Functional Organization Research Articles

On the Functional Nature of Cognitive Systems

The functional nature of cognitive systems is outlined as a general conceptual model where typical notions of cognition are analyzed apart from the physical realization (biological or artificial) of such systems. The notion of function, one of the main logical bases of mathematics, logic, linguistics, physics, and computer science, is shown to be a unifying concept in analyzing cognition components: learning, meaning, comprehension, language, knowledge, and consciousness are related to increasing levels in the functional organization of cognition.

Spectral graph model for fMRI: A biophysical, connectivity-based generative model for the analysis of frequency-resolved resting-state fMRI

Abstract Resting-state functional MRI (rs-fMRI) is a popular and widely used technique to explore the brain’s functional organization and to examine whether it is altered in neurological or mental disorders. The most common approach for its analysis targets the measurement of the synchronized fluctuations between brain regions, characterized as functional connectivity (FC), typically relying on pairwise correlations in activity across different brain regions. While hugely successful in exploring state- and disease-dependent network alterations, these statistical graph theory tools suffer from two key limitations. First, they discard useful information about the rich frequency content of the fMRI signal. The rich spectral information now achievable from advances in fast multiband acquisitions is consequently being underutilized. Second, the analyzed FCs are phenomenological without a direct neurobiological underpinning in the underlying structures and processes in the brain. There does not currently exist a complete generative model framework for whole brain resting fMRI that is informed by its underlying biological basis in the structural connectome. Here we propose that a different approach can solve both challenges at once: the use of an appropriately realistic yet parsimonious biophysics-informed signal generation model followed by graph spectral (i.e., eigen) decomposition. We call this model a spectral graph model (SGM) for fMRI, using which we can not only quantify the structure–function relationship in individual subjects, but also condense the variable and individual-specific repertoire of fMRI signal’s spectral and spatial features into a small number of biophysically interpretable parameters. We expect this model-based analysis of rs-fMRI that seamlessly integrates with structure can be used to examine state and trait characteristics of structure–function relationships in a variety of brain disorders.

Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors.

Dopamine (DA) release in striatal circuits, including the nucleus accumbens medial shell (mNAcSh), tracks separable features of reward like motivation and reinforcement. However, the cellular and circuit mechanisms by which DA receptors transform DA release into distinct constructs of reward remain unclear. Here we show that DA D3 receptor (D3R) signaling in the mNAcSh drives motivated behavior in mice by regulating local microcircuits. Furthermore, D3Rs coexpress with DA D1 receptors, which regulate reinforcement, but not motivation. Paralleling dissociable roles in reward function, we report nonoverlapping physiological actions of D3R and DA D1 receptor signaling in mNAcSh neurons. Our results establish a fundamental framework wherein DA signaling within the same nucleus accumbens cell type is physiologically compartmentalized via actions on distinct DA receptors. This structural and functional organization provides neurons in a limbic circuit with the unique ability to orchestrate dissociable aspects of reward-related behaviors relevant to the etiology of neuropsychiatric disorders.

Spatial Transcriptomics, Proteomics, and Epigenomics as Tools in Tissue Engineering and Regenerative Medicine

Spatial transcriptomics, proteomics, and epigenomics are innovative technologies which offer an unparalleled resolution and wealth of data in understanding and the interpretation of cellular functions and interactions. These techniques allow researchers to investigate gene and protein expressions at an individual cell level, revealing cellular heterogeneity within, for instance, bioengineered tissues and classifying novel and rare cell populations that could be essential for the function of the tissues and in disease processes. It is possible to analyze thousands of cells simultaneously, which gives thorough insights into the transcriptomic view of complex tissues. Spatial transcriptomics combines gene expressions with spatial information, conserving tissue architecture and making the mapping of gene activity across different tissue regions possible. Despite recent advancements in these technologies, they face certain limitations. Single-cell transcriptomics can suffer from technical noise and dropout events, leading to incomplete data. Its applicability has been limited by the complexity of data integration and interpretation, although better resolution and tools for the interpretation of data are developing fast. Spatial proteomics and spatial epigenomics provide data on the distribution of proteins and the gene regulatory aspects in tissues, respectively. The disadvantages of these approaches include rather costly and time-consuming analyses. Nevertheless, combining these techniques promises a more comprehensive understanding of cell function and tissue organization, which can be predicted to be useful in achieving better knowledge of cell guidance in tissue-engineered constructs and a higher quality of tissue technology products.

