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How is the information-processing architecture of the human brain organised, and how does its organisation support consciousness? Here, we combine network science and a rigorous information-theoretic notion of synergy to delineate a 'synergistic global workspace', comprising gateway regions that gather synergistic information from specialised modules across the human brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the human brain's default mode network, whereas broadcasters coincide with the executive control network. We find that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information., Competing Interests: AL, PM, FR, JA, JP, RC, GW, PF, AO, LN, DM, DB, ES No competing interests declared, MC currently employed by Valence Labs. The work contributing to the manuscript was performed as part of his graduate studies at the University of Cambridge, and is in no way related to his employment at Valence Labs, (© 2023, Luppi et al.)

Disentangling how cognitive functions emerge from the interplay of brain dynamics and network architecture is among the major challenges that neuroscientists face. Pharmacological and pathological perturbations of consciousness provide a lens to investigate these complex challenges. Here, we review how recent advances about consciousness and the brain's functional organisation have been driven by a common denominator: decomposing brain function into fundamental constituents of time, space, and information. Whereas unconsciousness increases structure-function coupling across scales, psychedelics may decouple brain function from structure. Convergent effects also emerge: anaesthetics, psychedelics, and disorders of consciousness can exhibit similar reconfigurations of the brain's unimodal-transmodal functional axis. Decomposition approaches reveal the potential to translate discoveries across species, with computational modelling providing a path towards mechanistic integration., Competing Interests: Declaration of interests The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Functional interactions between brain regions can be viewed as a network, enabling neuroscientists to investigate brain function through network science. Here, we systematically evaluate 768 data-processing pipelines for network reconstruction from resting-state functional MRI, evaluating the effect of brain parcellation, connectivity definition, and global signal regression. Our criteria seek pipelines that minimise motion confounds and spurious test-retest discrepancies of network topology, while being sensitive to both inter-subject differences and experimental effects of interest. We reveal vast and systematic variability across pipelines' suitability for functional connectomics. Inappropriate choice of data-processing pipeline can produce results that are not only misleading, but systematically so, with the majority of pipelines failing at least one criterion. However, a set of optimal pipelines consistently satisfy all criteria across different datasets, spanning minutes, weeks, and months. We provide a full breakdown of each pipeline's performance across criteria and datasets, to inform future best practices in functional connectomics., (© 2024. The Author(s).)

Scientific theories on the functioning and dysfunction of the human brain require an understanding of its development-before and after birth and through maturation to adulthood-and its evolution. Here we bring together several accounts of human brain evolution by focusing on the central role of oxygen and brain metabolism. We argue that evolutionary expansion of human transmodal association cortices exceeded the capacity of oxygen delivery by the vascular system, which led these brain tissues to rely on nonoxidative glycolysis for additional energy supply. We draw a link between the resulting lower oxygen tension and its effect on cytoarchitecture, which we posit as a key driver of genetic developmental programs for the human brain-favoring lower intracortical myelination and the presence of biosynthetic materials for synapse turnover. Across biological and temporal scales, this protracted capacity for neural plasticity sets the conditions for cognitive flexibility and ongoing learning, supporting complex group dynamics and intergenerational learning that in turn enabled improved nutrition to fuel the metabolic costs of further cortical expansion. Our proposed model delineates explicit mechanistic links among metabolism, molecular and cellular brain heterogeneity, and behavior, which may lead toward a clearer understanding of brain development and its disorders., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

To explain how the brain orchestrates information-processing for cognition, we must understand information itself. Importantly, information is not a monolithic entity. Information decomposition techniques provide a way to split information into its constituent elements: unique, redundant, and synergistic information. We review how disentangling synergistic and redundant interactions is redefining our understanding of integrative brain function and its neural organisation. To explain how the brain navigates the trade-offs between redundancy and synergy, we review converging evidence integrating the structural, molecular, and functional underpinnings of synergy and redundancy; their roles in cognition and computation; and how they might arise over evolution and development. Overall, disentangling synergistic and redundant information provides a guiding principle for understanding the informational architecture of the brain and cognition., Competing Interests: Declaration of interests The authors report no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

What is the role of the brain's ongoing activity for cognition? The predominant perspectives associate ongoing brain activity with resting state, the default-mode network (DMN), and internally oriented mentation. This triad is often contrasted with task states, non-DMN brain networks, and externally oriented mentation, together comprising a "dual model" of brain and cognition. In opposition to this duality, however, we propose that ongoing brain activity serves as a neuronal baseline; this builds upon Raichle's original search for the default mode of brain function that extended beyond the canonical default-mode brain regions. That entails what we refer to as the "baseline model." Akin to an internal biological clock for the rest of the organism, the ongoing brain activity may serve as an internal point of reference or standard by providing a shared neural code for the brain's rest as well as task states, including their associated cognition. Such shared neural code is manifest in the spatiotemporal organization of the brain's ongoing activity, including its global signal topography and dynamics like intrinsic neural timescales. We conclude that recent empirical evidence supports a baseline model over the dual model; the ongoing activity provides a global shared neural code that allows integrating the brain's rest and task states, its DMN and non-DMN, and internally and externally oriented cognition.

