Detailed mapping of the complex fiber structure and white matter pathways of the chimpanzee brain.

Long-standing questions about human brain evolution may only be resolved through comparisons with close living evolutionary relatives, such as chimpanzees. This applies in particular to structural white matter (WM) connectivity, which continuously expanded throughout evolution. However, due to legal restrictions on chimpanzee research, neuroscience research currently relies largely on data with limited detail or on comparisons with evolutionarily distant monkeys. Here, we present a detailed magnetic resonance imaging resource to study structural WM connectivity in the chimpanzee. This open-access resource contains (1) WM reconstructions of a postmortem chimpanzee brain, using the highest-quality diffusion magnetic resonance imaging data yet acquired from great apes; (2) an optimized and validated method for high-quality fiber orientation reconstructions; and (3) major fiber tract segmentations for cross-species morphological comparisons. This dataset enabled us to identify phylogenetically relevant details of the chimpanzee connectome, and we anticipate that it will substantially contribute to understanding human brain evolution.

White matter plasticity during second language learning within and across hemispheres.

Adult second language (L2) learning is a challenging enterprise inducing neuroplastic changes in the human brain. However, it remains unclear how the structural language connectome and its subnetworks change during adult L2 learning. The current study investigated longitudinal changes in white matter (WM) language networks in each hemisphere, as well as their interconnection, in a large group of Arabic-speaking adults who learned German intensively for 6 mo. We found a significant increase in WM-connectivity within bilateral temporal-parietal semantic and phonological subnetworks and right temporal-frontal pathways mainly in the second half of the learning period. At the same time, WM-connectivity between the two hemispheres decreased significantly. Crucially, these changes in WM-connectivity are correlated with L2 performance. The observed changes in subnetworks of the two hemispheres suggest a network reconfiguration due to lexical learning. The reduced interhemispheric connectivity may indicate a key role of the corpus callosum in L2 learning by reducing the inhibition of the language-dominant left hemisphere. Our study highlights the dynamic changes within and across hemispheres in adult language-related networks driven by L2 learning.

Morphological evolution of language-relevant brain areas.

Human language is supported by a cortical network involving Broca's area, which comprises Brodmann Areas 44 and 45 (BA44 and BA45). While cytoarchitectonic homolog areas have been identified in nonhuman primates, it remains unknown how these regions evolved to support human language. Here, we use histological data and advanced cortical registration methods to precisely compare the morphology of BA44 and BA45 in humans and chimpanzees. We found a general expansion of Broca's areas in humans, with the left BA44 enlarging the most, growing anteriorly into a region known to process syntax. Together with recent functional and receptorarchitectural studies, our findings support the conclusion that BA44 evolved from an action-related region to a bipartite system, with a posterior portion supporting action and an anterior portion supporting syntactic processes. Our findings add novel insights to the longstanding debate on the relationship between language and action, and the evolution of Broca's area.

Native language differences in the structural connectome of the human brain.

Is the neuroanatomy of the language structural connectome modulated by the life-long experience of speaking a specific language? The current study compared the brain white matter connections of the language and speech production network in a large cohort of 94 native speakers of two very different languages: an Indo-European morphosyntactically complex language (German) and a Semitic root-based language (Arabic). Using high-resolution diffusion-weighted MRI and tractography-based network statistics of the language connectome, we demonstrated that German native speakers exhibited stronger connectivity in an intra-hemispheric frontal to parietal/temporal dorsal language network, known to be associated with complex syntax processing. In comparison, Arabic native speakers showed stronger connectivity in the connections between semantic language regions, including the left temporo-parietal network, and stronger inter-hemispheric connections via the posterior corpus callosum connecting bilateral superior temporal and inferior parietal regions. The current study suggests that the structural language connectome develops and is modulated by environmental factors such as the characteristic processing demands of the native language.

Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (GTS) is a neuropsychiatric movement disorder with reported abnormalities in various neurotransmitter systems. Considering the integral role of iron in neurotransmitter synthesis and transport, it is hypothesized that iron exhibits a role in GTS pathophysiology. As a surrogate measure of brain iron, quantitative susceptibility mapping (QSM) was performed in 28 patients with GTS and 26 matched controls. Significant susceptibility reductions in the patients, consistent with reduced local iron content, were obtained in subcortical regions known to be implicated in GTS. Regression analysis revealed a significant negative association of tic scores and striatal susceptibility. To interrogate genetic mechanisms that may drive these reductions, spatially specific relationships between susceptibility and gene-expression patterns from the Allen Human Brain Atlas were assessed. Correlations in the striatum were enriched for excitatory, inhibitory, and modulatory neurochemical signaling mechanisms in the motor regions, mitochondrial processes driving ATP production and iron­sulfur cluster biogenesis in the executive subdivision, and phosphorylation-related mechanisms affecting receptor expression and long-term potentiation in the limbic subdivision. This link between susceptibility reductions and normative transcriptional profiles suggests that disruptions in iron regulatory mechanisms are involved in GTS pathophysiology and may lead to pervasive abnormalities in mechanisms regulated by iron-containing enzymes.

White matter brain structure predicts language performance and learning success.

Individual differences in the ability to process language have long been discussed. Much of the neural basis of these, however, is yet unknown. Here we investigated the relationship between long-range white matter connectivity of the brain, as revealed by diffusion tractography, and the ability to process syntactically complex sentences in the participants' native language as well as the improvement thereof by multiday training. We identified specific network motifs by singular value decomposition that indeed related white matter structural connectivity to individual language processing performance. First, for two such motifs, one in the left and one in the right hemisphere, their individual prevalence significantly predicted the individual language performance, suggesting an anatomical predisposition for the individual ability to process syntactically complex sentences. Both motifs comprise a number of cortical regions, but seem to be dominated by areas known for the involvement in working memory rather than the classical language network itself. Second, we identified another left hemispheric network motif, whose change of prevalence over the training period significantly correlated with the individual change in performance, thus reflecting training induced white matter plasticity. This motif comprises diverse cortical areas including regions known for their involvement in language processing, working memory and motor functions. The present findings suggest that individual differences in language processing and learning can be explained, in part, by individual differences in the brain's white matter structure. Brain structure may be a crucial factor to be considered when discussing variations in human cognitive performance, more generally.

Mapping the human connectome using diffusion MRI at 300 mT/m gradient strength: Methodological advances and scientific impact.

Tremendous efforts have been made in the last decade to advance cutting-edge MRI technology in pursuit of mapping structural connectivity in the living human brain with unprecedented sensitivity and speed. The first Connectom 3T MRI scanner equipped with a 300 mT/m whole-body gradient system was installed at the Massachusetts General Hospital in 2011 and was specifically constructed as part of the Human Connectome Project. Since that time, numerous technological advances have been made to enable the broader use of the Connectom high gradient system for diffusion tractography and tissue microstructure studies and leverage its unique advantages and sensitivity to resolving macroscopic and microscopic structural information in neural tissue for clinical and neuroscientific studies. The goal of this review article is to summarize the technical developments that have emerged in the last decade to support and promote large-scale and scientific studies of the human brain using the Connectom scanner. We provide a brief historical perspective on the development of Connectom gradient technology and the efforts that led to the installation of three other Connectom 3T MRI scanners worldwide - one in the United Kingdom in Cardiff, Wales, another in continental Europe in Leipzig, Germany, and the latest in Asia in Shanghai, China. We summarize the key developments in gradient hardware and image acquisition technology that have formed the backbone of Connectom-related research efforts, including the rich array of high-sensitivity receiver coils, pulse sequences, image artifact correction strategies and data preprocessing methods needed to optimize the quality of high-gradient strength diffusion MRI data for subsequent analyses. Finally, we review the scientific impact of the Connectom MRI scanner, including advances in diffusion tractography, tissue microstructural imaging, ex vivo validation, and clinical investigations that have been enabled by Connectom technology. We conclude with brief insights into the unique value of strong gradients for diffusion MRI and where the field is headed in the coming years.

Mapping the human lateral geniculate nucleus and its cytoarchitectonic subdivisions using quantitative MRI.

