Functional Organization Research Articles

Enhanced efficiency in the bilingual brain through the inter-hemispheric cortico-cerebellar pathway in early second language acquisition

Bilingualism has a profound impact on the structure and function of the brain, but it is not yet well understood how this experience influences brain functional organization. We examine a large sample (151 participants) of monolinguals and bilinguals with varied age of second language acquisition, who underwent resting-state functional magnetic brain imaging. Whole-brain network analyses reveal higher global efficiency in bilingual individuals than monolinguals, indicating enhanced functional integration in the bilingual brain. Moreover, the age at which the second language was acquired correlated with this increased efficiency, suggesting that earlier exposure to a second language has lasting positive effects on brain functional organization. Further investigation using the network-based statistics approach indicates that this effect is primarily driven by heightened functional connectivity between association networks and the cerebellum. These findings show that the timing of bilingual learning experience alters the brain functional organization at both global and local levels.

Thalamic Roles in Conscious Perception Revealed by Low-Intensity Focused Ultrasound Neuromodulation.

The neural basis of conscious perception remains incompletely understood. While cortical mechanisms of conscious content have been extensively investigated, the role of subcortical structures, including the thalamus, remains less explored. We aim to elucidate the causal contributions of different thalamic regions to conscious perception using transcranial low-intensity focused ultrasound (LIFU) neuromodulation. We hypothesize that modulating different thalamic regions would result in distinct perceptual outcomes. We apply LIFU in human volunteers to investigate region-specific and sonication parameter-dependent effects. We target anterior (transmodal-dominant) and posterior (unimodal-dominant) thalamic regions, further divided into ventral and dorsal regions, while participants perform a near-threshold visual perception task. Task performance is evaluated using Signal Detection Theory metrics. We find that the high duty cycle stimulation of the ventral anterior thalamus enhanced object recognition sensitivity. We also observe a general (i.e., region-independent) effect of LIFU on decision bias (i.e., a tendency toward a particular response) and object categorization accuracy. Specifically, high duty cycle stimulation decreases categorization accuracy, whereas low duty cycle shifts decision bias towards a more conservative stance. In conclusion, our results provide causal insight into the functional organization of the thalamus in shaping human visual experience and highlight the unique role of the transmodal-dominant ventral anterior thalamus.

Multi-echo Acquisition and Thermal Denoising Advances Precision Functional Imaging.

The characterization of individual functional brain organization with Precision Functional Mapping has provided important insights in recent years in adults. However, little is known about the ontogeny of inter-individual differences in brain functional organization during human development. Precise characterization of systems organization during periods of high plasticity is likely to be essential for discoveries promoting lifelong health. Obtaining precision fMRI data during development has unique challenges that highlight the importance of establishing new methods to improve data acquisition, processing, and analysis. Here, we investigate two methods that can facilitate attaining this goal: multi-echo (ME) data acquisition and thermal noise removal with Noise Reduction with Distribution Corrected (NORDIC) principal component analysis. We applied these methods to precision fMRI data from adults, children, and newborn infants. In adults, both ME acquisitions and NORDIC increased temporal signal to noise ratio (tSNR) as well as the split-half reliability of functional connectivity matrices, with the combination helping more than either technique alone. The benefits of NORDIC denoising replicated in both our developmental samples. ME acquisitions revealed longer and more variable T2* relaxation times across the brain in infants relative to older children and adults, leading to major differences in the echo weighting for optimally combining ME data. This result suggests ME acquisitions may be a promising tool for optimizing developmental fMRI, albeit application in infants needs further investigation. The present work showcases methodological advances that improve Precision Functional Mapping in adults and developmental populations and, at the same time, highlights the need for further improvements in infant specific fMRI.

High-resolution 7T fMRI reveals the visual zone of the human claustrum

Abstract The claustrum is a thin grey matter structure located between the insular cortex and the putamen. The function of the claustrum is largely unknown with diverse hypotheses ranging from multisensory integration and consciousness to attention and cognitive control. Much research on the function of the claustrum relies on invasive techniques in animal models, as the claustrum’s uniquely thin shape makes it difficult to image non-invasively in human subjects. In the current proof-of-concept study, we used high-resolution ultra-high field (7 Tesla) functional magnetic resonance imaging (fMRI) to measure activity in the human claustrum during the processing of naturalistic stimuli. We presented short video clips as visual only, auditory only or audiovisual conditions while participants performed a central fixation task. We found distinct visual responses in both the left and the right claustrum at a consistent spatial location across participants, hemispheres and sessions. We also found deactivations in response to auditory stimulation. These deactivations were confined to the right claustrum and did not overlap with visual activity. The deactivation in response to auditory stimulation demonstrates the complexity of claustrum’s functional organization and suggests functional differentiation within the claustrum. This is the first study to demonstrate sensory-specific effects within the human claustrum. It opens the possibility for studying the claustrum’s role in higher-level aspects of sensory processing in humans.

