Cerebral Cortex Communications

Understanding how the brain represents meaning at different levels of specificity, from general categories (bird) through combined phrases (nocturnal bird) to specific exemplars (owl), is a central question in semantic cognition and its disorders. The anterior temporal lobes (ATL) have been implicated in both activating stored conceptual representations and combining them, yet whether these two routes to conceptual content engage the ATL in the same way remains an open question. We recorded concurrent MEG-EEG from 36 participants reading 100 conceptual triads varying parametrically in specificity: general words (bird), adjective-noun phrases (nocturnal bird), and specific words (owl). Source analyses revealed a non-linear pattern in bilateral ATL (400-520ms): high-specificity concepts elicited greater activity than both low-specificity words and mid-specificity phrases. Bilateral inferior frontal cortex showed this effect with similar timing (430-630ms). N400 amplitude and ATL source activity showed a functional dissociation in their sensitivity to word frequency, ruling out a purely frequency account of the ATL and IFC effects. Results imply that accessing high-specificity concepts requires individuating stored representations among competitors, whereas phrases construct meaning through a different route. These findings extend the unified semantic hub account by revealing that computational operations within the ATL vary depending on task and stimulus demands.

Structural differences observed in collision-sport athletes may reflect repetitive head-impact exposure, broader effects of athletic training, or pre-existing individual variation, making inclusion of a non-collision athlete group important for interpretation of any differences seen. Here, structural T1-weighted MRI data from 17 collegiate American football players, 16 cross-country runners, and 9 non-athletes were analyzed using FSL voxel-based morphometry (VBM), FIRST subcortical volumetry and vertex-wise shape analysis, and FAST whole-brain tissue segmentation. Spatial inference used permutation testing with threshold-free cluster enhancement and family-wise error correction, while scalar analyses used multiplicity-corrected procedures. FAST-derived absolute tissue volumes were also examined in a sensitivity analysis adjusting for FreeSurfer estimated total intracranial volume (eTIV). VBM showed recurrent brainstem-centered differences, with non-athletes showing greater local gray matter measures than both athlete groups, whereas football players showed greater brainstem measures than runners. FIRST vertex-wise analysis identified corrected differences involving the brainstem and selected subcortical structures, while no total FIRST structure volume survived false discovery rate correction. Unadjusted FAST analysis identified a CSF group effect, F(2, 24.38) = 11.46, p < .001, q = .001. After eTIV adjustment, the CSF group effect remained, F(2, 38) = 14.30, q < .001, and a white matter group effect was also identified, F(2, 38) = 9.59, q < .001; gray matter and total segmented tissue did not show corrected adjusted effects. These findings indicate that structural variation depends on anatomical scale, comparison group, and head-size adjustment and cannot be attributed uniquely to collision-sport exposure.

Unveiling the plastic mechanisms of the primary visual cortex (V1) is crucial for understanding how visual processing can change and adapt, ultimately informing interventions to promote functional recovery following visual system damage. Paired associative stimulation (PAS) protocols can induce associative plasticity within the human V1. However, previous paradigms used full-field visual stimulation, engaging both hemispheres simultaneously, leaving unclear whether plasticity can be selectively targeted to a single visual pathway and whether it can modulate the non-stimulated hemisphere. Across three experiments in healthy participants, we investigated the neurophysiological, behavioural, and interhemispheric outcomes of a novel lateralized visual PAS protocol (vPAS). Pattern-reversal checkerboards were presented in a single visual hemifield and time-locked to transcranial magnetic stimulation (TMS) pulses delivered over the contralateral V1. Experiment 1 assessed neurophysiological effects by recording hemifield-lateralized visual-evoked potentials (VEPs) and testing three inter-stimulus intervals (ISIs: 75, 100, and 125 ms) between vPAS-paired stimuli. Experiment 2 evaluated perceptual changes in contrast detection, while Experiment 3 examined vPAS hemispheric specificity and aftereffects on interhemispheric visuomotor transfer. Only the 75-ms ISI consistently modulated visual processing in the non-conditioned hemisphere, reducing N75 amplitude and improving contrast detection for visual stimuli presented contralateral to the TMS side. Longer ISIs were not effective. Furthermore, this protocol altered interhemispheric transfer exclusively when the left, but not the right, V1 was targeted during vPAS. In conclusion, lateralized vPAS induces timing-dependent changes beyond the stimulated cortex, suggesting that associative plasticity can engage contralateral visual circuits and modulate visual processing.