Functional Connectivity Biomarker Extraction for Schizophrenia Based on Energy Landscape Machine Learning Techniques.

Brain connectivity represents the functional organization of the brain, which is an important indicator for evaluating neuropsychiatric disorders and treatment effects. Schizophrenia is associated with impaired functional connectivity but characterizing the complex abnormality patterns has been challenging. In this work, we used resting-state functional magnetic resonance imaging (fMRI) data to measure functional connectivity between 55 schizophrenia patients and 63 healthy controls across 246 regions of interest (ROIs) and extracted the disease-related connectivity patterns using energy landscape (EL) analysis. EL analysis captures the complexity of brain function in schizophrenia by focusing on functional brain state stability and region-specific dynamics. Age, sex, and smoker demographics between patients and controls were not significantly different. However, significant patient and control differences were found for the brief psychiatric rating scale (BPRS), auditory perceptual trait and state (APTS), visual perceptual trait and state (VPTS), working memory score, and processing speed score. We found that the brains of individuals with schizophrenia have abnormal energy landscape patterns between the right and left rostral lingual gyrus, and between the left lateral and orbital area in 12/47 regions. The results demonstrate the potential of the proposed imaging analysis workflow to identify potential connectivity biomarkers by indexing specific clinical features in schizophrenia patients.

Impact of agricultural land-use on functional feeding groups of Afrotropical Ephemeroptera, Plecoptera and Trichoptera in the Kat River, Eastern Cape, South Africa

Despite Africa experiencing a substantial rise in inadequately managed agricultural practices, studies examining the effects of these activities on the functional organisation of macroinvertebrates in tropical streams are underdeveloped. The responses of Ephemeroptera, Plecoptera and Trichoptera (EPTs) functional feeding groups (FFGs) to agricultural pollution were investigated in the Kat River, Eastern Cape, South Africa, to identify potential FFG indicators. Physicochemical parameters and macroinvertebrates were sampled from eight sites delineated into four land-use impact categories (highly impacted, HIC; impacted category, IC; moderately impacted, MIC; and least impacted, LIC) based on the percentage of agricultural land cover. The Permutational multivariate analyses of variance (PERMANOVA) results revealed land use (F = 4.2, 3.62; p < 0.05) and season (F = 2.89, p < 0.03) influenced FFGs in the river, with shredder abundances decreasing with increasing agricultural stress. Conversely, collectors, predators and scrapers were tolerant of agricultural disturbance. Nutrient variables (NO3-N, NO2-N and NH4-N), canopy and depth were the critical variables that affected FFG structure in the river. Our findings provided more understanding and insights into the functional structure of EPT in relation to agricultural pollution and can contribute to developing trait-based biomonitoring tools in Africa.

Track-Weighted Dynamic Functional Connectivity Profiles and Topographic Organization of the Human Pulvinar.

The human pulvinar is considered a prototypical associative thalamic nucleus as it represents a key node in several cortico-subcortical networks. Through this extensive connectivity to widespread brain areas, it has been suggested that the pulvinar may play a central role in modulating cortical oscillatory dynamics of complex cognitive and executive functions. Additionally, derangements of pulvinar activity are involved in different neuropsychiatric conditions including Lewy-body disease, Alzheimer's disease, and schizophrenia. Anatomical investigations in nonhuman primates have demonstrated a topographical organization of cortico-pulvinar connectivity along its dorsoventral and rostrocaudal axes; this specific organization shows only partial overlap with the traditional subdivision into subnuclei (anterior, lateral, medial, and inferior) and is thought to coordinate information processing within specific brain networks. However, despite its relevance in mediating higher-order cognitive functions, such a structural and functional organization of the pulvinar in the human brain remains poorly understood. Track-weighted dynamic functional connectivity (tw-dFC) is a recently developed technique that combines structural and dynamic functional connectivity, allowing the identification of white matter pathways underlying the fluctuations observed in functional connectivity between brain regions over time. Herein, we applied a data-driven parcellation approach to reveal topographically organized connectivity clusters within the human pulvinar complex, in two large cohorts of healthy human subjects. Unsupervised clustering of tw-dFC time series within the pulvinar complex revealed dorsomedial, dorsolateral, ventral anterior, and ventral posterior connectivity clusters. Each of these clusters shows functional coupling to specific, widespread cortico-subcortical white matter brain networks. Altogether, our findings represent a relevant step towards a better understanding of pulvinar anatomy and function, and a detailed characterization of his role in healthy and pathological conditions.