The relationship between white matter architecture and language lateralisation in the healthy brain.

Interhemispheric anatomical differences have long been thought to be related to language lateralisation. Previous studies have explored whether asymmetries in the diffusion characteristics of white matter language tracts are consistent with language lateralisation. These studies, typically with smaller cohorts, yielded mixed results. This study investigated whether connectomic analysis of quantitative anisotropy (QA) and shape features of white matter tracts across the whole brain are associated with language lateralisation. We analysed 1040 healthy individuals (562 females) from the Human Connectome Project database. Hemispheric language dominance for each participant was quantified using a laterality quotient (LQ) derived from fMRI activation in regions of interest (ROIs) associated with a language comprehension task compared against a math task. A linear regression model was used to examine the relationship between structural asymmetry and functional lateralisation. Connectometry revealed a significant negative correlation between LQs and QA of corpus callosum tracts, indicating that higher QA in these regions is associated with bilateral and right-hemisphere language representation in frontal and temporal regions, respectively. Left language laterality in temporal lobe was significantly associated with longer right inferior fronto-occipital fasciculus (IFOF) and forceps minor tracts. These results suggest that diffusion measures of microstructural architecture as well as geometrical features of reconstructed white matter tracts play a role in language lateralisation. People with increased dependence on right or both frontal hemispheres for language processing may have more developed commissural fibres, which may support more efficient interhemispheric communication.Significance statement The left cerebral hemisphere is dominant for language functions in most people. In some healthy people, language functions are lateralised to the right hemisphere or distributed across both hemispheres. The anatomy underlying patterns of hemispheric language dominance are not well established. Emerging evidence suggests that white matter connectivity and architecture is an important feature of cortical functional organisation. In this work, we report that people who have language functions distributed across both hemispheres have greater inter-hemispheric connectivity compared to lateralised people. Our findings provide further insights into the anatomical basis of language function and may have wider clinical implications.

Functional role of area 8A in the posterior dorsolateral frontal region of the human brain: A single case study.

Area 8A has traditionally been considered to be the frontal eye field (FEF), i.e. the area for the motor production of eye movements. However, recent research has shown that the FEF lies posteriorly in premotor area 6. Research in macaque monkeys has demonstrated that, in contrast to premotor area 6, which is involved in the production of motor actions, area 8A is implicated in the cognitive allocation of attention to stimuli based on instruction cues. The aim of the present study was to elucidate the specific cognitive role of area 8A by examining a unique patient with a lesion restricted to area 8A, i.e. sparing the premotor cortex. This right-handed male patient underwent neuropsychological assessment and testing on two conditional associative-learning tasks: the motor hand conditional associative-learning task (MCALT) assessing the selection of motor actions based on instruction cues and the visual conditional associative-learning task (VCALT) assessing the selection of visual stimuli based on instruction cues. The patient's performance on the VCALT was significantly impaired compared to control subjects, but performance on the MCALT and on an Eye Movement Control Task was preserved. The present study provides evidence that area 8A is critical for the cognitive process regulating the allocation of attention to different stimuli in the environment, but not in the production of eye movements. These findings enhance understanding of the functional organization of the posterior dorsolateral frontal region in the human brain and suggest a specialized role of area 8A in high-level cognitive processes.

Astrocytes contribute to the functional differentiation of the hippocampal longitudinal axis during reward and aversion processing in the adult male rat