The human lateral geniculate nucleus (LGN) of the visual thalamus is a key subcortical processing site for visual information analysis. Due to its small size and deep location within the brain, a non-invasive characterization of the LGN and its microstructurally distinct magnocellular (M) and parvocellular (P) subdivisions in humans is challenging. Here, we investigated whether structural quantitative MRI (qMRI) methods that are sensitive to underlying microstructural tissue features enable MR-based mapping of human LGN M and P subdivisions. We employed high-resolution 7 Tesla in-vivo qMRI in N = 27 participants and ultra-high resolution 7 Tesla qMRI of a post-mortem human LGN specimen. We found that a quantitative assessment of the LGN and its subdivisions is possible based on microstructure-informed qMRI contrast alone. In both the in-vivo and post-mortem qMRI data, we identified two components of shorter and longer longitudinal relaxation time (T1) within the LGN that coincided with the known anatomical locations of a dorsal P and a ventral M subdivision, respectively. Through ground-truth histological validation, we further showed that the microstructural MRI contrast within the LGN pertains to cyto- and myeloarchitectonic tissue differences between its subdivisions. These differences were based on cell and myelin density, but not on iron content. Our qMRI-based mapping strategy paves the way for an in-depth understanding of LGN function and microstructure in humans. It further enables investigations into the selective contributions of LGN subdivisions to human behavior in health and disease.

Language Without Speech: Segregating Distinct Circuits in the Human Brain.

Language is a fundamental part of human cognition. The question of whether language is processed independently of speech, however, is still heavily discussed. The absence of speech in deaf signers offers the opportunity to disentangle language from speech in the human brain. Using probabilistic tractography, we compared brain structural connectivity of adult deaf signers who had learned sign language early in life to that of matched hearing controls. Quantitative comparison of the connectivity profiles revealed that the core language tracts did not differ between signers and controls, confirming that language is independent of speech. In contrast, pathways involved in the production and perception of speech displayed lower connectivity in deaf signers compared to hearing controls. These differences were located in tracts towards the left pre-supplementary motor area and the thalamus when seeding in Broca's area, and in ipsilateral parietal areas and the precuneus with seeds in left posterior temporal regions. Furthermore, the interhemispheric connectivity between the auditory cortices was lower in the deaf than in the hearing group, underlining the importance of the transcallosal connection for early auditory processes. The present results provide evidence for a functional segregation of the neural pathways for language and speech.

Increased sensitivity and signal-to-noise ratio in diffusion-weighted MRI using multi-echo acquisitions.

Post-mortem diffusion MRI (dMRI) enables acquisitions of structural imaging data with otherwise unreachable resolutions - at the expense of longer scanning times. These data are typically acquired using highly segmented image acquisition strategies, thereby resulting in an incomplete signal decay before the MRI encoding continues. Especially in dMRI, with low signal intensities and lengthy contrast encoding, such temporal inefficiency translates into reduced image quality and longer scanning times. This study introduces Multi Echo (ME) acquisitions to dMRI on a human MRI system - a time-efficient approach, which increases SNR (Signal-to-Noise Ratio) and reduces noise bias for dMRI images. The benefit of the introduced ME-dMRI method was validated using numerical Monte Carlo simulations and showcased on a post-mortem brain of a wild chimpanzee. The proposed Maximum Likelihood Estimation echo combination results in an optimal SNR without detectable signal bias. The combined strategy comes at a small price in scanning time (here 30% additional) and leads to a substantial SNR increase (here white matter: ~ 1.6x, equivalent to 2.6 averages, grey matter: ~ 1.9x, equivalent to 3.6 averages) and a general reduction of the noise bias.

The Concurrence of Cortical Surface Area Expansion and White Matter Myelination in Human Brain Development.

The human brain undergoes dramatic structural changes during childhood that co-occur with behavioral development. These age-related changes are documented for the brain's gray matter and white matter. However, their interrelation is largely unknown. In this study, we investigated age-related effects in cortical thickness (CT) and in cortical surface area (SA) as parts of the gray matter volume as well as age effects in T1 relaxation times in the white matter. Data from N = 170 children between the ages of 3 and 7 years contributed to the sample. We found a high spatial overlap of age-related correlations between SA and T1 relaxation times of the corresponding white matter connections, but no such relation between SA and CT. These results indicate that during childhood the developmental expansion of the cortical surface goes hand-in-hand with age-related increase of white matter fiber connections terminating in the cortical surface.

Structural connectivity of right frontal hyperactive areas scales with stuttering severity.

