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Eye movements are considered to be informative with regard to the underlying cognitive processes of human beings. Previous studies have reported that eye movements are associated with which scientific concepts are retrieved correctly. Moreover, other studies have also suggested that eye movements involve the cooperative activity of the human brain's fronto-parietal circuits. Less research has been conducted to investigate whether fronto-parietal EEG oscillations are associated with the retrieval processing of scientific concepts. Our findings in this study demonstrated that the fronto-parietal network is indeed crucial for successful memory retrieval. In short, significantly lower theta augmentation in the frontal midline and lower alpha suppression in the right parietal region were observed at the 5th eye fixation for physics concepts that were correctly retrieved than for those that were incorrectly retrieved. Moreover, the visual cortex in the occipital lobe exhibits a significantly greater theta augmentation followed by an alpha suppression following each eye fixation, while a right fronto-parietal asymmetry was also found for the successful retrieval of presentations of physics concepts. In particular, the study results showed that eye fixation-related frontal midline theta power and right parietal alpha power at the 5th eye fixation have the greatest predictive power regarding the correctness of the retrieval of physics concepts.

To explore the issue of how the human brain processes sentences with different levels of complexity, we sought to compare the neural substrates underlying the processing of Chinese subject-extracted relative clause (SRC) and object-extracted relative clause (ORC) sentences in a trial-by-trial fashion. Previous neuroimaging studies have demonstrated that the involvement of the left inferior frontal gyrus (LIFG) and the left superior temporal gyrus (LSTG) is critical for the processing of relative clause (RC) sentences. In this study, we employed independent component analysis (ICA) to decompose brain activity into a set of independent components. Then, the independent component maps were spatially normalized using a surface-based approach in order to further spatially correlate and match the equivalent components from individual participants. The selected equivalent components indicated that the LIFG and the LSTG were consistently engaged in sentence processing among the participants. Subsequently, we observed alterations in the functional coupling between the LIFG and the LSTG in response to SRCs and ORCs using a Granger causality analysis. Specifically, comprehending Chinese ORCs with a canonical word order only involved a unidirectional connection from the LIFG to the LSTG for the integration of lexical-syntactic information. On the other hand, comprehending Chinese SRCs required bi-directional connectivity between the LIFG and the LSTG to fulfill increased integration demands in reconstructing the argument hierarchy due to a non-canonical word order. Furthermore, through a single-trial analysis, the strength of the connectivity from the LIFG to the LSTG was found to be significantly correlated with the complexity of the SRC sentences as quantified by eye-tracking measures. These findings indicated that the effective connectivity from the LIFG to the LSTG played an important role in the comprehension of complex sentences and that enhanced strength of this connectivity might reflect increased integration demands and restructuring attempts during sentence processing. Taken together, the results of the present study reveal that interregional interaction in the brain network for sentence processing can be dynamically engaged in response to different levels of complexity and also shed some light on the interpretation of neuroimaging and behavioral evidence when accounting for the nature of sentence complexity during reading.

Although the connection between the left inferior frontal gyrus (LIFG) and the left superior temporal gyrus (LSTG) has been found to be essential for the comprehension of relative clause (RC) sentences, it remains unclear how the LIFG and the LSTG interact with each other, especially during the processing of Chinese RC sentences with different processing difficulty. This study thus conducted a 2 × 2 (modifying position × extraction position) factorial analyses to examine how these two factors influences regional brain activation. The results showed that, regardless of the modifying position, greater activation in the LIFG was consistently elicited in Chinese subject-extracted relative clauses (SRCs) with non-canonical word order than object-extracted relative clauses (ORCs) with canonical word order, implying that the LIFG subserving the ordering process primarily contributes to the processing of information with increased integration demands due to the non-canonical sequence. Moreover, the directional connection between the LIFG and the LSTG appeared to be modulated by different modifying positions. When the RC was at the subject-modifying position, the effective connectivity from the LIFG to the LSTG was dominantly activated for sentence comprehension; whereas when the RC was at the object-modifying position thus being more difficult, it might be the feedback mechanism from the LSTG back to the LIFG that took place in sentence processing. These findings reveal that brain activation in between the LIFG and the LSTG may be dynamically modulated by different processing difficulty and suggest the relative specialization but extensive collaboration involved in the LIFG and the LSTG for sentence comprehension.