Sex differences in autism spectrum disorder using class imbalance adjusted functional connectivity

Autism spectrum disorder (ASD) is an atypical neurodevelopmental condition with a diagnostic ratio largely differing between male and female participants. Due to the sex imbalance in participants with ASD, we lack an understanding of the differences in connectome organization of the brain between male and female participants with ASD. In this study, we matched the sex ratio using a Gaussian mixture model-based oversampling technique and investigated the differences in functional connectivity between male and female participants with ASD using low-dimensional principal gradients. Between-group comparisons of the gradient values revealed significant interaction effects of sex in the sensorimotor, attention, and default mode networks. The sex-related differences in the gradients were highly associated with higher-order cognitive control processes. Transcriptomic association analysis provided potential biological underpinnings, specifying gene enrichment in the cortex, thalamus, and striatum during development. Finally, the principal gradients were differentially associated with symptom severity of ASD between sexes, highlighting significant effects in female participants with ASD. Our work proposed an oversampling method to mitigate sex imbalance in ASD and observed significant sex-related differences in functional connectome organization. The findings may advance our knowledge about the sex heterogeneity in large-scale brain networks in ASD.

Disruption of macroscale functional network organisation in patients with frontotemporal dementia.

Neurodegenerative dementias have a profound impact on higher-order cognitive and behavioural functions. Investigating macroscale functional networks through cortical gradients provides valuable insights into the neurodegenerative dementia process and overall brain function. This approach allows for the exploration of unimodal-multimodal differentiation and the intricate interplay between functional brain networks. We applied cortical gradients mapping to resting-state functional MRI data of patients with frontotemporal dementia (FTD) (behavioural-bvFTD, non-fluent and semantic) and healthy controls. In healthy controls, the principal gradient maximally distinguished sensorimotor from default-mode network (DMN) and the secondary gradient visual from salience network (SN). In all FTD variants, the principal gradient's unimodal-multimodal differentiation was disrupted. The secondary gradient, however, showed widespread disruptions impacting the interactions among all networks specifically in bvFTD, while semantic and non-fluent variants exhibited more focal alterations in limbic and sensorimotor networks. Additionally, the visual network showed responsive and/or compensatory changes in all patients. Importantly, these disruptions extended beyond atrophy distribution and related to symptomatology in patients with bvFTD. In conclusion, optimal brain function requires networks to operate in a segregated yet collaborative manner. In FTD, our findings indicate a collapse and loss of differentiation between networks not solely explained by atrophy. These specific cortical gradients' fingerprints could serve as a functional signature for identifying early changes in neurodegenerative diseases or potential compensatory processes.

Maintenance of Bodily Expressions Modulates Functional Connectivity Between Prefrontal Cortex and Extrastriate Body Area During Working Memory Processing