A neuronal sign of persistent developmental stuttering is the magnified coactivation of right frontal brain regions during speech production. Whether and how stuttering severity relates to the connection strength of these hyperactive right frontal areas to other brain areas is an open question. Scrutinizing such brain-behaviour and structure-function relationships aims at disentangling suspected underlying neuronal mechanisms of stuttering. Here, we acquired diffusion-weighted and functional images from 31 adults who stutter and 34 matched control participants. Using a newly developed structural connectivity measure, we calculated voxel-wise correlations between connection strength and stuttering severity within tract volumes that originated from functionally hyperactive right frontal regions. Correlation analyses revealed that with increasing speech motor deficits the connection strength increased in the right frontal aslant tract, the right anterior thalamic radiation, and in U-shaped projections underneath the right precentral sulcus. In contrast, with decreasing speech motor deficits connection strength increased in the right uncinate fasciculus. Additional group comparisons of whole-brain white matter skeletons replicated the previously reported reduction of fractional anisotropy in the left and right superior longitudinal fasciculus as well as at the junction of right frontal aslant tract and right superior longitudinal fasciculus in adults who stutter compared to control participants. Overall, our investigation suggests that right fronto-temporal networks play a compensatory role as a fluency enhancing mechanism. In contrast, the increased connection strength within subcortical-cortical pathways may be implied in an overly active global response suppression mechanism in stuttering. Altogether, this combined functional MRI-diffusion tensor imaging study disentangles different networks involved in the neuronal underpinnings of the speech motor deficit in persistent developmental stuttering.

Pathological glutamatergic neurotransmission in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome is a hereditary, neuropsychiatric movement disorder with reported abnormalities in the neurotransmission of dopamine and γ-aminobutyric acid (GABA). Spatially focalized alterations in excitatory, inhibitory and modulatory neurochemical ratios within specific functional subdivisions of the basal ganglia, may lead to the expression of diverse motor and non-motor features as manifested in Gilles de la Tourette syndrome. Current treatment strategies are often unsatisfactory thus provoking the need for further elucidation of the underlying pathophysiology. In view of (i) the close spatio-temporal synergy exhibited between excitatory, inhibitory and modulatory neurotransmitter systems; (ii) the crucial role played by glutamate (Glu) in tonic/phasic dopaminergic signalling; and (iii) the interdependent metabolic relationship exhibited between Glu and GABA via glutamine (Gln); we postulated that glutamatergic signalling is related to the pathophysiology of Gilles de la Tourette syndrome. As such, we examined the neurochemical profile of three cortico-striato-thalamo-cortical regions in 37 well-characterized, drug-free adult patients and 36 age/gender-matched healthy control subjects via magnetic resonance spectroscopy at 3 T. To interrogate the influence of treatment on metabolite concentrations, spectral data were acquired from 15 patients undergoing a 4-week treatment with aripiprazole. Test-retest reliability measurements in 23 controls indicated high repeatability of voxel localization and metabolite quantitation. We report significant reductions in striatal concentrations of Gln, Glu + Gln (Glx) and the Gln:Glu ratio, and thalamic concentrations of Glx in Gilles de la Tourette syndrome in comparison to controls. ON-treatment patients exhibited no significant metabolite differences when compared to controls but significant increases in striatal Glu and Glx, and trends for increases in striatal Gln and thalamic Glx compared to baseline measurements. Multiple regression analysis revealed a significant negative correlation between (i) striatal Gln and actual tic severity; and (ii) thalamic Glu and premonitory urges. Our results indicate that patients with Gilles de la Tourette syndrome exhibit an abnormality in the flux of metabolites in the GABA-Glu-Gln cycle, thus implying perturbations in astrocytic-neuronal coupling systems that maintain the subtle balance between excitatory and inhibitory neurotransmission within subcortical nuclei.

Emotion regulation and trait anxiety are predicted by the microstructure of fibers between amygdala and prefrontal cortex.

Diffusion tensor imaging revealed that trait anxiety predicts the microstructural properties of a prespecified fiber tract between the amygdala and the perigenual anterior cingulate cortex. Besides this particular pathway, it is likely that other pathways are also affected. We investigated white matter differences in persons featuring an anxious or a nonanxious personality, taking into account all potential pathway connections between amygdala and anxiety-related regions of the prefrontal cortex (PFC). Diffusion-weighted images, measures of trait anxiety and of reappraisal use (an effective emotion-regulation style), were collected in 48 females. With probabilistic tractography, pathways between the amygdala and the dorsolateral PFC, dorsomedial PFC, ventromedial PFC, and orbitofrontal cortex (OFC) were delineated. The resulting network showed a direct ventral connection between amygdala and PFC and a second limbic connection following the fornix and the anterior limb of the internal capsule. Reappraisal use predicted the microstructure of pathways to all calculated PFC regions in the left hemisphere, indicating stronger pathways for persons with high reappraisal use. Trait anxiety predicted the microstructure in pathways to the ventromedial PFC and OFC, indexing weaker connections in trait-anxious persons. These effects appeared in the right hemisphere, supporting lateralization and top-down inhibition theories of emotion processing. Whereas a specific microstructure is associated with an anxious personality, a different structure subserves emotion regulation. Both are part of a broad fiber tract network between amygdala and PFC.