Making choices about whether and when to engage cognitive effort is a common feature of human everyday experience with important consequences for academic, career, and health outcomes. Yet, despite its importance, little is understood about the neurochemical mechanisms that underlie individual differences in the willingness to engage in cognitively effortful activities. To examine this question, we employed a multi-modal neuroimaging approach in which participants performed the Cognitive Effort Discounting paradigm (Cog-ED) while simultaneous PET-fMRI was acquired. We assessed both individual differences in dopamine-D2 receptor availability and brain activity during decision-making. In addition, the same participants performed a parametric working memory task (N-Back) and reported the cognitive effort associated with their daily life activities through a seven-day Ecological Momentary Assessment (EMA) protocol. The findings suggest a central role for caudate dopamine-D2 receptors in modulating cognitive effort-related motivation. People with higher caudate dopamine-D2 receptor availability had better working memory function, heightened sensitivity to effort costs, and greater modulation of brain activity during effort valuation. These laboratory findings also translated directly to daily life: higher levels of caudate dopamine-D2 receptors were associated with greater engagement in cognitively effortful activities. Together, the results suggest that how individuals determine the motivational value of cognitively effortful activities strongly depends on the dopamine system.

Our knowledge of the neural basis of sensory and motor information processing comes largely from recording brain activity in controlled settings. This approach, while insightful, blinds us from understanding natural behaviors, which involve far richer visual inputs and far larger range of movements. The prevailing belief is that, during natural behaviors, movement information would modulate visual cortex, and visual inputs would modulate motor cortex. Alternatively, this mixing might only reflect correlations between sensory inputs and movements present during natural behavior. To resolve this issue, we performed wireless recordings from high-level visual (IT) and motor regions (PMv/PFC) in freely moving monkeys while they performed a natural task and a fixation task. In each task, we extracted visual and movement features and asked to what degree these features explained neural activity. In the fixation task, we found a striking double dissociation whereby visual (but not movement) features predicted neural activity in IT, whereas motor (but not visual) features predicted neural activity in PMv & PFC. This dissociation was far weaker in the natural task but present particularly at key events when the visual and motor features were less correlated. Thus, high-level sensory and motor regions in the brain are doubly dissociated under controlled conditions, and remain so at specific times during natural behavior.

Homeostatic mechanisms adjust synaptic strengths to regulate neuronal activity across wake-sleep cycles. Although sleep supports memory consolidation, limited research has explored how sleep-induced homeostatic changes influence memory outcomes in humans. The EEG-derived aperiodic slope (1/f) could be a candidate measure of homeostatic memory processes through its reflection of neural excitation-inhibition balance. In this study, 27 participants learned object-word pairs, and completed an immediate recognition test before either a nap or equivalent wakeful period. Resting-state EEG was recorded, both before and after learning and the interval, to derive changes in aperiodic slope values. A delayed recognition test then assessed whether changes in the aperiodic slope (i.e., homeostatic activity) across learning and the interval predicted memory accuracy and N400 amplitude, an index of stimulus expectancy and recognition. Our study found evidence to suggest homeostatic renormalisation, for the nap condition only, indicated by a shift towards inhibition across sleep which was inversely related to the slope change across learning. Although the aperiodic slope change across the nap and wake intervals did not predict delayed memory accuracy, a shift towards inhibition during learning was beneficial for memory accuracy, only in the nap condition. Similarly, a shift towards inhibition across learning, followed by a shift towards excitation in the nap condition, predicted reduced N400 amplitudes. This suggests that homeostatic renormalisation across the nap influenced model updating and stimulus expectancy. This study provides evidence for a link between synaptic homeostatic processes and memory consolidation, emphasising the importance of encoding-related aperiodic activity in this relationship.

