Investigating the heterogeneity within the somatosensory-motor network and its relationship with the attention and default systems.

The somatosensory-motor network (SMN) not only plays an important role in primary somatosensory and motor processing but is also central to many disorders. However, the SMN heterogeneity related to higher-order systems still remains unclear. Here, we investigated SMN heterogeneity from multiple perspectives. To characterize the SMN substructures in more detail, we used ultra-high-field functional MRI to delineate a finer-grained cortical parcellation containing 430 parcels that is more homogenous than the state-of-the-art parcellation. We personalized the new parcellation to account for individual differences and identified multiscale individual-specific brain structures. We found that the SMN subnetworks showed distinct resting-state functional connectivity (RSFC) patterns. The Hand subnetwork was central within the SMN and exhibited stronger RSFC with the attention systems than the other subnetworks, whereas the Tongue subnetwork exhibited stronger RSFC with the default systems. This two-fold differentiation was observed in the temporal ordering patterns within the SMN. Furthermore, we characterized how the distinct attention and default streams were carried forward into the functions of the SMN using dynamic causal modeling and identified two behavioral domains associated with this SMN fractionation using meta-analytic tools. Overall, our findings provided important insights into the heterogeneous SMN organization at the system level and suggested that the Hand subnetwork may be preferentially involved in exogenous processes, whereas the Tongue subnetwork may be more important in endogenous processes.

Functional connectivity in people at clinical and familial high risk for schizophrenia.

Patients diagnosed with schizophrenia (SZ) exhibit compromised functional connectivity within extensive brain networks. However, the precise development of this impairment during disease progression in the clinical high-risk (CHR) population and their relatives remains unclear. Our study leveraged data from 128 resting electroencephalography (EEG) channels acquired from 30 SZ patients, 21 CHR individuals, 17 unaffected healthy relatives (RSs; those at heightened SZ risk due to family history), and 31 healthy controls (HCs). These data were harnessed to establish functional connectivity patterns. By calculating the geometric distance between EEG sequences, we unveiled local and global nonlinear relationships within the entire brain. The process of dimensionality reduction led to low-dimensional representations, providing insights into high-dimensional EEG data. Our findings indicated that CHR participants exhibited aberrant functional connectivity across hemispheres, whereas RS individuals showcased anomalies primarily concentrated within hemispheres. In the realm of low-dimensional analysis, RS participants' third-dimensional occipital lobe values lay between those of the CHR individuals and HCs, significantly correlating with scale scores. This low-dimensional approach facilitated the visualization of brain states, potentially offering enhanced comprehension of brain structure, function, and early-stage functional impairment, such as occipital visual deficits, in RS individuals before cognitive decline onset.

Individual-level functional connectomes predict the motor symptoms of Parkinson's disease.

Abnormalities in functional connectivity networks are associated with sensorimotor networks in Parkinson's disease (PD) based on group-level mapping studies, but these results are controversial. Using individual-level cortical segmentation to construct individual brain atlases can supplement the individual information covered by group-level cortical segmentation. Functional connectivity analyses at the individual level are helpful for obtaining clinically useful markers and predicting treatment response. Based on the functional connectivity of individualized regions of interest, a support vector regression model was trained to estimate the severity of motor symptoms for each subject, and a correlation analysis between the estimated scores and clinical symptom scores was performed. Forty-six PD patients aged 50-75 years were included from the Parkinson's Progression Markers Initiative database, and 63 PD patients were included from the Beijing Rehabilitation Hospital database. Only patients below Hoehn and Yahr stage III were included. The analysis showed that the severity of motor symptoms could be estimated by the individualized functional connectivity between the visual network and sensorimotor network in early-stage disease. The results reveal individual-level connectivity biomarkers related to motor symptoms and emphasize the importance of individual differences in the prediction of the treatment response of PD.

Individual functional parcellation revealed compensation of dynamic limbic network organization in healthy ageing.

