Measure Of Functional Integrity Research Articles

Prenatal Magnesium Sulfate and Functional Connectivity in Offspring at Term-Equivalent Age

Understanding the effect of antenatal magnesium sulfate (MgSO4) treatment on functional connectivity will help elucidate the mechanism by which it reduces the risk of cerebral palsy and death. To determine whether MgSO4 administered to women at risk of imminent preterm birth at a gestational age between 30 and 34 weeks is associated with increased functional connectivity and measures of functional segregation and integration in infants at term-equivalent age, possibly reflecting a protective mechanism of MgSO4. This cohort study was nested within a randomized placebo-controlled trial performed across 24 tertiary maternity hospitals. Participants included infants born to women at risk of imminent preterm birth at a gestational age between 30 and 34 weeks who participated in the MAGENTA (Magnesium Sulphate at 30 to 34 Weeks' Gestational Age) trial and underwent magnetic resonance imaging (MRI) at term-equivalent age. Ineligibility criteria included illness precluding MRI, congenital or genetic disorders likely to affect brain structure, and living more than 1 hour from the MRI center. One hundred and fourteen of 159 eligible infants were excluded due to incomplete or motion-corrupted MRI. Recruitment occurred between October 22, 2014, and October 25, 2017. Participants were followed up to 2 years of age. Analysis was performed from February 1, 2021, to February 27, 2024. Observers were blind to patient groupings during data collection and processing. Women received 4 g of MgSO4 or isotonic sodium chloride solution given intravenously over 30 minutes. Prior to data collection, it was hypothesized that infants who were exposed to MgSO4 would show enhanced functional connectivity compared with infants who were not exposed. A total of 45 infants were included in the analysis: 24 receiving MgSO4 treatment and 21 receiving placebo; 23 (51.1%) were female and 22 (48.9%) were male; and the median gestational age at scan was 40.0 (IQR, 39.1-41.1) weeks. Treatment with MgSO4 was associated with greater voxelwise functional connectivity in the temporal and occipital lobes and deep gray matter structures and with significantly greater clustering coefficients (Hedge g, 0.47 [95% CI, -0.13 to 1.07]), transitivity (Hedge g, 0.51 [95% CI, -0.10 to 1.11]), local efficiency (Hedge g, 0.40 [95% CI, -0.20 to 0.99]), and global efficiency (Hedge g, 0.31 [95% CI, -0.29 to 0.90]), representing enhanced functional segregation and integration. In this cohort study, infants exposed to MgSO4 had greater voxelwise functional connectivity and functional segregation, consistent with increased brain maturation. Enhanced functional connectivity is a possible mechanism by which MgSO4 protects against cerebral palsy and death.

Mechanical pain sensitivity is associated with hippocampal structural integrity.

Rodents and human studies indicate that the hippocampus, a brain region necessary for memory processing, responds to noxious stimuli. However, the hippocampus has yet to be considered a key brain region directly involved in the human pain experience. One approach to answer this question is to perform quantitative sensory testing on patients with hippocampal damage-ie, medial temporal lobe epilepsy. Some case studies and case series have performed such tests in a handful of patients with various types of epilepsy and have reported mixed results. Here, we aimed to determine whether mechanical pain sensitivity was altered in patients diagnosed with temporal lobe epilepsy. We first investigated whether mechanical pain sensitivity in patients with temporal lobe epilepsy differs from that of healthy individuals. Next, in patients with temporal lobe epilepsy, we evaluated whether the degree of pain sensitivity is associated with the degree of hippocampal integrity. Structural integrity was based on hippocampal volume, and functional integrity was based on verbal and visuospatial memory scores. Our findings show that patients with temporal lobe epilepsy have lower mechanical pain sensitivity than healthy individuals. Only left hippocampal volume was positively associated with mechanical pain sensitivity-the greater the hippocampal damage, the lower the sensitivity to mechanical pain. Hippocampal measures of functional integrity were not significantly associated with mechanical pain sensitivity, suggesting that the mechanisms of hippocampal pain processing may be different than its memory functions. Future studies are necessary to determine the mechanisms of pain processing in the hippocampus.

