Rumination and Overrecruitment of Cognitive Control Circuits in Depression.

BACKGROUND: Rumination is associated with greater cognitive dysfunction and treatment resistance in major depressive disorder (MDD), but its underlying neural mechanisms are not well understood. Because rumination is characterized by difficulty in controlling negative thoughts, the current study investigated whether rumination was associated with aberrant cognitive control in the absence of negative emotional information. METHODS: Individuals with MDD (n = 176) and healthy control individuals (n = 52) completed the stop signal task with varied stop signal difficulty during functional magnetic resonance imaging. In the task, a longer stop signal asynchrony made stopping difficult (hard stop), whereas a shorter stop signal asynchrony allowed more time for stopping (easy stop). RESULTS: In participants with MDD, higher rumination intensity was associated with greater neural activity in response to difficult inhibitory control in the frontoparietal regions. Greater activation for difficult inhibitory control associated with rumination was also positively related to state fear. The imaging results provide compelling evidence for the neural basis of inhibitory control difficulties in individuals with MDD with high rumination. CONCLUSIONS: The association between higher rumination intensity and greater neural activity in regions involved in difficult inhibitory control tasks may provide treatment targets for interventions aimed at improving inhibitory control and reducing rumination in this population.

Nanoporous MoS2 Field-Effect Transistor Based Artificial Olfaction: Achieving Enhanced Volatile Organic Compound Detection Inspired by the Drosophila Olfactory System.

Olfaction, a primal and effective sense, profoundly impacts our emotions and instincts. This sensory system plays a crucial role in detecting volatile organic compounds (VOCs) and realizing the chemical environment. Animals possess superior olfactory systems compared to humans. Thus, taking inspiration from nature, artificial olfaction aims to achieve a similar level of excellence in VOC detection. In this study, we present the development of an artificial olfaction sensor utilizing a nanostructured bio-field-effect transistor (bio-FET) based on transition metal dichalcogenides and the Drosophila odor-binding protein LUSH. To create an effective sensing platform, we prepared a hexagonal nanoporous structure of molybdenum disulfide (MoS2) using block copolymer lithography and selective etching techniques. This structure provides plenty of active sites for the integration of the LUSH protein, enabling enhanced binding with ethanol (EtOH) for detection purposes. The coupling of the biomolecule with EtOH influences the bio-FETs potential, which generates indicative electrical signals. By mimicking the sniffing techniques observed in Drosophila, these bio-FETs exhibit an impressive limit of detection of 10-6% for EtOH, with high selectivity, sensitivity, and detection ability even in realistic environments. This bioelectric sensor demonstrates substantial potential in the field of artificial olfaction, offering advancements in VOC detection.

Polygenic risk for neuroticism is associated with less efficient control in more difficult situations.

Neuroticism is a heritable trait and a risk factor for mental health due to its relevance to poor control of negative events. To examine the relationship between genetic propensity for neuroticism and control processing, we used the polygenic risk score (PRS) approach and a stop signal task during fMRI. We hypothesized that genetic propensity for neuroticism may moderate control processing as a function of control difficulty. PRSs for neuroticism were computed from a transdiagnostic group of individuals (n=406) who completed the stop signal task. The level of control difficulty was a function of the stop signal asynchrony: shorter asynchrony allows easier stopping whereas longer asynchrony makes stopping difficult. The relationship between PRS for neuroticism and neural activity for controlling responses was examined by the stop signal asynchrony. Although PRS for neuroticism did not relate to the overall inhibitory control, individuals with high PRS for neuroticism showed greater activity in left dorsal prefrontal cortex, middle temporal gyrus, and dorsal posterior cingulate cortex for difficult control. Thus, the genetic propensity for neuroticism affects neural processing in a difficult control context, which may help to explain why individuals with high levels of neuroticism exert poor control of negative events in difficult situations.

Optical Enhancement of Indirect Bandgap 2D Transition Metal Dichalcogenides for Multi-Functional Optoelectronic Sensors.