Ketamine has been used for medical purposes, most typically as an anesthetic, and recent studies support its use in the treatment of depression. However, ketamine tends to be abused by adolescents and young adults. In the current study, we examined the effects of early ketamine exposure on brain structure and function. We employed MRI to assess the effects of ketamine abuse on cerebral gray matter volume (GMV) and functional connectivity (FC) in 34 users and 19 non-users, employing covariates. Ketamine users were categorized as adolescent-onset and adult-onset based on when they were first exposed to ketamine. Imaging data were processed by published routines in SPM and AFNI. The results revealed lower GMV in the left precuneus in ketamine users, with a larger decrease in the adolescent-onset group. The results from a seed-based correlation analysis show that both ketamine groups had higher functional connectivity between left precuneus (seed) and right precuneus than the control group. Compared to controls, ketamine users showed decreased GMV in the right insula, left inferior parietal lobule, left dorsolateral prefrontal cortex/superior frontal gyrus, and left medial orbitofrontal cortex. These preliminary results characterize the effects of ketamine misuse on brain structure and function and highlight the influence of earlier exposure to ketamine on the development of the brain. The precuneus, a structure of central importance to cerebral functional organization, may be particularly vulnerable to the influences of early ketamine exposure. How these structural and functional brain changes may relate to the cognitive and affective deficits remains to be determined with a large cohort of participants.

Chronic ketamine use leads to cognitive and affective deficits including depression. Here, we examined sex differences and neural bases of depression in chronic ketamine users. Compared to non-drug using healthy controls (HC), ketamine-using females but not males showed increased depression score as assessed by the Center of Epidemiological Studies Depression Scale (CES-D). We evaluated resting state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC), a prefrontal structure consistently implicated in the pathogenesis of depression. Compared to HC, ketamine users (KU) did not demonstrate significant changes in sgACC connectivities at a corrected threshold. However, in KU, a linear regression against CES-D score showed less sgACC connectivity to the orbitofrontal cortex (OFC) with increasing depression severity. Examined separately, male and female KU showed higher sgACC connectivity to bilateral superior temporal gyrus and dorsomedial prefrontal cortex (dmPFC), respectively, in correlation with depression. The linear correlation of sgACC-OFC and sgACC-dmPFC connectivity with depression was significantly different in slope between KU and HC. These findings highlighted changes in rsFC of the sgACC as associated with depression and sex differences in these changes in chronic ketamine users.

In the traditional neural sensing microstructure, the limited metal line pitch and the metal layer numbers restrict the neural signal routing ability from electrodes to circuit chips. Miniature packaging and excessive noise interference bottlenecks are some of the challenges faced by the electrodes and circuit chips integration with traditional wire bonding. This paper proposes a 2.5-D heterogeneous integration neural sensing microsystem based on the silicon substrate to overcome these issues. With standard semiconductor and 3-D integration processes, high-channel-density (256 channels at 25 mm2) neural sensing microsystem is achieved. Through silicon via provides the shortest vertical interconnection and dramatically minimizes the packaging. Furthermore, the interposer can carry multiple chips to enhance the function of the biosensor. Electrical characteristics and reliability examinations reveal its high quality and great performance as compared to traditional approaches. This novel highly integrated neural sensing microsystem is expected to contribute to the biomedical field for exploring and solving unknown biological mysteries.