Background/Objectives: As a form of visual input, bodily expressions can be maintained and manipulated in visual working memory (VWM) over a short period of time. While the prefrontal cortex (PFC) plays an indispensable role in top-down control, it remains largely unclear whether this region also modulates the VWM storage of bodily expressions during a delay period. Therefore, the two primary goals of this study were to examine whether the emotional bodies would elicit heightened brain activity among areas such as the PFC and extrastriate body area (EBA) and whether the emotional effects subsequently modulate the functional connectivity patterns for active maintenance during delay periods. Methods: During functional magnetic resonance imaging (fMRI) scanning, participants performed a delayed-response task in which they were instructed to view and maintain a body stimulus in working memory before emotion categorization (happiness, anger, and neutral). If processing happy and angry bodies consume increased cognitive demands, stronger PFC activation and its functional connectivity with perceptual areas would be observed. Results: Results based on univariate and multivariate analyses conducted on the data collected during stimulus presentation revealed an enhanced processing of the left PFC and left EBA. Importantly, subsequent functional connectivity analyses performed on delayed-period data using a psychophysiological interaction model indicated that functional connectivity between the PFC and EBA increases for happy and angry bodies compared to neutral bodies. Conclusions: The emotion-modulated coupling between the PFC and EBA during maintenance deepens our understanding of the functional organization underlying the VWM processing of bodily information.

Impact of Islamic Art on the Architectural Design of Mosques in Amman

Objectives: This article aims to highlight and study traditional and contemporary Islamic Art in Jordanian mosques. Methods:. Comparative analysis of Islamic Art concerning the mosque architecture in Amman, analysis of theoretical works on this topic, and historical approach. The study will also include a study of mosques in Amman. Results: When designing new mosques, architects need to study not only traditions, design experience, the space-planning solution of the mosque, and the functional organization of space but also the meaning of ornaments. The ornaments on the facade and interior, as well as various art objects in the interior, are the most expressive differences that indicate that the building belongs to the culture of Islam and forms a religion. Conclusions: Islamic art and architecture in Jordan have deep roots in the history of the religion. Many buildings and structures were built during the reign of the Umayyads, Abbasids, and other dynasties, who left their mark on architecture and design. Islamic sculptures and decorations also reflect Jordan&amp;apos;s culture and heritage richness.

The cell-type underpinnings of the human functional cortical connectome.

The functional properties of the human brain arise, in part, from the vast assortment of cell types that pattern the cerebral cortex. The cortical sheet can be broadly divided into distinct networks, which are embedded into processing streams, or gradients, that extend from unimodal systems through higher-order association territories. Here using microarray data from the Allen Human Brain Atlas and single-nucleus RNA-sequencing data from multiple cortical territories, we demonstrate that cell-type distributions are spatially coupled to the functional organization of cortex, as estimated through functional magnetic resonance imaging. Differentially enriched cells follow the spatial topography of both functional gradients and associated large-scale networks. Distinct cellular fingerprints were evident across networks, and a classifier trained on postmortem cell-type distributions was able to predict the functional network allegiance of cortical tissue samples. These data indicate that the in vivo organization of the cortical sheet is reflected in the spatial variability of its cellular composition.

Macro-scale patterns in functional connectivity associated with ongoing thought patterns and dispositional traits

Complex macro-scale patterns of brain activity that emerge during periods of wakeful rest provide insight into the organisation of neural function, how these differentiate individuals based on their traits, and the neural basis of different types of self-generated thoughts. Although brain activity during wakeful rest is valuable for understanding important features of human cognition, its unconstrained nature makes it difficult to disentangle neural features related to personality traits from those related to the thoughts occurring at rest. Our study builds on recent perspectives from work on ongoing conscious thought that highlight the interactions between three brain networks – ventral and dorsal attention networks, as well as the default mode network. We combined measures of personality with state-of-the-art indices of ongoing thoughts at rest and brain imaging analysis and explored whether this ‘tri-partite’ view can provide a framework within which to understand the contribution of states and traits to observed patterns of neural activity at rest. To capture macro-scale relationships between different brain systems, we calculated cortical gradients to describe brain organisation in a low-dimensional space. Our analysis established that for more introverted individuals, regions of the ventral attention network were functionally more aligned to regions of the somatomotor system and the default mode network. At the same time, a pattern of detailed self-generated thought was associated with a decoupling of regions of dorsal attention from regions in the default mode network. Our study, therefore, establishes that interactions between attention systems and the default mode network are important influences on ongoing thought at rest and highlights the value of integrating contemporary perspectives on conscious experience when understanding patterns of brain activity at rest.