The unique electrical and optical properties of transition metal dichalcogenides (TMDs) make them attractive nanomaterials for optoelectronic applications, especially optical sensors. However, the optical characteristics of these materials are dependent on the number of layers. Monolayer TMDs have a direct bandgap that provides higher photoresponsivity compared to multilayer TMDs with an indirect bandgap. Nevertheless, multilayer TMDs are more appropriate for various photodetection applications due to their high carrier density, broad spectral response from UV to near-infrared, and ease of large-scale synthesis. Therefore, this review focuses on the modification of the optical properties of devices based on indirect bandgap TMDs and their emerging applications. Several successful developments in optical devices are examined, including band structure engineering, device structure optimization, and heterostructures. Furthermore, it introduces cutting-edge techniques and future directions for optoelectronic devices based on multilayer TMDs.

Repetitive Negative Thinking-Specific and -Nonspecific White Matter Tracts Engaged by Historical Psychosurgical Targets for Depression.

BACKGROUND: Repetitive negative thinking (RNT) is a frequent symptom of major depressive disorder (MDD) that is associated with poor outcomes and treatment resistance. While most studies on RNT have focused on structural and functional characteristics of gray matter, this study aimed to examine the association between white matter (WM) tracts and interindividual variability in RNT. METHODS: A probabilistic tractography approach was used to characterize differences in the size and anatomical trajectory of WM fibers traversing psychosurgery targets historically useful in the treatment of MDD (anterior capsulotomy, anterior cingulotomy, and subcaudate tractotomy) in patients with MDD and low (n = 53) or high (n = 52) RNT, and healthy control subjects (n = 54). MDD samples were propensity matched on depression and anxiety severity and demographics. RESULTS: WM tracts traversing left hemisphere targets and reaching the ventral anterior body of the corpus callosum (thus extending to contralateral regions) were larger in the high-RNT MDD group compared with low-RNT (effect size D = 0.27, p = .042) and healthy control (D = 0.23, p = .02) groups. MDD was associated with greater size of tracts that converge onto the right medial orbitofrontal cortex regardless of RNT intensity. Other RNT-nonspecific findings in MDD involved tracts reaching the left primary motor and right primary somatosensory cortices. CONCLUSIONS: This study provides the first evidence to our knowledge that WM connectivity patterns, which could become targets of intervention, differ between high- and low-RNT participants with MDD. These WM differences extend to circuits that are not specific to RNT, possibly subserving reward mechanisms and psychomotor activity.

A Wafer-Scale Nanoporous 2D Active Pixel Image Sensor Matrix with High Uniformity, High Sensitivity, and Rapid Switching.

2D transition-metal dichalcogenides (TMDs) have been successfully developed as novel ubiquitous optoelectronics owing to their excellent electrical and optical characteristics. However, active-matrix image sensors based on TMDs have limitations owing to the difficulty of fabricating large-area integrated circuitry and achieving high optical sensitivity. Herein, a large-area uniform, highly sensitive, and robust image sensor matrix with active pixels consisting of nanoporous molybdenum disulfide (MoS2 ) phototransistors and indium-gallium-zinc oxide (IGZO) switching transistors is reported. Large-area uniform 4-inch wafer-scale bilayer MoS2 films are synthesized by radio-frequency (RF) magnetron sputtering and sulfurization processes and patterned to be a nanoporous structure consisting of an array of periodic nanopores on the MoS2 surface via block copolymer lithography. Edge exposure on the nanoporous bilayer MoS2 induces the formation of subgap states, which promotes a photogating effect to obtain an exceptionally high photoresponsivity of 5.2 × 104 A W-1 . A 4-inch-wafer-scale image mapping is successively achieved using this active-matrix image sensor by controlling the device sensing and switching states. The high-performance active-matrix image sensor is state-of-the-art in 2D material-based integrated circuitry and pixel image sensor applications.

Neural substrates of continuous and discrete inhibitory control.

