Alterations in the default mode network (DMN) are associated with aging. We assessed age-dependent changes of DMN interactions and correlations with a battery of neuropsychological tests, to understand the differences of DMN directed connectivity between young and older subjects. Using a novel multivariate analysis method on resting-state functional MRI data from fifty young and thirty-one healthy older subjects, we calculated intra- and inter-DMN 4-nodes directed pathways. For the old subject group, we calculated the partial correlations of inter-DMN pathways with: psychomotor speed and working memory, executive function, language, long-term memory and visuospatial function. Pathways connecting the DMN with visual and limbic regions in older subjects engaged at BOLD low frequency and involved the dorsal posterior cingulate cortex (PCC), whereas in young subjects, they were at high frequency and involved the ventral PCC. Pathways combining the sensorimotor (SM) cortex and the DMN, were SM efferent in the young subjects and SM afferent in the older subjects. Most DMN efferent pathways correlated with reduced speed and working memory. We suggest that the reduced sensorimotor efferent and the increased need to control such activities, cause a higher dependency on external versus internal cues thus suggesting how physical activity might slow aging.
- MeSH
- Memory, Short-Term MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Brain Mapping * methods MeSH
- Brain * diagnostic imaging MeSH
- Neural Pathways MeSH
- Aged MeSH
- Aging MeSH
- Healthy Volunteers MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Studies in the sensorimotor system of older versus young individuals have shown alterations in functional connectivity and organization. Our objective was to explore the implications of these differences in terms of local organizations, and to identify processes that correlate with neuropsychological parameters. METHODS: Using a novel multivariate analysis method on resting-state functional MRI data obtained from 50 young and 31 older healthy individuals, we identified directed 4-node functional pathways within the sensorimotor system and examined their correlations with neuropsychological assessments. RESULTS: In young individuals, the functional pathways were unidirectional, flowing from the primary motor and sensory cortices to higher motor and visual regions. In older individuals, the functional pathways were more complex. They originated either from the calcarine sulcus or the insula and passed through mutually coupled high-order motor areas before reaching the primary sensory and motor cortices. Additionally, the pathways in older individuals that resembled those found in young individuals exhibited a positive correlation with years of education. DISCUSSION: The flow pattern of young individuals suggests efficient and fast information transfer. In contrast, the mutual coupling of high-order motor regions in older individuals suggests an inefficient and slow transfer, a less segregated and a more integrated organization. The differences in the number of sensorimotor pathways and of their directionality suggests reduced efferent degenerated pathways and increased afferent compensated pathways. Furthermore, the positive effect of years of education may be associated with the Cognitive Reserve Hypothesis, implying that cognitive reserve could be maintained through specific information transfer pathways.
- Publication type
- Journal Article MeSH
CONTEXT: Research in lipodystrophy (LD) and its treatment with metreleptin has not only helped patients with LD but has opened new directions in investigating leptin's role in metabolism and the regulation of eating behavior. Previously, in a study with patients with LD undergoing metreleptin treatment using functional magnetic resonance imaging (MRI), we found significantly increased resting-state brain connectivity in 3 brain areas including the hypothalamus. OBJECTIVE: In this study, we aimed to reproduce our functional MRI findings in an independent sample and compare results to healthy participants. DESIGN: Measurements in 4 female patients with LD undergoing metreleptin treatment and 3 healthy untreated controls were performed at 4 different time points over 12 weeks. To identify treatment-related brain connectivity alterations, eigenvector centrality was computed from resting-state functional MRI data for each patient and each session. Thereafter, analysis aimed at detecting consistent brain connectivity changes over time across all patients. RESULTS: In parallel to metreleptin treatment of the patients with LD, we found a significant brain connectivity increase in the hypothalamus and bilaterally in posterior cingulate gyrus. Using a 3-factorial model, a significant interaction between group and time was found in the hypothalamus. CONCLUSIONS: Investigating brain connectivity alterations with metreleptin treatment using an independent sample of patients with LD, we have reproduced an increase of brain connectivity in hedonic and homeostatic central nervous networks observed previously with metreleptin treatment. These results are an important contribution to ascertain brain leptin action and help build a foundation for further research of central nervous effects of this important metabolic hormone.