Compositional syntax - the ability to combine meaningful units into structured sequences whose overall meaning depends on both the meanings of the parts and their combination - is a hallmark of human language. Recent work suggests that chimpanzees may exhibit similar capacities, raising the possibility that compositionality predates the emergence of language in humans. However, a key challenge has been to exclude simpler explanations in which call combinations are processed as independent utterances rather than integrated structures. Here, we address this issue using a source-manipulation paradigm in playback experiments with captive chimpanzees (n = 6) at the Sigean African Reserve, France. We presented sequences combining alarm and recruitment calls either from a single source (one loudspeaker) or from two spatially distinct sources (two loudspeakers). If sequences are interpreted as independent calls, responses should not differ between conditions. Instead, chimpanzees responded significantly faster when sequences originated from a single source. Bayesian survival analyses confirmed this effect. These results support a non-trivial form of compositionality, whereby the meaning of call combinations depends on their integration into a unified sequence produced by a single individual. Our findings provide experimental evidence that key features of linguistic compositionality may have evolutionary roots in the primate lineage.

Abstract Background The neuropsychiatric sequelae (cognitive deficits, anxiety and depression) post-COVID-19 exist as part of the spectrum of the multisystemic long COVID. People with these symptoms have been shown to have worse functional outcomes. Hence, this significantly impacts the economy, primarily due to productivity losses. Yet, the precise underlying pathogenesis remains unknown, as do any diagnostic or prognostic biomarkers. Aim This study aims to identify functionally impacted brain regions in those with post-COVID-19 neurological sequelae and to evaluate how alterations in brain function relate to acute serum inflammatory mediators and brain injury biomarkers. Methods The study will utilise data from the COVID-19 Clinical Neuroscience Study (CNS), a large UK multicentre study conducted during the pandemic. This sub-study will be a secondary analysis of the COVID-19 CNS, a prospective observational study that compared COVID-19-positive participants with negative controls. Participants had an MRI, blood tested for acute serum inflammatory mediators and brain injury biomarkers, and neuropsychiatric assessment (cognitron test, PHQ-9 and GAD-7) post-acutely and at follow-up. The DPABI (Data Processing & Analysis for Brain Imaging) toolbox will be used for pre-processing and analysis of the neuroimaging data (resting state functional MRI) to obtain regional homogeneity (ReHo). The association between ReHO and neuropsychiatric symptoms, acute inflammatory mediators and brain injury biomarkers will be explored. Regression models would be used to determine the risk and protective factors for developing these symptoms. Conclusion It is anticipated that the study will provide new insights into the functional basis of post-acute COVID-19 neuropsychiatric manifestations and identify new diagnostic biomarkers. Key words: Regional Homogeneity, COVID-19, functional MRI, neuropsychiatry, biomarkers

Gait impairments are a major contributor to disability in patients with Parkinson's disease despite dopaminergic and neuromodulation therapies. External cues (e.g., visual targets, rhythmic auditory sounds) are commonly used to improve gait quality and reduce freezing of gait (FOG), yet their effectiveness varies across patients and contexts. Improved understanding of the neural mechanisms of cueing benefits is essential to personalize rehabilitation strategies and improve outcomes. We use mobile electroencephalography (EEG) to test the hypothesis that cues improve gait through engagement of voluntary motor control mechanisms to compensate for impaired gait automaticity. In addition, we investigate whether this mechanism is related to cueing benefits or freezing status. Eighteen PD patients with a history of freezing (PD-F), 21 patients without freezing (PD-NF) and 19 age-matched healthy controls (HC) walked overground under three conditions: normal walking, synchronizing to auditory cues, and stepping over visual cues. Stride-locked beta band (13-30 Hz) power dynamics in sensorimotor cortex were used to measure cortical control of stepping. Spatiotemporal gait parameters improved with cues in all groups. However, PD-F had smaller cue-related gains in speed and stride length when compared with PD-NF for both cue types, and did not improve gait speed with visual cues. EEG revealed greater contralateral sensorimotor cortex swing-phase beta suppression in PD-F than PD-NF patients, with visual cues eliciting the most robust response. In contrast, beta suppression with cues was less pronounced in PD-NF and HC, despite greater behavioral gains. In addition, engagement of sensorimotor cortex during visual cueing was associated with divergent gait effects across PD subgroups: In PD-NF greater beta suppression was associated with less gait improvement, whereas in PD-F the opposite was observed. These findings suggest distinct sensorimotor control mechanisms for cue utilization in PD-F and PD-NF, and indicate that engagement of voluntary motor control circuits may underlie cueing benefits primarily in PD-F.