Measures of resting-state brain network segregation and integration vary in relation to data quantity: implications for within and between subject comparisons of functional brain network organization.

Measures of functional brain network segregation and integration vary with an individual's age, cognitive ability, and health status. Based on these relationships, these measures are frequently examined to study and quantify large-scale patterns of network organization in both basic and applied research settings. However, there is limited information on the stability and reliability of the network measures as applied to functional time-series; these measurement properties are critical to understand if the measures are to be used for individualized characterization of brain networks. We examine measurement reliability using several human datasets (Midnight Scan Club and Human Connectome Project [both Young Adult and Aging]). These datasets include participants with multiple scanning sessions, and collectively include individuals spanning a broad age range of the adult lifespan. The measurement and reliability of measures of resting-state network segregation and integration vary in relation to data quantity for a given participant's scan session; notably, both properties asymptote when estimated using adequate amounts of clean data. We demonstrate how this source of variability can systematically bias interpretation of differences and changes in brain network organization if appropriate safeguards are not included. These observations have important implications for cross-sectional, longitudinal, and interventional comparisons of functional brain network organization.

Supersymmetric localization: \U0001d4a9 = (2, 2) theories on S2 and AdS2

Application of the supersymmetric localization method to theories on anti-de Sitter spacetime has received recent interest, yet still remains as a challenging problem. In this paper, we focus on (global) Euclidean AdS2, on which we consider an Abelian \U0001d4a9 = (2, 2) theory and implement localization computation to obtain the exact partition function. For comparison, we also revisit the theory on S2 and perform a parallel computation. We refine the notion of equivariant supersymmetry and use appropriate functional integration measure. For AdS2 we choose a supersymmetric boundary condition which is compatible with the principle of variation. To evaluate the 1-loop determinant about the localization saddle, we use index theory and fixed point formula, where we pay attention to the effect of zero modes and their superpartners. The existence of fermionic superpartner of 1-form boundary zero modes is proven. Obtaining the 1-loop determinant requires expansion of the index that presents an ambiguity, which we resolve using boundary condition. The resulting partition function reveals an overall dependence on the size of the background manifold, AdS2 as well as S2, as a sum of two types of contributions: a local one from local conformal anomaly through the index computation and a global one coming from zero modes. This overall size dependence matches with the perturbative 1-loop evaluation using heat kernel method.

Excitatory and inhibitory imbalances in the trisynaptic pathway in the hippocampus in schizophrenia: a postmortem ultrastructural study.

A preponderance of evidence suggests that the hippocampus is a key region of dysfunction in schizophrenia. Neuroimaging and other studies indicate a relationship between hippocampal dysfunction and the degree of psychosis. Clinical data indicate hyperactivity in the hippocampus that precedes the onset of psychosis, and is correlated with symptom severity. In this study, we sought to identify circuitry at the electron microscopic level that could contribute to region-specific imbalances in excitation and inhibition in the hippocampus in schizophrenia. We used postmortem tissue from the anterior hippocampus from patients with schizophrenia and matched controls. Using stereological techniques, we counted and measured synapses, postsynaptic densities (PSDs), and evaluated size, number and optical density of mitochondria and parvalbumin-containing interneurons in key nodes of the trisynaptic pathway. Compared to controls, the schizophrenia group had decreased numbers of inhibitory synapses in CA3 and increased numbers of excitatory synapses in CA1; together, this indicates deficits in inhibition and an increase in excitation. The thickness of the PSD was larger in excitatory synapses in CA1, suggesting greater synaptic strength. In the schizophrenia group, there were fewer mitochondria in the dentate gyrus and a decrease in the optical density, a measure of functional integrity, in CA1. The number and optical density of parvalbumin interneurons were lower in CA3. The results suggest region-specific increases in excitatory circuitry, decreases in inhibitory neurotransmission and fewer or damaged mitochondria. These results are consistent with the hyperactivity observed in the hippocampus in schizophrenia in previous studies.