Motor imagery (MI) has been widely used to operate brain-computer interface (BCI) systems for rehabilitation and some life assistive devices. However, the current performance of an MI-based BCI cannot fully meet the needs of its in-field applications. Most of the BCIs utilizing a generalized feature for all participants have been found to greatly hamper the efficacy of the BCI system. Hence, some attempts have made on the exploration of subject-dependent parameters, but it remains challenging to enhance BCI performance as expected. To this end, in this study, we used the independent component analysis (ICA), which has been proved capable of isolating the pure motor-related component from non-motor-related brain processes and artifacts and extracting the common motor-related component across MI, motor execution (ME), and motor observation (MO) conditions. Then, a sliding window approach was used to detect significant mu-suppression from the baseline using the electroencephalographic (EEG) alpha power time course and, thus, the success rate of the mu-suppression detection could be assessed on a single-trial basis. By comparing the success rates using different parameters, we further quantified the extent of the improvement in each motor condition to evaluate the effectiveness of both generalized and individualized parameters. The results showed that in ME condition, the success rate under individualized latency and that under generalized latency was 90.0% and 77.75%, respectively; in MI condition, the success rate was 74.14% for individual latency and 58.47% for generalized latency, and in MO condition, the success rate was 67.89% and 61.26% for individual and generalized latency, respectively. As can be seen, the success rate in each motor condition was significantly improved by utilizing an individualized latency compared to that using the generalized latency. Moreover, the comparison of the individualized window latencies for the mu-suppression detection across different runs of the same participant as well as across different participants showed that the window latency was significantly more consistent in the intra-subject than in the inter-subject settings. As a result, we proposed that individualizing the latency for detecting the mu-suppression feature for each participant might be a promising attempt to improve the MI-based BCI performance.

BACKGROUND: The striatum supports motivated behavior and impulse control. Altered striatal activation and connectivity has been observed in link with impulse control dysfunction in individuals with drug addiction. OBJECTIVES: We examined how resting state functional connectivity (rsFC) of the striatum is altered as a result of chronic ketamine misuse. METHODS: Thirty-six ketamine users (10 women) and 20 healthy controls (9 women) completed an assessment with the Barratt Impulsiveness Scale (BIS-11) and magnetic resonance imaging. In SPM we examined voxel-wise connectivities of the caudate, pallidum, putamen, and ventral striatum in ketamine users (versus healthy controls) and in association with BIS-11 score and duration of use, all at a corrected threshold. RESULTS: Compared to controls, ketamine users showed higher connectivity between caudate and dorsal anterior cingulate cortex and between pallidum and bilateral cerebellum. In ketamine users, putamen showed higher connectivity with the left orbitofrontal cortex (OFC) in association with both BIS-11 score and months of ketamine use. Mediation analyses suggest that the connectivity z score mediated the relationship between impulsivity and duration of use. CONCLUSIONS: These preliminary findings highlighted altered striatal connectivity in chronic ketamine users, and the potential role of putamen OFC connectivity in supporting the correlation between impulsivity and duration of ketamine use. If replicated in a larger sample, these findings may represent neural markers of ketamine misuse.

Most prior studies have reported that subject-extracted relative clauses (SRCs) are easier to process than object-extracted relative clauses (ORCs). However, whether such an SRC preference is universal across different languages remains an open question. Several reports from Chinese have provided conflicting results; thus, in the present study, we conducted two self-paced reading experiments to examine the comprehension of Chinese relative clauses. The results demonstrated a clear ORC preference that Chinese ORCs were easier to comprehend than Chinese SRCs. These findings were most compatible with the prediction of the integration cost account, which claims that the processing difference between SRCs and ORCs arises at the point of dependency formation. The ORC preference in Chinese poses a challenge to the universality of the SRC preference assumed by the structural distance hypothesis and highlights the values of cross-linguistic research.

Previous studies investigating the processing of complex sentences have demonstrated the involvement of the left inferior frontal gyrus (LIFG) and left superior temporal gyrus (LSTG), which might subserve ordering and storage of linguistic components, respectively, for sentence comprehension. However, how these brain regions are interconnected, especially during the processing of Chinese sentences, need to be further explored. In this study, the neural network supporting the comprehension of Chinese relative clause was identified. Both the LIFG and LSTG exhibited higher activation in processing subject-extracted relative clauses (SRCs) than object-extracted relative clauses (ORCs). Moreover, a Granger causality analysis revealed that the effective connectivity from the LIFG to LSTG was significant only when participants read Chinese SRCs, which were argued to be more difficult than ORCs. Contrary to the observations of an SRC advantage in most other languages, the present results provide clear neuroimaging evidence for an ORC advantage in Chinese.

