A Precuneal Causal Loop Mediates External and Internal Information Integration in the Human Brain.

Human brains interpret external stimuli based on internal representations. One untested hypothesis is that the default-mode network (DMN), widely considered responsible for internally oriented cognition, can decode external information. Here, we posit that the unique structural and functional fingerprint of the precuneus (PCu) supports a prominent role for the posterior part of the DMN in this process. By analyzing the imaging data of 100 participants performing two attention-demanding tasks, we found that the PCu is functionally divided into dorsal and ventral subdivisions. We then conducted a comprehensive examination of their connectivity profiles and found that at rest, both the ventral PCu (vPCu) and dorsal PCu (dPCu) are mainly connected with the DMN but also are differentially connected with internally oriented networks (IoN) and externally oriented networks (EoN). During tasks, the double associations between the v/dPCu and the IoN/EoN are correlated with task performance and can switch depending on cognitive demand. Furthermore, dynamic causal modeling (DCM) revealed that the strength and direction of the effective connectivity (EC) between v/dPCu is modulated by task difficulty in a manner potentially dictated by the balance of internal versus external cognitive demands. Our study provides evidence that the posterior medial part of the DMN may drive interactions between large-scale networks, potentially allowing access to stored representations for moment-to-moment interpretation of an ever-changing environment.SIGNIFICANCE STATEMENT The default-mode network (DMN) is widely known for its association with internalized thinking processes, e.g., spontaneous thoughts, which is the most interesting but least understood component in human consciousness. The precuneus (PCu), a posteromedial DMN hub, is thought to play a role in this, but a mechanistic explanation has not yet been established. In this study we found that the associations between ventral PCu (vPCu)/dorsal PCu (dPCu) subdivisions and internally oriented network (IoN)/externally oriented network (EoN) are flexibly modulated by cognitive demand and correlate with task performance. We further propose that the recurrent causal connectivity between the ventral and dorsal PCu supports conscious processing by constantly interpreting external information based on an internal model, meanwhile updating the internal model with the incoming information.

Causal Cortical and Thalamic Connections in the Human Brain.

The brain's functional architecture is intricately shaped by causal connections between its cortical and subcortical structures. Here, we studied 27 participants with 4864 electrodes implanted across the anterior, mediodorsal, and pulvinar thalamic regions, and the cortex. Using data from electrical stimulation procedures and a data-driven approach informed by neurophysiological standards, we dissociated three unique spectral patterns generated by the perturbation of a given brain area. Among these, a novel waveform emerged, marked by delayed-onset slow oscillations in both ipsilateral and contralateral cortices following thalamic stimulations, suggesting a mechanism by which a thalamic site can influence bilateral cortical activity. Moreover, cortical stimulations evoked earlier signals in the thalamus than in other connected cortical areas suggesting that the thalamus receives a copy of signals before they are exchanged across the cortex. Our causal connectivity data can be used to inform biologically-inspired computational models of the functional architecture of the brain.

Causal Cortical and Thalamic Connections in the Human Brain.

The brain's functional architecture is intricately shaped by causal connections between its cortical and subcortical structures. Here, we studied 27 participants with 4864 electrodes implanted across the anterior, mediodorsal, and pulvinar thalamic regions, and the cortex. Using data from electrical stimulation procedures and a data-driven approach informed by neurophysiological standards, we dissociated three unique spectral patterns generated by the perturbation of a given brain area. Among these, a novel waveform emerged, marked by delayed-onset slow oscillations in both ipsilateral and contralateral cortices following thalamic stimulations, suggesting a mechanism by which a thalamic site can influence bilateral cortical activity. Moreover, cortical stimulations evoked earlier signals in the thalamus than in other connected cortical areas suggesting that the thalamus receives a copy of signals before they are exchanged across the cortex. Our causal connectivity data can be used to inform biologically-inspired computational models of the functional architecture of the brain.

Causal evidence for the processing of bodily self in the anterior precuneus.

To probe the causal importance of the human posteromedial cortex (PMC) in processing the sense of self, we studied a rare cohort of nine patients with electrodes implanted bilaterally in the precuneus, posterior cingulate, and retrosplenial regions with a combination of neuroimaging, intracranial recordings, and direct cortical stimulations. In all participants, the stimulation of specific sites within the anterior precuneus (aPCu) caused dissociative changes in physical and spatial domains. Using single-pulse electrical stimulations and neuroimaging, we present effective and resting-state connectivity of aPCu hot zone with the rest of the brain and show that they are located outside the boundaries of the default mode network (DMN) but connected reciprocally with it. We propose that the function of this subregion of the PMC is integral to a range of cognitive processes that require the self's physical point of reference, given its location within a spatial environment.