Indicators of functional integrity in production animals

An ability to describe the quality of lived experience across the course of an animal’s life is of increasing interest in studies on wellbeing in farm animals. Integrity of physical functions is an important aspect of the tripartite model of wellbeing: feeling, functioning and interacting well. This review examines measures of functional integrity as potential indicators of functional (eudaimonic) wellbeing. Copious literature shows that coping with day-to-day fluctuations in the environment influences (1) periodicity of biorhythms, (2) allocation of resources to growth, defence and repair, and (3) rate of biological aging. Here we review opportunities for assessing functional integrity through analysis of (1) the dynamic status of physiological and behavioural variables, (2) the accretion of resources in production tissues (milk, eggs, body mass, offspring) and physical structures (fibre, hoof, bone, tooth, placoid scale, otolith, beak), and (3) biological age. A reduction in periodicity of biorhythms, complexity of behaviours, or uniformity of trajectories of growth and production is often associated with poorer current and future health outcomes and shorter functional longevity. These analytical approaches are grounded in statistical measures of stability in complex dynamic systems. Additionally, the cumulative effect of wear and tear on biological age can be assessed via telomere length, DNA methylation, biomarkers of allostatic load, hair cortisol, and physiological functional capacity. Timeseries of behaviour, physiology and accretion provide a richer record of functional integrity than do cumulative indicators of biological age. Indicators of integrity are needed for each phase of the animal’s life course including attainment of developmental competencies, stability of mature performance, and rate of decline with advancing age, to provide a comprehensive record across the whole of the animal’s life. The utility of measures may differ between real-time and retrospective assessments and between application to every individual versus sentinels. Further validation is required for interpretating measures of functional integrity as indicators of the functional aspect of wellbeing, together with determining their practicality and reliability before translation to commercial settings is feasible. A single type of indicator of functional wellbeing (e.g. DNA methylation) is unlikely to have utility for all life stages, species, production systems, and environments.

The strong CP problem solved by itself due to long-distance vacuum effects

The vacuum of quantum chromodynamics has an incredibly rich structure at the nonperturbative level, which is intimately connected with the topology of gauge fields, and put to a test by the strong CP problem. We investigate the long-distance properties of the theory in the presence of the topological θ term. This is done on the lattice, using the gradient flow to isolate the long-distance modes in the functional integral measure and tracing it over successive length scales. The key point is that the vacuum splits into disconnected topological sectors with markedly different physical characteristics, which gives rise to a nontrivial behavior depending on θ. We find that the color fields produced by quarks and gluons are screened, and confinement is lost, for bare vacuum angles |θ|>0, thus providing a natural solution of the strong CP problem. The renormalized vacuum angle θ is found to flow to zero in the infrared limit, leading to a self-consistent solution within QCD.

Supersymmetric large-order perturbation with the Nicolai map

In rigidly supersymmetric quantum theories, the Nicolai map allows one to turn on a coupling constant (from zero to a finite value) by keeping the (free) functional integration measure but subjecting the fields to a particular nonlocal and nonlinear transformation. A recursive perturbative construction of the Nicolai-transformed field configuration expresses it as a power series in the coupling, with its coefficient function at order n being a sum of particular tree diagrams. For a quantum-mechanical example, the size of these tree diagrams (under a certain functional norm) is estimated by the (n+1)st power of the field size, and their number grows like n−3/2×4.967n. Such an asymptotic behaviour translates to a finite convergence radius for the formal perturbative expansion of the Nicolai map, which establishes its non-perturbative existence. The known factorial growth of the number of Feynman diagrams for quantum correlators is reproduced by the combinatorics of free-field Wick contractions as usual. We expect our results to extend to higher dimensions, including super Yang–Mills theory.

