Electrocorticographic evidence of a common neurocognitive sequence for mentalizing about the self and others.

Neuroimaging studies of mentalizing (i.e., theory of mind) consistently implicate the default mode network (DMN). Nevertheless, the social cognitive functions of individual DMN regions remain unclear, perhaps due to limited spatiotemporal resolution in neuroimaging. Here we use electrocorticography (ECoG) to directly record neuronal population activity while 16 human participants judge the psychological traits of themselves and others. Self- and other-mentalizing recruit near-identical cortical sites in a common spatiotemporal sequence. Activations begin in the visual cortex, followed by temporoparietal DMN regions, then finally in medial prefrontal regions. Moreover, regions with later activations exhibit stronger functional specificity for mentalizing, stronger associations with behavioral responses, and stronger self/other differentiation. Specifically, other-mentalizing evokes slower and longer activations than self-mentalizing across successive DMN regions, implying lengthier processing at higher levels of representation. Our results suggest a common neurocognitive pathway for self- and other-mentalizing that follows a complex spatiotemporal gradient of functional specialization across DMN and beyond.

A Platform for Spatiotemporal "Matrix" Stimulation in Brain Networks Reveals Novel Forms of Circuit Plasticity.

Here we demonstrate a facile method by which to deliver complex spatiotemporal stimulation to neural networks in fast patterns, to trigger interesting forms of circuit-level plasticity in cortical areas. We present a complete platform by which patterns of electricity can be arbitrarily defined and distributed across a brain circuit, either simultaneously, asynchronously, or in complex patterns that can be easily designed and orchestrated with precise timing. Interfacing with acute slices of mouse cortex, we show that our system can be used to activate neurons at many locations and drive synaptic transmission in distributed patterns, and that this elicits new forms of plasticity that may not be observable via traditional methods, including interesting measurements of associational and sequence plasticity. Finally, we introduce an automated "network assay" for imaging activation and plasticity across a circuit. Spatiotemporal stimulation opens the door for high-throughput explorations of plasticity at the circuit level, and may provide a basis for new types of adaptive neural prosthetics.

Fast temporal dynamics and causal relevance of face processing in the human temporal cortex.

We measured the fast temporal dynamics of face processing simultaneously across the human temporal cortex (TC) using intracranial recordings in eight participants. We found sites with selective responses to faces clustered in the ventral TC, which responded increasingly strongly to marine animal, bird, mammal, and human faces. Both face-selective and face-active but non-selective sites showed a posterior to anterior gradient in response time and selectivity. A sparse model focusing on information from the human face-selective sites performed as well as, or better than, anatomically distributed models when discriminating faces from non-faces stimuli. Additionally, we identified the posterior fusiform site (pFUS) as causally the most relevant node for inducing distortion of conscious face processing by direct electrical stimulation. These findings support anatomically discrete but temporally distributed response profiles in the human brain and provide a new common ground for unifying the seemingly contradictory modular and distributed modes of face processing.

Direct Cortical Recordings Suggest Temporal Order of Task-Evoked Responses in Human Dorsal Attention and Default Networks.

The past decade has seen a large number of neuroimaging studies focused on the anticorrelated functional relationship between the default mode network (DMN) and the dorsal attention network (DAN). Due principally to the low temporal resolution of functional neuroimaging modalities, the fast-neuronal dynamics across these networks remain poorly understood. Here we report novel human intracranial electrophysiology data from six neurosurgical patients (four males) with simultaneous coverage of well characterized nodes of the DMN and DAN. Subjects performed an arithmetic processing task, shown previously to evoke reliable deactivations (below baseline) in the DMN, and activations in the DAN. In this cohort, we show that DMN deactivations lag DAN activations by approximately 200 ms. Our findings suggest a clear temporal order of processing across the two networks during the current task and place the DMN further than the DAN in a plausible information-processing hierarchy.SIGNIFICANCE STATEMENT The human brain contains an intrinsic and strictly organized network architecture. Our understanding of the interplay across association networks has relied primarily on the slow fluctuations of the hemodynamic response, and as such it has lacked essential evidence regarding the temporal dynamics of activity across these networks. The current study presents evidence from high spatiotemporal methods showing that well studied areas of the default mode network display delayed task-induced activity relative to divergent responses in dorsal attention network nodes. This finding provides direct and critical evidence regarding the temporal chronology of neuronal events across opposing brain networks.