Using group-level functional parcellations and constant-length sliding window analysis, dynamic functional connectivity studies have revealed network-specific impairment and compensation in healthy ageing. However, functional parcellation and dynamic time windows vary across individuals; individual-level ageing-related brain dynamics are uncertain. Here, we performed individual parcellation and individual-length sliding window clustering to characterize ageing-related dynamic network changes. Healthy participants (n = 637, 18-88 years) from the Cambridge Centre for Ageing and Neuroscience dataset were included. An individual seven-network parcellation, varied from group-level parcellation, was mapped for each participant. For each network, strong and weak cognitive brain states were revealed by individual-length sliding window clustering and canonical correlation analysis. The results showed negative linear correlations between age and change ratios of sizes in the default mode, frontoparietal, and salience networks and a positive linear correlation between age and change ratios of size in the limbic network (LN). With increasing age, the occurrence and dwell time of strong states showed inverted U-shaped patterns or a linear decreasing pattern in most networks but showed a linear increasing pattern in the LN. Overall, this study reveals a compensative increase in emotional networks (i.e., the LN) and a decline in cognitive and primary sensory networks in healthy ageing. These findings may provide insights into network-specific and individual-level targeting during neuromodulation in ageing and ageing-related diseases.

Characterizing cortical responses to short-term multidisciplinary intensive rehabilitation treatment in patients with Parkinson's disease: A transcranial magnetic stimulation and electroencephalography study.

Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) is a powerful non-invasive tool for qualifying the neurophysiological effects of interventions by recording TMS-induced cortical activation with high temporal resolution and generates reproducible and reliable waves of activity without participant cooperation. Cortical dysfunction contributes to the pathogenesis of the clinical symptoms of Parkinson's disease (PD). Here, we examined changes in cortical activity in patients with PD following multidisciplinary intensive rehabilitation treatment (MIRT). Forty-eight patients with PD received 2 weeks of MIRT. The cortical response was examined following single-pulse TMS over the primary motor cortex by 64-channel EEG, and clinical symptoms were assessed before and after MIRT. TMS-evoked potentials were quantified by the global mean field power, as well as oscillatory power in theta, alpha, beta, and gamma bands, and their clinical correlations were calculated. After MIRT, motor and non-motor symptoms improved in 22 responders, and only non-motor function was enhanced in 26 non-responders. Primary motor cortex stimulation reduced global mean field power amplitudes in responders but not significantly in non-responders. Oscillations exhibited attenuated power in the theta, beta, and gamma bands in responders but only reduced gamma power in non-responders. Associations were observed between beta oscillations and motor function and between gamma oscillations and non-motor symptoms. Our results suggest that motor function enhancement by MIRT may be due to beta oscillatory power modulation and that alterations in cortical plasticity in the primary motor cortex contribute to PD recovery.

Treatment Enhances Betweenness Centrality of Fronto-Parietal Network in Parkinson's Patients.

Previous studies have demonstrated a close relationship between early Parkinson's disease and functional network abnormalities. However, the pattern of brain changes in the early stages of Parkinson's disease has not been confirmed, which has important implications for the study of clinical indicators of Parkinson's disease. Therefore, we investigated the functional connectivity before and after treatment in patients with early Parkinson's disease, and further investigated the relationship between some topological properties and clinicopathological indicators. We included resting state-fMRI (rs-fMRI) data from 27 patients with early Parkinson's disease aged 50-75 years from the Parkinson's Disease Progression Markers Initiative (PPMI). The results showed that the functional connectivity of 6 networks, cerebellum network (CBN), cingulo_opercular network (CON), default network (DMN), fronto-parietal network (FPN), occipital network (OCC), and sensorimotor network (SMN), was significantly changed. Compared to before treatment, the main functional connections were concentrated in the CBN after treatment. In addition, the coefficients of these nodes have also changed. For betweenness centrality (BC), the FPN showed a significant improvement in treatment (p < 0.001). In conclusion, the alteration of functional networks in early Parkinson's patients is critical for clarifying the mechanisms of early diagnosis of the disease.

Impaired Self-Referential Cognitive Processing in Bipolar Disorder: A Functional Connectivity Analysis.

Patients with bipolar disorder have deficits in self-referenced information. The brain functional connectivity during social cognitive processing in bipolar disorder is unclear. Electroencephalogram (EEG) was recorded in 23 patients with bipolar disorder and 19 healthy comparison subjects. We analyzed the time-frequency distribution of EEG power for each electrode associated with self, other, and font reflection conditions and used the phase lag index to characterize the functional connectivity between electrode pairs for 4 frequency bands. Then, the network properties were assessed by graph theoretic analysis. The results showed that bipolar disorder induced a weaker response power and phase lag index values over the whole brain in both self and other reflection conditions. Moreover, the characteristic path length was increased in patients during self-reflection processing, whereas the global efficiency and the node degree were decreased. In addition, when discriminating patients from normal controls, we found that the classification accuracy was high. These results suggest that patients have impeded integration of attention, memory, and other resources of the whole brain, resulting in a deficit of efficiency and ability in self-referential processing.