Typical consciousness can be defined as an individual-specific stream of experiences. Modern consciousness research on dynamic functional connectivity uses clustering techniques to create common bases on which to compare different individuals. We propose an alternative approach by combining modern theories of consciousness and insights arising from phenomenology and dynamical systems theory. This approach enables a representation of an individual's connectivity dynamics in an intrinsically-defined, individual-specific landscape. Given the wealth of evidence relating functional connectivity to experiential states, we assume this landscape is a proxy measure of an individual's stream of consciousness. By investigating the properties of this landscape in individuals in different states of consciousness, we show that consciousness is associated with short term transitions that are less predictable, quicker, but, on average, more constant. We also show that temporally-specific connectivity states are less easily describable by network patterns that are distant in time, suggesting a richer space of possible states. We show that the cortex, cerebellum and subcortex all display consciousness-relevant dynamics and discuss the implication of our results in forming a point of contact between dynamical systems interpretations and phenomenology., (© 2022. The Author(s).)

The dynamic interplay of integration and segregation in the brain is at the core of leading theoretical accounts of consciousness. The human brain dynamically alternates between a sub-state where integration predominates, and a predominantly segregated sub-state, with different roles in supporting cognition and behaviour. Here, we combine graph theory and dynamic functional connectivity to compare resting-state functional MRI data from healthy volunteers before, during, and after loss of responsiveness induced with different concentrations of the inhalational anaesthetic, sevoflurane. We show that dynamic states characterised by high brain integration are especially vulnerable to general anaesthesia, exhibiting attenuated complexity and diminished small-world character. Crucially, these effects are reversed upon recovery, demonstrating their association with consciousness. Higher doses of sevoflurane (3% vol and burst-suppression) also compromise the temporal balance of integration and segregation in the human brain. Additionally, we demonstrate that reduced anticorrelations between the brain's default mode and executive control networks dynamically reconfigure depending on the brain's state of integration or segregation. Taken together, our results demonstrate that the integrated sub-state of brain connectivity is especially vulnerable to anaesthesia, in terms of both its complexity and information capacity, whose breakdown represents a generalisable biomarker of loss of consciousness and its recovery., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Investigating changes in brain function induced by mind-altering substances such as LSD is a powerful method for interrogating and understanding how mind interfaces with brain, by connecting novel psychological phenomena with their neurobiological correlates. LSD is known to increase measures of brain complexity, potentially reflecting a neurobiological correlate of the especially rich phenomenological content of psychedelic-induced experiences. Yet although the subjective stream of consciousness is a constant ebb and flow, no studies to date have investigated how LSD influences the dynamics of functional connectivity in the human brain. Focusing on the two fundamental network properties of integration and segregation, here we combined graph theory and dynamic functional connectivity from resting-state functional MRI to examine time-resolved effects of LSD on brain networks properties and subjective experiences. Our main finding is that the effects of LSD on brain function and subjective experience are non-uniform in time: LSD makes globally segregated sub-states of dynamic functional connectivity more complex, and weakens the relationship between functional and anatomical connectivity. On a regional level, LSD reduces functional connectivity of the anterior medial prefrontal cortex, specifically during states of high segregation. Time-specific effects were correlated with different aspects of subjective experiences; in particular, ego dissolution was predicted by increased small-world organisation during a state of high global integration. These results reveal a more nuanced, temporally-specific picture of altered brain connectivity and complexity under psychedelics than has previously been reported., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The human brain exhibits a rich functional repertoire in terms of complex functional connectivity patterns during rest and tasks. However, how this is developed upon a fixed structural anatomy remains poorly understood. Here we investigated the hypothesis that resting state functional connectivity and the manner in which it changes during tasks related to a set of underlying structural connections that promote optimal communication in the brain. We used a game-theoretic model to identify such optimal connections in the structural connectome of 50 healthy individuals and subsequently used the optimal structural connections to predict resting-state functional connectivity with high accuracy. In contrast, we found that nonoptimal connections accurately predicted functional connectivity during a working memory task. We further found that this balance between optimal and nonoptimal connections between brain regions was associated with a specific gene expression linked to neurotransmission. This multimodal evidence shows for the first time that structure-function relationships in the human brain are related to how brain networks navigate information along different white matter connections as well as the brain's underlying genetic profile., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Recent evidence suggests that the quantity and quality of conscious experience may be a function of the complexity of activity in the brain and that consciousness emerges in a critical zone between low and high-entropy states. We propose fractal shapes as a measure of proximity to this critical point, as fractal dimension encodes information about complexity beyond simple entropy or randomness, and fractal structures are known to emerge in systems nearing a critical point. To validate this, we tested several measures of fractal dimension on the brain activity from healthy volunteers and patients with disorders of consciousness of varying severity. We used a Compact Box Burning algorithm to compute the fractal dimension of cortical functional connectivity networks as well as computing the fractal dimension of the associated adjacency matrices using a 2D box-counting algorithm. To test whether brain activity is fractal in time as well as space, we used the Higuchi temporal fractal dimension on BOLD time-series. We found significant decreases in the fractal dimension between healthy volunteers (n = 15), patients in a minimally conscious state (n = 10), and patients in a vegetative state (n = 8), regardless of the mechanism of injury. We also found significant decreases in adjacency matrix fractal dimension and Higuchi temporal fractal dimension, which correlated with decreasing level of consciousness. These results suggest that cortical functional connectivity networks display fractal character and that this is associated with level of consciousness in a clinically relevant population, with higher fractal dimensions (i.e. more complex) networks being associated with higher levels of consciousness. This supports the hypothesis that level of consciousness and system complexity are positively associated, and is consistent with previous EEG, MEG, and fMRI studies., Competing Interests: The authors have declared that no competing interests exist.