Left posterior-dorsal area 44 couples with parietal areas to promote speech fluency, while right area 44 activity promotes the stopping of motor responses.

Area 44 is a cytoarchitectonically distinct portion of Broca's region. Parallel and overlapping large-scale networks couple with this region thereby orchestrating heterogeneous language, cognitive, and motor functions. In the context of stuttering, area 44 frequently comes into focus because structural and physiological irregularities affect developmental trajectories, stuttering severity, persistency, and etiology. A remarkable phenomenon accompanying stuttering is the preserved ability to sing. Speaking and singing are connatural behaviours recruiting largely overlapping brain networks including left and right area 44. Analysing which potential subregions of area 44 are malfunctioning in adults who stutter, and what effectively suppresses stuttering during singing, may provide a better understanding of the coordination and reorganization of large-scale brain networks dedicated to speaking and singing in general. We used fMRI to investigate functionally distinct subregions of area 44 during imagery of speaking and imaginary of humming a melody in 15 dextral males who stutter and 17 matched control participants. Our results are fourfold. First, stuttering was specifically linked to a reduced activation of left posterior-dorsal area 44, a subregion that is involved in speech production, including phonological word processing, pitch processing, working memory processes, sequencing, motor planning, pseudoword learning, and action inhibition. Second, functional coupling between left posterior area 44 and left inferior parietal lobule was deficient in stuttering. Third, despite the preserved ability to sing, males who stutter showed bilaterally a reduced activation of area 44 when imagine humming a melody, suggesting that this fluency-enhancing condition seems to bypass posterior-dorsal area 44 to achieve fluency. Fourth, time courses of the posterior subregions in area 44 showed delayed peak activations in the right hemisphere in both groups, possibly signaling the offset response. Because these offset response-related activations in the right hemisphere were comparably large in males who stutter, our data suggest a hyperactive mechanism to stop speech motor responses and thus possibly reflect a pathomechanism, which, until now, has been neglected. Overall, the current results confirmed a recently described co-activation based parcellation supporting the idea of functionally distinct subregions of left area 44.

Functional network mirrored in the prefrontal cortex, caudate nucleus, and thalamus: high-resolution functional imaging and structural connectivity.

Despite myriads of studies on a parallel organization of cortico-striatal-thalamo-cortical loops, direct evidence of this has been lacking for the healthy human brain. Here, we scrutinize the functional specificity of the cortico-subcortical loops depending on varying levels of cognitive hierarchy as well as their structural connectivity with high-resolution fMRI and diffusion-weighted MRI (dMRI) at 7 tesla. Three levels of cognitive hierarchy were implemented in two domains: second language and nonlanguage. In fMRI, for the higher level, activations were found in the ventroanterior portion of the prefrontal cortex (PFC), the head of the caudate nucleus (CN), and the ventral anterior nucleus (VA) in the thalamus. Conversely, for the lower level, activations were located in the posterior region of the PFC, the body of the CN, and the medial dorsal nucleus (MD) in the thalamus. This gradient pattern of activations was furthermore shown to be tenable by the parallel connectivity in dMRI tractography connecting the anterior regions of the PFC with the head of the CN and the VA in the thalamus, whereas the posterior activations of the PFC were linked to the body of the CN and the MD in the thalamus. This is the first human in vivo study combining fMRI and dMRI showing that the functional specificity is mirrored within the cortico-subcortical loop substantiated by parallel networks.

Orientation dependence of magnetization transfer parameters in human white matter.