Task-induced activation transmitted by structural connectivity is associated with behavioral performance.

It is thought that brain structure is the primary determinant of functions of brain regions. For example, cortical areas with functional differences also have different structural connectivity (SC) patterns. We used SCs derived from diffusion tensor imaging (DTI) data in 100 healthy adults included in the Human Connectome Project (HCP) to successfully predict cortical activation responses across distinct cognitive tasks and found that predictive performance varied among tasks. We also observed that predictive performance could be used to characterize task load in both relational reasoning and N-back working memory tasks and was significantly positively associated with behavioral performance. Moreover, we found that the default mode network (DMN) played a more dominant role in both activation prediction and behavioral performance than was found for other functional networks. These results support our hypothesis that individuals who performed tasks better might exhibit a more accurate predicted activation pattern as task-evoked activities are more inclined to flow over inherent structural networks than over more flexible paths. In the high difficulty condition, the decreased correlation between predicted and empirical activation may be associated with the more random brain activity in these conditions/participants due to the lack of engagement. Together, our findings highlight the feasibility of using SCs to estimate various cognitive task activations and thus further facilitate the exploration of the relationship between the brain and behavior by providing strong evidence for the relevance of structure to function in the human brain.

Development of a Non-invasive Deep Brain Stimulator With Precise Positioning and Real-Time Monitoring of Bioimpedance.

Methods by which to achieve non-invasive deep brain stimulation via temporally interfering with electric fields have been proposed, but the precision of the positioning of the stimulation and the reliability and stability of the outputs require improvement. In this study, a temporally interfering electrical stimulator was developed based on a neuromodulation technique using the interference modulation waveform produced by several high-frequency electrical stimuli to treat neurodegenerative diseases. The device and auxiliary software constitute a non-invasive neuromodulation system. The technical problems related to the multichannel high-precision output of the device were solved by an analog phase accumulator and a special driving circuit to reduce crosstalk. The function of measuring bioimpedance in real time was integrated into the stimulator to improve effectiveness. Finite element simulation and phantom measurements were performed to find the functional relations among the target coordinates, current ratio, and electrode position in the simplified model. Then, an appropriate approach was proposed to find electrode configurations for desired target locations in a detailed and realistic mouse model. A mouse validation experiment was carried out under the guidance of a simulation, and the reliability and positioning accuracy of temporally interfering electric stimulators were verified. Stimulator improvement and precision positioning solutions promise opportunities for further studies of temporally interfering electrical stimulation.

Enhancing Working Memory Based on Mismatch Negativity Neurofeedback in Subjective Cognitive Decline Patients: A Preliminary Study.

Mismatch negativity (MMN) is suitable for studies of preattentive auditory discriminability and the auditory memory trace. Subjective cognitive decline (SCD) is an ideal target for early therapeutic intervention because SCD occurs at preclinical stages many years before the onset of Alzheimer's disease (AD). According to a novel lifespan-based model of dementia risk, hearing loss is considered the greatest potentially modifiable risk factor of dementia among nine health and lifestyle factors, and hearing impairment is associated with cognitive decline. Therefore, we propose a neurofeedback training based on MMN, which is an objective index of auditory discriminability, to regulate sensory ability and memory as a non-pharmacological intervention (NPI) in SCD patients. Seventeen subjects meeting the standardized clinical evaluations for SCD received neurofeedback training. The auditory frequency discrimination test, the visual digital N-back (1-, 2-, and 3-back), auditory digital N-back (1-, 2-, and 3-back), and auditory tone N-back (1-, 2-, and 3-back) tasks were used pre- and post-training in all SCD patients. The intervention schedule comprised five 60-min training sessions over 2 weeks. The results indicate that the subjects who received neurofeedback training had successfully improved the amplitude of MMN at the parietal electrode (Pz). A slight decrease in the threshold of auditory frequency discrimination was observed after neurofeedback training. Notably, after neurofeedback training, the working memory (WM) performance was significantly enhanced in the auditory tone 3-back test. Moreover, improvements in the accuracy of all WM tests relative to the baseline were observed, although the changes were not significant. To the best of our knowledge, our preliminary study is the first to investigate the effects of MMN neurofeedback training on WM in SCD patients, and our results suggest that MMN neurofeedback may represent an effective treatment for intervention in SCD patients and the elderly with aging memory decline.