The brain is possibly the most complex system known to mankind, and its complexity has been called upon to explain the emergence of consciousness. However, complexity has been defined in many ways by multiple different fields: here, we investigate measures of algorithmic and process complexity in both the temporal and topological domains, testing them on functional MRI BOLD signal data obtained from individuals undergoing various levels of sedation with the anaesthetic agent propofol, replicating our results in two separate datasets. We demonstrate that the various measures are differently able to discriminate between levels of sedation, with temporal measures showing higher sensitivity. Further, we show that all measures are strongly related to a single underlying construct explaining most of the variance, as assessed by Principal Component Analysis, which we interpret as a measure of "overall complexity" of our data. This overall complexity was also able to discriminate between levels of sedation and serum concentrations of propofol, supporting the hypothesis that consciousness is related to complexity - independent of how the latter is measured.

Background: Functional brain connectivity studies can provide important information about changes in brain-state dynamics during general anesthesia. In adults, γ-aminobutyric acid-mediated agents disrupt integration of information from local to the whole-brain scale. Beginning around 3 to 4 months postnatal age, γ-aminobutyric acid-mediated anesthetics such as sevoflurane generate α-electroencephalography oscillations. In previous studies of sevoflurane-anesthetized infants 0 to 3.9 months of age, α-oscillations were absent, and power spectra did not distinguish between anesthetized and emergence from anesthesia conditions. Few studies detailing functional connectivity during general anesthesia in infants exist. This study's aim was to identify changes in functional connectivity of the infant brain during anesthesia., Methods: A retrospective cohort study was performed using multichannel electroencephalograph recordings of 20 infants aged 0 to 3.9 months old who underwent sevoflurane anesthesia for elective surgery. Whole-brain functional connectivity was evaluated during maintenance of a surgical state of anesthesia and during emergence from anesthesia. Functional connectivity was represented as networks, and network efficiency indices (including complexity and modularity) were computed at the sensor and source levels., Results: Sevoflurane decreased functional connectivity at the δ-frequency (1 to 4 Hz) in infants 0 to 3.9 months old when comparing anesthesia with emergence. At the sensor level, complexity decreased during anesthesia, showing less whole-brain integration with prominent alterations in the connectivity of frontal and parietal sensors (median difference, 0.0293; 95% CI, -0.0016 to 0.0397). At the source level, similar results were observed (median difference, 0.0201; 95% CI, -0.0025 to 0.0482) with prominent alterations in the connectivity between default-mode and frontoparietal regions. Anesthesia resulted in fragmented modules as modularity increased at the sensor (median difference, 0.0562; 95% CI, 0.0048 to 0.1298) and source (median difference, 0.0548; 95% CI, -0.0040 to 0.1074) levels., Conclusions: Sevoflurane is associated with decreased capacity for efficient information transfer in the infant brain. Such findings strengthen the hypothesis that conscious processing relies on an efficient system of integrated information transfer across the whole brain.

Prominent theories of consciousness emphasise different aspects of neurobiology, such as the integration and diversity of information processing within the brain. Here, we combine graph theory and dynamic functional connectivity to compare resting-state functional MRI data from awake volunteers, propofol-anaesthetised volunteers, and patients with disorders of consciousness, in order to identify consciousness-specific patterns of brain function. We demonstrate that cortical networks are especially affected by loss of consciousness during temporal states of high integration, exhibiting reduced functional diversity and compromised informational capacity, whereas thalamo-cortical functional disconnections emerge during states of higher segregation. Spatially, posterior regions of the brain's default mode network exhibit reductions in both functional diversity and integration with the rest of the brain during unconsciousness. These results show that human consciousness relies on spatio-temporal interactions between brain integration and functional diversity, whose breakdown may represent a generalisable biomarker of loss of consciousness, with potential relevance for clinical practice.

The default mode network (DMN) is typically associated with off-task internal mentation, or with goal-oriented tasks that require self-referential processing such as autobiographical planning. However, recent reports suggest a broader involvement of the DMN in higher cognition. In line with this view, we report global connectivity changes that are centered on the main DMN hubs of precuneus and posterior cingulate cortex during a functional magnetic resonance imaging-based visuospatial version of the Tower of London planning task. Importantly, functional connectivity of these regions with the left caudate shows a significant relationship with faster reaction time to correct responses only during the high-demand planning condition, thus offering further evidence for the DMN's engagement during visuospatial planning. The results of this study not only provide robust evidence against the widely held notion of DMN disengagement during goal-oriented, attention-demanding, externally directed tasks but also support its involvement in a broader cognitive context with a memory-related role that extends beyond self-referential, internally directed mentation.

