Distinct Connectivity Profiles Research Articles

Distinct dynamic connectivity profiles promote enhanced conscious perception of auditory stimuli

The neuroscience of consciousness aims to identify neural markers that distinguish brain dynamics in healthy individuals from those in unconscious conditions. Recent research has revealed that specific brain connectivity patterns correlate with conscious states and diminish with loss of consciousness. However, the contribution of these patterns to shaping conscious processing remains unclear. Our study investigates the functional significance of these neural dynamics by examining their impact on participants’ ability to process external information during wakefulness. Using fMRI recordings during an auditory detection task and rest, we show that ongoing dynamics are underpinned by brain patterns consistent with those identified in previous research. Detection of auditory stimuli at threshold is specifically improved when the connectivity pattern at stimulus presentation corresponds to patterns characteristic of conscious states. Conversely, the occurrence of these conscious state-associated patterns increases after detection, indicating a mutual influence between ongoing brain dynamics and conscious perception. Our findings suggest that certain brain configurations are more favorable to the conscious processing of external stimuli. Targeting these favorable patterns in patients with consciousness disorders may help identify windows of greater receptivity to the external world, guiding personalized treatments.

Neural underpinnings of ethical decisions in life and death dilemmas in naïve and expert firefighters

When a single choice impacts on life outcomes, faculties to make ethical judgments come into play. Here we studied decisions in a real-life setting involving life-and-death outcomes that affect others and the decision-maker as well. We chose a genuine situation where prior training and expertise play a role: firefighting in life-threatening situations. By studying the neural correlates of dilemmas involving life-saving decisions, using realistic firefighting situations, allowed us to go beyond previously used hypothetical dilemmas, while addressing the role of expertise and the use of coping strategies (n = 47). We asked the question whether the neural underpinnings of deontologically based decisions are affected by expertise. These realistic life-saving dilemmas activate the same core reward and affective processing network, in particular the ventromedial prefrontal cortex, nucleus accumbens and amygdala, irrespective of prior expertise, thereby supporting general domain theories of ethical decision-making. We found that brain activity in the hippocampus and insula parametrically increased as the risk increased. Connectivity analysis showed a larger directed influence of the insula on circuits related to action selection in non-experts, which were slower than experts in non rescuing decisions. Relative neural activity related to the decision to rescue or not, in the caudate nucleus, insula and anterior cingulate cortex was negatively associated with coping strategies, in experts (firefighters) suggesting practice-based learning. This shows an association between activity and expert-related usage of coping strategies. Expertise enables salience network activation as a function of behavioural coping dimensions, with a distinct connectivity profile when facing life-rescuing dilemmas.

Dissociable Contributions of the Medial Parietal Cortex to Recognition Memory.

Human neuroimaging studies of episodic memory retrieval routinely observe the engagement of specific cortical regions beyond the medial temporal lobe. Of these, medial parietal cortex (MPC) is of particular interest given its distinct functional characteristics during different retrieval tasks. Specifically, while recognition and autobiographical recall tasks are both used to probe episodic retrieval, these paradigms consistently drive distinct spatial patterns of response within MPC. However, other studies have emphasized alternate MPC functional dissociations in terms of brain network connectivity profiles or stimulus category selectivity. As the unique contributions of MPC to episodic memory remain unclear, adjudicating between these different accounts can provide better consensus regarding MPC function. Therefore, we used a precision-neuroimaging dataset (7T functional magnetic resonance imaging) to examine how MPC regions are differentially engaged during recognition memory and how these task-related dissociations may also reflect distinct connectivity and stimulus category functional profiles. We observed interleaved, though spatially distinct, subregions of MPC where responses were sensitive to either recognition decisions or the semantic representation of stimuli. In addition, this dissociation was further accentuated by functional subregions displaying distinct profiles of connectivity with the hippocampus during task and rest. Finally, we show that recent observations of dissociable person and place selectivity within the MPC reflect category-specific responses from within identified semantic regions that are sensitive to mnemonic demands. Together, by examining precision functional mapping within individuals, these data suggest that previously distinct observations of functional dissociation within MPC conform to a common principle of organization throughout hippocampal-neocortical memory systems.