To enhance the signal integrity of high-density neural-sensing signals, this work presents an implantable high spatial resolution μ-probe array with through-silicon via (TSV) 2.5D integration technology that realizes a miniaturized implantable device on flexible printed circuit (FPC) interposer. The proposed microsystem was composed of two 32-channel neural sensing chips and one radio frequency chip for neural signal processing. The μ-probe array can achieve better signal-to-noise ratio with neural-signal acquisition and processing circuit composed of a pseudo-resistor-based analog front-end amplifier. Moreover, a receiving antenna is also implemented on the backside of FPC for wireless data and power transmission. The feasibility of the proposed μ-probe array, Tx and Rx antenna, 32-channel neural sensing circuits in the 64-channel wireless microsystem have been successfully demonstrated for future integration and animal experiments.

For implanted neural-sensing devices, one of the remaining challenges is to transmit stable power/data (P/D) transmission for high spatiotemporal resolution neural data. This paper presents a miniaturized implantable 128-channel wireless neural-sensing microsystem using TSV-embedded dissolvable μ-needle array, a flexible interposer and 4 dies by 2.5D/3D TSV heterogeneous SiP technology. The 4 dies are 2 neural-signal acquisition ICs implemented by 90nm CMOS, 1 neural-signal processor by 40nm CMOS and 1 wireless P/D transmission circuitry by 0.18μm CMOS. Thus, the proposed wireless microsystem realizes 128-channel neural-signal sensing within the area of 5mm × 5mm, neural feature extraction and wireless P/D transmission using an on-interposer inductor. The overall average power of the circuits in this microsystem is only 9.85mW.

Highly integrated neural sensing microsystems are crucial to capture accurate signals for brain function investigations. In this paper, a 256-channel neural sensing microsystem with a sensing area of 5 × 5 mm 2 is presented based on 2.5-D through-silicon-via (TSV) integration. This microsystem composes of dissolvable μ-needles, TSV-embedded μ-probes, 256-channel neural amplifiers, 11-bit area-power-efficient successive approximation register analog-to-digital converters, and serializers. This microsystem can detect 256 electrocorticography and local field potential signals within a small area of 5 mm × 5 mm. The neural amplifier realizes 57.8 dB gain with only 9.8 μW per channel. The overall power of this microsystem is only 3.79 mW for 256-channel neural sensing. A smaller microsystem with dimension of 6 mm × 4 mm has been also implanted into rat brain for somatosensory evoked potentials (SSEPs) recording by using contralateral and ipsilateral electrical stimuli with intensity from 0.2 to 1.0 mA, and successfully observed different SSEPs from left somatosensory cortex of a rat.

This study investigates the relationship between heart rate variability (HRV) and the level of motion sickness (MS) induced by simulated tunnel driving. The HRV indices, normalized low frequency (NLF, 0.04-0.15 Hz), normalized high frequency (NHF, 0.15-0.4 Hz), and LF/HF ratio were correlated with the subjectively and continuously rated MS levels of 20 participants. The experimental results showed that for 13 of the subjects, the MS levels positively correlated with the NLF and the LF/HF ratio and negatively correlated with the NHF. The remaining seven subjects had negative correlations between the MS levels and the NLF and the LF/HF ratio and a positive correlation between the MS levels and the NHF. To clarify this contradiction, this study also inspected the effects of subjects' self-adjustments on the correlations between the MS levels and the HRV indices and showed that the variations in the relationship might be attributed to the subjects' self-adjustments, which they used to relieve the discomfort of MS.

Oral cancer is a serious and growing problem in many developing and developed countries. To improve the cancer screening procedure, we developed a portable light-emitting-diode (LED)-induced autofluorescence (LIAF) imager that contains two wavelength LED excitation light sources and multiple filters to capture ex vivo oral tissue autofluorescence images. Compared with conventional means of oral cancer diagnosis, the LIAF imager is a handier, faster, and more highly reliable solution. The compact design with a tiny probe allows clinicians to easily observe autofluorescence images of hidden areas located in concave deep oral cavities. The ex vivo trials conducted in Taiwan present the design and prototype of the portable LIAF imager used for analyzing 31 patients with 221 measurement points. Using the normalized factor of normal tissues under the excitation source with 365 nm of the central wavelength and without the bandpass filter, the results revealed that the sensitivity was larger than 84%, the specificity was not smaller than over 76%, the accuracy was about 80%, and the area under curve of the receiver operating characteristic (ROC) was achieved at about 87%, respectively. The fact shows the LIAF spectroscopy has the possibilities of ex vivo diagnosis and noninvasive examinations for oral cancer.

