Functional imaging and anatomical connections in squirrel monkeys reveal parietal-frontal circuits underlying eye movements.

The posterior parietal cortex (PPC) of squirrel monkeys contains subregions where long trains of intracortical microstimulation evoke complex, behaviorally meaningful movements. Recently, we showed that such stimulation of a part of the PPC in the caudal lateral sulcus (LS) elicits eye movements in these monkeys. Here, we studied the functional and anatomical connections of this oculomotor region we call parietal eye field (PEF) with frontal eye field (FEF) and other cortical regions in 2 squirrel monkeys. We demonstrated these connections with intrinsic optical imaging and injections of anatomical tracers. Optical imaging of frontal cortex during stimulation of the PEF evoked focal functional activation within FEF. Tracing studies confirmed the functional PEF-FEF connections. Moreover, tracer injections revealed PEF connections with other PPC regions on the dorsolateral and medial brain surface, cortex in the caudal LS, and visual and auditory cortical association areas. Subcortical projections of PEF were primarily with superior colliculus, and pontine nuclei as well as nuclei of the dorsal posterior thalamus and caudate. These findings suggest that PEF in squirrel monkey is homologous to lateral intraparietal (LIP) area of macaque, supporting the notion that these brain circuits are organized similarly to mediate ethologically relevant oculomotor behaviors.

Interactions within and between parallel parietal-frontal networks involved in complex motor behaviors in prosimian galagos and a squirrel monkey.

Long-train intracortical microstimulation (ICMS) of motor (M1) and posterior parietal cortices (PPC) in primates reveals cortical domains for different ethologically relevant behaviors. How functional domains interact with each other in producing motor behaviors is not known. In this study, we tested our hypothesis that matching domains interact to produce a specific complex movement, whereas connections between nonmatching domains are involved in suppression of conflicting motor outputs to prevent competing movements. In anesthetized galagos, we used 500-ms trains of ICMS to evoke complex movements from a functional domain in M1 or PPC while simultaneously stimulating another mismatched or matched domain. We considered movements of different and similar directions evoked from chosen cortical sites distant or close to each other. Their trajectories and speeds were analyzed and compared with those evoked by simultaneous stimulation. Stimulation of two sites evoking same or complementary movements produced a similar but more pronounced movement or a combined movement, respectively. Stimulation of two sites representing movements of different directions resulted in partial or total suppression of one of these movements. Thus interactions between domains in M1 and PPC were additive when they were functionally matched across fields or antagonistic between functionally conflicting domains, especially in PPC, suggesting that mismatched domains are involved in mutual suppression. Simultaneous stimulation of unrelated domains (forelimb and face) produced both movements independently. Movements produced by the simultaneous stimulation of sites in domains of two cerebral hemispheres were largely independent, but some interactions were observed.NEW & NOTEWORTHY Long trains of electrical pulses applied simultaneously to two sites in motor cortical areas (M1, PPC) have shown that interactions of functionally matched domains (evoking similar movements) within these areas were additive to produce a specific complex movement. Interactions between functionally mismatched domains (evoking different movements) were mostly antagonistic, suggesting their involvement in mutual suppression of conflicting motor outputs to prevent competing movements. Simultaneous stimulation of unrelated domains (forelimb and face) produced both movements independently.

Histologically derived fiber response functions for diffusion MRI vary across white matter fibers-An ex vivo validation study in the squirrel monkey brain.

Understanding the relationship between the diffusion-weighted MRI signal and the arrangement of white matter fibers is fundamental for accurate voxel-wise reconstruction of the fiber orientation distribution (FOD) and subsequent fiber tractography. Spherical deconvolution reconstruction techniques model the diffusion signal as the convolution of the FOD with a response function that represents the signal profile of a single fiber orientation. Thus, given the signal and a fiber response function, the FOD can be estimated in every imaging voxel by deconvolution. However, the selection of the appropriate response function remains relatively under-studied, and requires further validation. In this work, using 3D histologically defined FODs and the corresponding diffusion signal from three ex vivo squirrel monkey brains, we derive the ground truth response functions. We find that the histologically derived response functions differ from those conventionally used. Next, we find that response functions statistically vary across brain regions, which suggests that the practice of using the same kernel throughout the brain is not optimal. We show that different kernels lead to different FOD reconstructions, which in turn can lead to different tractography results depending on algorithmic parameters, with large variations in the accuracy of resulting reconstructions. Together, these results suggest there is room for improvement in estimating and understanding the relationship between the diffusion signal and the underlying FOD.