Bimanual coordination requires the control of each hand to account for movements of the other hand. To enable such coordination, it has been hypothesized that the brain has a representation of bimanual movements that supersedes a linear combination of the unimanual movements. To test for such a representation, we mapped the encoding of movement direction during unimanual and bimanual wrist movements in the human brain using functional magnetic resonance imaging (fMRI). For unimanual movements, we found that both the contralateral and ipsilateral movement directions were represented across most cortical motor regions. The representations were similar for mirror-symmetric movements across the hands, revealing an intrinsic (body-centric) code in premotor and parietal regions. For bimanual movements, the neural representations of movement directions could be explained by three components. First, the contralateral movement direction was represented as in the unimanual condition, whereas the representation of the ipsilateral movement direction disappeared. Second, in higher-order regions (rostral premotor and posterior parietal cortex) we found relatively elevated activity when the two movements were directed in unrelated directions. This activity was likely caused by the extra effort to deal with incongruent spatial targets across the hands. Third, and independent of this congruency effect, we found a non-linear interaction between contra- and ipsilateral movement that encoded the specific bimanual movement combination across sensorimotor, premotor, and parietal regions. This representation was suited to facilitate bimanual coordination and learning.

Naming pictures from the same semantic category can interfere with subsequent word retrieval. Although the left inferior frontal gyrus (LIFG) has been implicated in resolving this semantic interference, its causal role in this process remains unclear. Across three experiments, we investigated the contribution of the LIFG to interference resolution during blocked-cyclic naming. Experiment 1 tested whether continuous theta-burst stimulation over the LIFG increased semantic interference relative to vertex stimulation. Although the overall interference effect did not differ significantly between stimulation sites, exploratory analyses revealed an unexpected pattern based on the initial context (related vs. unrelated) with which items were named, suggesting that LIFG disruption affected retrieval of previously related items even when they were subsequently named in unrelated contexts. This observation motivated two further experiments examining the consequences of prior naming context more directly. Experiment 2 established that, without stimulation, interference observed in related blocks was no longer evident after the items were redistributed into unrelated blocks. Experiment 3 combined this design with cathodal or sham transcranial direct current stimulation (tDCS) over the LIFG. Planned comparisons showed that cathodal stimulation slowed naming of initially related items both within related blocks and after redistribution into unrelated blocks; corresponding comparisons for items named consistently in unrelated blocks were not significant. The similar patterns across two stimulation methods suggest that LIFG-mediated control may influence both selection under current competition and subsequent retrieval of previously competing words. These findings could be accommodated within a hybrid account in which working memory supports context-guided selection and selection-related control helps recalibrate lexical accessibility, limiting the carryover of interference into subsequent naming.

Pulsed infrared neural stimulation (INS, 1875nm the peak of energy absorption by water) is a non-viral method developed to activate single submillimeter sites in the brain. When used in ultrahigh-field fMRI, it reveals functionally specific brain-wide columnar networks comprising synaptically activated nodes. INS is non-damaging and effective for use in the human cortex and is useful for neural and behavioral neuromodulation in primates. To investigate how physiological state influences its cellular effects, we performed in vivo two-photon calcium imaging with GCaMP6s in mice and tracked identified cortical neurons in awake vs anesthetized states. Across the tested radiant exposures, INS-evoked responses differed markedly between states: under anesthesia, stimulation produced predominantly positive-going calcium responses, whereas during wakefulness the same identified neurons exhibited negative-going responses. Pharmacological manipulation of this baseline level by GABAergic signaling shifted response polarity in opposite directions: picrotoxin under anesthesia produced awake-like negative responses, whereas muscimol during wakefulness produced anesthetized-like positive responses. Trial-by-trial analyses further showed that the relationship between pre-stimulus baseline level and INS-evoked response depended on physiological state. Because INS relies on transient tissue heating, we also developed an in situ EGFP-based calibration approach to estimate temperature-related fluorescence changes. These fluoro-thermal contributions were modest at lower radiant exposures and became increasingly important at higher exposures, particularly near the fiber pathway. The low-intensity results are consistent with, but do not establish, a state-dependent feed-forward inhibitory framework. Together, these findings show that the neuronal response to focal INS is shaped by ongoing brain state and provide a practical framework for separating state-dependent calcium responses from temperature-related fluorescence effects, making INS a potentially versatile tool for neuroscience and clinical applications.