Hippocampal-cortical functional connectivity during memory encoding and retrieval

Memory encoding and retrieval are critical sub-processes of episodic memory. While the hippocampus is involved in both, less is known about its connectivity with the neocortex during memory processing in humans. This is partially due to variations in demands in common memory tasks, which inevitably recruit cognitive processes other than episodic memory. Conjunctive analysis of data from different tasks with the same core elements of encoding and retrieval can reduce the intrusion of patterns related to subsidiary perceptual and cognitive processing. Leveraging data from two large-scale functional resonance imaging studies with different episodic memory tasks (514 and 237 participants), we identified hippocampal-cortical networks active during memory tasks. Whole-brain functional connectivity maps were similar during resting state, encoding, and retrieval. Anterior and posterior hippocampus had distinct connectivity profiles, which were also stable across resting state and memory tasks. When contrasting encoding and retrieval connectivity, conjunctive encoding-related connectivity was sparse. During retrieval hippocampal connectivity was increased with areas known to be active during recollection, including medial prefrontal, inferior parietal, and parahippocampal cortices. This indicates that the stable functional connectivity of the hippocampus along its longitudinal axis is superposed by increased functional connectivity with the recollection network during retrieval, while auxiliary encoding connectivity likely reflects contextual factors.

Precision functional MRI mapping reveals distinct connectivity patterns for depression associated with traumatic brain injury.

Depression associated with traumatic brain injury (TBI) is believed to be clinically distinct from primary major depressive disorder (MDD) and may be less responsive to conventional treatments. Brain connectivity differences between the dorsal attention network (DAN), default mode network (DMN), and subgenual cingulate have been implicated in TBI and MDD. To characterize these distinctions, we applied precision functional mapping of brain network connectivity to resting-state functional magnetic resonance imaging data from five published patient cohorts, four discovery cohorts (n = 93), and one replication cohort (n = 180). We identified a distinct brain connectivity profile in TBI-associated depression that was independent of TBI, MDD, posttraumatic stress disorder (PTSD), depression severity, and cohort. TBI-associated depression was independently associated with decreased DAN-subgenual cingulate connectivity, increased DAN-DMN connectivity, and the combined effect of both. This effect was stronger when using precision functional mapping relative to group-level network maps. Our results support the possibility of a physiologically distinct "TBI affective syndrome," which may benefit from individualized neuromodulation approaches to target its distinct neural circuitry.

Electrical Stimulation of Temporal and Limbic Circuitry Produces Distinct Responses in Human Ventral Temporal Cortex.

The human ventral temporal cortex (VTC) is highly connected to integrate visual perceptual inputs with feedback from cognitive and emotional networks. In this study, we used electrical brain stimulation to understand how different inputs from multiple brain regions drive unique electrophysiological responses in the VTC. We recorded intracranial EEG data in 5 patients (3 female) implanted with intracranial electrodes for epilepsy surgery evaluation. Pairs of electrodes were stimulated with single-pulse electrical stimulation, and corticocortical evoked potential responses were measured at electrodes in the collateral sulcus and lateral occipitotemporal sulcus of the VTC. Using a novel unsupervised machine learning method, we uncovered 2-4 distinct response shapes, termed basis profile curves (BPCs), at each measurement electrode in the 11-500 ms after stimulation interval. Corticocortical evoked potentials of unique shape and high amplitude were elicited following stimulation of several regions and classified into a set of four consensus BPCs across subjects. One of the consensus BPCs was primarily elicited by stimulation of the hippocampus; another by stimulation of the amygdala; a third by stimulation of lateral cortical sites, such as the middle temporal gyrus; and the final one by stimulation of multiple distributed sites. Stimulation also produced sustained high-frequency power decreases and low-frequency power increases that spanned multiple BPC categories. Characterizing distinct shapes in stimulation responses provides a novel description of connectivity to the VTC and reveals significant differences in input from cortical and limbic structures.SIGNIFICANCE STATEMENT Disentangling the numerous input influences on highly connected areas in the brain is a critical step toward understanding how brain networks work together to coordinate human behavior. Single-pulse electrical stimulation is an effective tool to accomplish this goal because the shapes and amplitudes of signals recorded from electrodes are informative of the synaptic physiology of the stimulation-driven inputs. We focused on targets in the ventral temporal cortex, an area strongly implicated in visual object perception. By using a data-driven clustering algorithm, we identified anatomic regions with distinct input connectivity profiles to the ventral temporal cortex. Examining high-frequency power changes revealed possible modulation of excitability at the recording site induced by electrical stimulation of connected regions.