Histological validation of diffusion MRI fiber orientation distributions and dispersion.

Diffusion magnetic resonance imaging (dMRI) is widely used to probe tissue microstructure, and is currently the only non-invasive way to measure the brain's fiber architecture. While a large number of approaches to recover the intra-voxel fiber structure have been utilized in the scientific community, a direct, 3D, quantitative validation of these methods against relevant histological fiber geometries is lacking. In this study, we investigate how well different high angular resolution diffusion imaging (HARDI) models and reconstruction methods predict the ground-truth histologically defined fiber orientation distribution (FOD), as well as investigate their behavior over a range of physical and experimental conditions. The dMRI methods tested include constrained spherical deconvolution (CSD), Q-ball imaging (QBI), diffusion orientation transform (DOT), persistent angular structure (PAS), and neurite orientation dispersion and density imaging (NODDI) methods. Evaluation criteria focus on overall agreement in FOD shape, correct assessment of the number of fiber populations, and angular accuracy in orientation. In addition, we make comparisons of the histological orientation dispersion with the fiber spread determined from the dMRI methods. As a general result, no HARDI method outperformed others in all quality criteria, with many showing tradeoffs in reconstruction accuracy. All reconstruction techniques describe the overall continuous angular structure of the histological FOD quite well, with good to moderate correlation (median angular correlation coefficient > 0.70) in both single- and multiple-fiber voxels. However, no method is consistently successful at extracting discrete measures of the number and orientations of FOD peaks. The major inaccuracies of all techniques tend to be in extracting local maxima of the FOD, resulting in either false positive or false negative peaks. Median angular errors are ∼10° for the primary fiber direction and ∼20° for the secondary fiber, if present. For most methods, these results did not vary strongly over a wide range of acquisition parameters (number of diffusion weighting directions and b value). Regardless of acquisition parameters, all methods show improved successes at resolving multiple fiber compartments in a voxel when fiber populations cross at near-orthogonal angles, with no method adequately capturing low to moderate angle (<60°) crossing fibers. Finally, most methods are limited in their ability to capture orientation dispersion, resulting in low to moderate, yet statistically significant, correlation with histologically-derived dispersion with both HARDI and NODDI methodologies. Together, these results provide quantitative measures of the reliability and limitations of dMRI reconstruction methods and can be used to identify relative advantages of competing approaches as well as potential strategies for improving accuracy.

Tests of cortical parcellation based on white matter connectivity using diffusion tensor imaging.

The cerebral cortex is conventionally divided into a number of domains based on cytoarchitectural features. Diffusion tensor imaging (DTI) enables noninvasive parcellation of the cortex based on white matter connectivity patterns. However, the correspondence between DTI-connectivity-based and cytoarchitectural parcellation has not been systematically established. In this study, we compared histological parcellation of New World monkey neocortex to DTI- connectivity-based classification and clustering in the same brains. First, we used supervised classification to parcellate parieto-frontal cortex based on DTI tractograms and the cytoarchitectural prior (obtained using Nissl staining). We performed both within and across sample classification, showing reasonable classification performance in both conditions. Second, we used unsupervised clustering to parcellate the cortex and compared the clusters to the cytoarchitectonic standard. We then explored the similarities and differences with several post-hoc analyses, highlighting underlying principles that drive the DTI-connectivity-based parcellation. The differences in parcellation between DTI-connectivity and Nissl histology probably represent both DTI's bias toward easily-tracked bundles and true differences between cytoarchitectural and connectivity defined domains. DTI tractograms appear to cluster more according to functional networks, rather than mapping directly onto cytoarchitectonic domains. Our results show that caution should be used when DTI-tractography classification, based on data from another brain, is used as a surrogate for cytoarchitectural parcellation.

