol injection into dPL. At the local level, no significant changes in firing rates or LFP power were observed in LIP or in V4 following dPL inactivation. Synchronization between pulvinar spikes and cortical LFP phase decreased in low frequencies (4-15 Hz) both in LIP and V4, while the low frequency synchronization between LIP spikes and pulvinar phase increased. These results indicate a causal role for pulvinar in synchronizing neural activity between interconnected cortical nodes of a large-scale network, even in the absence of an active task state.

Neural Basis of Biased Competition in Development: Sensory Competition in Visual Cortex of School-Aged Children.

The fundamental receptive field (RF) architecture in human visual cortex becomes adult-like by age 5. However, visuo-spatial functions continue to develop until teenage years. This suggests that, despite the early maturation of the RF structure, functional interactions within and across RFs may mature slowly. Here, we used fMRI to investigate functional interactions among multiple stimuli in the visual cortex of school children (ages 8 to 12) in the context of biased competition theory. In the adult visual system, multiple objects presented in the same visual field compete for neural representation. These competitive interactions occur at the level of the RF and are therefore closely linked to the RF architecture. Like in adults, we found suppression of evoked responses in children's visual cortex when multiple stimuli were presented simultaneously. Such suppression effects were modulated by the spatial distance between the stimuli as a function of RF size across the visual system. Our findings suggest that basic competitive interactions in the visual cortex of children above age 8 operate in an adult-like manner, with subtle differences in early visual areas and area MT. Our study establishes a paradigm and provides baseline data to investigate the neural basis of visuo-spatial processing in typical and atypical development.

Large-scale resculpting of cortical circuits in children after surgical resection.

Despite the relative successes in the surgical treatment of pharmacoresistant epilepsy, there is rather little research on the neural (re)organization that potentially subserves behavioral compensation. Here, we examined the post-surgical functional connectivity (FC) in children and adolescents who have undergone unilateral cortical resection and, yet, display remarkably normal behavior. Conventionally, FC has been investigated in terms of the mean correlation of the BOLD time courses extracted from different brain regions. Here, we demonstrated the value of segregating the voxel-wise relationships into mutually exclusive populations that were either positively or negatively correlated. While, relative to controls, the positive correlations were largely normal, negative correlations among networks were increased. Together, our results point to reorganization in the contralesional hemisphere, possibly suggesting competition for cortical territory due to the demand for representation of function. Conceivably, the ubiquitous negative correlations enable the differentiation of function in the reduced cortical volume following a unilateral resection.

Distinct auditory and visual tool regions with multisensory response properties in human parietal cortex.

Left parietal cortex has been associated with the human-specific ability of sophisticated tool use. Yet, it is unclear how tool information is represented across senses. Here, we compared auditory and visual tool-specific activations within healthy human subjects to probe the relation of tool-specific networks, uni- and multisensory response properties, and functional and structural connectivity using functional and diffusion-weighted MRI. In each subject, we identified an auditory tool network with regions in left anterior inferior parietal cortex (aud-aIPL), bilateral posterior lateral sulcus, and left inferior precentral sulcus, and a visual tool network with regions in left aIPL (vis-aIPL) and bilateral inferior temporal gyrus. Aud-aIPL was largely separate and anterior/inferior from vis-aIPL, with varying degrees of overlap across subjects. Both regions displayed a strong preference for tools versus other stimuli presented within the same modality. Despite their modality preference, aud-aIPL and vis-aIPL and a region in left inferior precentral sulcus displayed multisensory response properties, as revealed in multivariate analyses. Thus, two largely separate tool networks are engaged by the visual and auditory modalities with nodes in parietal and prefrontal cortex potentially integrating information across senses. The diversification of tool processing in human parietal cortex underpins its critical role in complex object processing.

Microstructural organization of human insula is linked to its macrofunctional circuitry and predicts cognitive control.

The human insular cortex is a heterogeneous brain structure which plays an integrative role in guiding behavior. The cytoarchitectonic organization of the human insula has been investigated over the last century using postmortem brains but there has been little progress in noninvasive in vivo mapping of its microstructure and large-scale functional circuitry. Quantitative modeling of multi-shell diffusion MRI data from 413 participants revealed that human insula microstructure differs significantly across subdivisions that serve distinct cognitive and affective functions. Insular microstructural organization was mirrored in its functionally interconnected circuits with the anterior cingulate cortex that anchors the salience network, a system important for adaptive switching of cognitive control systems. Furthermore, insular microstructural features, confirmed in Macaca mulatta, were linked to behavior and predicted individual differences in cognitive control ability. Our findings open new possibilities for probing psychiatric and neurological disorders impacted by insular cortex dysfunction, including autism, schizophrenia, and fronto-temporal dementia.

Author Correction: Organizing principles of pulvino-cortical functional coupling in humans.

The original version of this Article contained an error in the author affiliations. Affiliation 3 incorrectly read 'Department of Biological and Brain Sciences, Johns Hopkins University, Baltimore, MD 21218, USA'.

The mediodorsal pulvinar coordinates the macaque fronto-parietal network during rhythmic spatial attention.