Connectomic Basis for Tremor Control in Stereotactic Radiosurgical Thalamotomy.

Given the increased use of stereotactic radiosurgical thalamotomy and other ablative therapies for tremor, new biomarkers are needed to improve outcomes. Using resting-state fMRI and MR tractography, we hypothesized that a "connectome fingerprint" can predict tremor outcomes and potentially serve as a targeting biomarker for stereotactic radiosurgical thalamotomy. We evaluated 27 patients who underwent unilateral stereotactic radiosurgical thalamotomy for essential tremor or tremor-predominant Parkinson disease. Percentage postoperative improvement in the contralateral limb Fahn-Tolosa-Marin Clinical Tremor Rating Scale (TRS) was the primary end point. Connectome-style resting-state fMRI and MR tractography were performed before stereotactic radiosurgery. Using the final lesion volume as a seed, "connectivity fingerprints" representing ideal connectivity maps were generated as whole-brain R-maps using a voxelwise nonparametric Spearman correlation. A leave-one-out cross-validation was performed using the generated R-maps. The mean improvement in the contralateral tremor score was 55.1% (SD, 38.9%) at a mean follow-up of 10.0 (SD, 5.0) months. Structural connectivity correlated with contralateral TRS improvement (r = 0.52; P = .006) and explained 27.0% of the variance in outcome. Functional connectivity correlated with contralateral TRS improvement (r = 0.50; P = .008) and explained 25.0% of the variance in outcome. Nodes most correlated with tremor improvement corresponded to areas of known network dysfunction in tremor, including the cerebello-thalamo-cortical pathway and the primary and extrastriate visual cortices. Stereotactic radiosurgical targets with a distinct connectivity profile predict improvement in tremor after treatment. Such connectomic fingerprints show promise for developing patient-specific biomarkers to guide therapy with stereotactic radiosurgical thalamotomy.

The hidden brain-state dynamics of tACS aftereffects

Non-invasive techniques to electrically stimulate the brain such as transcranial direct and alternating current stimulation (tDCS/tACS) are increasingly used in human neuroscience and offer potential new avenues to treat brain disorders. Previous research has shown that stimulation effects may depend on brain-states. However, this work mostly focused on experimentally induced brain-states over the course of several minutes. Besides such global, long-term changes in brain-states, previous research suggests, that the brain is likely to spontaneously alternate between states in sub-second ranges, which is much closer to the time scale at which it is generally believed to operate. Here, we utilized Hidden Markov Models (HMM) to decompose magnetoencephalography data obtained before and after tACS into spontaneous, transient brain-states with distinct spatial, spectral and connectivity profiles. Only one out of four spontaneous brain-states, likely reflecting default mode network activity, showed evidence for an effect of tACS on the power of spontaneous α-oscillations. The identified state appears to disproportionally drive the overall (non-state resolved) tACS effect. No or only marginal effects were found in the remaining states. We found no evidence that tACS influenced the time spent in each state. Although stimulation was applied continuously, our results indicate that spontaneous brain-states and their underlying functional networks differ in their susceptibility to tACS. Global stimulation aftereffects may be disproportionally driven by distinct time periods during which the susceptible state is active. Our results may pave the ground for future work to understand which features make a specific brain-state susceptible to electrical stimulation.

Mapping effective connectivity of human amygdala subdivisions with intracranial stimulation

The primate amygdala is a complex consisting of over a dozen nuclei that have been implicated in a host of cognitive functions, individual differences, and psychiatric illnesses. These functions are implemented through distinct connectivity profiles, which have been documented in animals but remain largely unknown in humans. Here we present results from 25 neurosurgical patients who had concurrent electrical stimulation of the amygdala with intracranial electroencephalography (electrical stimulation tract-tracing; es-TT), or fMRI (electrical stimulation fMRI; es-fMRI), methods providing strong inferences about effective connectivity of amygdala subdivisions with the rest of the brain. We quantified functional connectivity with medial and lateral amygdala, the temporal order of these connections on the timescale of milliseconds, and also detail second-order effective connectivity among the key nodes. These findings provide a uniquely detailed characterization of human amygdala functional connectivity that will inform functional neuroimaging studies in healthy and clinical populations.

Structural Connectivity of Human Inferior Colliculus Subdivisions Using in vivo and post mortem Diffusion MRI Tractography.