Improving risk indexes for Alzheimer's disease and related dementias for use in midlife.

Knowledge of a person’s risk for Alzheimer’s disease and related dementias (ADRDs) is required to triage candidates for preventive interventions, surveillance, and treatment trials. ADRD risk indexes exist for this purpose, but each includes only a subset of known risk factors. Information missing from published indexes could improve risk prediction. In the Dunedin Study of a population-representative New Zealand-based birth cohort followed to midlife (N = 938, 49.5% female), we compared associations of four leading risk indexes with midlife antecedents of ADRD against a novel benchmark index comprised of nearly all known ADRD risk factors, the Dunedin ADRD Risk Benchmark (DunedinARB). Existing indexes included the Cardiovascular Risk Factors, Aging, and Dementia index (CAIDE), LIfestyle for BRAin health index (LIBRA), Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI), and risks selected by the Lancet Commission on Dementia. The Dunedin benchmark was comprised of 48 separate indicators of risk organized into 10 conceptually distinct risk domains. Midlife antecedents of ADRD treated as outcome measures included age-45 measures of brain structural integrity [magnetic resonance imaging-assessed: (i) machine-learning-algorithm-estimated brain age, (ii) log-transformed volume of white matter hyperintensities, and (iii) mean grey matter volume of the hippocampus] and measures of brain functional integrity [(i) objective cognitive function assessed via the Wechsler Adult Intelligence Scale-IV, (ii) subjective problems in everyday cognitive function, and (iii) objective cognitive decline measured as residualized change in cognitive scores from childhood to midlife on matched Weschler Intelligence scales]. All indexes were quantitatively distributed and proved informative about midlife antecedents of ADRD, including algorithm-estimated brain age (β's from 0.16 to 0.22), white matter hyperintensities volume (β's from 0.16 to 0.19), hippocampal volume (β's from −0.08 to −0.11), tested cognitive deficits (β's from −0.36 to −0.49), everyday cognitive problems (β's from 0.14 to 0.38), and longitudinal cognitive decline (β's from −0.18 to −0.26). Existing indexes compared favourably to the comprehensive benchmark in their association with the brain structural integrity measures but were outperformed in their association with the functional integrity measures, particularly subjective cognitive problems and tested cognitive decline. Results indicated that existing indexes could be improved with targeted additions, particularly of measures assessing socioeconomic status, physical and sensory function, epigenetic aging, and subjective overall health. Existing premorbid ADRD risk indexes perform well in identifying linear gradients of risk among members of the general population at midlife, even when they include only a small subset of potential risk factors. They could be improved, however, with targeted additions to more holistically capture the different facets of risk for this multiply determined, age-related disease.

Strong CP problem, electric dipole moment, and fate of the axion

Three hard problems! In this talk I investigate the long-distance properties of quantum chromodynamics in the presence of a topological \mathbf{\theta}𝛉 term. This is done on the lattice, using the gradient flow to isolate the long-distance modes in the functional integral measure and tracing it over successive length scales. It turns out that the color fields produced by quarks and gluons are screened, and confinement is lost, for vacuum angles \mathbf{|\theta| > 0}|𝛉|>0, thus providing a natural solution of the strong CP problem. This solution is compatible with recent lattice calculations of the electric dipole moment of the neutron, while it excludes the axion extension of the Standard Model.