Neuronal Population Responses in the Human Ventral Temporal and Lateral Parietal Cortex during Arithmetic Processing with Digits and Number Words.

Past research has identified anatomically specific sites within the posterior inferior temporal gyrus (PITG) and the intraparietal sulcus (IPS) areas that are engaged during arithmetic processing. Although a small region of the PITG (known as the number form area) is selectively engaged in the processing of numerals, its surrounding area is activated during both digit and number word processing. In eight participants with intracranial electrodes, we compared the timing and selectivity of electrophysiological responses in the number form area-surround and IPS regions during arithmetic processing with digits and number words. Our recordings revealed stronger electrophysiological responses in the high-frequency broadband range in both regions to digits than number words, with the difference that number words elicited delayed activity in the IPS but not PITG. Our findings of distinct profiles of responses in the PITG and the IPS to digits compared with number words provide novel information that is relevant to existing theoretical models of mathematical cognition.

Spatial and temporal heterogeneity of neural responses in human posteromedial cortex.

Neuroimaging evidence supports a role of the default mode network (DMN) in spontaneous thought and goal-driven internally oriented processes, such as recalling an autobiographical event, and has demonstrated its deactivation during focused, externally oriented attention. Recent work suggests that the DMN is not a homogeneous network but rather is composed of at least several subnetworks, which are engaged in distinct functions; however, it is still unclear if these different functions rely on the same neuronal populations. In this study, we used intracranial EEG to record from the posteromedial cortex (PMC), a core hub of the DMN, in 13 human subjects, during autobiographical memory retrieval (internally oriented), arithmetic processing (externally oriented), and cued rest (spontaneous thought), allowing us to measure activity from anatomically precise PMC sites with high temporal resolution. We observed a heterogeneous, yet spatially organized, pattern of activity across tasks. Many sites, primarily in the more ventral portion of PMC, were engaged during autobiographical recall and suppressed during arithmetic processing. Other more dorsal PMC sites were engaged during the cued-rest condition. Of these rest-active sites, some exhibited variable temporal dynamics across trials, possibly reflecting various forms of spontaneous thought, while others showed only transient activity at the beginning of cued-rest trials (i.e., after a switch from a task to cued rest), possibly involved in shifting the brain from a more focused to a more exploratory attentional state. These results suggest heterogeneity of function even within an individual node of the DMN.

Intracranial Electrophysiology of the Human Default Network.

The human default network (DN) plays a critical role in internally directed cognition, behavior, and neuropsychiatric disease. Despite much progress with functional neuroimaging, persistent questions still linger concerning the electrophysiological underpinnings, fast temporal dynamics, and causal importance of the DN. Here, we review how direct intracranial recording and stimulation of the DN provides a unique combination of high spatiotemporal resolution and causal information that speaks directly to many of these outstanding questions. Our synthesis highlights the electrophysiological basis of activation, suppression, and connectivity of the DN, each key areas of debate in the literature. Integrating these unique electrophysiological data with extant neuroimaging findings will help lay the foundation for a mechanistic account of DN function in human behavior and cognition.

Distinct phase-amplitude couplings distinguish cognitive processes in human attention.