Spatial attention is discontinuous, sampling behaviorally relevant locations in theta-rhythmic cycles (3-6 Hz). Underlying this rhythmic sampling are intrinsic theta oscillations in frontal and parietal cortices that provide a clocking mechanism for two alternating attentional states that are associated with either engagement at the presently attended location (and enhanced perceptual sensitivity) or disengagement (and diminished perceptual sensitivity). It has remained unclear, however, how these theta-dependent states are coordinated across the large-scale network that directs spatial attention. The pulvinar is a candidate for such coordination, having been previously shown to regulate cortical activity. Here, we examined pulvino-cortical interactions during theta-rhythmic sampling by simultaneously recording from macaque frontal eye fields (FEF), lateral intraparietal area (LIP), and pulvinar. Neural activity propagated from pulvinar to cortex during periods of engagement, and from cortex to pulvinar during periods of disengagement. A rhythmic reweighting of pulvino-cortical interactions thus defines functional dissociations in the attention network.

Organizing principles of pulvino-cortical functional coupling in humans.

The pulvinar influences communication between cortical areas. We use fMRI to characterize the functional organization of the human pulvinar and its coupling with cortex. The ventral pulvinar is sensitive to spatial position and moment-to-moment transitions in visual statistics, but also differentiates visual categories such as faces and scenes. The dorsal pulvinar is modulated by spatial attention and is sensitive to the temporal structure of visual input. Cortical areas are functionally coupled with discrete pulvinar regions. The spatial organization of this coupling reflects the functional specializations and anatomical distances between cortical areas. The ventral pulvinar is functionally coupled with occipital-temporal cortices. The dorsal pulvinar is functionally coupled with frontal, parietal, and cingulate cortices, including the attention, default mode, and human-specific tool networks. These differences mirror the principles governing cortical organization of dorsal and ventral cortical visual streams. These results provide a functional framework for how the pulvinar facilitates and regulates cortical processing.

A Dynamic Interplay within the Frontoparietal Network Underlies Rhythmic Spatial Attention.

Classic studies of spatial attention assumed that its neural and behavioral effects were continuous over time. Recent behavioral studies have instead revealed that spatial attention leads to alternating periods of heightened or diminished perceptual sensitivity. Yet, the neural basis of these rhythmic fluctuations has remained largely unknown. We show that a dynamic interplay within the macaque frontoparietal network accounts for the rhythmic properties of spatial attention. Neural oscillations characterize functional interactions between the frontal eye fields (FEF) and the lateral intraparietal area (LIP), with theta phase (3-8 Hz) coordinating two rhythmically alternating states. The first is defined by FEF-dominated beta-band activity, associated with suppressed attentional shifts, and LIP-dominated gamma-band activity, associated with enhanced visual processing and better behavioral performance. The second is defined by LIP-specific alpha-band activity, associated with attenuated visual processing and worse behavioral performance. Our findings reveal how network-level interactions organize environmental sampling into rhythmic cycles.

The Anatomical and Functional Organization of the Human Visual Pulvinar.

The pulvinar is the largest nucleus in the primate thalamus and contains extensive, reciprocal connections with visual cortex. Although the anatomical and functional organization of the pulvinar has been extensively studied in old and new world monkeys, little is known about the organization of the human pulvinar. Using high-resolution functional magnetic resonance imaging at 3 T, we identified two visual field maps within the ventral pulvinar, referred to as vPul1 and vPul2. Both maps contain an inversion of contralateral visual space with the upper visual field represented ventrally and the lower visual field represented dorsally. vPul1 and vPul2 border each other at the vertical meridian and share a representation of foveal space with iso-eccentricity lines extending across areal borders. Additional, coarse representations of contralateral visual space were identified within ventral medial and dorsal lateral portions of the pulvinar. Connectivity analyses on functional and diffusion imaging data revealed a strong distinction in thalamocortical connectivity between the dorsal and ventral pulvinar. The two maps in the ventral pulvinar were most strongly connected with early and extrastriate visual areas. Given the shared eccentricity representation and similarity in cortical connectivity, we propose that these two maps form a distinct visual field map cluster and perform related functions. The dorsal pulvinar was most strongly connected with parietal and frontal areas. The functional and anatomical organization observed within the human pulvinar was similar to the organization of the pulvinar in other primate species. SIGNIFICANCE STATEMENT: The anatomical organization and basic response properties of the visual pulvinar have been extensively studied in nonhuman primates. Yet, relatively little is known about the functional and anatomical organization of the human pulvinar. Using neuroimaging, we found multiple representations of visual space within the ventral human pulvinar and extensive topographically organized connectivity with visual cortex. This organization is similar to other nonhuman primates and provides additional support that the general organization of the pulvinar is consistent across the primate phylogenetic tree. These results suggest that the human pulvinar, like other primates, is well positioned to regulate corticocortical communication.

Functional and structural architecture of the human dorsal frontoparietal attention network.