Inferior colliculus (IC) is an obligatory station along the ascending auditory pathway that also has a high degree of top-down convergence via efferent pathways, making it a major computational hub. Animal models have attributed critical roles for the IC in in mediating auditory plasticity, egocentric selection, and noise exclusion. IC contains multiple functionally distinct subdivisions. These include a central nucleus that predominantly receives ascending inputs and external and dorsal nuclei that receive more heterogeneous inputs, including descending and multisensory connections. Subdivisions of human IC have been challenging to identify and quantify using standard brain imaging techniques such as MRI, and the connectivity of each of these subnuclei has not been identified in the human brain. In this study, we estimated the connectivity of human IC subdivisions with diffusion MRI (dMRI) tractography, using both anatomical-based seed analysis as well as unsupervised k-means clustering. We demonstrate sensitivity of tractography to overall IC connections in both high resolution post mortem and in vivo datasets. k-Means clustering of the IC streamlines in both the post mortem and in vivo datasets generally segregated streamlines based on their terminus beyond IC, such as brainstem, thalamus, or contralateral IC. Using fine-grained anatomical segmentations of the major IC subdivisions, the post mortem dataset exhibited unique connectivity patterns from each subdivision, including commissural connections through dorsal IC and lateral lemniscal connections to central and external IC. The subdivisions were less distinct in the context of in vivo connectivity, although lateral lemniscal connections were again highest to central and external IC. Overall, the unsupervised and anatomically driven methods provide converging evidence for distinct connectivity profiles for each of the IC subdivisions in both post mortem and in vivo datasets, suggesting that dMRI tractography with high quality data is sensitive to neural pathways involved in auditory processing as well as top-down control of incoming auditory information.

Distinct connectivity profiles predict different in-time processes of motor skill learning

Learning through intensive practice has been largely observed in motor, sensory and higher-order cognitive processing. Neuroimaging studies have shown that learning phases are associated with different patterns of functional and structural neural plasticity in spatially distributed brain systems. Yet, it is unknown whether distinct neural signatures before practice can foster different subsequent learning stages over time. Here, we employed a bimanual implicit sequence reaction time task (SRTT) to investigate whether the rates of early (one day after practice) and late (one month after practice) post-training motor skill learning were predicted by distinct patterns of pre-training resting state functional connectivity (rs-FC), recorded with functional MRI. We observed that both motor learning descriptors were positively correlated with the strength of rs-FC among pairs of regions within a SRTT-relevant network comprising cerebellar as well as cortical and subcortical motor areas. Crucially, we detected a double dissociation such that early post-training learning was significantly associated with the functional connections within cerebellar regions, whereas late post-training learning was significantly related to the functional connections between cortical and subcortical motor areas. These findings indicate that spontaneous brain activity prospectively carries out behaviorally relevant information to perform experience-dependent cognitive operations far distant in time.

Hippocampal hub neurons maintain distinct connectivity throughout their lifetime

The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as ‘hubs’ by orchestrating population synchrony. However, their adult fate remains largely unknown. To fill this gap, we have examined CA1 ebGABAs using a combination of electrophysiology, neurochemical analysis, optogenetic connectivity mapping as well as ex vivo and in vivo calcium imaging. We show that CA1 ebGABAs not only operate as hubs during development, but also maintain distinct morpho-physiological and connectivity profiles, including a bias for long-range targets and local excitatory inputs. In vivo, ebGABAs are activated during locomotion, correlate with CA1 cell assemblies and display high functional connectivity. Hence, ebGABAs are specified from birth to ensure unique functions throughout their lifetime. In the adult brain, this may take the form of a long-range hub role through the coordination of cell assemblies across distant regions.

Corticostriatal Projections of Macaque Area 44.

Ventrolateral frontal area 44 is implicated in inhibitory motor functions and facilitating prefrontal control over vocalization. The contribution of corticostriatal circuits to area 44 functions is unclear, as prior investigation of area 44 projections to the striatum—a central structure in motor circuits—is limited. Here, we used anterograde and retrograde tracing in macaques to map the innervation zone of area 44 corticostriatal projections, quantify their strengths, and evaluate their convergence with corticostriatal projections from other frontal cortical regions. First, whereas terminal fields from a rostral area 44 injection site were found primarily in the central caudate nucleus, those from a caudal area 44 injection site were found primarily in the ventrolateral putamen. Second, amongst sampled injection sites, area 44 input as a percentage of total frontal cortical input was highest in the ventral putamen at the level of the anterior commissure. Third, area 44 projections converged with orofacial premotor area 6VR and other motor-related projections (in the putamen), and with nonmotor prefrontal projections (in the caudate nucleus). Findings support the role of area 44 as an interface between motor and nonmotor functional domains, possibly facilitated by rostral and caudal area 44 subregions with distinct corticostriatal connectivity profiles.

