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Significance In this manuscript, we report a rare case of a patient with localized seizures originating from the right anterior and dorsal posteromedial cortex (PMC). We mapped the electrophysiological and neuroimaging connectivity of the ictal onset site and replicated seizure auras by stimulating the homotopical PMC site in the left hemisphere. Our findings provide a causal link between PMC and the sense of self and provide unique clues about the pathophysiology of self-dissociation in neuropsychiatric conditions., The posteromedial cortex (PMC) is known to be a core node of the default mode network. Given its anatomical location and blood supply pattern, the effects of targeted disruption of this part of the brain are largely unknown. Here, we report a rare case of a patient (S19_137) with confirmed seizures originating within the PMC. Intracranial recordings confirmed the onset of seizures in the right dorsal posterior cingulate cortex, adjacent to the marginal sulcus, likely corresponding to Brodmann area 31. Upon the onset of seizures, the patient reported a reproducible sense of self-dissociation—a condition he described as a distorted awareness of the position of his body in space and feeling as if he had temporarily become an outside observer to his own thoughts, his “me” having become a separate entity that was listening to different parts of his brain speak to each other. Importantly, 50-Hz electrical stimulation of the seizure zone and a homotopical region within the contralateral PMC induced a subjectively similar state, reproducibly. We supplement our clinical findings with the definition of the patient’s network anatomy at sites of interest using cortico-cortical–evoked potentials, experimental and resting-state electrophysiological connectivity, and individual-level functional imaging. This rare case of patient S19_137 highlights the potential causal importance of the PMC for integrating self-referential information and provides clues for future mechanistic studies of self-dissociation in neuropsychiatric populations.

Distinct regions of the cerebellum connect to separate regions of the cerebral cortex forming a complex topography. Although cerebellar organization has been examined in group-averaged data, study of individuals provides an opportunity to discover features that emerge at a higher spatial resolution. Here, functional connectivity MRI was used to examine the cerebellum of two intensively sampled individuals (each scanned 31 times). Connectivity to somatomotor cortex showed the expected crossed laterality and topography of the body maps. A surprising discovery was connectivity to the primary visual cortex along the vermis with evidence for representation of the central field. Within the hemispheres, each individual displayed a hierarchical progression from the inverted anterior lobe somatomotor map through to higher-order association zones. The hierarchy ended at Crus I/II and then progressed in reverse order through to the upright somatomotor map in the posterior lobe. Evidence for a third set of networks was found in the most posterior extent of the cerebellum. Detailed analysis of the higher-order association networks revealed robust representations of two distinct networks linked to the default network, multiple networks linked to cognitive control, as well as a separate representation of a language network. Although idiosyncratic spatial details emerged between subjects, each network could be detected in both individuals, and seed regions placed within the cerebellum recapitulated the full extent of the spatially specific cerebral networks. The observation of multiple networks in juxtaposed regions at the Crus I/II apex confirms the importance of this zone to higher-order cognitive function and reveals new organizational details. NEW & NOTEWORTHY Stable, within-individual maps of cerebellar organization reveal orderly macroscale representations of the cerebral cortex with local juxtaposed zones representing distinct networks. In addition, individuals reveal idiosyncratic organizational features.

Distinct regions of the cerebellum connect to separate regions of the cerebral cortex forming a complex topography. While key properties of cerebellar organization have been revealed in group-averaged data, in-depth study of individuals provides an opportunity to discover functional-anatomical features that emerge at a higher spatial resolution. Here functional connectivity MRI was used to examine the cerebellum of two intensively-sampled individuals (each scanned across 31 MRI sessions). Connectivity to somatomotor cortex showed the expected crossed laterality and inversion of the body maps between the anterior and posterior lobes. A surprising discovery was connectivity to the primary visual cortex along the vermis with evidence for representation of the central field. Within the hemispheres, each individual displayed a hierarchical progression from the inverted anterior lobe somatomotor map through to higher-order association zones. The hierarchy ended near Crus I/II and then progressed in reverse order through to the upright somatomotor map in the posterior lobe. Evidence for a third set of networks was found in the most posterior extent of the cerebellum. Detailed analysis of the higher-order association networks around the Crus I/II apex revealed robust representations of two distinct networks linked to the default network, multiple networks linked to cognitive control, as well as a separate representation of a language network. While idiosyncratic spatial details emerged between subjects, each of these networks could be detected in both individuals, and small seed regions placed within the cerebellum recapitulated the full extent of the spatially-specific cerebral networks. The observation of multiple networks in juxtaposed regions at the Crus I/II apex confirms the importance of this zone to higher-order cognitive function and reveals new organizational details.

Association cortex is organized into large-scale distributed networks. One such network, the default network (DN), is linked to diverse forms of internal mentation, opening debate about whether shared or distinct anatomy supports multiple forms of cognition. Using within-individual analysis procedures that preserve idiosyncratic anatomical details, we probed whether multiple tasks from two domains, episodic projection and theory of mind (ToM), rely on the same or distinct networks. In an initial experiment (6 subjects, each scanned 4 times), we found evidence that episodic projection and ToM tasks activate separate regions distributed throughout the cortex, with adjacent regions in parietal, temporal, prefrontal, and midline zones. These distinctions were predicted by the hypothesis that the DN comprises two parallel, interdigitated networks. One network, linked to parahippocampal cortex (PHC), is preferentially recruited during episodic projection, including both remembering and imagining the future. A second juxtaposed network, which includes the temporoparietal junction (TPJ), is differentially engaged during multiple forms of ToM. In two prospectively acquired independent experiments, we replicated and triplicated the dissociation (each with 6 subjects scanned 4 times). Furthermore, the dissociation was found in all zones when analyzed independently, including robustly in midline regions previously described as hubs. The TPJ-linked network is interwoven with the PHC-linked network across the cortex, making clear why it is difficult to fully resolve the two networks in group-averaged or lower-resolution data. These results refine our understanding of the functional-anatomical organization of association cortex and raise fundamental questions about how specialization might arise in parallel, juxtaposed association networks. NEW & NOTEWORTHY Two distributed, interdigitated networks exist within the bounds of the canonical default network. Here we used repeated scanning of individuals, across three independent samples, to provide evidence that tasks requiring episodic projection or theory of mind differentially recruit the two networks across multiple cortical zones. The two distributed networks thus appear to preferentially subserve distinct functions.