Confirmation of a gyral bias in diffusion MRI fiber tractography.

Diffusion MRI fiber tractography has been increasingly used to map the structural connectivity of the human brain. However, this technique is not without limitations; for example, there is a growing concern over anatomically correlated bias in tractography findings. In this study, we demonstrate that there is a bias for fiber tracking algorithms to terminate preferentially on gyral crowns, rather than the banks of sulci. We investigate this issue by comparing diffusion MRI (dMRI) tractography with equivalent measures made on myelin-stained histological sections. We begin by investigating the orientation and trajectories of axons near the white matter/gray matter boundary, and the density of axons entering the cortex at different locations along gyral blades. These results are compared with dMRI orientations and tract densities at the same locations, where we find a significant gyral bias in many gyral blades across the brain. This effect is shown for a range of tracking algorithms, both deterministic and probabilistic, and multiple diffusion models, including the diffusion tensor and a high angular resolution diffusion imaging technique. Additionally, the gyral bias occurs for a range of diffusion weightings, and even for very high-resolution datasets. The bias could significantly affect connectivity results using the current generation of tracking algorithms.

Can increased spatial resolution solve the crossing fiber problem for diffusion MRI?

It is now widely recognized that voxels with crossing fibers or complex geometrical configurations present a challenge for diffusion MRI (dMRI) reconstruction and fiber tracking, as well as microstructural modeling of brain tissues. This "crossing fiber" problem has been estimated to affect anywhere from 30% to as many as 90% of white matter voxels, and it is often assumed that increasing spatial resolution will decrease the prevalence of voxels containing multiple fiber populations. The aim of this study is to estimate the extent of the crossing fiber problem as we progressively increase the spatial resolution, with the goal of determining whether it is possible to mitigate this problem with higher resolution spatial sampling. This is accomplished using ex vivo MRI data of the macaque brain, followed by histological analysis of the same specimen to validate these measurements, as well as to extend this analysis to resolutions not yet achievable in practice with MRI. In both dMRI and histology, we find unexpected results: the prevalence of crossing fibers increases as we increase spatial resolution. The problem of crossing fibers appears to be a fundamental limitation of dMRI associated with the complexity of brain tissue, rather than a technical problem that can be overcome with advances such as higher fields and stronger gradients.

Cortical Connections of the Caudal Portion of Posterior Parietal Cortex in Prosimian Galagos.

Posterior parietal cortex (PPC) of prosimian galagos includes a rostral portion (PPCr) where electrical stimulation evokes different classes of complex movements from different subregions, and a caudal portion (PPCc) where such stimulation fails to evoke movements in anesthetized preparations ( Stepniewska, Fang et al. 2009). We placed tracer injections into PPCc to reveal patterns of its cortical connections. There were widespread connections within PPCc as well as connections with PPCr and extrastriate visual areas, including V2 and V3. Weaker connections were with dorsal premotor cortex, and the frontal eye field. The connections of different parts of PPCc with visual areas were roughly retinotopic such that injections to dorsal PPCc labeled more neurons in the dorsal portions of visual areas, representing lower visual quadrant, and injections to ventral PPCc labeled more neurons in ventral portions of these visual areas, representing the upper visual quadrant. We conclude that much of the PPCc contains a crude representation of the contralateral visual hemifield, with inputs largely, but not exclusively, from higher-order visual areas that are considered part of the dorsal visuomotor processing stream. As in galagos, the caudal half of PPC was likely visual in early primates, with the rostral PPC half mediating sensorimotor functions.

Reversible Deactivation of Motor Cortex Reveals Functional Connectivity with Posterior Parietal Cortex in the Prosimian Galago (Otolemur garnettii).