High-density recording reveals sparse clusters (but not columns) for shape and texture encoding in macaque V4.

Macaque area V4 includes neurons that exhibit exquisite selectivity for visual form and surface texture, but their functional organization across laminae is unknown. We used high-density Neuropixels probes in two awake monkeys (one female and one male) to characterize shape and texture tuning of dozens of neurons simultaneously across layers. We found sporadic clusters of neurons that exhibit similar tuning for shape and texture: ∼20% exhibited similar tuning with their neighbors. Importantly, these clusters were confined to a few layers, seldom 'columnar' in structure. This was the case even when neurons were strongly driven, and exhibited robust contrast invariance for shape and texture tuning. We conclude that functional organization in area V4 is not columnar for shape and texture stimulus features and in general organization maybe at a coarser stimulus category scale (e.g. selectivity for stimuli with vs without 3D cues), and a coarser spatial scale (assessed by optical imaging), rather than at a fine scale in terms of similarity in single neuron tuning for specific features. We speculate that this may be a direct consequence of the great diversity of inputs integrated by V4 neurons to build variegated tuning manifolds in a high-dimensional space.Significance Statement In the primary visual cortex of the macaque monkey, studies have demonstrated columnar functional organization, i.e. shared tuning across layers for stimulus orientation, spatial frequency, ocular dominance, etc. In mid and higher level visual form processing stages, where neurons exhibit high-dimensional tuning, functional organization has been harder to evaluate. Here, leveraging the use of the high-density Neuropixels probes to record simultaneously from dozens of neurons across cortical layers, we demonstrate that functional organization is not columnar for shape and texture tuning in area V4, a midlevel stage critical for form processing. Our results contribute to the debate about the functional significance of cortical columns providing support to the idea that they emerge due to one-to-many representational expansion.

Resting state functional connectivity in adolescents with substance use disorder and their unaffected siblings

We aimed to examine resting-state functional connectivity (rsFC) in adolescents with substance use disorder (SUD) and their unaffected biological siblings (SIB), relative to typically-developing controls (TDC) in order to identify alterations in functional network organization that may be associated with the familial risk for SUD. Resting-state functional magnetic resonance imaging analysis included 20 adolescents with SUD, 20 SIB, and 18 TDC. Network‐based analysis revealed that adolescents with SUD had significantly both weaker and higher rsFC compared to TDC mainly within the default-mode network (DMN) and between the DMN, fronto-parietal (FPN) and salience networks. In addition, adolescents with SUD showed lower rsFC between the visual network and other functional networks. Although the SIB group did not differ from TDC in the whole brain analysis, they showed lower rsFC within DMN and also between the visual network and other large-scale networks as well as higher rsFC between DMN and FPN compared to TDC in connections found to be abnormal in SUD group. Our results suggest that lower rsFC within DMN and higher rsFC between the DMN with FPN which were evident both in SUD and in SIB groups, and might be related to the familial predisposition for SUD.

A data-driven analysis of the perceptual and neural responses to natural objects reveals organising principles of human visual cognition.

A key challenge in understanding the functional organisation of visual cortex stems from the fact that only a small proportion of the objects experienced during natural viewing can be presented in a typical experiment. This constraint often leads to experimental designs that compare responses to objects from experimenter-defined stimulus conditions, potentially limiting the interpretation of the data. To overcome this issue, we used images from the THINGS initiative, which provides a systematic sampling of natural objects. A data-driven analysis was then applied to reveal the functional organisation of the visual brain, incorporating both perceptual and neural responses to these objects. Perceptual properties of the objects were taken from an analysis of similarity judgements, and neural properties were taken from whole brain fMRI responses to the same objects. Partial least squares regression (PLSR) was then used to predict neural responses across the brain from the perceptual properties while simultaneously applying dimensionality reduction. The PLSR model accurately predicted neural responses across visual cortex using only a small number of components. These components revealed smooth, graded neural topographies, which were similar in both hemispheres, and captured a variety of object properties including animacy, real-world size, and object category. However, they did not accord in any simple way with previous theoretical perspectives on object perception. Instead, our findings suggest that visual cortex encodes information in a statistically efficient manner, reflecting natural variability among objects.Significance statement The ability to recognise objects is fundamental to how we interact with our environment, yet the organising principles underlying neural representations of visual objects remain contentious. In this study, we sought to address this question by analysing perceptual and neural responses to a large, unbiased sample of objects. Using a data-driven approach, we leveraged perceptual properties of objects to predict neural responses using a small number of components. This model predicted neural responses with a high degree of accuracy across visual cortex. The components did not directly align with previous explanations of object perception. Instead, our findings suggest the organisation of the visual brain is based on the statistical properties of objects in the natural world.