Two Ecological Tools for Testing Slowness of Information Processing in Italian Patients with Moderate-to-Severe Traumatic Brain Injury.

we aimed to adapt two ecological instruments assessing SIP in Italian patients with moderate-to-severe TBI, as formerly proposed by Winkens and colleagues for persons with stroke, testing also its possible relation with other neuropsychological processes and functional outcomes. we performed an observational study on 37 patients with moderate-to-severe TBI and 35 demographically matched healthy controls, who underwent the Mental Slowness Observation Test (MSOT) and the Mental Slowness Questionnaire (MSQ), which had been adapted through a pilot study on independent sample of participants; extensive neuropsychological and functional evaluations were performed as well. We found good clinical and psychometric properties of the Italian adaptation of the MSOT and MSQ; also, performance on MSOT significantly correlated with executive functions. Moreover, patients with TBI are significantly slower and less accurate than healthy controls on the MSOT, in particular in tasks with time limits. Even if the subjective feeling of SIP does not differ between patients and controls, we found a significant correlation between MSQ and MSOT. Finally, the performances on the MSOT correlated with measures of functional outcome and community integration. the results support the use of the MSOT and the MSQ to measure SIP in an ecological fashion in patients with TBI, so that specific treatments for persons with acquired brain injury can be prescribed.

Modulation of functional network properties in major depressive disorder following electroconvulsive therapy (ECT): a resting-state EEG analysis

Electroconvulsive therapy (ECT) is a highly effective neuromodulatory intervention for treatment-resistant major depressive disorder (MDD). Presently, however, understanding of its neurophysiological effects remains incomplete. In the present study, we utilised resting-state electroencephalography (RS-EEG) to explore changes in functional connectivity, network topology, and spectral power elicited by an acute open-label course of ECT in a cohort of 23 patients with treatment-resistant MDD. RS-EEG was recorded prior to commencement of ECT and again within 48 h following each patient’s final treatment session. Our results show that ECT was able to enhance connectivity within lower (delta and theta) frequency bands across subnetworks largely confined to fronto-central channels, while, conversely, more widespread subnetworks of reduced connectivity emerged within faster (alpha and beta) bands following treatment. Graph-based topological analyses revealed changes in measures of functional segregation (clustering coefficient), integration (characteristic path length), and small-world architecture following ECT. Finally, post-treatment enhancement of delta and theta spectral power was observed, which showed a positive association with the number of ECT sessions received. Overall, our findings indicate that RS-EEG can provide a sensitive measure of dynamic neural activity following ECT and highlight network-based analyses as a promising avenue for furthering mechanistic understanding of the effects of convulsive therapies.

Modulation of Brain Functional Connectivity and Efficiency During an Endurance Cycling Task: A Source-Level EEG and Graph Theory Approach.

Various methods have been employed to investigate different aspects of brain activity modulation related to the performance of a cycling task. In our study, we examined how functional connectivity and brain network efficiency varied during an endurance cycling task. For this purpose, we reconstructed EEG signals at source level: we computed current densities in 28 anatomical regions of interest (ROIs) through the eLORETA algorithm, and then we calculated the lagged coherence of the 28 current density signals to define the adjacency matrix. To quantify changes of functional network efficiency during an exhaustive cycling task, we computed three graph theoretical indices: local efficiency (LE), global efficiency (GE), and density (D) in two different frequency bands, Alpha and Beta bands, that indicate alertness processes and motor binding/fatigue, respectively. LE is a measure of functional segregation that quantifies the ability of a network to exchange information locally. GE is a measure of functional integration that quantifies the ability of a network to exchange information globally. D is a global measure of connectivity that describes the extent of connectivity in a network. This analysis was conducted for six different task intervals: pre-cycling; initial, intermediate, and final stages of cycling; and active recovery and passive recovery. Fourteen participants performed an incremental cycling task with simultaneous EEG recording and rated perceived exertion monitoring to detect the participants’ exhaustion. LE remained constant during the endurance cycling task in both bands. Therefore, we speculate that fatigue processes did not affect the segregated neural processing. We observed an increase of GE in the Alpha band only during cycling, which could be due to greater alertness processes and preparedness to stimuli during exercise. Conversely, although D did not change significantly over time in the Alpha band, its general reduction in the Beta bands during cycling could be interpreted within the framework of the neural efficiency hypothesis, which posits a reduced neural activity for expert/automated performances. We argue that the use of graph theoretical indices represents a clear methodological advancement in studying endurance performance.