We examined the functional macrocircuitry of frontoparietal networks in the neocortex of prosimian primates (Otolemur garnettii) using a microfluidic thermal regulator to reversibly deactivate selected regions of motor cortex (M1). During deactivation of either forelimb or mouth/face movement domains within M1, we used long-train intracortical microstimulation techniques to evoke movements from the rostral division of posterior parietal cortex (PPCr). We found that deactivation of M1 movement domains in most instances abolished movements evoked in PPCr. The most common effect of deactivating M1 was to abolish evoked movements in a homotopic domain in PPCr. For example, deactivating M1 forelimb lift domains resulted in loss of evoked movement in forelimb domains in PPCr. However, at some sites, we also observed heterotopic effects; deactivating a specific domain in M1 (e.g., forelimb lift) resulted in loss of evoked movement in a different movement domain in PPCr (e.g., hand-to-mouth or eye-blink). At most sites examined in PPCr, rewarming M1 resulted in a reestablishment of the baseline movement at the same amplitude as that observed before cooling. However, at some sites, reactivation did not result in a return to baseline movement or to the full amplitude of the baseline movement. We discuss our findings in the context of frontoparietal circuits and how they may subserve a repertoire of ecologically relevant behaviors. SIGNIFICANCE STATEMENT: The posterior parietal cortex (PPC) of primates integrates sensory information used to guide movements. Different modules within PPC and motor cortex (M1) appear to control various motor behaviors (e.g., reaching, defense, and feeding). How these modules work together may vary across species and may explain differences in dexterity and even the capacity for tool use. We investigated the functional connectivity of these modules in galagos, a prosimian primate with relatively simple frontoparietal circuitry. By deactivating a reaching module in M1, we interfered with the function of similar PPC modules and occasionally unrelated PPC modules as well (e.g., eye blink). This circuitry in galagos, therefore, is more complex than in nonprimates, indicating that it has been altered with the expansion of primate PPC.

Comparison of 3D orientation distribution functions measured with confocal microscopy and diffusion MRI.

The ability of diffusion MRI (dMRI) fiber tractography to non-invasively map three-dimensional (3D) anatomical networks in the human brain has made it a valuable tool in both clinical and research settings. However, there are many assumptions inherent to any tractography algorithm that can limit the accuracy of the reconstructed fiber tracts. Among them is the assumption that the diffusion-weighted images accurately reflect the underlying fiber orientation distribution (FOD) in the MRI voxel. Consequently, validating dMRI's ability to assess the underlying fiber orientation in each voxel is critical for its use as a biomedical tool. Here, using post-mortem histology and confocal microscopy, we present a method to perform histological validation of orientation functions in 3D, which has previously been limited to two-dimensional analysis of tissue sections. We demonstrate the ability to extract the 3D FOD from confocal z-stacks, and quantify the agreement between the MRI estimates of orientation information obtained using constrained spherical deconvolution (CSD) and the true geometry of the fibers. We find an orientation error of approximately 6° in voxels containing nearly parallel fibers, and 10-11° in crossing fiber regions, and note that CSD was unable to resolve fibers crossing at angles below 60° in our dataset. This is the first time that the 3D white matter orientation distribution is calculated from histology and compared to dMRI. Thus, this technique serves as a gold standard for dMRI validation studies - providing the ability to determine the extent to which the dMRI signal is consistent with the histological FOD, and to establish how well different dMRI models can predict the ground truth FOD.

Effects of muscimol inactivations of functional domains in motor, premotor, and posterior parietal cortex on complex movements evoked by electrical stimulation.

