Schizophrenia is a psychiatric disorder with heterogeneous clinical manifestations and complex aetiology. Notably, the triple-network model proposes an interesting framework for investigating abnormal neurocircuit activity at rest in schizophrenia. The present study on 30 chronic schizophrenia individuals and 30 controls aimed to explore the differences in EEG resting state effective connectivity within a triple-network model using source-localization-based Directed Transfer Function. Our findings revealed multiband effective connectivity disturbances within default mode (DMN), central executive (CEN), and salience (SN) networks in schizophrenia. The most significant difference was manifested in a global DMN hyperconnectivity, accompanied by low-band hyperconnectivity and high-band hypoconnectivity in CEN, along with the aberrant information flows in SN. In conclusion, our study presents novel insights into schizophrenia neuropathology, with a particular emphasis on the reversed directionality in information flows between hubs of SN, DMN, and CEN. This may be suggested as a promising biomarker of schizophrenia.

• Keywords
• Central executive network, Default mode network, EEG, Effective connectivity, Resting-state, Schizophrenia,
• MeSH
• Default Mode Network * physiopathology   MeSH
• Adult MeSH
• Electroencephalography MeSH
• Connectome * methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Nerve Net * physiopathology   diagnostic imaging   MeSH
• Schizophrenia * physiopathology   diagnostic imaging   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Brain imaging studies in complex regional pain syndrome (CRPS) have found mixed evidence for functional and structural changes in CRPS. In this cross-sectional study, we evaluated two patient cohorts from different centers and examined functional connectivity (rsFC) in 51 CRPS patients and 50 matched controls. rsFC was compared in predefined ROI pairs, but also in non-hypothesis driven analyses. Resting state (rs)fMRI changes in default mode network (DMN) and the degree rank order disruption index (kD) were additionally evaluated. Finally, imaging parameters were correlated with clinical severity and somatosensory function. Among predefined pairs, we found only weakly to moderately lower functional connectivity between the right nucleus accumbens and bilateral ventromedial prefrontal cortex in the infra-slow oscillations (ISO) band. The unconstrained ROI-to-ROI analysis revealed lower rsFC between the periaqueductal gray matter (PAG) and left anterior insula, and higher rsFC between the right sensorimotor thalamus and nucleus accumbens. In the correlation analysis, pain was positively associated with insulo-prefrontal rsFC, whereas sensorimotor thalamo-cortical rsFC was positively associated with tactile spatial resolution of the affected side. In contrast to previous reports, we found no group differences for kD or rsFC in the DMN, but detected overall lower data quality in patients. In summary, while some of the previous results were not replicated despite the larger sample size, novel findings from two independent cohorts point to potential down-regulated antinociceptive modulation by the PAG and increased connectivity within the reward system as pathophysiological mechanisms in CRPS. However, in light of the detected systematic differences in data quality between patients and healthy subjects, validity of rsFC abnormalities in CRPS should be carefully scrutinized in future replication studies.

• Keywords
• Biomarker, CRPS, Functional connectivity, Neuropathic pain, Resting-state fMRI,
• MeSH
• Default Mode Network diagnostic imaging   physiopathology   MeSH
• Adult MeSH
• Complex Regional Pain Syndromes * physiopathology   diagnostic imaging   MeSH
• Connectome methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Brain physiopathology   diagnostic imaging   MeSH
• Nerve Net physiopathology   diagnostic imaging   MeSH
• Cross-Sectional Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Brain activity during the resting state is widely used to examine brain organization, cognition and alterations in disease states. While it is known that neuromodulation and the state of alertness impact resting-state activity, neural mechanisms behind such modulation of resting-state activity are unknown. In this work, we used a computational model to demonstrate that change in excitability and recurrent connections, due to cholinergic modulation, impacts resting-state activity. The results of such modulation in the model match closely with experimental work on direct cholinergic modulation of Default Mode Network (DMN) in rodents. We further extended our study to the human connectome derived from diffusion-weighted MRI. In human resting-state simulations, an increase in cholinergic input resulted in a brain-wide reduction of functional connectivity. Furthermore, selective cholinergic modulation of DMN closely captured experimentally observed transitions between the baseline resting state and states with suppressed DMN fluctuations associated with attention to external tasks. Our study thus provides insight into potential neural mechanisms for the effects of cholinergic neuromodulation on resting-state activity and its dynamics.