- Publication type
- Journal Article MeSH
We spend much our lives interacting with others in various social contexts. Although we deal with this myriad of interpersonal exchanges with apparent ease, each one relies upon a broad array of sophisticated cognitive processes. Recent research suggests that the cognitive operations supporting interactive behaviour are themselves underpinned by several canonical functional brain networks (CFNs) that integrate dynamically with one another in response to changing situational demands. Dynamic integrations among these CFNs should therefore play a pivotal role in coordinating interpersonal behaviour. Further, different types of interaction should present different demands on cognitive systems, thereby eliciting distinct patterns of dynamism among these CFNs. To investigate this, the present study performed functional magnetic resonance imaging (fMRI) on 30 individuals while they interacted with one another cooperatively or competitively. By applying a novel combination of analytical techniques to these brain imaging data, we identify six states of dynamic functional connectivity characterised by distinct patterns of integration and segregation among specific CFNs that differ systematically between these opposing types of interaction. Moreover, applying these same states to fMRI data acquired from an independent sample engaged in the same kinds of interaction, we were able to classify interpersonal exchanges as cooperative or competitive. These results provide the first direct evidence for the systematic involvement of CFNs during social interactions, which should guide neurocognitive models of interactive behaviour and investigations into biomarkers for the interpersonal dysfunction characterizing many neurological and psychiatric disorders.
- MeSH
- Mental Disorders * MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Brain Mapping MeSH
- Brain physiology MeSH
- Social Interaction * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: The aim of this study was to analyze the relation between the hepatic fibrosis markers, liver morphology and hemodynamics assessed by magnetic resonance imaging (MRI) after total cavopulmonary connection (TCPC). MATERIALS AND METHODS: Adult patients after TCPC performed in childhood between 1993 and 2003 are the subjects of this observational study. The follow-up protocol consisted of clinical and echocardiographic examination, liver elastography, cardiopulmonary exercise test, MRI hemodynamics and liver morphology assessment and direct enhanced liver fibrosis (ELF) test. RESULTS: The cohort consisted of 39 patients (46% female) with a median age at study 26 (IQR 23-28) years and interval from TCPC 21 (IQR 20-23) years. There was no correlation between ELF test and any MRI variables, but procollagen III amino-terminal peptide (PIIINP), a single component of ELF test, correlated significantly with ventricular end-diastolic volume (r = 0.33; p = 0.042) and inferior vena cava flow (r = 0.47; p = 0.003). Fifteen (38%) patients with liver nodules had compared to other 24 patients higher end-diastolic volume (ml/m2) 102.8 ± 20.0 vs. 88.2 ± 17.7; p = 0.023, respectively. PIIINP correlated significantly with inferior vena cava flow (r = 0.56; p = 0.030) and with end-diastolic volume (r = 0.53; p = 0.043), but only in patients with liver nodules. CONCLUSION: Gradual progression of liver fibrosis, particularly hepatic arterialization caused by liver nodules formation, increases inferior vena cava flow and subsequent ventricular volume overload may further compromise single ventricle functional reserve in adult patients after TCPC.
- Publication type
- Journal Article MeSH
BACKGROUND: Deep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms. OBJECTIVES: The aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome. METHODS: This open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity). RESULTS: Compared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls. CONCLUSIONS: All in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia.
- MeSH
- Dystonia * therapy MeSH
- Globus Pallidus physiology MeSH
- Deep Brain Stimulation * MeSH
- Humans MeSH
- Cross-Sectional Studies MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Dopamine depletion in the axons of Parkinson's disease (PD) patients precedes depletion in cell bodies thus proposing that macroscopic connectivity can be used to understand disease mechanism. A novel multivariate functional connectivity analysis, based on high order coherence among four fMRI BOLD signals was applied on resting-state fMRI data of controls and PD patients (OFF and ON medication states) and unidirectional multiple-region pathways in the sensorimotor system were identified. Pathways were classified as "preserved" (unaffected by the disease), "damaged" (not observed in patients) and "corrected" (observed in controls and in PD-ON state). The majority of all pathways were feedforward, most of them with the pattern "S1→M1→SMA." Of these pathways, 67% were "damaged," 28% "preserved," and 5% "corrected." Prefrontal cortex (PFC) afferent and efferent pathways that corresponded to goal directed and habitual activities corresponded to recurrent circuits. Eighty-one percent of habitual afferent had internal cue (i.e., M1→S1→), of them 79% were "damaged" and the rest "preserved." All goal-directed afferent had external cue (i.e., S1→M1→) with third "damaged," third "preserved," and third "corrected." Corrected pathways were initiated in the dorsolateral PFC. Reduced connectivity of the SMA and PFC resulted from reduced sensorimotor afferent to these regions. Reduced sensorimotor internal cues to the PFC resulted with reduced habitual processes. Levodopa effects were for pathways that started in region reach with dopamine receptors. This methodology can enrich understudying of PD mechanisms in other (e.g., the default mode network) systems.