Parietal and frontal cortex are central to controlling forelimb movements. We previously showed that movements such as reach, grasp, and defense can be evoked from primary motor (M1), premotor (PMC), and posterior parietal (PPC) cortex when 500-ms trains of electrical pulses are delivered via microelectrodes. Stimulation sites that evoked a specific movement clustered into domains, which shared a topographic pattern in New World monkeys and prosimian galagos. Matched functional domains in parietal and frontal cortex were preferentially interconnected. We reasoned that matched functional domains form parallel networks involved in specific movements. To test the roles of domains in M1, PMC, and PPC, we systematically inactivated with muscimol domains in one region and determined if functional changes occurred in matching domains in other regions. The most common changes were higher current thresholds for stimulation-evoked movements and shorter, not fully developed, trajectories of movements. Inactivations of an M1 functional domain greatly reduced or abolished movements evoked from the matching domains in PMC or PPC, whereas movements evoked from nonmatching domains remained mostly unaffected. In contrast, inactivating PMC or PPC domains did not consistently abolish the ability to evoke movements from matching M1 domains. However, inactivation of PMC domains suppressed or altered the movements evoked from PPC domains. Thus movement sequences evoked from PMC depend on M1 and movement sequences evoked from PPC depend on both M1 and PMC. Overall, the results support the conclusion that PPC, PMC, and M1 are subdivided into functional domains that are hierarchically related within parallel networks.

Optical imaging in galagos reveals parietal-frontal circuits underlying motor behavior.

The posterior parietal cortex (PPC) of monkeys and prosimian galagos contains a number of subregions where complex, behaviorally meaningful movements, such as reaching, grasping, and body defense, can be evoked by electrical stimulation with long trains of electrical pulses through microelectrodes. Shorter trains of pulses evoke no or simple movements. One possibility for the difference in effectiveness of intracortical microstimulation is that long trains activate much larger regions of the brain. Here, we show that long-train stimulation of PPC does not activate widespread regions of frontal motor and premotor cortex but instead, produces focal, somatotopically appropriate activations of frontal motor and premotor cortex. Shorter stimulation trains activate the same frontal foci but less strongly, showing that longer stimulus trains do not produce less specification. Because the activated sites in frontal cortex correspond to the locations of direct parietal-frontal anatomical connections from the stimulated PPC subregions, the results show the usefulness of optical imaging in conjunction with electrical stimulation in showing functional pathways between nodes in behavior-specific cortical networks. Thus, long-train stimulation is effective in evoking ethologically relevant sequences of movements by activating nodes in a cortical network for a behaviorally relevant period rather than spreading activation in a nonspecific manner.

Cortical networks for ethologically relevant behaviors in primates.

Parietal-frontal networks in primate brains are central to mediating actions. Physiological and anatomical investigations have shown that the parietal-frontal network is consistently organized across several branches of primate evolution that include prosimian galagos, New World owl and squirrel monkeys, and Old World macaque monkeys. Electrical stimulation with 0.5-sec trains of pulses delivered via microelectrodes evoked ethologically relevant actions from both posterior parietal cortex (PPC) and frontal motor cortex (FMC). Reaching, grasping, defensive, and other complex movement patterns were evoked from domains that had a characteristic organization in both FMC and PPC. Although a PPC domain (e.g. reaching) may be connected with other PPC domains (e.g. grasping and defensive), its connections with FMC are preferential for a matching domain (reaching). Similarly, electrical stimulation of a PPC domain and concurrent optical imaging of FMC, showed activation patterns consistent with the preferential connectivity of PPC and FMC domains. The evidence for similar arrangements of interconnected functional domains in PPC and FMC of members of three major branches of the primate radiation suggests that the parietal-frontal networks emerged early in the evolution of primates. The small size of PPC in the close relatives of primates including lagomorphs, rodents, and tree shrews, suggests a limited involvement of PPC in motor behavior before archaic primates emerged. However, functional domains may have evolved in motor cortex before the emergence of archaic primates.

The basal ganglia are a target for sensorimotor domains in posterior parietal, premotor, and motor cortex in primates.