• MeSH
• Acetylcholine metabolism   MeSH
• Default Mode Network physiology   diagnostic imaging   MeSH
• Adult MeSH
• Connectome * MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Models, Neurological * MeSH
• Brain * physiology   diagnostic imaging   MeSH
• Nerve Net physiology   diagnostic imaging   MeSH
• Rest * physiology   MeSH
• Computer Simulation MeSH
• Computational Biology MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Acetylcholine MeSH

Alcohol Use Disorder (AUD) adversely affects the lives of millions of people, but still lacks effective treatment options. Recent advancements in psychedelic research suggest psilocybin to be potentially efficacious for AUD. However, major knowledge gaps remain regarding (1) psilocybin's general mode of action and (2) AUD-specific alterations of responsivity to psilocybin treatment in the brain that are crucial for treatment development. Here, we conducted a randomized, placebo-controlled crossover pharmaco-fMRI study on psilocybin effects using a translational approach with healthy rats and a rat model of alcohol relapse. Psilocybin effects were quantified with resting-state functional connectivity using data-driven whole-brain global brain connectivity, network-based statistics, graph theory, hypothesis-driven Default Mode Network (DMN)-specific connectivity, and entropy analyses. Results demonstrate that psilocybin induced an acute wide-spread decrease in different functional connectivity domains together with a distinct increase of connectivity between serotonergic core regions and cortical areas. We could further provide translational evidence for psilocybin-induced DMN hypoconnectivity reported in humans. Psilocybin showed an AUD-specific blunting of DMN hypoconnectivity, which strongly correlated to the alcohol relapse intensity and was mainly driven by medial prefrontal regions. In conclusion, our results provide translational validity for acute psilocybin-induced neural effects in the rodent brain. Furthermore, alcohol relapse severity was negatively correlated with neural responsivity to psilocybin treatment. Our data suggest that a clinical standard dose of psilocybin may not be sufficient to treat severe AUD cases; a finding that should be considered for future clinical trials.

• MeSH
• Alcoholism * diagnostic imaging   drug therapy   MeSH
• Default Mode Network MeSH
• Ethanol MeSH
• Hallucinogens * pharmacology   MeSH
• Rats MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Brain diagnostic imaging   MeSH
• Psilocybin pharmacology   MeSH
• Recurrence MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Ethanol MeSH
• Hallucinogens * MeSH
• Psilocybin MeSH

The salience network (SN), ventral attention network (VAN), dorsal attention network (DAN) and default mode network (DMN) have shown significant interactions and overlapping functions in bottom-up and top-down mechanisms of attention. In the present study, we tested if the SN, VAN, DAN and DMN connectivity can infer the gestational age (GA) at birth in a study group of 88 healthy neonates, scanned at 40 weeks of post-menstrual age, and with GA at birth ranging from 28 to 40 weeks. We also ascertained whether the connectivity within each of the SN, VAN, DAN and DMN was able to infer the average functional connectivity of the others. The ability to infer GA at birth or another network's connectivity was evaluated using a multivariate data-driven framework. The VAN, DAN and the DMN inferred the GA at birth (p < 0.05). The SN, DMN and VAN were able to infer the average connectivity of the other networks (p < 0.05). Mediation analysis between VAN's and DAN's inference on GA at birth found reciprocal transmittance of change with GA at birth of VAN's and DAN's connectivity (p < 0.05). Our findings suggest that the VAN has a prominent role in bottom-up salience detection in early infancy and that the role of the VAN and the SN may overlap in the bottom-up control of attention.

• Keywords
• Bottom-up salience detection, Data-driven analysis, Default mode network, Dorsal attention network, Mediation analysis, Salience network, Ventral attention network,
• MeSH
• Default Mode Network * MeSH
• Gestational Age MeSH
• Infant MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain Mapping * MeSH
• Brain diagnostic imaging   MeSH
• Nerve Net diagnostic imaging   MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Publication type
• Journal Article MeSH

The disproportionate evolutionary expansion of the human cerebral cortex with reinforcement of cholinergic innervations warranted a major rise in the functional and metabolic load of the conserved basal forebrain (BF) cholinergic system. Given that acetylcholine (ACh) regulates properties of the microtubule-associated protein (MAP) tau and promotes non-amyloidogenic processing of amyloid precursor protein (APP), growing neocortex predicts higher demands for ACh, while the emerging role of BF cholinergic projections in Aβ clearance infers greater exposure of source neurons and their innervation fields to amyloid pathology. The higher exposure of evolutionary most recent cortical areas to the amyloid pathology of Alzheimer's disease (AD) with synaptic impairments and atrophy, therefore, might involve attenuated homeostatic effects of BF cholinergic projections, in addition to fall-outs of inherent processes of expanding association areas. This unifying model, thus, views amyloid pathology and loss of cholinergic cells as a quid pro quo of the allometric evolution of the human brain, which in combination with increase in life expectancy overwhelm the fine homeostatic balance and trigger the disease process.

• Keywords
• Alzheimer’s disease, Amyloid deposition, Brain evolution, Cholinergic neurons, Cortical expansion, Default mode networks, p75 NTR,
• MeSH
• Alzheimer Disease metabolism   pathology   MeSH
• Default Mode Network metabolism   pathology   MeSH
• Phylogeny * MeSH
• Humans MeSH
• Cerebral Cortex metabolism   pathology   MeSH
• Cholinergic Neurons metabolism   pathology   MeSH
• Nerve Tissue Proteins metabolism   MeSH
• Receptors, Nerve Growth Factor metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• NGFR protein, human MeSH Browser
• Nerve Tissue Proteins MeSH
• Receptors, Nerve Growth Factor MeSH