On the discrete version of the black hole solution

A Schwarzschild-type solution in Regge calculus is considered. Earlier, we considered a mechanism of loose fixing of edge lengths due to the functional integral measure arising from integration over connection in the functional integral for the connection representation of the Regge action. The length scale depends on a free dimensionless parameter that determines the final functional measure. For this parameter and the length scale large in Planck units, the resulting effective action is close to the Regge action. Earlier, we considered the Regge action in terms of affine connection matrices as functions of the metric inside the 4-simplices and found that it is a finite-difference form of the Hilbert–Einstein action in the leading order over metric variations between the 4-simplices. Now we take the (continuum) Schwarzschild problem in the form where spherical symmetry is not set a priori and arises just in the solution, take the finite-difference form of the corresponding equations and get the metric (in fact, in the Lemaitre or Painlevé–Gullstrand like frame), which is nonsingular at the origin, just as the Newtonian gravitational potential, obeying the difference Poisson equation with a point source, is cutoff at the elementary length and is finite at the source.

Nonlocal Scalar Quantum Field Theory—Functional Integration, Basis Functions Representation and Strong Coupling Expansion

Nonlocal quantum field theory (QFT) of one-component scalar field φ in D-dimensional Euclidean spacetime is considered. The generating functional (GF) of complete Green functions Z as a functional of external source j, coupling constant g and spatial measure d μ is studied. An expression for GF Z in terms of the abstract integral over the primary field φ is given. An expression for GF Z in terms of integrals over the primary field and separable Hilbert space (HS) is obtained by means of a separable expansion of the free theory inverse propagator L ^ over the separable HS basis. The classification of functional integration measures D φ is formulated, according to which trivial and two nontrivial versions of GF Z are obtained. Nontrivial versions of GF Z are expressed in terms of 1-norm and 0-norm, respectively. In the 1-norm case in terms of the original symbol for the product integral, the definition for the functional integration measure D φ over the primary field is suggested. In the 0-norm case, the definition and the meaning of 0-norm are given in terms of the replica-functional Taylor series. The definition of the 0-norm generator Ψ is suggested. Simple cases of sharp and smooth generators are considered. An alternative derivation of GF Z in terms of 0-norm is also given. All these definitions allow to calculate corresponding functional integrals over φ in quadratures. Expressions for GF Z in terms of integrals over the separable HS, aka the basis functions representation, with new integrands are obtained. For polynomial theories φ 2 n , n = 2 , 3 , 4 , … , and for the nonpolynomial theory sinh 4 φ , integrals over the separable HS in terms of a power series over the inverse coupling constant 1 / g for both norms (1-norm and 0-norm) are calculated. Thus, the strong coupling expansion in all theories considered is given. “Phase transitions” and critical values of model parameters are found numerically. A generalization of the theory to the case of the uncountable integral over HS is formulated—GF Z for an arbitrary QFT and the strong coupling expansion for the theory φ 4 are derived. Finally a comparison of two GFs Z , one on the continuous lattice of functions and one obtained using the Parseval–Plancherel identity, is given.

Markers of neuroinflammation influence measures of cortical thickness in bipolar depression

We tested if peripheral levels of cytokines and chemokines associate to grey matter volumes, cortical thickness and fMRI neural responses to a moral valence decision task in bipolar patients. ICAM1 and CCL4 negatively correlated with cortical thickness in Inferior Temporal Gyrus, and sCD25 in Parahippocampal Gyrus. TNF-α, Interleukine-8, and CCL2 correlated positively with cortical thickness in the Anterior Cingulate Cortex, and with lower BOLD responses to negative stimuli. Markers of immune activation are associated with measures of brain structural and functional integrity in bipolar depression.