Our research focused on defining and characterizing parieto-frontal circuits for specific actions in primates. Part of the posterior parietal cortex is divided into eight or more domains where electrical stimulation evokes a meaningful complex movement. Domains in the posterior parietal cortex compete with each other over excitatory connections that activate inhibitory neurons, while selectively activating functionally matched domains in the premotor cortex and motor cortex. Thus, the selection process involves competition and cooperation between domains over three different regions of cortex. In addition, projections from functionally matched domains in motor regions converge in the matrix of the striatum, whereas projections from different functionally unmatched domains are separate. Thus, the projections of action-specific domains include the basal ganglia, where actions can be permitted or blocked.

The dorsal stream of visual processing and action-specific domains in parietal and frontal cortex in primates.

This review summarizes our findings obtained from over 15 years of research on parietal-frontal networks involved in the dorsal stream of cortical processing. We have presented considerable evidence for the existence of similar, partially independent, parietal-frontal networks involved in specific motor actions in a number of primates. These networks are formed by connections between action-specific domains representing the same complex movement evoked by electrical microstimulation. Functionally matched domains in the posterior parietal (PPC) and frontal (M1-PMC) motor regions are hierarchically related. M1 seems to be a critical link in these networks, since the outputs of M1 are essential to the evoked behavior, whereas PPC and PMC mediate complex movements mostly via their connections with M1. Thus, lesioning or deactivating M1 domains selectively blocks matching PMC and PPC domains, while having limited impact on other domains. When pairs of domains are stimulated together, domains within the same parietal-frontal network (matching domains) are cooperative in evoking movements, while they are mainly competitive with other domains (mismatched domains) within the same set of cortical areas. We propose that the interaction of different functional domains in each cortical region (as well as in striatum) occurs mainly via mutual suppression. Thus, the domains at each level are in competition with each other for mediating one of several possible behavioral outcomes.

Thalamic connections of the caudal part of the posterior parietal cortex differ from the rostral part in galagos (Otolemur garnettii).

In this study, thalamic connections of the caudal part of the posterior parietal cortex (PPCc) are described and compared to connections of the rostral part of PPC (PPCr) in strepsirrhine galagos. PPC of galagos is divided into two parts, PPCr and PPCc, based on the responsiveness to electrical stimulation. Stimulation of PPC with long trains of electrical pulses evokes different types of ethologically relevant movements from different subregions ("domains") of PPCr, while it fails to evoke any movements from PPCc. Anatomical tracers were placed in both dorsal and ventral divisions of PPCc to reveal thalamic origins and targets of PPCc connections. We found major thalamic connections of PPCc with the lateral posterior and lateral pulvinar nuclei, distinct from those of PPCr that were mainly with the ventral lateral, anterior pulvinar, and posterior nuclei. The anterior, medial, and inferior pulvinar, ventral anterior, ventral lateral, and intralaminar nuclei had fewer connections with PPCc. Dominant connections of PPCc with lateral posterior and lateral pulvinar nuclei provide evidence that unlike the sensorimotor-orientated PPCr, PPCc is more involved in visual-related functions.

Thalamocortical and corticothalamic connections of multiple functional domains in posterior parietal cortex of galagos.

In prosimian galagos, the posterior parietal cortex (PPC) is subdivided into a number of functional domains where long-train intracortical microstimulation evoked different types of complex movements. Here, we placed anatomical tracers in multiple locations of PPC to reveal the origins and targets of thalamic connections of four PPC domains for different types of hindlimb, forelimb, or face movements. Thalamic connections of all four domains included nuclei of the motor thalamus, ventral anterior and ventral lateral nuclei, as well as parts of the sensory thalamus, the anterior pulvinar, posterior and ventral posterior superior nuclei, consistent with the sensorimotor functions of PPC domains. PPC domains also projected to the thalamic reticular nucleus in a somatotopic pattern. Quantitative differences in the distributions of labeled neurons in thalamic nuclei suggested that connectional patterns of these domains differed from each other.

Multiple parietal-frontal pathways mediate grasping in macaque monkeys.