Using procedures optimized to explore network organization within the individual, the topography of a candidate language network was characterized and situated within the broader context of adjacent networks. The candidate network was first identified using functional connectivity and replicated across individuals, datasets, acquisition tasks, and analytic methods. In addition to classical language regions near to perisylvian cortex and temporal pole, additional regions were observed in dorsal posterior cingulate, midcingulate, anterior superior frontal and inferior temporal cortex. The candidate network was selectively activated when processing meaningful (as contrast to non-word) sentences, while spatially adjacent networks showed minimal or even decreased activity. Examined in relation to adjacent networks, the topography of the language network was found to parallel the motif of other association networks including the transmodal association networks linked to theory of mind and episodic remembering (often collectively called the default network). The several networks contained juxtaposed regions in multiple association zones. Outside of these juxtaposed higher-order networks, we further noted a distinct frontotemporal network situated between language regions and a frontal orofacial motor region and a temporal auditory region. A possibility is that these functionally-related sensorimotor regions might anchor specialization of neighboring association regions that develop into the language network. What is most striking is that the canonical language network appears to be just one of multiple similarly organized, differentially specialized distributed networks that populate the evolutionarily expanded zones of human association cortex.

Examination of large-scale distributed networks within the individual reveals details of cortical network organization that are absent in group-averaged studies. One recent discovery is that a distributed transmodal network, often referred to as the ‘default network’, is comprised of two separate but closely interdigitated networks, only one of which is coupled to posterior parahippocampal cortex. Not all studies of individuals have identified the same networks and questions remain about the degree to which the two networks are separate, particularly within regions hypothesized to be interconnected hubs. Here we replicate the observation of network separation across analytical (seed-based connectivity and parcellation) and data projection (volume and surface) methods in 2 individuals each scanned 31 times. Additionally, 3 individuals were examined with high-resolution fMRI to gain further insight into the anatomical details. The two networks were identified with separate regions localized to adjacent portions of the cortical ribbon, sometimes inside the same sulcus. Midline regions previously implicated as hubs revealed near complete spatial separation of the two networks, displaying a complex spatial topography in the posterior cingulate and precuneus. The network coupled to parahippocampal cortex also revealed a separate region directly within the hippocampus at or near the subiculum. These collective results support that the default network is composed of at least two spatially juxtaposed networks. Fine spatial details and juxta-positions of the two networks can be identified within individuals at high resolution, providing insight into the network organization of association cortex and placing further constraints on interpretation of group-averaged neuroimaging data.

Intrinsic connectivity networks (ICNs), such as the default mode, frontoparietal control, and salience networks, provide a useful large-scale description of the functional architecture of the brain. Although ICNs are functionally specialized, the information that they process needs to be integrated for coherent cognition, perception, and behavior. A region capable of performing this integration might be expected to contain traces, or “echoes,” of the neural signals from multiple ICNs. Here, using fMRI in humans, we show the existence of specific “transmodal” regions containing echoes of multiple ICNs. These regions include core nodes of the default mode network, as well as multimodal association regions of the temporoparietal and temporo-occipito-parietal junction, right middle frontal gyrus, and dorsal anterior cingulate cortex. In contrast, “unimodal” regions such as the primary sensory and motor cortices show a much more singular pattern of activity, containing traces of few or even single ICNs. The presence of ICN echoes might explain how transmodal regions are involved in multiple different cognitive states. Our results suggest that these transmodal regions have a particular local spatial organization containing topographic maps that relate to multiple ICNs. This makes transmodal regions uniquely placed to be able to mediate the cross talk between the brain's functional networks through local modulation of adjacent regions that communicate with different ICNs.

There is considerable uncertainty about the function of the posterior cingulate cortex (PCC). The PCC is a major node within the default mode network (DMN) and has high metabolic activity and dense structural connectivity to widespread brain regions, which suggests it has a role as a cortical hub. The region appears to be involved in internally directed thought, for example, memory recollection. However, recent nonhuman primate work provides evidence for a more active role in the control of cognition, through signaling an environmental change and the need to alter behavior. For an organism to flexibly react to a changing environment, information processed in functionally distinct brain networks needs to be integrated by such a cortical hub. If the PCC is involved in this process, its brain activity should show a complex and dynamic pattern that partially reflects activity in other brain networks. Using fMRI in humans and a multivariate analysis, we demonstrate that the PCC shows this type of complex functional architecture, where echoes of multiple other brain networks are seen in separable yet overlapping subregions. For example, a predominantly ventral region shows strong functional connectivity to the rest of the DMN, whereas two subregions within the dorsal PCC show high connectivity to frontoparietal networks involved in cognitive control. PCC subregions showed distinct patterns of activity modulation during the performance of an attentionally demanding task, suggesting that parts of the dorsal PCC interact with frontoparietal networks to regulate the balance between internally and externally directed cognition.

Literacy implies convergence, with heard and read narratives directed from separate sensory pathways towards common linguistic and semantic brain systems – very ‘bottom-up'. But we also actively infer, relate, remember, attend and, above all, imagine – very ‘top-down'. We comment on an interesting investigation of the listening and reading brain.