Default mode network (DMN) functional connectivity is thought to occur primarily in low frequencies (<0.1 Hz), resulting in most studies removing high frequencies during data preprocessing. In contrast, subtractive task analyses include high frequencies, as these are thought to be task relevant. An emerging line of research explores resting fMRI data at higher-frequency bands, examining the possibility that functional connectivity is a multiband phenomenon. Furthermore, recent studies suggest DMN involvement in cognitive processing; however, without a systematic investigation of DMN connectivity during tasks, its functional contribution to cognition cannot be fully understood. We bridged these concurrent lines of research by examining the contribution of high frequencies in the relationship between DMN and dorsal attention network at rest and during task execution. Our findings revealed that the inclusion of high frequencies alters between network connectivity, resulting in reduced anticorrelation and increased positive connectivity between DMN and dorsal attention network. Critically, increased positive connectivity was observed only during tasks, suggesting an important role for high-frequency fluctuations in functional integration. Moreover, within-DMN connectivity during task execution correlated with RT only when high frequencies were included. These results show that DMN does not simply deactivate during task execution and suggest active recruitment while performing cognitively demanding paradigms.

Despite evidence for beneficial use of methylphenidate in response inhibition, no studies so far have investigated the effects of this drug in the neurobiology of inhibitory control in traumatic brain injury (TBI), even though impulsive behaviours are frequently reported in this patient group. We investigated the neural basis of response inhibition in a group of TBI patients using functional magnetic resonance imaging and a stop-signal paradigm. In a randomised double-blinded crossover study, the patients received either a single 30mg dose of methylphenidate or placebo and performed the stop-signal task. Activation in the right inferior frontal gyrus (RIFG), an area associated with response inhibition, was significantly lower in patients compared to healthy controls. Poor response inhibition in this group was associated with greater connectivity between the RIFG and a set of regions considered to be part of the default mode network (DMN), a finding that suggests the interplay between DMN and frontal executive networks maybe compromised. A single dose of methylphenidate rendered activity and connectivity profiles of the patients RIFG near normal. The results of this study indicate that the neural circuitry involved in response inhibition in TBI patients may be partially restored with methylphenidate. Given the known mechanisms of action of methylphenidate, the effect we observed may be due to increased dopamine and noradrenaline levels., (Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.)

Background/objective: Obesity has been associated with brain alterations characterised by poorer interaction between a hypersensitive reward system and a comparatively weaker prefrontal-cognitive control system. These alterations may occur as early as in adolescence, but this notion remains unclear, as no studies so far have examined global functional connectivity in adolescents with excess weight., Subjects/methods: We investigated functional connectivity in a sample of 60 adolescents with excess weight and 55 normal weight controls. We first identified parts of the brain displaying between-group global connectivity differences and then characterised the extent of the differences in functional network integrity and their association with reward sensitivity., Results: Adolescent obesity was linked to neuroadaptations in functional connectivity within brain hubs linked to interoception (insula), emotional memory (middle temporal gyrus) and cognitive control (dorsolateral prefrontal cortex) (pFWE < 0.05). The connectivity between the insula and the anterior cingulate cortex was reduced in comparison to controls, as was the connectivity between the middle temporal gyrus and the posterior cingulate cortex and cuneus/precuneus (pFWE < 0.05). Conversely, the middle temporal gyrus displayed increased connectivity with the orbitofrontal cortex (pFWE < 0.05). Critically, these networks were correlated with sensitivity to reward (p < 0.05)., Conclusions: These findings suggest that adolescent obesity is linked to disrupted functional connectivity in brain networks relevant to maintaining balance between reward, emotional memories and cognitive control. Our findings may contribute to reconceptualization of obesity as a multi-layered brain disorder leading to compromised motivation and control, and provide a biological account to target prevention strategies for adolescent obesity.

Introduction: Despite the mounting evidence that depression is one of the most common psychiatric sequelae in survivors of traumatic brain injury (TBI), no studies so far have attempted to provide an explanation in terms of functional network integrity. This proof of concept study investigated the association between the severity of depressive symptoms and resting network integrity in a sample of patients with TBI and a group of healthy controls., Methods: We first examined the association between depression symptomatology and global functional connectivity and then attempted to characterize the extent of differences in functional network integrity., Results: The severity of depressive symptoms in patients with TBI was associated with neuroadaptations within the insula, the thalamus and the subgenual anterior cingulate cortex (ACC). Specifically, patients with TBI displayed increased connectivity between the insula and a region encompassing the rolandic operculum and the superior temporal cortex and reduced connectivity between the thalamus and the dorsolateral prefrontal cortex., Conclusions: These findings show the network level involvement of the insula, the thalamus and the subgenual ACC in the depressive symptomatology of patients with TBI and tentatively propose that TBI-induced depression may result from altered functional connectivity of a set of networks associated with emotional regulation. However, other factors including a number of adjustment issues and challenges may also lead to depression in this population.