Local brain connectivity is expected to lead to new models for neurological diseases, which may in turn result in advanced understanding and better treatment. This paper presents a neural sensing microsystem integrated with TSV-embedded dissolvable µ-needles array, ENIG bonding technology, biocompatible Au-TSV flexible interposer and neural recording circuits, for neural sensing implantation. An ultra-thin film bonding approach is proposed for integration of interposer assembly. Removing bonding wire by proposed bonding technology, the dimension of neural sensing system can be minimized to reduce surgical area and promote implant success rate. The signal quality of neural recording can be significantly improved by eliminating complex signal paths with 2.5D TSV integration from neural sensing interface to neural recording circuits.

Highly integrated neural sensing microsystems are crucial to capture accurate signals for brain function investigations. In this paper, a 256-channel/25 mm2 neural sensing microsystem is presented based on through-silicon-via (TSV) 2.5D integration. This microsystem composes of dissolvable μ-needles, TSV-embedded μ-probes, 256-channel neural amplifiers, 11-bit area-power-efficient SAR ADCs and serializers. Based on the dissolvable μ-needles and TSV 2.5D integration, this microsystem can detect 256 ECoG/LFP signals within the small area of 5mm × 5mm. Additionally, the neural amplifier realizes 57.8dB gain with only 9.8μW for each channel, and the 9.7-bit ENOB of the SAR ADC at 32kS/s can be achieved with 0.42μW and 0.036 mm2. The overall power of this microsystem is only 3.79mW for 256-channel neural sensing.

Parkinson’s disease (PD) and essential tremor (ET) are characterized with motor dysfunctions. Motor circuit dysfunctions can be complementarily investigated by paired associative stimulation (PAS)-induced long-term potentiation (LTP)-like plasticity and diffusion tensor imaging (DTI) of the corticospinal tract (CST). Three groups of twelve subjects with moderate severity PD, ET with intention tremor and healthy controls (HC) were studied. The primary motor cortex (M1) excitability, measured by motor evoked potential (MEP) amplitude and by short-interval and long-interval intracortical inhibition (SICI and LICI) was compared between the three groups before and after PAS. The DTI measures of fractional anisotropy (FA) and mean diffusivity (MD) were acquired. PAS effects and DTI data were simultaneously examined between groups. PAS increased MEP amplitude in HC but not in PD and ET. SICI and LICI were significantly reduced after PAS irrespective of groups. No significant differences of the mean FA and MD were found between groups. There was no significant correlation between the PAS effects and the DTI measures. Findings suggest that both PD and ET with intention tremor have impairment of the associative LTP-like corticospinal excitability change in M1. The microstructure of the CST is not relevant to the deficiency of M1 associative plasticity in PD and ET.

The present study investigated the brain dynamics accompanying spatial navigation based on distinct reference frames. Participants preferentially using an allocentric or an egocentric reference frame navigated through virtual tunnels and reported their homing direction at the end of each trial based on their spatial representation of the passage. Task-related electroencephalographic (EEG) dynamics were analyzed based on independent component analysis (ICA) and subsequent clustering of independent components. Parietal alpha desynchronization during encoding of spatial information predicted homing performance for participants using an egocentric reference frame. In contrast, retrosplenial and occipital alpha desynchronization during retrieval covaried with homing performance of participants using an allocentric reference frame. These results support the assumption of distinct neural networks underlying the computation of distinct reference frames and reveal a direct relationship of alpha modulation in parietal and retrosplenial areas with encoding and retrieval of spatial information for homing behavior.