Spatial attention is the cognitive function that coordinates the selection of visual stimuli with appropriate behavioral responses. Recent studies have reported that phase-amplitude coupling (PAC) of low and high frequencies covaries with spatial attention, but differ on the direction of covariation and the frequency ranges involved. We hypothesized that distinct phase-amplitude frequency pairs have differentiable contributions during tasks that manipulate spatial attention. We investigated this hypothesis with electrocorticography (ECoG) recordings from participants who engaged in a cued spatial attention task. To understand the contribution of PAC to spatial attention we classified cortical sites by their relationship to spatial variables or behavioral performance. Local neural activity in spatial sites was sensitive to spatial variables in the task, while local neural activity in behavioral sites correlated with reaction time. We found two PAC frequency clusters that covaried with different aspects of the task. During a period of cued attention, delta-phase/high-gamma (DH) PAC was sensitive to cue direction in spatial sites. In contrast, theta-alpha-phase/beta-low-gamma-amplitude (TABL) PAC robustly correlated with future reaction times in behavioral sites. Finally, we investigated the origins of TABL PAC and found it corresponded to behaviorally relevant, sharp waveforms, which were also coupled to a low frequency rhythm. We conclude that TABL and DH PAC correspond to distinct mechanisms during spatial attention tasks and that sharp waveforms are elements of a coupled dynamical process.

Mapping human temporal and parietal neuronal population activity and functional coupling during mathematical cognition.

Brain areas within the lateral parietal cortex (LPC) and ventral temporal cortex (VTC) have been shown to code for abstract quantity representations and for symbolic numerical representations, respectively. To explore the fast dynamics of activity within each region and the interaction between them, we used electrocorticography recordings from 16 neurosurgical subjects implanted with grids of electrodes over these two regions and tracked the activity within and between the regions as subjects performed three different numerical tasks. Although our results reconfirm the presence of math-selective hubs within the VTC and LPC, we report here a remarkable heterogeneity of neural responses within each region at both millimeter and millisecond scales. Moreover, we show that the heterogeneity of response profiles within each hub mirrors the distinct patterns of functional coupling between them. Our results support the existence of multiple bidirectional functional loops operating between discrete populations of neurons within the VTC and LPC during the visual processing of numerals and the performance of arithmetic functions. These findings reveal information about the dynamics of numerical processing in the brain and also provide insight into the fine-grained functional architecture and connectivity within the human brain.

Frequency-specific mechanism links human brain networks for spatial attention.

Selective attention allows us to filter out irrelevant information in the environment and focus neural resources on information relevant to our current goals. Functional brain-imaging studies have identified networks of broadly distributed brain regions that are recruited during different attention processes; however, the dynamics by which these networks enable selection are not well understood. Here, we first used functional MRI to localize dorsal and ventral attention networks in human epileptic subjects undergoing seizure monitoring. We subsequently recorded cortical physiology using subdural electrocorticography during a spatial-attention task to study network dynamics. Attention networks become selectively phase-modulated at low frequencies (δ, θ) during the same task epochs in which they are recruited in functional MRI. This mechanism may alter the excitability of task-relevant regions or their effective connectivity. Furthermore, different attention processes (holding vs. shifting attention) are associated with synchrony at different frequencies, which may minimize unnecessary cross-talk between separate neuronal processes.

Environmental experience within and across testing days determines the strength of human visuomotor adaptation.

The use of vision allows us to guide and modify our movements by appropriately transforming external sensory information into proper motor commands. We investigated how people learned visuomotor transformations in different visual feedback environments. These environments presented perturbations of visual sense of movement direction. Across experiments and testing days, we altered the likelihood of visual perturbation occurrence and the distribution of sign and strength of visual perturbation angles. We then observed how transformation of sensed error into incremental adaptation depended on visual perturbation angle and on environmental experience. We found that environmental context affected adaptive responses within a day and across days. The across-day effect was profound enough that people exhibited very weak or very strong adaptive sensitivity to identical stimuli, dependent solely on prior days' experience. We conclude that trial-by-trial adaptation to visual feedback is not fixed, but dependent on environmental experiences on both short and long time scales.