The default mode network (DMN) has been traditionally assumed to hinder behavioral performance in externally focused, goal-directed paradigms and to provide no active contribution to human cognition. However, recent evidence suggests greater DMN activity in an array of tasks, especially those that involve self-referential and memory-based processing. Although data that robustly demonstrate a comprehensive functional role for DMN remains relatively scarce, the global workspace framework, which implicates the DMN in global information integration for conscious processing, can potentially provide an explanation for the broad range of higher-order paradigms that report DMN involvement. We used graph theoretical measures to assess the contribution of the DMN to global functional connectivity dynamics in 22 healthy volunteers during an fMRI-based n-back working-memory paradigm with parametric increases in difficulty. Our predominant finding is that brain modularity decreases with greater task demands, thus adapting a more global workspace configuration, in direct relation to increases in reaction times to correct responses. Flexible default mode regions dynamically switch community memberships and display significant changes in their nodal participation coefficient and strength, which may reflect the observed whole-brain changes in functional connectivity architecture. These findings have important implications for our understanding of healthy brain function, as they suggest a central role for the DMN in higher cognitive processing., Significance Statement: The default mode network (DMN) has been shown to increase its activity during the absence of external stimulation, and hence was historically assumed to disengage during goal-directed tasks. Recent evidence, however, implicates the DMN in self-referential and memory-based processing. We provide robust evidence for this network's active contribution to working memory by revealing dynamic reconfiguration in its interactions with other networks and offer an explanation within the global workspace theoretical framework. These promising findings may help redefine our understanding of the exact DMN role in human cognition., (Copyright © 2015 Vatansever et al.)

Combining resting-state functional magnetic resonance imaging (fMRI) connectivity and behavioral analysis during sedation, we factored out general effects of the anesthetic drug propofol and a specific index of conscious report, participants' level of responsiveness. The factorial analysis shows that increasing concentration of propofol in blood specifically decreases the connectivity strength of fronto-parietal cortical loops. In contrast, loss of responsiveness is indexed by a functional disconnection between the thalamus and the frontal cortex, balanced by an increase in connectivity strength of the thalamus to the occipital and temporal regions of the cortex.

Sedation has a graded effect on brain responses to auditory stimuli: perceptual processing persists at sedation levels that attenuate more complex processing. We used fMRI in healthy volunteers sedated with propofol to assess changes in neural responses to spoken stimuli. Volunteers were scanned awake, sedated, and during recovery, while making perceptual or semantic decisions about nonspeech sounds or spoken words respectively. Sedation caused increased error rates and response times, and differentially affected responses to words in the left inferior frontal gyrus (LIFG) and the left inferior temporal gyrus (LITG). Activity in LIFG regions putatively associated with semantic processing, was significantly reduced by sedation despite sedated volunteers continuing to make accurate semantic decisions. Instead, LITG activity was preserved for words greater than nonspeech sounds and may therefore be associated with persistent semantic processing during the deepest levels of sedation. These results suggest functionally distinct contributions of frontal and temporal regions to semantic decision making. These results have implications for functional imaging studies of language, for understanding mechanisms of impaired speech comprehension in postoperative patients with residual levels of anesthetic, and may contribute to the development of frameworks against which EEG based monitors could be calibrated to detect awareness under anesthesia., (Copyright © 2013 Wiley Periodicals, Inc.)

Cognitive models claim that spoken words are recognized by an optimally efficient sequential analysis process. Evidence for this is the finding that nonwords are recognized as soon as they deviate from all real words (Marslen-Wilson 1984), reflecting continuous evaluation of speech inputs against lexical representations. Here, we investigate the brain mechanisms supporting this core aspect of word recognition and examine the processes of competition and selection among multiple word candidates. Based on new behavioral support for optimal efficiency in lexical access from speech, a functional magnetic resonance imaging study showed that words with later nonword points generated increased activation in the left superior and middle temporal gyrus (Brodmann area [BA] 21/22), implicating these regions in dynamic sound-meaning mapping. We investigated competition and selection by manipulating the number of initially activated word candidates (competition) and their later drop-out rate (selection). Increased lexical competition enhanced activity in bilateral ventral inferior frontal gyrus (BA 47/45), while increased lexical selection demands activated bilateral dorsal inferior frontal gyrus (BA 44/45). These findings indicate functional differentiation of the fronto-temporal systems for processing spoken language, with left middle temporal gyrus (MTG) and superior temporal gyrus (STG) involved in mapping sounds to meaning, bilateral ventral inferior frontal gyrus (IFG) engaged in less constrained early competition processing, and bilateral dorsal IFG engaged in later, more fine-grained selection processes.