This study aims to investigate whether glial cells, in particular putative astrocytes, contribute to functional distinctions between the dorsal (DH), intermediate (IH), and ventral (VH) hippocampus. To evaluate this, we performed three different behavioral tasks (i.e., Morris water maze; MWM, Passive avoidance; PA, T-maze place preference; TPP) to determine whether the DH, IH, and VH are necessary for each task. Sensitivity of behavioral tasks was confirmed using lidocaine (2 %, 1 μl) reversible inactivation. Subsequently, we examined the effects of silencing astrocytes, using fluorocitrate (FC, 1 mM/1 μl), into the DH, IH, and VH on these tasks. The effects of drugs were examined separately. We observed that injection of FC into the DH resulted in a significant impairment in MWM performance. In contrast, while FC injections into the IH or VH did not prevent platform localization during the acquisition phase, rats showed difficulty recalling the target zone during the retrieval phase. In the PA test, FC injection into the VH impaired task learning and memory. During the acquisition phase, FC injection into the DH or IH did not differ from the control in the number of shocks; however, during retrieval, there was a significant decrease in the latency before entering the dark chamber. The TPP test performance was impaired by FC injection in the IH. In sum, we show that glial cells, especially astrocytes in specific functional regions of the hippocampus, play distinct roles in processing aversive and rewarding experiences and contribute to the functional organization of the hippocampal longitudinal axis.

A spatially constrained independent component analysis jointly informed by structural and functional network connectivity

Abstract There are a growing number of neuroimaging studies motivating joint structural and functional brain connectivity. The brain connectivity of different modalities provides an insight into brain functional organization by leveraging complementary information, especially for brain disorders such as schizophrenia. In this paper, we propose a multimodal independent component analysis (ICA) model that utilizes information from both structural and functional brain connectivity guided by spatial maps to estimate intrinsic connectivity networks (ICNs). Structural connectivity is estimated through whole-brain tractography on diffusion-weighted MRI (dMRI), while functional connectivity is derived from resting-state functional MRI (rs-fMRI). The proposed structural-functional connectivity and spatially constrained ICA (sfCICA) model estimates ICNs at the subject level using a multiobjective optimization framework. We evaluated our model using synthetic and real datasets (including dMRI and rs-fMRI from 149 schizophrenia patients and 162 controls). Multimodal ICNs revealed enhanced functional coupling between ICNs with higher structural connectivity, improved modularity, and network distinction, particularly in schizophrenia. Statistical analysis of group differences showed more significant differences in the proposed model compared with the unimodal model. In summary, the sfCICA model showed benefits from being jointly informed by structural and functional connectivity. These findings suggest advantages in simultaneously learning effectively and enhancing connectivity estimates using structural connectivity.

Impaired brain ability of older adults to transit and persist to latent states with well-organized structures at wakeful rest.

The intrinsic brain functional network organization continuously changes with aging. By integrating spatial and temporal information, the process of how brain networks temporally reconfigure and remain well-organized spatial structure largely reflects the brain function, thereby holds the potential to capture its age-related declines. In this study, we examined the spatiotemporal brain dynamics from resting-state functional Magnetic Resonance Imaging (fMRI) data of healthy young and older adults using a Hidden Markov Model (HMM). Six brain states were generated by HMM, with the young group showing higher fractional occupancy and mean dwell time in states 1, 3, and 4 (SY1, SY2 and SY3), and the older group in states 2, 5, and 6 (SO1, SO2 and SO3). Importantly, comparisons of transition probabilities revealed that the older group showed a reduced brain ability to transition into states dominated by the younger group, as well as a diminished capacity to persist in them. Moreover, graph analysis revealed that these young-specific states exhibited higher modularity and k-coreness. Collectively, these findings suggested that the older group showed impaired brain ability of both transition into and sustain well spatially organized states. This emphasized that the temporal changes in brain state organization, rather than its static mode, could be a key biomarker for detecting age-related functional decline. These insights may pave the way for targeted interventions aimed at mitigating cognitive decline in the aging population.

Mitochondrial Structure, Dynamics, and Physiology: Light Microscopy to Disentangle the Network.

Mitochondria serve as energetic and signaling hubs of the cell: This function results from the complex interplay between their structure, function, dynamics, interactions, and molecular organization. The ability to observe and quantify these properties often represents the puzzle piece critical for deciphering the mechanisms behind mitochondrial function and dysfunction. Fluorescence microscopy addresses this critical need and has become increasingly powerful with the advent of superresolution methods and context-sensitive fluorescent probes. In this review, we delve into advanced light microscopy methods and analyses for studying mitochondrial ultrastructure, dynamics, and physiology, and highlight notable discoveries they enabled.