Accelerated Aging of Functional Brain Networks Supporting Cognitive Function in Psychotic Disorders

BackgroundAcross networks, connectivity within the frontoparietal network (FPN) and cingulo-opercular network (CON) exhibits reductions earliest during healthy aging, contributing to cognitive impairment. Individuals with psychotic disorders demonstrate evidence of accelerated aging across multiple biological systems. By leveraging a large sample of patients with psychosis from early to chronic illness stages, this study sought to determine whether the CON and FPN exhibit evidence of accelerated aging in psychotic disorders, confirm associations between network efficiency and cognition, and determine whether reduced network efficiency is observed in early-stage psychosis. MethodsResting-state functional magnetic resonance imaging and cognitive data were obtained on 240 patients with psychotic disorder and 178 healthy control participants (HCs). Global efficiency, a measure of functional integration, was calculated for the CON, FPN, subcortical network, and visual network. Associations with age and cognition were assessed and compared between groups. ResultsConsistent with accelerated aging, significant group by age interactions reflected significantly stronger relationships between efficiency and age in patients with psychosis than in HCs for both the CON (psychosis: r = −.37; HC: r = −.16) and FPN (psychosis: r = −.31; HC: r = −.05). Accelerated aging was not observed in either the subcortical or visual network, suggesting specificity for cognitive networks that decline earliest in healthy aging. Replicating prior findings, efficiency of both the CON and FPN correlated with cognitive function across all participants (rs > .11, ps < .031). Furthermore, patients with chronic psychosis (p = .004), but not patients with early psychosis (p = .553), exhibited significantly lower FPN efficiency compared with HCs. ConclusionsFunctional integration of higher-order cognitive networks is intact in early psychosis but exhibits evidence of accelerated aging, suggesting the potential for intervention targeting cognition within the early psychosis period.

Alterations in basal ganglia-cerebello-thalamo-cortical connectivity and whole brain functional network topology in Tourette's syndrome.

Tourette Syndrome (TS) is a neuropsychiatric disorder characterized by the presence of motor and vocal tics. Major pathophysiological theories posit a dysfunction of the cortico-striato-thalamo-cortical circuits as being a representative hallmark of the disease. Recent evidence suggests a more widespread dysfunction of brain networks in TS including the cerebellum and going even beyond classic motor pathways.In order to characterize brain network dysfunction in TS, in this study we investigated functional and effective-like connectivity as well as topological changes of basal ganglia-thalamo-cortical and cortico-cerebellar brain networks. We collected resting-state fMRI data from 28 TS patients (age: 32 ± 11 years) and 28 age-matched, healthy controls (age: 31 ± 9 years). Region of interest based (ROI-ROI) bivariate correlation and ROI-ROI bivariate regression were employed as measures of functional and effective-like connectivity, respectively. Graph theoretical measures of centrality (degree, cost, betweenness centrality), functional segregation (clustering coefficient, local efficiency) and functional integration (average path length, global efficiency) were used to assess topological brain network changes.In this study, TS patients exhibited increased basal ganglia-cortical and thalamo-cortical connectivity, reduced cortico-cerebellar connectivity, and an increase in parallel communication through the basal ganglia, thalamus and cerebellum (increased global efficiency). Additionally, we observed a reduction in serial information transfer (reduction in average path length) within the default mode and the salience network.In summary, our findings show that TS is characterized by increased connectivity and functional integration of multiple basal ganglia-thalamo-cortical circuits, suggesting a predominance of excitatory neurotransmission and a lack of brain maturation. Moreover, topological changes of cortico-cerebellar and brain networks involved in interoception may be underestimated neural correlates of tics and the crucial premonitory urge feeling.