The study of substance-abuse-related neuropsychological deficits and brain alterations may provide a better understanding of the neuroadaptations associated with addiction. In this study we investigated the association between performance on neuropsychological tests of cold and hot executive functions and regional brain metabolism. Measured with positron emission tomography (PET), in a sample of 49 substance-dependent individuals (SDI). Neuropsychological performance in the SDI group was compared to that of a non-drug-using control group of 30 participants, and associated with two sets of PET-derived dependent measures: one based on regions of interest (examining mean uptake in selected regions), and a second based on voxel uptake measures (using Statistical Parametric Mapping voxel-based whole-brain analyses). Behavioral analyses showed that SDI had poorer performance than controls across executive function and emotion processing measures. Regression models showed that SDI's performance in "cold" executive tests (i.e., updating, inhibition and flexibility) was associated with regional metabolism in the dorsolateral prefrontal cortex (DLPFC), mid-superior frontal gyrus, superior and inferior temporal gyrus and inferior parietal cortex, whereas performance in "hot" executive functions (i.e., self-regulation, decision-making and emotion perception) was associated with DLPFC, mid-superior frontal gyrus, anterior and mid-posterior cingulate, and temporal and fusiform gyrus. These results are discussed in terms of their relevance for the understanding of cognitive dysfunction and neuroadaptations linked to addiction., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Functional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and the severity of use of cocaine, heroin, alcohol, MDMA and cannabis in a sample of polysubstance users with prolonged abstinence from all drugs used., Methods: Our sample consisted of 49 polysubstance users enrolled in residential treatment. We conducted correlation analyses between estimates of use of cocaine, heroin, alcohol, MDMA and cannabis and brain metabolism (BM) (using Statistical Parametric Mapping voxel-based (VB) whole-brain analyses). In all correlation analyses conducted for each of the drugs we controlled for the co-abuse of the other drugs used., Results: The analysis showed significant negative correlations between severity of heroin, alcohol, MDMA and cannabis use and BM in the dorsolateral prefrontal cortex (DLPFC) and temporal cortex. Alcohol use was further associated with lower metabolism in frontal premotor cortex and putamen, and stimulants use with parietal cortex., Conclusions: Duration of use of different drugs negatively correlated with overlapping regions in the DLPFC, whereas severity of cocaine, heroin and alcohol use selectively impact parietal, temporal, and frontal-premotor/basal ganglia regions respectively. The knowledge of these associations could be useful in the clinical practice since different brain alterations have been associated with different patterns of execution that may affect the rehabilitation of these patients.

Although widespread neural atrophy is an inevitable consequence of normal aging, not all cognitive abilities decline as we age. For example, spoken language comprehension tends to be preserved, despite atrophy in neural regions involved in language function. Here, we combined measures of behavior, functional activation, and gray matter (GM) change in a younger (19-34 years) and older group (49-86 years) of participants to identify the mechanisms leading to preserved language comprehension across the adult life span. We focussed primarily on syntactic functions because these are strongly left lateralized, providing the potential for contralateral recruitment. In an functional magnetic resonance imaging study, we used a word-monitoring task to minimize working memory demands, manipulating the availability of semantics and syntax to ask whether syntax is preserved in aging because of the functional recruitment of other brain regions, which successfully compensate for neural atrophy. Performance in the older group was preserved despite GM loss. This preservation was related to increased activity in right hemisphere frontotemporal regions, which was associated with age-related atrophy in the left hemisphere frontotemporal network activated in the young. We argue that preserved syntactic processing across the life span is due to the shift from a primarily left hemisphere frontotemporal system to a bilateral functional language network.

The role of morphological structure in word recognition raises issues about the nature and structure of the language system. One major issue is whether morphological factors provide an independent principle for lexical organization and processing, or whether morphological effects can be reduced to the joint contribution of form and meaning. The independence of form, meaning, and morphological structure can be directly investigated using derivationally complex words, because derived words can share form but need not share meaning (e.g., archer-arch). We used an event-related functional magnetic resonance imaging paradigm to investigate priming between pairs of words that potentially shared a stem, where this link was either semantically transparent (e.g., bravely-brave) or opaque (e.g., archer-arch). These morphologically related pairs were contrasted with identity priming (e.g., mist-mist) and priming for pairs of words that shared only form (e.g., scandal-scan) or meaning (e.g., accuse-blame). Morphologically related words produced significantly reduced activation in left frontal regions, whether the pairs were semantically transparent or opaque. The effect was not found for any of the control conditions (identity, form, or meaning). Morphological effects were observed separately from processing form and meaning and we propose that they reflect segmentation of complex derived words, a process triggered by surface morphological structure of complex words.

Knowledge of objects in the world is stored in our brains as rich, multimodal representations. Because the neural pathways that process this diverse sensory information are largely anatomically distinct, a fundamental challenge to cognitive neuroscience is to explain how the brain binds the different sensory features that comprise an object to form meaningful, multimodal object representations. Studies with nonhuman primates suggest that a structure at the culmination of the object recognition system (the perirhinal cortex) performs this critical function. In contrast, human neuroimaging studies implicate the posterior superior temporal sulcus (pSTS). The results of the functional MRI study reported here resolve this apparent discrepancy by demonstrating that both pSTS and the perirhinal cortex contribute to crossmodal binding in humans, but in different ways. Significantly, only perirhinal cortex activity is modulated by meaning variables (e.g., semantic congruency and semantic category), suggesting that these two regions play complementary functional roles, with pSTS acting as a presemantic, heteromodal region for crossmodal perceptual features, and perirhinal cortex integrating these features into higher-level conceptual representations. This interpretation is supported by the results of our behavioral study: Patients with lesions, including the perirhinal cortex, but not patients with damage restricted to frontal cortex, were impaired on the same crossmodal integration task, and their performance was significantly influenced by the same semantic factors, mirroring the functional MRI findings. These results integrate nonhuman and human primate research by providing converging evidence that human perirhinal cortex is also critically involved in processing meaningful aspects of multimodal object representations.