Effects of aerobic, strength, and combined exercise on cognitive functions in older adults: a systematic review

Introduction: Aging is associated with a decline in cognitive functions, increasing the risk of neurocognitive impairment and limitation of activities of daily living and participation. Previous literature has pointed to physical exercise as an effective intervention; however, its characteristics still need to be specified. Objective: The aim was to synthesize the appropriate intensity, duration, frequency, and type of exercise for different types of cognitive variables. Method: A systematic review was carried out according to PRISMA, using three databases: PubMed, Scopus, and Web of Science. Experimental longitudinal studies were included, whether randomised or not, which performed physical exercise and with a control group in people over 60 years of age. Methodological quality was assessed using the PEDro scale. Results: The results yielded 11 studies finding significant improvements in all of them after performing the intervention (7 of aerobic exercise, 3 of resistance exercise and 2 of combined exercise) finding improvements in attention, memory, processing speed, executive function, inhibition, concentration, perceptual reasoning, orientation, visuospatial perception, and visuomotor organisation. Conclusions: Physical exercise appears to be a beneficial intervention for cognition in older people, with aerobic exercise being the most studied, although further research is needed. The results could benefit decision-making in rehabilitation to work on cognition in cognitively healthy older people. Keywords: prevention; aging; cognition; cognitive impairment; rehabilitation.

Decoding sound content in the early visual cortex of aphantasic participants.

Listening to natural auditory scenes leads to distinct neuronal activity patterns in the early visual cortex (EVC) of blindfolded sighted and congenitally blind participants.1,2 This pattern of sound decoding is organized by eccentricity, with the accuracy of auditory information increasing from foveal to far peripheral retinotopic regions in the EVC (V1, V2, and V3). This functional organization by eccentricity is predicted by primate anatomical connectivity,3,4 where cortical feedback projections from auditory and other non-visual areas preferentially target the periphery of early visual areas. In congenitally blind participants, top-down feedback projections to the visual cortex proliferate,5 which might account for even higher sound-decoding accuracy in the EVC compared with blindfolded sighted participants.2 In contrast, studies in participants with aphantasia suggest an impairment of feedback projections to early visual areas, leading to a loss of visual imagery experience.6,7 This raises the question of whether impaired visual feedback pathways in aphantasia also reduce the transmission of auditory information to early visual areas. We presented auditory scenes to 23 blindfolded aphantasic participants. We found overall decreased sound decoding in early visual areas compared to blindfolded sighted ("control") and blind participants. We further explored this difference by modeling eccentricity effects across the blindfolded control, blind, and aphantasia datasets, and with a whole-brain searchlight analysis. Our findings suggest that the feedback of auditory content to the EVC is reduced in aphantasic participants. Reduced top-down projections might lead to both less sound decoding and reduced subjective experience of visual imagery.

Levodopa therapy affects brain functional network dynamics in Parkinson's disease

Levodopa (L-dopa) therapy is the most effective pharmacological treatment for motor symptoms of Parkinson's disease (PD). However, its effect on brain functional network dynamics is still unclear. Here, we recruited 26 PD patients and 24 healthy controls, and acquired their resting-state functional MRI data before (PD-OFF) and after (PD-ON) receiving 400 mg L-dopa. Using the independent component analysis and the sliding-window approach, we estimated the dynamic functional connectivity (dFC) and examined the effect of L-dopa on the temporal properties of dFC states, the variability of dFC and functional network topological organization. We found that PD-ON showed decreased mean dwell time in sparsely connected State 2 than PD-OFF, the transformation of the dFC state is more frequent and the variability of dFC was decreased within the auditory network and sensorimotor network in PD-ON. Our findings provide new insights to understand the dynamic neural activity induced by L-dopa therapy in PD patients.

Effects of Aerobic Exercise on Vascular Wall Thickness: A Meta-Analysis of Pre-Clinical Trials on Rat Model.

Exercise instigates adaptations in structural as well as functional organisation of the body at tissue and organ levels. However, the effect of exercise on vascular wall morphology is still under investigation. The objective of the review is to provide a meta-analysis of data from the previously published research to provide compiled analysis to determine the effect of exercise on the thickness of large-sized vessel walls. This meta-analysis was executed at the Ziauddin College of Rehabilitation Sciences with an extensive literature search using databases and search engines such as Pubmed, CINAHL, Web of Science, Scopus, and Google Scholar between September 2022 and January 2023. Studies were appraised according to an estimate of mean difference and pooled effect size was calculated using a random effect model. The risk of bias was also calculated using SYRCLE's risk of bias tool and CAMARADES. Overall, five eligible pre-clinical trials using rat models with pertinent data to determine the effect of exercise on vessel wall thickness were included in the meta-analysis. The results showed that aerobic exercise significantly reduced the vessel wall thickness (SMD -0.854 5%; CI: -1.365 to -0.344; p <0.001). Moreover, no significant publication bias was found through funnel plot and statistical test (Egger's p = 0.276; Begg's p = 0.624). However, an extensive review of the literature currently available on the topic has shown mixed findings that are consistent with the study and vice versa. Therefore, it indicated the need for sub-group analysis with different types of exercises for more peculiar clinical approaches. Key Words: Morphometry, Animal studies meta-analysis, Media thickness, Physical activity, Vascular morphology.