Intrinsic brain dynamics in the Default Mode Network predict involuntary fluctuations of visual awareness.

Brain activity is intrinsically organised into spatiotemporal patterns, but it is still not clear whether these intrinsic patterns are functional or epiphenomenal. Using a simultaneous fMRI-EEG implementation of a well-known bistable visual task, we showed that the latent transient states in the intrinsic EEG oscillations can predict upcoming involuntarily perceptual transitions. The critical state predicting a dominant perceptual transition was characterised by the phase coupling between the precuneus (PCU), a key node of the Default Mode Network (DMN), and the primary visual cortex (V1). The interaction between the lifetime of this state and the PCU- > V1 Granger-causal effect is correlated with the perceptual fluctuation rate. Our study suggests that the brain's endogenous dynamics are phenomenologically relevant, as they can elicit a diversion between potential visual processing pathways, while external stimuli remain the same. In this sense, the intrinsic DMN dynamics pre-empt the content of consciousness.

[Effect of IFN-α on Cytokines in Serum of Patients with Chronic Myeloid Leukemia].

OBJECTIVE: To investigate the effect of IFN-α on cytokines in serum of patients with chronic myeloid leukemia(CML). METHODS: Fifty patients with CML from March 2012 to December 2015 in our hospital were randomly divided into routine treatment group (n=25) and combined treatment group (n=25), 30 healthy persons were selected as control (control group). The CML patients in routine treatment group were given orally hydroxyurea, the CML patients in combined treatment group were treated with recombinant human interferon α2b injection based on routine treatment (hydroxyurea plus IFN-α group). The levels of ALP, IL-6, PGE-2, MMP-2, and bFGF in serum were detected by ELISA. The cytogenetic, molecular and hematologic responses of patients in routine treatment group and combined treatment group, including patients in chronic and accelerated blastic phases were compared after 6 weeks of treatment. RESULTS: The servum levels of ALP, IL-6, PGE-2, MMP-2 and bFGF in CML patients with chronic and accelerated blastic phases all were higher than those in control group(P<0.05). The levels of MMP-2 and bFGF in CML patients with chronic phase were highr than those of CML patients with accelerated blastic phase (P<0.05), the levels of ALP, PGE-2 and IL-6 of patients with chronic phase were significantly lower than those of patients in accelerated blastic phase (P<0.05). The ALP, IL-6, PGE-2, MMP-2 and bFGF levels in combined treatment group were significantly lower than those in the routine treatment group after 2 weeks and 6 weeks of treatment(P<0.05); After the end of treatment, the CHR of routine treatment group was 56%, which was lower than that of combined treatment group 84%(χ2=18.667, P<0.001); the CCyR of routine treatment group was 32% which was significantly higher than 12% in combined treatment group(χ2=11.655, P<0.001); the CMR of routine treatment group was 12% that was significantly higher than 4% in combined treatment group (χ2=4.347, P=0.037). The median survival time of routine treatment group was significantly shorter than that of the combined treatment group, but there was no significant difference during follow-up (P>0.05). CONCLUSION: IFN-α can alleviate the symptoms of patients with CML and inhibit the process of disease with CML patients, effectively inhibit the expression of disease-related cytokines.

Low-temperature direct copper-to-copper bonding enabled by creep on (111) surfaces of nanotwinned Cu.

Direct Cu-to-Cu bonding was achieved at temperatures of 150-250 °C using a compressive stress of 100 psi (0.69 MPa) held for 10-60 min at 10(-3) torr. The key controlling parameter for direct bonding is rapid surface diffusion on (111) surface of Cu. Instead of using (111) oriented single crystal of Cu, oriented (111) texture of extremely high degree, exceeding 90%, was fabricated using the oriented nano-twin Cu. The bonded interface between two (111) surfaces forms a twist-type grain boundary. If the grain boundary has a low angle, it has a hexagonal network of screw dislocations. Such network image was obtained by plan-view transmission electron microscopy. A simple kinetic model of surface creep is presented; and the calculated and measured time of bonding is in reasonable agreement.