Unlabelled: This study investigated regional cerebral blood flow in head-injured patients using statistical parametric mapping (SPM) to detect hypoperfusion on (99m)Tc-hexamethylpropyleneamine oxime (HMPAO) SPECT scans., Methods: Acute and follow-up SPECT and MRI scans from 61 patients who were admitted to a regional neurosurgical unit were examined. Patients had acute MRI and SPECT at 2-18 d after injury and on follow-up between 130 and 366 d after injury. Thirty-two scans from non-head-injured patients were used as a SPECT control group. The SPECT images were first aligned to the Talairach-Tournoux atlas and then analyzed statistically with SPM., Results: SPECT detected more extensive abnormality than MRI in acute and follow-up stages. This effect was more pronounced on follow-up of patients with diffuse injury. Examination of a focal injury group indicated the involvement of frontal and temporal lobes and the anterior cingulate. Blood flow abnormalities persist, to a lesser extent, on follow-up scans. The diffuse group displayed low blood flow in the frontal and temporal lobes, including cingulate involvement, which persists at follow-up with additional involvement of the thalamus., Conclusion: SPM has a role in SPECT image interpretation because it allows better visualization than other methods of quantitative analysis of the spatial distribution of abnormalities in focal and diffuse head injury. Frontal lobe blood flow abnormality (particularly anterofrontal regions and mesiofrontal areas) is common after head injury.

How is the information-processing architecture of the human brain organised, and how does its organisation support consciousness? Here, we combine network science and a rigorous information-theoretic notion of synergy to delineate a synergistic global workspace, comprising gateway regions that gather synergistic information from specialised modules across the human brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the human brains default mode network, whereas broadcasters coincide with the executive control network. We find that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information.

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain's rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradients of brain structure and function. Last, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganization of the brain's functional architecture.

A central question in neuroscience is how consciousness arises from the dynamic interplay of brain structure and function. Here we decompose functional MRI signals from pathological and pharmacologically-induced perturbations of consciousness into distributed patterns of structure-function dependence across scales: the harmonic modes of the human structural connectome. We show that structure-function coupling is a generalisable indicator of consciousness that is under bi-directional neuromodulatory control. We find increased structure-function coupling across scales during loss of consciousness, whether due to anaesthesia or brain injury, capable of discriminating between behaviourally indistinguishable sub-categories of brain-injured patients, tracking the presence of covert consciousness. The opposite harmonic signature characterises the altered state induced by LSD or ketamine, reflecting psychedelic-induced decoupling of brain function from structure and correlating with physiological and subjective scores. Overall, connectome harmonic decomposition reveals how neuromodulation and the network architecture of the human connectome jointly shape consciousness and distributed functional activation across scales.

Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain's control energy landscape, which can be observed using network control theory to quantify the energy required to transition between recurrent brain states. Using brain states derived from existing functional magnetic resonance imaging (fMRI) datasets, we show that LSD and psilocybin reduce control energy required for brain state transitions compared to placebo. Furthermore, across individuals, reduction in control energy correlates with more frequent state transitions and increased entropy of brain state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors (obtained from publicly available positron emission tomography (PET) data under non-drug conditions), we demonstrate an association between the 5-HT2a receptor and reduced control energy. Our findings provide evidence that 5-HT2a receptor agonist compounds allow for more facile state transitions and more temporally diverse brain activity. More broadly, we demonstrate that receptor-informed network control theory can model the impact of neuropharmacological manipulation on brain activity dynamics.

Integrating independent but converging lines of research on brain function and neurodevelopment across scales, this article proposes that serotonin 2A receptor (5-HT2AR) signalling is an evolutionary and developmental driver and potent modulator of the macroscale functional organization of the human cerebral cortex. A wealth of evidence indicates that the anatomical and functional organization of the cortex follows a unimodal-to-transmodal gradient. Situated at the apex of this processing hierarchy—where it plays a central role in the integrative processes underpinning complex, human-defining cognition—the transmodal cortex has disproportionately expanded across human development and evolution. Notably, the adult human transmodal cortex is especially rich in 5-HT2AR expression and recent evidence suggests that, during early brain development, 5-HT2AR signalling on neural progenitor cells stimulates their proliferation—a critical process for evolutionarily-relevant cortical expansion. Drawing on multimodal neuroimaging and cross-species investigations, we argue that, by contributing to the expansion of the human cortex and being prevalent at the apex of its hierarchy in the adult brain, 5-HT2AR signalling plays a major role in both human cortical expansion and functioning. Owing to its unique excitatory and downstream cellular effects, neuronal 5-HT2AR agonism promotes neuroplasticity, learning and cognitive and psychological flexibility in a context-(hyper)sensitive manner with therapeutic potential. Overall, we delineate a dual role of 5-HT2ARs in enabling both the expansion and modulation of the human transmodal cortex. [ABSTRACT FROM AUTHOR]