A hierarchical atlas of the human cerebellum for functional precision mapping

The human cerebellum is activated by a wide variety of cognitive and motor tasks. Previous functional atlases have relied on single task-based or resting-state fMRI datasets. Here, we present a functional atlas that integrates information from seven large-scale datasets, outperforming existing group atlases. The atlas has three further advantages. First, the atlas allows for precision mapping in individuals: the integration of the probabilistic group atlas with an individual localizer scan results in a marked improvement in prediction of individual boundaries. Second, we provide both asymmetric and symmetric versions of the atlas. The symmetric version, which is obtained by constraining the boundaries to be the same across hemispheres, is especially useful in studying functional lateralization. Finally, the regions are hierarchically organized across three levels, allowing analyses at the appropriate level of granularity. Overall, the present atlas is an important resource for the study of the interdigitated functional organization of the human cerebellum in health and disease.

Neurocardiology: translational advancements and potential.

In our original white paper published in the The Journal of Physiology in 2016, we set out our knowledge of the structural and functional organization of cardiac autonomic control, how it remodels during disease, and approaches to exploit such knowledge for autonomic regulation therapy. The aim of this update is to build on this original blueprint, highlighting the significant progress which has been made in the field since and major challenges and opportunities that exist with regard to translation. Imbalances in autonomic responses, while beneficial in the short term, ultimately contribute to the evolution of cardiac pathology. As our understanding emerges of where and how to target in terms of actuators (including the heart and intracardiac nervous system (ICNS), stellate ganglia, dorsal root ganglia (DRG), vagus nerve, brainstem, and even higher centres), there is also a need to develop sensor technology to respond to appropriate biomarkers (electrophysiological, mechanical, and molecular) such that closed-loop autonomic regulation therapies can evolve. The goal is to work with endogenous control systems, rather than in opposition to them, to improve outcomes.

Enhanced Correlation between Arousal and Infra-Slow Brain Activity in Experienced Meditators.

Meditation induces changes in the nervous system, which presumably underpin positive psychological and physiological effects. Such neural changes include alterations in the arousal fluctuation, as well as in infraslow brain activity (ISA, <0.1 Hz). Furthermore, it is known that fluctuations of arousal over time correlate with the oscillatory phase of ISA. However, whether this arousal-ISA correlation changes after meditation practices remains unanswered.; Methods: The present study aims to address this question by analyzing a publicly available electroencephalogram (EEG) dataset recorded during meditation sessions in the groups of experienced meditators and novices. The arousal fluctuation is measured by galvanic skin responses (GSR), and arousal-ISA correlations are measured by phase synchronization between GSR and EEG ISAs.; Results: While both groups exhibit arousal-ISA correlations, experienced meditators display higher correlations than novices. These increased arousal-ISA correlations in experienced meditators manifest more clearly when oscillatory phase differences between GSR and EEG ISAs are either 0 or π radians. As such, we further investigate the characteristics of these phase differences with respect to spatial distribution over the brain. We found that brain regions with the phase difference of either 0 or π radians form distinct spatial clusters, and that these clusters are spatially correlated with functional organization estimated by the principal gradient, based on functional connectivity.; Conclusions: Since increased arousal-ISA correlations reflect enhanced global organization of the central and autonomic nervous systems, our findings imply that the positive effects of meditation might be mediated by enhanced global organization of the nervous system.

Expression of Smyd1b_tv1 by Alternative Splicing in Cardiac Muscle is Critical for Sarcomere Organization in Cardiomyocytes and Heart Function.