- MeSH
- Levodopa MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Brain Mapping MeSH
- Neural Pathways MeSH
- Rest MeSH
- Parkinson Disease * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Many cognitive functions, including working memory, are processed within large-scale brain networks. We targeted the right frontoparietal network (FPN) with one session of transcranial direct current stimulation (tDCS) in an attempt to modulate the cognitive speed of a visual working memory task (WMT) in 27 young healthy subjects using a double-blind crossover design. We further explored the neural underpinnings of induced changes by performing resting-state fMRI prior to and immediately after each stimulation session with the main focus on the interaction between a task-positive FPN and a task-negative default mode network (DMN). Twenty minutes of 2 mA anodal tDCS was superior to sham stimulation in terms of cognitive speed manipulation of a subtask with processing of objects and tools in unconventional views (i.e., the higher cognitive load subtask of the offline WMT). This result was linked to the magnitude of resting-state functional connectivity decreases between the stimulated FPN seed and DMN seeds. We provide the first evidence for the action reappraisal mechanism of object and tool processing. Modulation of cognitive speed of the task by tDCS was reflected by FPN-DMN cross-talk changes.
- MeSH
- Frontal Lobe diagnostic imaging physiopathology MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Cross-Over Studies MeSH
- Memory, Short-Term physiology MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Adolescent MeSH
- Young Adult MeSH
- Neuropsychological Tests MeSH
- Transcranial Direct Current Stimulation MeSH
- Reaction Time physiology MeSH
- Parietal Lobe diagnostic imaging physiopathology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Developing sensitive and reliable methods to distinguish normal and abnormal brain states is a key neuroscientific challenge. Topological Data Analysis, despite its relative novelty, already generated many promising applications, including in neuroscience. We conjecture its prominent tool of persistent homology may benefit from going beyond analysing structural and functional connectivity to effective connectivity graphs capturing the direct causal interactions or information flows. Therefore, we assess the potential of persistent homology to directed brain network analysis by testing its discriminatory power in two distinctive examples of disease-related brain connectivity alterations: epilepsy and schizophrenia. We estimate connectivity from functional magnetic resonance imaging and electrophysiology data, employ Persistent Homology and quantify its ability to distinguish healthy from diseased brain states by applying a support vector machine to features quantifying persistent homology structure. We show how this novel approach compares to classification using standard undirected approaches and original connectivity matrices. In the schizophrenia classification, topological data analysis generally performs close to random, while classifications from raw connectivity perform substantially better; potentially due to topographical, rather than topological, specificity of the differences. In the easier task of seizure discrimination from scalp electroencephalography data, classification based on persistent homology features generally reached comparable performance to using raw connectivity, albeit with typically smaller accuracies obtained for the directed (effective) connectivity compared to the undirected (functional) connectivity. Specific applications for topological data analysis may open when direct comparison of connectivity matrices is unsuitable - such as for intracranial electrophysiology with individual number and location of measurements. While standard homology performed overall better than directed homology, this could be due to notorious technical problems of accurate effective connectivity estimation.
- MeSH
- Electroencephalography MeSH
- Epilepsy diagnostic imaging physiopathology MeSH
- Connectome * MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Brain Mapping MeSH
- Models, Neurological * MeSH
- Brain diagnostic imaging physiopathology MeSH
- Nerve Net diagnostic imaging physiopathology MeSH
- Schizophrenia diagnostic imaging physiopathology MeSH
- Seizures diagnostic imaging physiopathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Figurative language processing (e.g. metaphors) is commonly impaired in schizophrenia. In the present study, we investigated the neural activity and propagation of information within neural circuits related to the figurative speech, as a neural substrate of impaired conventional metaphor processing in schizophrenia. The study included 30 schizophrenia outpatients and 30 healthy controls, all of whom were assessed with a functional Magnetic Resonance Imaging (fMRI) and electroencephalography (EEG) punchline-based metaphor comprehension task including literal (neutral), figurative (metaphorical) and nonsense (absurd) endings. The blood oxygenation level-dependent signal was recorded with 3T MRI scanner and direction and strength of cortical information flow in the time course of task processing was estimated with a 64-channel EEG input for directed transfer function. The presented results revealed that the behavioral manifestation of impaired figurative language in schizophrenia is related to the hypofunction in the bilateral fronto-temporo-parietal brain regions (fMRI) and various differences in effective connectivity in the fronto-temporo-parietal circuit (EEG). Schizophrenia outpatients showed an abnormal pattern of connectivity during metaphor processing which was related to bilateral (but more pronounced at the left hemisphere) hypoactivation of the brain. Moreover, we found reversed lateralization patterns, i.e. a rightward-shifted pattern during metaphor processing in schizophrenia compared to the control group. In conclusion, the presented findings revealed that the impairment of the conventional metaphor processing in schizophrenia is related to the bilateral brain hypofunction, which supports the evidence on reversed lateralization of the language neural network and the existence of compensatory recruitment of alternative neural circuits in schizophrenia.