Quantification of magnetization-transfer (MT) experiments is typically based on a model comprising a liquid pool "a" of free water and a semisolid pool "b" of motionally restricted macromolecules or membrane compounds. By a comprehensive fitting approach, high quality MT parameter maps of the human brain are obtained. In particular, a distinct correlation between the diffusion-tensor orientation with respect to the B0-magnetic field and the apparent transverse relaxation time, T2(b), of the semisolid pool (i.e., the width of its absorption line) is observed. This orientation dependence is quantitatively explained by a refined dipolar lineshape for pool b that explicitly considers the specific geometrical arrangement of lipid bilayers wrapped around a cylindrical axon. The model inherently reduces the myelin membrane to its lipid constituents, which is motivated by previous studies on efficient interaction sites (e.g., cholesterol or galactocerebrosides) in the myelin membrane and on the origin of ultrashort T2 signals in cerebral white matter. The agreement between MT orientation effects and corresponding forward simulations using empirical diffusion imaging results as input as well as results from fits employing the novel lineshape support previous suggestions that the fiber orientation distribution in a voxel can be modeled as a scaled Bingham distribution.

Validation of tractography: Comparison with manganese tracing.

In this study, we used invasive tracing to evaluate white matter tractography methods based on ex vivo diffusion-weighted magnetic resonance imaging (dwMRI) data. A representative selection of tractography methods were compared to manganese tracing on a voxel-wise basis, and a more qualitative assessment examined whether, and to what extent, certain fiber tracts and gray matter targets were reached. While the voxel-wise agreement was very limited, qualitative assessment revealed that tractography is capable of finding the major fiber tracts, although there were some differences between the methods. However, false positive connections were very common and, in particular, we discovered that it is not possible to achieve high sensitivity (i.e., few false negatives) and high specificity (i.e., few false positives) at the same time. Closer inspection of the results led to the conclusion that these problems mainly originate from regions with complex fiber arrangements or high curvature and are not easily resolved by sophisticated local models alone. Instead, the crucial challenge in making tractography a truly useful and reliable tool in brain research and neurology lies in the acquisition of better data. In particular, the increase of spatial resolution, under preservation of the signal-to-noise-ratio, is key.

The Neurobiological Grounding of Persistent Stuttering: from Structure to Function.

Neuroimaging and transcranial magnetic stimulation provide insights into the neuronal mechanisms underlying speech disfluencies in chronic persistent stuttering. In the present paper, the goal is not to provide an exhaustive review of existing literature, but rather to highlight robust findings. We, therefore, conducted a meta-analysis of diffusion tensor imaging studies which have recently implicated disrupted white matter connectivity in stuttering. A reduction of fractional anisotropy in persistent stuttering has been reported at several different loci. Our meta-analysis revealed consistent deficits in the left dorsal stream and in the interhemispheric connections between the sensorimotor cortices. In addition, recent fMRI meta-analyses link stuttering to reduced left fronto-parieto-temporal activation while greater fluency is associated with boosted co-activations of right fronto-parieto-temporal areas. However, the physiological foundation of these irregularities is not accessible with MRI. Complementary, transcranial magnetic stimulation (TMS) reveals local excitatory and inhibitory regulation of cortical dynamics. Applied to a speech motor area, TMS revealed reduced speech-planning-related neuronal dynamics at the level of the primary motor cortex in stuttering. Together, this review provides a focused view of the neurobiology of stuttering to date and may guide the rational design of future research. This future needs to account for the perpetual dynamic interactions between auditory, somatosensory, and speech motor circuits that shape fluent speech.

Connectivity architecture and subdivision of the human inferior parietal cortex revealed by diffusion MRI.

The human inferior parietal cortex convexity (IPCC) is an important association area, which integrates auditory, visual, and somatosensory information. However, the structural organization of the IPCC is a controversial issue. For example, cytoarchitectonic parcellations reported in the literature range from 2 to 7 areas. Moreover, anatomical descriptions of the human IPCC are often based on experiments in the macaque monkey. In this study, we used diffusion-weighted magnetic resonance imaging combined with probabilistic tractography to quantify the connectivity of the human IPCC, and used this information to parcellate this cortex area. This provides a new structural map of the human IPCC, comprising 3 subareas (inferior parietal cortex anterior, IPC middle, and IPC posterior) of comparable size, in a rostro-caudal arrangement in the left and right hemispheres. Each subarea is characterized by a connectivity fingerprint, and the parcellation is similar to the subdivision reported for the macaque IPCC with 3 areas in a rostro-caudal arrangement (PF, PFG, and PG). However, the present study also reliably demonstrates new structural features in the connectivity pattern of the human IPCC, which are not known to exist in the macaque. This study quantifies intersubject variability by providing a population representation of the subarea arrangement and demonstrates the substantial lateralization of the connectivity patterns of the IPCC.