Smyd1, a member of the Smyd lysine methyltransferase family, plays an important role in myofibrillogenesis of skeletal and cardiac muscles. Loss of Smyd1b (a Smyd1 ortholog) function in zebrafish results in embryonic death from heart malfunction. smyd1b encodes two isoforms, Smyd1b_tv1 and Smyd1b_tv2, differing by 13 amino acids due to alternative splicing. While smyd1 alternative splicing is evolutionarily conserved, the isoform-specific expression and function of Smyd1b_tv1 and Smyd1b_tv2 remained unknown. Here we analyzed their expression and function in skeletal and cardiac muscles. Our analysis revealed expression of smyd1b_tv1 predominately in cardiac and smyd1b_tv2 in skeletal muscles. Using zebrafish models expressing only one isoform, we demonstrated that Smyd1b_tv1 is essential for cardiomyocyte differentiation and fish viability, whereas Smyd1b_tv2 is dispensable for heart development and fish survival. Cellular and biochemical analyses revealed that Smyd1b_tv1 differs from Smyd1b_tv2 in protein localization and binding with myosin chaperones. While Smyd1b_tv2 diffused in the cytosol of muscle cells, Smyd1b_tv1 was localized to M-lines and essential for sarcomere organization in cardiomyocytes. Co-IP analysis revealed a stronger binding of Smyd1b_tv1 with chaperones and cochaperones compared with Smyd1b_tv2. Collectively, these findings highlight the nonequivalence of Smyd1b isoforms in cardiomyocyte differentiation, emphasizing the critical role of Smyd1b_tv1 in cardiac function.

Peculiar k-mer Spectra Are Correlated with 3D Contact Frequencies and Breakpoint Regions in the Human Genome.

It is widely accepted that the 3D chromatin organization in human cell nuclei is not random and recent investigations point towards an interactive relation of epigenetic functioning and chromatin (re-)organization. Although chromatin organization seems to be the result of self-organization of the entirety of all molecules available in the cell nucleus, a general question remains open as to what extent chromatin organization might additionally be predetermined by the DNA sequence and, if so, if there are characteristic differences that distinguish typical regions involved in dysfunction-related aberrations from normal ones, since typical DNA breakpoint regions involved in disease-related chromosome aberrations are not randomly distributed along the DNA sequence. Highly conserved k-mer patterns in intronic and intergenic regions have been reported in eukaryotic genomes. In this article, we search and analyze regions deviating from average spectra (ReDFAS) of k-mer word frequencies in the human genome. This includes all assembled regions, e.g., telomeric, centromeric, genic as well as intergenic regions. A positive correlation between k-mer spectra and 3D contact frequencies, obtained exemplarily from given Hi-C datasets, has been found indicating a relation of ReDFAS to chromatin organization and interactions. We also searched and found correlations of known functional annotations, e.g., genes correlating with ReDFAS. Selected regions known to contain typical breakpoints on chromosomes 9 and 5 that are involved in cancer-related chromosomal aberrations appear to be enriched in ReDFAS. Since transposable elements like ALUs are often assigned as major players in 3D genome organization, we also studied their impact on our examples but could not find a correlation between ALU regions and breakpoints comparable to ReDFAS. Our findings might show that ReDFAS are associated with instable regions of the genome and regions with many chromatin contacts which is in line with current research indicating that chromatin loop anchor points lead to genomic instability.

Charting the brain networks of impulsivity: Meta-analytic synthesis, functional connectivity modelling, and neurotransmitter associations

Abstract Impulsivity is a multi-dimensional construct that plays a crucial role in human behaviour and is believed to be a transdiagnostic marker of several psychiatric disorders. However, given its multi-faceted nature, investigations of its neural correlates are challenging and systematic comparisons across dimensions are lacking. In this study, we used a comprehensive multi-modal approach to investigate the functional network organisation of two dimensions in which impulsivity manifests: decision-making and response inhibition. Activation likelihood estimation (ALE) meta-analyses of task-based fMRI studies within each dimension identified two distinct and non-overlapping functional systems. One located in the default-mode network, associated with value-based judgements and goal-directed decision-making, and the other distributed across higher-order networks associated with cognitive control. Resting-state functional connectivity revealed the two systems were organised into four specialised communities of default-mode, cingulo-insular, fronto-parietal, and temporal regions. Finally, given the widespread use of neurotransmitter-acting medication to treat conditions with impulsive symptoms, we investigated the association between this organisation and neurochemistry and found that integration across communities was associated with PET-derived serotonin receptor density. Our findings reinforce insights from previous behavioural research and provide substantial evidence for the multi-dimensional nature of impulsivity on the neural level. This highlights the necessity for a comprehensive dimensional ontology on all levels of investigation to address impulsivity in a transdiagnostic manner.