The nodes of a parietal-frontal pathway that mediates grasping in primates are in anterior intraparietal area (AIP) and ventral premotor cortex (PMv). Nevertheless, multiple somatosensory and motor representations of the hand, in parietal and frontal cortex, respectively, suggest that additional pathways remain unrealized. We explored this possibility in macaque monkeys by injecting retrograde tracers into grasp zones identified in primary motor cortex (M1), PMv, and area 2 with long train electrical stimulation. The M1 grasp zone was densely connected with other frontal cortex motor regions. The remainder of the connections originated from somatosensory areas 3a and second somatosensory cortex/parietal ventral area (S2/PV), and from the medial bank and fundus of the intraparietal sulcus (IPS). The PMv grasp zone was also densely connected with frontal cortex motor regions, albeit to a lesser extent than the M1 grasp zone. The remainder of the connections originated from areas S2/PV and aspects of the inferior parietal lobe such as PF, PFG, AIP, and the tip of the IPS. The area 2 grasp zone was densely connected with the hand representations of somatosensory areas 3b, 1, and S2/PV. The remainder of the connections was with areas 3a and 5 and the medial bank and fundus of the IPS. Connections with frontal cortex were relatively weak and concentrated in caudal M1. Thus, the three grasp zones may be nodes of parallel parietal-frontal pathways. Differential points of origin and termination of each pathway suggest varying functional specializations. Direct and indirect connections between those parietal-frontal pathways likely coordinate their respective functions into an accurate grasp.

Cortical connections of functional zones in posterior parietal cortex and frontal cortex motor regions in new world monkeys.

We examined the connections of posterior parietal cortex (PPC) with motor/premotor cortex (M1/PM) and other cortical areas. Electrical stimulation (500 ms trains) delivered to microelectrode sites evoked movements of reach, defense, and grasp, from distinct zones in M1/PM and PPC, in squirrel and owl monkeys. Tracer injections into M1/PM reach, defense, and grasp zones showed dense connections with M1/PM hand/forelimb representations. The densest inputs outside of frontal cortex were from PPC zones. M1 zones were additionally connected with somatosensory hand/forelimb representations in areas 3a, 3b, and 1 and the somatosensory areas of the upper bank of the lateral sulcus (S2/PV). Injections into PPC zones showed primarily local connections and the densest inputs outside of PPC originated from M1/PM zones. The PPC reach zone also received dense inputs from cortex caudal to PPC, which likely relayed visual information. In contrast, the PPC grasp zone was densely connected with the hand/forelimb representations of areas 3a, 3b, 1, and S2/PV. Thus, the dorsal parietal-frontal network involved in reaching was preferentially connected to visual cortex, whereas the more ventral network involved in grasping received somatosensory inputs. Additional weak interlinks between dissimilar zones (e.g., PPC reach and PPC grasp) were apparent and may coordinate actions.

Escaping the nocturnal bottleneck, and the evolution of the dorsal and ventral streams of visual processing in primates.

Early mammals were small and nocturnal. Their visual systems had regressed and they had poor vision. After the extinction of the dinosaurs 66 mya, some but not all escaped the 'nocturnal bottleneck' by recovering high-acuity vision. By contrast, early primates escaped the bottleneck within the age of dinosaurs by having large forward-facing eyes and acute vision while remaining nocturnal. We propose that these primates differed from other mammals by changing the balance between two sources of visual information to cortex. Thus, cortical processing became less dependent on a relay of information from the superior colliculus (SC) to temporal cortex and more dependent on information distributed from primary visual cortex (V1). In addition, the two major classes of visual information from the retina became highly segregated into magnocellular (M cell) projections from V1 to the primate-specific temporal visual area (MT), and parvocellular-dominated projections to the dorsolateral visual area (DL or V4). The greatly expanded P cell inputs from V1 informed the ventral stream of cortical processing involving temporal and frontal cortex. The M cell pathways from V1 and the SC informed the dorsal stream of cortical processing involving MT, surrounding temporal cortex, and parietal-frontal sensorimotor domains. This article is part of the theme issue 'Systems neuroscience through the lens of evolutionary theory'.