Increased inflammation and brain glutamate define a subtype of depression with decreased regional homogeneity, impaired network integrity, and anhedonia

Combined increases in peripheral inflammation and brain glutamate may identify a subtype of depression with distinct neuroimaging signatures. Two contrasting subgroups of depressed subjects—with and without combined elevations in plasma C-reactive protein (CRP) and basal ganglia glutamate (high and low CRP-Glu, respectively) were identified by hierarchical clustering using plasma CRP (indexing peripheral inflammation) and magnetic resonance spectroscopy (MRS)-based measurement of left basal ganglia glutamate. High CRP-Glu group status was associated with greater severity of anhedonia and cognitive and motor slowing. Local- and network-level measures of functional integrity were determined using brain oxygen level-dependent (BOLD)-oscillatory activity and graph theory. Greater decreases in concordance of oscillatory activity between neighboring voxels (Regional Homogeneity ‘ReHo’, p < 0.01) within the MRS volume-of-interest was associated with the High CRP-Glu subgroup. Using brain-wide, CRP-Glu ReHo contrast maps, a covariance network of 41 regions-of-interest (ROIs) with similar ReHo decreases was identified in the High CRP-Glu group and was located to brain structures previously implicated in depression. The 41-ROI network was further decomposed into four subnetworks. ReHo decreases within Subnetwork4—comprised of reward processing regions —was associated with anhedonia. Subnetwork4 ReHo also predicted decreased network integrity, which mediated the link between local ReHo and anhedonia in the Low but not High CRP-Glu group. These findings suggest that decreased ReHo and related disruptions in network integrity may reflect toxic effects of inflammation-induced increases in extrasynaptic glutamate signaling. Moreover, local BOLD oscillatory activity as reflected in ReHo might be a useful measure of target-engagement in the brain for treatment of inflammation-induced behaviors.

Distinct spatiotemporal patterns of neuronal functional connectivity in primary progressive aphasia variants.

Primary progressive aphasia is a syndrome characterized by progressive loss of language abilities with three main phenotypic clinical presentations, including logopenic, non-fluent/agrammatic, and semantic variants. Previous imaging studies have shown unique anatomic impacts within language networks in each variant. However, direct measures of spontaneous neuronal activity and functional integrity of these impacted neural networks in primary progressive aphasia are lacking. The aim of this study was to characterize the spatial and temporal patterns of resting state neuronal synchronizations in primary progressive aphasia syndromes. We hypothesized that resting state brain oscillations will show unique deficits within language network in each variant of primary progressive aphasia. We examined 39 patients with primary progressive aphasia including logopenic variant (n = 14, age = 61 ± 9 years), non-fluent/agrammatic variant (n = 12, age = 71 ± 8 years) and semantic variant (n = 13, age = 65 ± 7 years) using magnetoencephalographic imaging, compared to a control group that was matched in age and gender to each primary progressive aphasia subgroup (n = 20, age = 65 ± 5 years). Each patient underwent a complete clinical evaluation including a comprehensive battery of language tests. We examined the whole-brain resting state functional connectivity as measured by imaginary coherence in each patient group compared to the control cohort, in three frequency oscillation bands-delta-theta (2-8 Hz); alpha (8-12 Hz); beta (12-30 Hz). Each variant showed a distinct spatiotemporal pattern of altered functional connectivity compared to age-matched controls. Specifically, we found significant hyposynchrony of alpha and beta frequency within the left posterior temporal and occipital cortices in patients with the logopenic variant, within the left inferior frontal cortex in patients with the non-fluent/agrammatic variant, and within the left temporo-parietal junction in patients with the semantic variant. Patients with logopenic variant primary progressive aphasia also showed significant hypersynchrony of delta-theta frequency within bilateral medial frontal and posterior parietal cortices. Furthermore, region of interest-based analyses comparing the spatiotemporal patterns of variant-specific regions of interest identified in comparison to age-matched controls showed significant differences between primary progressive aphasia variants themselves. We also found distinct patterns of regional spectral power changes in each primary progressive aphasia variant, compared to age-matched controls. Our results demonstrate neurophysiological signatures of network-specific neuronal dysfunction in primary progressive aphasia variants. The unique spatiotemporal patterns of neuronal synchrony signify diverse neurophysiological disruptions and pathological underpinnings of the language network in each variant.