Functional connectivity fingerprints of the human pulvinar: Decoding its role in cognition

The pulvinar is the largest thalamic nucleus in the brain and considered as a key structure in sensory processing and attention. Although its anatomy is well known, in particular thanks to studies in non-human primates, its role in perception and cognition remains poorly understood. Here, we used resting-state functional connectivity from a large sample of high-resolution data provided by the Human Connectome Project, combined with a large-scale meta-analysis approach to segregate and characterize the functional organization of the pulvinar nucleus. We identified five clusters per pulvinar with distinct connectivity profiles and determined their respective co-activation patterns. Using the Neurosynth database, we then investigated the functional significance of these co-activation networks. Our results confirm the functional heterogeneity of the pulvinar, revealing clearcut differences across clusters in terms of their connectivity patterns and associated cognitive domains. While the anterior and lateral clusters appear to be involved in action and attention domains, the ventromedial and dorsomedial clusters may preferentially subserve emotional processes and saliency detection. In contrast, the inferior cluster shows less specificity but correlates with perception and memory processes. Collectively, our results suggest that the pulvinar underwrites different components of cognition, supporting a central role in the coordination of cortico-subcortical processes mediated by distributed brain networks.

Functional neuroanatomy of racial categorization from visual perception: A meta-analytic study

We effortlessly sort people into different racial groups from their visual appearance and implicitly generate racial bias affecting cognition and behavior. As these mental activities provide the proximate mechanisms for social behaviours, it becomes essential to understand the neural activity underlying differences between own-race and other-race visual categorization. Yet intrinsic limitations of individual neuroimaging studies, owing to reduced sample size, inclusion of multiple races, and interactions between races in the participants and in the displayed visual stimuli, dampens generalizability of results. In the present meta-analytic study, we applied multimodal techniques to partly overcome these hurdles, and we investigated the entire functional neuroimaging literature on race categorization, therefore including more than 2000 Black, White and Asian participants. Our data-driven approach shows that own- and other-race visual categorization involves partly segregated neural networks, with distinct connectivity and functional profiles, and defined hierarchical organization. Categorization of own-race mainly engages areas related to cognitive components of empathy and mentalizing, such as the medial prefrontal cortex and the inferior frontal gyrus. These areas are functionally co-activated with cortical structures involved in auto-biographical memories and social knowledge. Conversely, other-race categorization recruits areas implicated in, and functionally connected with, visuo-attentive processing, like the fusiform gyrus and the inferior parietal lobule, and areas engaged in affective functions, like the amygdala. These results contribute to a better definition of the neural networks involved in the visual parcelling of social categories based on race, and help to situate these processes within a common neural space.

The heterogeneous functional architecture of the posteromedial cortex is associated with selective functional connectivity differences in Alzheimer's disease.

The posteromedial cortex (PMC) is a key region involved in the development and progression of Alzheimer's disease (AD). Previous studies have demonstrated a heterogenous functional architecture of the region that is composed of discrete functional modules reflecting a complex pattern of functional connectivity. However, little is understood about the mechanisms underpinning this complex network architecture in neurodegenerative disease, and the differential vulnerability of connectivity‐based subdivisions in the PMC to AD pathogenesis. Using a data‐driven approach, we applied a constrained independent component analysis (ICA) on healthy adults from the Human Connectome Project to characterise the local functional connectivity patterns within the PMC, and its unique whole‐brain functional connectivity. These distinct connectivity profiles were subsequently quantified in the Alzheimer's Disease Neuroimaging Initiative study, to examine functional connectivity differences in AD patients and cognitively normal (CN) participants, as well as the entire AD pathological spectrum. Our findings revealed decreased functional connectivity in the anterior precuneus, dorsal posterior cingulate cortex (PCC), and the central precuneus in AD patients compared to CN participants. Functional abnormalities in the dorsal PCC and central precuneus were also related to amyloid burden and volumetric hippocampal loss. Across the entire AD spectrum, functional connectivity of the central precuneus was associated with disease severity and specific deficits in memory and executive function. These findings provide new evidence showing that the PMC is selectively impacted in AD, with prominent network failures of the dorsal PCC and central precuneus underpinning the neurodegenerative and cognitive dysfunctions associated with the disease.