The intrinsic propagation directionality of fMRI infra-slow activity during visual tasks

The temporal order of propagation in the blood-oxygen-level-dependent (BOLD) infra-slow activity (ISA, 0.01–0.1 Hz) of functional magnetic resonance imaging (fMRI) can indicate the functional organization of the brain. While prior studies have revealed the temporal order of propagation of BOLD ISA during rest, how it emerges during cognitive tasks remains unclear. Furthermore, its differences between the gray and white matters at the whole-brain scale are unexplored. In this study, we probed the propagation of BOLD ISA using a publicly available fMRI dataset from participants performing visual detection and discrimination tasks (N = 46, 29 females). We examined the temporal order of propagation based on ISA oscillatory phase differences among brain parcels. During visual task performance, ISA in both the gray and white matters propagated in a direction from the visual cortex to the association cortex, including the default mode network (DMN). This result differs from the previously reported propagation direction during rest that traveled from the visual and somatosensory cortices to the DMN, suggesting that the functional organization may change when performing cognitive tasks. In addition, the propagation in the white matter represented more complex patterns than that in the gray matter, exhibiting that the cingulum preceded DMN. Our results may help the understanding of how task performance alters the sensory-DMN propagation according of ISA.

A Ni4O4-cubane-squarate coordination framework for molecular recognition

Molecular recognition is a fundamental function of natural systems that ensures biological activity. This is achieved through the sieving effect, host-guest interactions, or both in biological environments. Recent advancements in multifunctional proteins reveal a new dimension of functional organization that goes beyond single-function molecular recognition, emphasizing the need for artificial multifunctional materials in industrial applications. Herein, we have designed a porous Ni4O4-cubane squarate coordination polymer as an artificial molecular recognition host, drawing inspiration from the structural and functional features of natural enzymes. A comprehensive assessment of the material’s ability to distinguish target species under different operating conditions was carried out. The results confirm its sieving function through hexane isomers separation, host-guest interaction function via xenon/krypton separation, and dual presence of sieving and interaction through carbon dioxide/nitrogen separation. Additionally, the material demonstrates good stability and feasibility for large-scale production, indicating its practical potential. Our findings provide a bio-inspired multifunctional recognition material for chemical separations as proof-of-concept while offering solutions to advance artificial multifunctional materials adaptable to other applications beyond chemical separations.

Project of functional zoning of the territory of Lianozovsky park in Moscow

Classifying the factors that cause anthropogenic impact on natural complexes and their consequences, three main types can be identified: mechanical, physico-chemical, and biological. One of the applied approaches in the work is to ensure compliance with the maximum recreational loads on the projected tourist routes of the “Lianozovsky Park” Park of Culture and Recreation. The work pays attention to the condition of management and organization of the recreational function, which is aimed at regulating the potential number of visitors based on the proposed regulations on the use of appropriate functional subzones calculated by the authors. The number of visitors to the natural and anthropogenic tourist complex (NATC) was determined, a comparative analysis of the recreational load for compliance with the normative value was carried out, a functional zoning project was proposed, including the design of three subzones of various functional purposes and a mode of their use was proposed.

Codon Usage Insights into the Functional Organization of Acinetobacter baumannii Virulence and Resistance Genes

Codon Usage Insights into the Functional Organization of Acinetobacter baumannii Virulence and Resistance Genes