Reward operates as a cycle in which a stimulus produces a pleasure response, and the degree of pleasure experienced reinforces the behaviours that lead back to it. Music provides a useful model for examining this cycle because it is intrinsically pleasurable, can be learned, and engages reward-related frontostriatal circuitry that overlaps with circuitry involved in primary and secondary rewards, such as food, sex, and money. Transcranial magnetic stimulation (TMS), a non-invasive stimulation method, has been shown to produce bidirectional effects on music-evoked pleasure by increasing or decreasing activity in cortical regions, such as the left dorsolateral prefrontal cortex (DLPFC), that are functionally connected to subcortical regions, including the striatum. Here, we further characterize the reward cycle by incorporating TMS into a paradigm that combines musical pleasure ratings with an early musical skill acquisition task. In a within-subjects, counterbalanced crossover design, 23 participants with 2-10 years of musical experience received intermittent TBS (iTBS; excitatory) and continuous TBS (cTBS; inhibitory) over the left DLPFC in separate sessions. Participants rated the pleasantness of short piano melodies before stimulation (T0), immediately afterwards (T1), and 24 hours later (T2). After stimulation, they learned to play the melodies, and pitch and rhythm accuracy were assessed during three performance phases, namely acquisition, immediately after acquisition, and 24 hours later. Liking did not differ between conditions at T1; however, the increase in liking from baseline (T0) to T2 was significantly larger following iTBS than cTBS, a divergence that emerged across the 24-hour interval spanning both learning and sleep. Pitch and rhythm accuracy did not differ between conditions at any phase, despite improvement across trials in both. These results indicate that TMS to the left DLPFC can produce delayed, condition-dependent shifts in musical liking without a parallel change in early skill acquisition.

We investigated how auditory and visual presentation of small numerical magnitudes and non- numerical magnitudes are passively processed at the neural level. Earlier research suggests automatic processing of quantities occurs rapidly in the brain. However, there are no studies on passive, pre-attentive change detection of magnitudes utilizing mismatch negativity (MMN) across sensory modalities in same participants, important to understand amodal processing of magnitudes. We recorded EEG in passive auditory and visual multi-feature oddball and control paradigms from the same adult individuals (N=104/105, respectively). In the auditory paradigm, the standard stimulus was a 2-part sound, while the deviant stimuli varied in frequency, intensity, gap length, and number of sounds (1-part and 3-part stimuli). In the visual paradigm, the standard stimulus was a dot array containing two medium-sized dots, while the deviant stimuli varied in numerosity (1 or 3 dots) and dot size (small or large). The results for the auditory paradigm showed significant MMN across all features, including comparisons with deviant-alone control stimuli, except for the 2-part vs. 1-part contrast. The results for the visual paradigm suggested differences in processing across all features apart from large and medium-size stimuli. These results replicate earlier MMN findings that the brain distinguishes pre-attentively changes in sound frequency, amplitude and gap. Auditorily presented small numerical magnitudes also showed pre-attentive processing but less robustly to the contrast 2 vs. 1. Visual pre-attentive processing of small numerical magnitudes was also observed. Together these findings could be interpreted to support the existence of abstract, pre- attentive processing of numerical magnitudes. Highlights* Auditory and visual processing of numerical and non-numerical magnitudes was examined with EEG * Auditory non-numerical magnitudes and medium vs. small dots replicated earlier MMN studies * aMMN and vMMN showed pre-attentive processing of changes in small numerosities 2 vs. 3 and 2 vs. 1 * 2 vs. 1 tone processing was less robust than 2 vs. 3 or the processing of the visual contrasts * The brain processes changes in small non-symbolic magnitudes pre-attentively