This study explores the electroencephalographic(EEG) correlates of emotional experience during musiclistening. Independent component analysis and analysisof variance were used to separate statistically independentspectral changes of the EEG in response to music-inducedemotional processes. An independent brain processwith equivalent dipole located in the fronto-centralregion exhibited distinct d-band and h-band powerchanges associated with self-reported emotional states.Specifically, the emotional valence was associatedwith d-power decreases and h-power increases in thefrontal-central area, whereas the emotional arousal wasaccompanied by increases in both d and h powers.The resultant emotion-related component activationsthat were less interfered by the activities from otherbrain processes complement previous EEG studiesof emotion perception to music. NeuroReport 21:410–415

This study investigates motion-sickness-related brain responses using a VR-based driving simulator on a motion platform with six degrees of freedom, which provides both visual and vestibular stimulations to induce motion sickness in a manner that is close to that in daily life. Subjects' brain dynamics associated with motion sickness were measured using a 32-channel EEG system. Their degree of motion sickness was simultaneously and continuously reported using an onsite joystick, providing non-stop behavioral references to the recorded EEG changes. The acquired EEG signals were parsed by independent component analysis (ICA) into maximally independent processes. The decomposition enables the brain dynamics that are induced by the motion of the platform and motion sickness to be disassociated. Five MS-related brain processes with equivalent dipoles located in the left motor, the parietal, the right motor, the occipital and the occipital midline areas were consistently identified across all subjects. The parietal and motor components exhibited significant alpha power suppression in response to vestibular stimuli, while the occipital components exhibited MS-related power augmentation in mainly theta and delta bands; the occipital midline components exhibited a broadband power increase. Further, time series cross-correlation analysis was employed to evaluate relationships between the spectral changes associated with different brain processes and the degree of motion sickness. According to our results, it is suggested both visual and vestibular stimulations should be used to induce motion sickness in brain dynamic studies.

Biomedical signal monitoring systems have rapidly advanced in recent years, propelled by significant advances in electronic and information technologies. Brain-computer interface (BCI) is one of the important research branches and has become a hot topic in the study of neural engineering, rehabilitation, and brain science. Traditionally, most BCI systems use bulky, wired laboratory-oriented sensing equipments to measure brain activity under well-controlled conditions within a confined space. Using bulky sensing equipments not only is uncomfortable and inconvenient for users, but also impedes their ability to perform routine tasks in daily operational environments. Furthermore, owing to large data volumes, signal processing of BCI systems is often performed off-line using high-end personal computers, hindering the applications of BCI in real-world environments. To be practical for routine use by unconstrained, freely-moving users, BCI systems must be noninvasive, nonintrusive, lightweight and capable of online signal processing. This work reviews recent online BCI systems, focusing especially on wearable, wireless and real-time systems.

Neural prosthetic technologies have helped many patients by restoring vision, hearing, or movement and relieving chronic pain or neurological disorders. While most neural prosthetic systems to date have used invasive or implantable devices for patients with inoperative or malfunctioning external body parts or internal organs, a much larger population of ldquohealthyrdquo people who suffer episodic or progressive cognitive impairments in daily life can benefit from noninvasive neural prostheses. For example, reduced alertness, lack of attention, or poor decision-making during monotonous, routine tasks can have catastrophic consequences. This study proposes a noninvasive mobile prosthetic platform for continuously monitoring high-temporal resolution brain dynamics without requiring application of conductive gels on the scalp. The proposed system features dry microelectromechanical system electroencephalography sensors, low-power signal acquisition, amplification and digitization, wireless telemetry, online artifact cancellation, and signal processing. Its implications for neural prostheses are examined in two sample studies: 1) cognitive-state monitoring of participants performing realistic driving tasks in the virtual-reality-based dynamic driving simulator and 2) the neural correlates of motion sickness in driving. The experimental results of these studies provide new insights into the understanding of complex brain functions of participants actively performing ordinary tasks in natural body positions and situations within real operational environments.

Background: Tendinomuscular Meridians (TMM) are adopted as a treatment paradigm for studying the neuronal mechanisms of acupuncture analgesia in acute thermal pain. The effect of needle combination on analgesia and the corresponding neuronal mechanisms have yet to be fully delineated. Objective: To assess the role of different needle groups in the TMM treatment paradigms of acute pain by determining the peripheral thermal thresholds before and after electroacupuncture (EA) and the corresponding behavioral feedback of thermal pain stimulation and the De Qi sensation of EA. Design, Setting, and Participants: A prospective study of 13 individuals conducted at the University of California, San Diego Medical Center. Interventions: Participants' baseline thermal thresholds (cold, warm, cold and hot pain) were measured at premarked testing sites along the medial aspects of the bilateral lower extremities. Hot pain was delivered for 5 seconds to the testing sites and the corresponding pain visual analog scale (VA...