Background: To determine whether depressive symptoms in traumatic brain injury (TBI) patients were associated with altered resting-state functional connectivity (rs-fc) or voxel-based morphology in brain regions involved in emotional regulation and associated with depression. Methods: In the present study, we examined 79 patients (57 males; age range = 17–70 years, M ± s.d. = 38 ± 16.13; BDI-II, M ± s.d. = 9.84 ± 8.67) with TBI. We used structural MRI and resting-state fMRI to examine whether there was a relationship between depression, as measured with the Beck Depression Inventory (BDI-II), and the voxel-based morphology or functional connectivity in regions previously identified as involved in emotional regulation in patients following TBI. Patients were at least 4 months post-TBI (M ± s.d. = 15.13 ± 11.67 months) and the severity of the injury included mild to severe cases [Glasgow Coma Scale (GCS), M ± s.d. = 6.87 ± 3.31]. Results: Our results showed that BDI-II scores were unrelated to voxel-based morphology in the examined regions. We found a positive association between depression scores and rs-fc between limbic regions and cognitive control regions. Conversely, there was a negative association between depression scores and rs-fc between limbic and frontal regions involved in emotion regulation. Conclusion: These findings lead to a better understanding of the exact mechanisms that contribute to depression following TBI and better inform treatment decisions. [ABSTRACT FROM AUTHOR]

Previous neuroimaging studies have shown an increased sensory cortical response (i.e., heightened weight on sensory evidence) under higher levels of predictive uncertainty. The signal enhancement theory proposes that attention improves the quality of the stimulus representation, and therefore reduces uncertainty by increasing the gain of the sensory signal. The present study employed functional magnetic resonance imaging (fMRI) to investigate the neural correlates for ambiguous valence inferences signaled by auditory information within an emotion recognition paradigm. Participants categorized sound stimuli of three distinct levels of consonance/dissonance controlled by interval content. Separate behavioural and neuroscientific experiments were conducted. Behavioural results revealed that, compared with the consonance condition (perfect fourths, fifths and octaves) and the strong dissonance condition (minor/major seconds and tritones), the intermediate dissonance condition (minor thirds) was the most ambiguous, least salient and more cognitively demanding category (slowest reaction times). The neuroscientific findings were consistent with a heightened weight on sensory evidence whilst participants were evaluating intermediate dissonances, which was reflected in an increased neural response of the right Heschl’s gyrus. The results support previous studies that have observed enhanced precision of sensory evidence whilst participants attempted to represent and respond to higher degrees of uncertainty, and converge with evidence showing preferential processing of complex spectral information in the right primary auditory cortex. These findings are discussed with respect to music-theoretical concepts and recent Bayesian models of perception, which have proposed that attention may heighten the weight of information coming from sensory channels to stimulate learning about unknown predictive relationships. [ABSTRACT FROM AUTHOR]

Primary objective: Investigation of the impact of traumatic brain injury (TBI) on the functional brain network that mediates working memory function. Research design: Functional magnetic resonance imaging (fMRI) during an n-back working memory task in nine chronic-stage patients with TBI and nine age-matched healthy controls. In addition to classical analyses investigating regional activity, the authors examined functional connectivity of the brain regions critical to working memory performance using psychophysiological interaction (PPI) analyses. Main outcomes and results: Patients with TBI made a greater percentage of errors than controls at high working memory load conditions. The fMRI data showed that the activation of the left inferior parietal gyrus (LIPG) was significantly reduced, whereas the activation of the right inferior frontal gyrus (RIFG) was significantly increased in patients compared with controls. Task performance accuracy was significantly associated with the activation of the LIPG in controls and the activation of the RIFG in patients. PPI analyses on fMRI data further suggested that the functional connectivity between the RIFG and LIPG was compromised in patients. Conclusion: The abnormal functional connectivity between LIPG and RIFG may underlie the observed working memory deficits and abnormal brain activation pattern in patients. [ABSTRACT FROM AUTHOR]

The study of neuropsychological disorders has been greatly facilitated by the localization of brain lesions on MRI scans. Current popular approaches for the assessment of MRI brain scans mostly depend on the successful segmentation of the brain into grey and white matter. These methods cannot be used effectively with large lesions because lesions usually impair segmentation. We propose a novel, fully automated approach for the delineation of brain lesions on MR scans. This method involves comparing a skull stripped. smoothed, unsegmented T1 images to a control group using the general linear model. We tested this method by using images with simulated lesions of different sizes and images containing real lesions from patients with language deficits. We also tested how varying the size of the Gaussian smoothing kernel affects detection. The simulation was informed by findings of a lesion morphological study also presented here. The proposed method detected simulated lesions effectively in the range of 30-90% < normal signal. Smoothing kernels in the range of 8-12 mm resulted in the most accurate lesion detection. Both artificial and real lesions were optimally detected when the results were uncorrected for multiple comparisons at p < .001. This proposed method produced highly satisfactory results and can be used to generate reproducible detection of lesions. [ABSTRACT FROM AUTHOR]