Humans routinely encounter speech in languages they have never heard, yet how the brain responds to such input and whether bilingual experience shapes this response remains unknown. Here, we used electroencephalography (EEG) and temporal response function (TRF) modeling to examine cortical tracking of the speech envelope in 24 English-monolingual and 24 English-Mandarin bilingual adults. Participants listened to naturally produced continuous speech in three languages: English (familiar to all), Mandarin (familiar to bilinguals only), and Vietnamese (unfamiliar to all). We report two main findings. First, both monolinguals and bilinguals showed enhanced cortical tracking for unfamiliar relative to familiar languages, evidenced by higher EEG prediction accuracy (PA). Monolinguals showed enhanced tracking for both Mandarin and Vietnamese, whereas bilinguals showed enhancement only for Vietnamese, consistent with Mandarin being a familiar language for this group. This finding suggests that enhanced cortical encoding of unfamiliar speech is a general property of the listening brain, not a signature of listening to a non-native language or reduced language proficiency. Second, bilinguals strikingly showed stronger cortical tracking than monolinguals overall, in both PA and TRF peak weights, with the TRF peak weight advantage present across all three languages, suggesting a difference in how bilingual experience shapes the neural encoding of speech. These findings have implications for understanding how the brain navigates the linguistic diversity of everyday life in an increasingly global, multilingual world.

Reading behaviour is sensitive to contextual demands. For example, when reading to study or answer questions, readers strategically allocate more attention to goal-relevant sections, read slower, and regress more frequently to extract specific information based on task demands. This suggests that readers flexibly adapt their strategies according to goals and situational constraints. However, the neurocognitive mechanisms supporting this flexibility remain unclear. To test this, we combined eye-tracking with EEG during naturalistic reading and examined how short-term reading goals modulated the neural tracking of hierarchical linguistic features at the orthographic (orthographic neighbourhood size), lexical (word frequency), and contextual-semantic (Surprisal) levels. Forty native English speakers read narratives in three goal conditions: Baseline (no goal), Proofreading (detect spelling errors), and Comprehension (attend to content). Fixation-aligned word-level EEG activity was modelled using multivariate temporal response function to estimate the strength of feature-specific neural tracking. Orthographic tracking was significantly enhanced during Proofreading relative to Baseline, and predicted better Proofreading accuracy. Conversely, stronger frequency tracking predicted better Comprehension accuracy. Contextual-semantic tracking was not modulated by task goal. These findings suggest that reading goals selectively bias neural processing towards linguistic features (sublexical vs. lexical) that support successful task performance, providing evidence for short-term functional plasticity in linguistic processing and supporting a flexible predictive processing account of goal-directed reading.

Understanding how native speakers and second language (L2) learners process language differently is fundamental to theories of language acquisition, comprehension, and use. A central debate in this literature concerns the inconsistent findings in emotional prosody processing between native speakers and L2 learners, partly attributable to stimulus lexicality: some studies use real words, whereas others use pseudowords. To resolve this discrepancy, we measured fMRI responses in 15 native speakers and 15 L2 learners while they listened to Mandarin real-word and pseudoword stimuli. Both groups engaged in overlapping auditory, cognitive, and affective regions, including the auditory cortex, inferior frontal cortex, superior temporal cortex, and the temporoparietal junction. However, the two groups showed distinct responses depending on lexicality: native speakers showed stronger recruitment of temporal regions for pseudowords, whereas L2 learners showed greater frontoparietal activation for real words. These patterns were consistent across positive and negative prosody conditions. Furthermore, among L2 learners, higher proficiency was associated with greater frontal activation for real words, but not pseudowords. Together, these findings demonstrate that the differences between native speakers and L2 learners depend critically on stimulus lexicality, highlighting the role of lexicality in bilingual emotion processing.