Functional connectivity in obsessive-compulsive disorder and its subtypes.

Obsessive-compulsive disorder (OCD) is an anxiety disorder with significant morbidity whose pathophysiology is not fully understood. Neuroimaging studies have characterized OCD in terms of elevated striatal and prefrontal reactivity to emotion provocation. This neural model may be informed by investigation of functional connectivity in OCD, identifying alterations in how sensory information is integrated into frontostriatal regions. The current study employed functional magnetic resonance imaging (fMRI) to compare neural activity and connectivity in 31 OCD patients (12 washing and 19 checking subtypes) and 17 healthy volunteers in an emotion provocation paradigm using visual stimuli. OCD status was associated with hyper-activation of the posterior cingulate (PCg) in response to emotion provocation. Additionally, OCD patients demonstrated elevated PCg functional connectivity with the visual cortices and frontostriatal regions. Exploratory analyses suggested that stimulus-provoked activity and connectivity was elevated for checking subtypes in motor cortices, and elevated in washing subtypes in the anterior insula and orbitofrontal cortex. The PCg's role in moderating connectivity between the visual cortex and frontolimbic regions is muted in OCD, consistent with the PCg's suggested role in regulating attention towards emotional stimuli. Exploratory analyses suggest distinct PCg connectivity profiles in OCD subtypes, with checking linked to motor activation, but washing linked to a network supporting emotional salience. The study was not powered to fully investigate the effects of medication, patients often endorsed secondary symptom subtypes that muddied washing/checking distinctions, and the emotion provocation paradigm was of limited intensity compared to life stressors.

F192. Abnormal Insula Functional Connectivity Explains Specific Domains of Psychosis in Schizophrenia

The insula is a comprised of multiple cortical regions including: dorsal anterior (dAI), ventral anterior (vAI), and posterior (PI), all with distinct connectivity profiles and behavioral functions. Previous studies have shown the insula to be abnormal in schizophrenia. Here we tested the hypothesis that dAI connectivity is related to cognitive impairment, whereas PI and vAI connectivity is related to positive and negative symptoms, respectively, in schizophrenia.

Rostro-caudal organization of the human posterior superior temporal sulcus revealed by connectivity profiles.

The posterior superior temporal sulcus (pSTS) plays an important role in biological motion perception but is also thought to be essential for speech and facial processing. However, although there are many previous investigations of distinct functional modules within the pSTS, the functional organization of the pSTS in its full functional heterogeneity has not yet been established. Here we applied a connectivity-based parcellation strategy to delineate the human pSTS subregions based on distinct anatomical connectivity profiles and divided it into rostral and caudal subregions using diffusion tensor imaging. Subsequent multimodal connection pattern analyses revealed distinct subregional connectivity profiles. From this we inferred that the two subregions are involved in distinct functional circuits, the language processing loop and the cognition attention network. These results indicate a convergent functional architecture of the pSTS that can be revealed based on different types of connectivity and is reflected in different functions and interactions. In addition, when the subregions were performing their processing in the different functional circuits, we found asymmetry in the bilateral pSTS. Our findings may improve the understanding of the functional organization of the pSTS and provide new insights into its interactions and integration of information at the subregional level.

The Mouse Cortical Connectome, Characterized by an Ultra-Dense Cortical Graph, Maintains Specificity by Distinct Connectivity Profiles

The inter-areal wiring pattern of the mouse cerebral cortex was analyzed in relation to a refined parcellation of cortical areas. Twenty-seven retrograde tracer injections were made in 19 areas of a 47-area parcellation of the mouse neocortex. Flat mounts of the cortex and multiple histological markers enabled detailed counts of labeled neurons in individual areas. The observed log-normal distribution of connection weights to each cortical area spans 5 orders of magnitude and reveals a distinct connectivity profile for each area, analogous to that observed in macaques. The cortical network has a density of 97%, considerably higher than the 66% density reported in macaques. A weighted graph analysis reveals a similar global efficiency but weaker spatial clustering compared with that reported in macaques. The consistency, precision of the connectivity profile, density, and weighted graph analysis of the present data differ significantly from those obtained in earlier studies in the mouse.