The dorsal frontoparietal attention network has been subdivided into at least eight areas in humans. However, the circuitry linking these areas and the functions of different circuit paths remain unclear. Using a combination of neuroimaging techniques to map spatial representations in frontoparietal areas, their functional interactions, and structural connections, we demonstrate different pathways across human dorsal frontoparietal cortex for the control of spatial attention. Our results are consistent with these pathways computing object-centered and/or viewer-centered representations of attentional priorities depending on task requirements. Our findings provide an organizing principle for the frontoparietal attention network, where distinct pathways between frontal and parietal regions contribute to multiple spatial representations, enabling flexible selection of behaviorally relevant information.

Electrophysiological low-frequency coherence and cross-frequency coupling contribute to BOLD connectivity.

Brain networks are commonly defined using correlations between blood oxygen level-dependent (BOLD) signals in different brain areas. Although evidence suggests that gamma-band (30-100 Hz) neural activity contributes to local BOLD signals, the neural basis of interareal BOLD correlations is unclear. We first defined a visual network in monkeys based on converging evidence from interareal BOLD correlations during a fixation task, task-free state, and anesthesia, and then simultaneously recorded local field potentials (LFPs) from the same four network areas in the task-free state. Low-frequency oscillations (<20 Hz), and not gamma activity, predominantly contributed to interareal BOLD correlations. The low-frequency oscillations also influenced local processing by modulating gamma activity within individual areas. We suggest that such cross-frequency coupling links local BOLD signals to BOLD correlations across distributed networks.

The pulvinar regulates information transmission between cortical areas based on attention demands.

Selective attention mechanisms route behaviorally relevant information through large-scale cortical networks. Although evidence suggests that populations of cortical neurons synchronize their activity to preferentially transmit information about attentional priorities, it is unclear how cortical synchrony across a network is accomplished. Based on its anatomical connectivity with the cortex, we hypothesized that the pulvinar, a thalamic nucleus, regulates cortical synchrony. We mapped pulvino-cortical networks within the visual system, using diffusion tensor imaging, and simultaneously recorded spikes and field potentials from these interconnected network sites in monkeys performing a visuospatial attention task. The pulvinar synchronized activity between interconnected cortical areas according to attentional allocation, suggesting a critical role for the thalamus not only in attentional selection but more generally in regulating information transmission across the visual cortex.

Visuotopic organization of macaque posterior parietal cortex: a functional magnetic resonance imaging study.

Macaque anatomy and physiology studies have revealed multiple visual areas in posterior parietal cortex (PPC). While many response properties of PPC neurons have been probed, little is known about PPC's large-scale functional topography-specifically related to visuotopic organization. Using high-resolution functional magnetic resonance imaging at 3 T with a phase-encoded retinotopic mapping paradigm in the awake macaque, a large-scale visuotopic organization along lateral portions of PPC anterior to area V3a and extending into the lateral intraparietal sulcus (LIP) was found. We identify two new visual field maps anterior to V3a within caudal PPC, referred to as caudal intraparietal-1 (CIP-1) and CIP-2. The polar angle representation in CIP-1 extends from regions near the upper vertical meridian (that is the shared border with V3a and dorsal prelunate) to those within the lower visual field (that is the shared border with CIP-2). The polar angle representation in CIP-2 is a mirror reversal of the CIP-1 representation. CIP-1 and CIP-2 share a representation of central space on the lateral border. Anterior to CIP-2, a third polar angle representation was found within LIP, referred to as visuotopic LIP. The polar angle representation in LIP extends from regions near the upper vertical meridian (that is the shared border with CIP-2) to those near the lower vertical meridian. Representations of central visual space were identified within dorsal portions of LIP with peripheral representations in ventral portions. We also consider the topographic large-scale organization found within macaque PPC relative to that observed in human PPC.

Neural representations of faces and body parts in macaque and human cortex: a comparative FMRI study.

Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part-selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part-selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas.

Speech perception: linking comprehension across a cortical network.

Listening to speech amidst noise is facilitated by a variety of cues, including the predictable use of certain words in certain contexts. A recent fMRI study of the interaction between noise and semantic predictability has identified a cortical network involved in speech comprehension.

The evolution of prefrontal inputs to the cortico-pontine system: diffusion imaging evidence from Macaque monkeys and humans.

The cortico-ponto-cerebellar system is one of the largest projection systems in the primate brain, but in the human brain the nature of the information processing in this system remains elusive. Determining the areas of the cerebral cortex which contribute projections to this system will allow us to better understand information processing within it. Information from the cerebral cortex is conveyed to the cerebellum by topographically arranged fibres in the cerebral peduncle - an important fibre system in which all cortical outputs spatially converge on their way to the cerebellum via the pontine nuclei. Little is known of their anatomical organization in the human brain. New in vivo diffusion imaging and probabilistic tractography methods now offer a way in which input tracts in the cerebral peduncle can be characterized in detail. Here we use these methods to contrast their organization in humans and macaque monkeys. We confirm the dominant contribution of the cortical motor areas to the macaque monkey cerebral peduncle. However, we also present novel anatomical evidence for a relatively large prefrontal contribution to the human cortico-ponto-cerebellar system in the cerebral peduncle. These findings suggest the selective evolution of prefrontal inputs to the human cortico-ponto-cerebellar system.