Adaptive behaviour requires the flexible allocation of attention between sensory information arising from the external environment (exteroception) and signals originating within the body (interoception). While the neural mechanisms supporting exteroceptive attention have been extensively characterised, considerably less is known about how attention is allocated between competing interoceptive and exteroceptive sources of information. To address this question, we used functional magnetic resonance imaging (fMRI) to compare cardiac interoceptive attention during heartbeat counting with a carefully matched visual target counting task. Importantly, external visual input was held constant during both tasks, and behavioural accuracy and subjective confidence ratings for task difficulty did not differ significantly between conditions. This provided a controlled comparison in which attention was selectively allocated between internal bodily signals and external sensory information. Cardiac interoceptive and visual exteroceptive attention engaged largely distinct cortical networks. Cardiac interoceptive attention recruited a distributed insula-centred network supporting interoceptive processing and cognitive control. In contrast, visual target counting engaged a dorsal frontoparietal attention network and selectively shaped activity within visual cortex, enhancing regions representing task-relevant central visual information while suppressing regions representing task-irrelevant peripheral visual information. Despite this functional segregation, activity within these systems was not independent of where attention was directed. Exteroceptive attention suppressed activity within the posterior insula, suggesting down-regulation of interoceptive processing. Conversely, peripheral visual regions remained suppressed during interoceptive attention, suggesting that externally directed sensory processing is also down-regulated when attention is directed towards the body. More accurate heartbeat counting was additionally associated with less engagement of the right inferior parietal lobule, consistent with reduced bottom-up attentional capture by external sensory information. Together, these findings are consistent with competitive allocation of attentional resources between neural systems supporting internal bodily signals and external sensory information. More broadly, they provide a system-level account of how the human brain flexibly balances internal and external information during goal-directed behaviour.

Inhibitory control is an essential executive function that encompasses both the stopping of an action in response to an unexpected stop signal (reactive response inhibition) and slowing of responses in anticipation of stopping (proactive response inhibition). Fronto-basal-ganglia circuits are thought to differentially contribute to response inhibition, with the indirect pathway implicated in proactive inhibition. Given the high expression of dopamine D2 receptors in the indirect pathway, pharmacological blockade of D2 receptors is expected to impact proactive inhibition, as indicated by response times on Go trials. The current study aimed to investigate this experimentally and study the effect of 600 mg of sulpiride, a D2 receptor antagonist, on behavioural and electrophysiological measures of proactive and reactive inhibition in humans. Human participants (N=24) completed an anticipated response version of the stop-signal task on either sulpiride or placebo in a double-blind within-subjects design. Sulpiride led to increased variability of Go response times and attenuation of the frontocentral negativity/readiness potential, considered to be a signature of proactive inhibition. In contrast, sulpiride had no effect on stop-signal reaction time or event-related potential components associated with reactive inhibition. These findings suggest that D2 receptor blockade selectively alters processes involved in proactive inhibition while leaving reactive inhibition unaffected, consistent with a key role for the indirect basal ganglia pathway in proactive response inhibition.

Mapping brain connections is paramount in neuroscience. Lacking has been a method that can systematically map mesoscale (<1mm) connections in the brain in vivo at brainwide scale. Mesoscale mapping is particularly important for NHPs in which information is represented in submillimeter clusters (e.g. cortical columns, striosomes, thalamic rods). Here, we present a method called INS-fMRI, which comprises optical stimulation of single sites in the brain using pulsed Infrared Neural Stimulation (INS), coupled with mapping of functionally connected sites in the brain using ultrahigh field fMRI. It is the only method available for mapping mesoscale connections rapidly (multiple networks mapped within single MRI sessions), systematically (allowing comparison of networks within single individuals), in vivo (no animal sacrifice needed), at whole brain scale, and without viral transfection. This method has broad applicability to a wide range of neuroscience questions. It can be used at any brain site, on different animal models, and on different MRI platforms. The ability to probe circuits repeatedly within single individuals also opens doors for studying changes in mesoscale circuits over time (e.g. for development, aging, disease studies). In addition, as this method circumvents the need for viral transfection, there is exciting potential for human clinical application.