Inhibitory control dysfunctions play an important role in psychiatric disorders but the precise nature of these dysfunctions is still not well understood. Advances in computational modeling of real-time motor control using a proportion-integral-derivative (PID) control framework have parsed continuous motor inhibition into a preemptive drive component (signified by the Kp parameter) and a reactive damping component (signified by the Kd parameter). This investigation examined the relationship between inhibitory control processing during a stop signal task and continuous motor control during a simulated one-dimensional driving task in a transdiagnostic sample of participants. A transdiagnostic psychiatric sample of 492 individuals completed a stop signal task during functional magnetic resonance imaging and a simple behavioral motor control task, which was modeled using the PID framework. We examined associations between the Kp and Kd parameters and behavioral indices as well as neural activation on the stop signal task. Individuals with higher damping, controlling for a drive, on the driving task exhibited relatively less strategic adjustment after a stop trial (indexed by the difference in go trial reaction time and by stop trial accuracy) on the stop signal task. Individuals with higher damping, controlling for a drive, additionally exhibited increased activity in the frontal and parietal regions as well as the insula and caudate during response inhibition on the stop signal task. The results suggest that computational indices of motor control performance may serve as behavioral markers of the functioning of neural systems involved in inhibitory control.

Attenuated interoceptive processing in individuals with major depressive disorder and high repetitive negative thinking.

Repetitive negative thinking (RNT) is a transdiagnostic symptom associated with poor outcomes in major depressive disorder (MDD). MDD is characterized by altered interoception, which has also been associated with poor outcomes. The present study investigated whether RNT is directly associated with altered interoceptive processing. Interoceptive awareness toward the heart and stomach was probed on the Visceral Interoceptive Attention (VIA) task with fMRI in MDD individuals who were propensity-matched on the severity of depression and anxiety symptoms and relevant demographics but different in RNT intensity (High RNT [H-RNT, n = 48] & Low RNT [L-RNT, n = 49]), and in matched healthy volunteers (HC, n = 27). Both H-RNT and L-RNT MDD individuals revealed reduced stomach interoceptive processing compared to HC in the left medial frontal region and insular cortex (H-RNT: ß = -1.04, L-RNT: ß = -0.97), perirhinal cortex (H-RNT: ß = -0.99, L-RNT: ß = -1.03), and caudate nucleus (H-RNT: ß = -1.06, L-RNT: ß = -0.89). However, H-RNT was associated with decreased right medial temporal lobe activity including the hippocampus and amygdala during stomach interoceptive trials (ß = -0.61) compared to L-RNT. Insular interoceptive processing was similar in H-RNT and L-RNT participants (ß = -0.07, p = 0.92). MDD individuals with high RNT exhibited altered gastric interoceptive responses in brain areas that are important for associating the information with specific contexts and emotions. Attenuated interoceptive processing may contribute to RNT generation, non-adaptive information processing, action selection, and thus poor treatment outcome.

Probing the Efficacy of Large-Scale Nonporous IGZO for Visible-to-NIR Detection Capability: An Approach toward High-Performance Image Sensor Circuitry.

The technological ability to detect a wide spectrum range of illuminated visible-to-NIR is substantially improved for an amorphous metal oxide semiconductor, indium gallium zinc oxide (IGZO), without employing an additional photoabsorber. The fundamentally tuned morphology via structural engineering results in the creation of nanopores throughout the entire thickness of ∼30 nm. See-through nanopores have edge functionalization with vacancies, which leads to a large density of substates near the conduction band minima and valence band maxima. The presence of nanoring edges with a high concentration of vacancies is investigated using chemical composition analysis. The process of creating a nonporous morphology is sophisticated and is demonstrated using a wafer-scale phototransistor array. The performance of the phototransistors is assessed in terms of photosensitivity (S) and photoresponsivity (R); both are of high magnitudes (S = 8.6 × 104 at λex = 638 nm and Pinc = 512 mW cm2-; R = 120 A W1- at Pinc = 2 mW cm2- for the same λex). Additionally, the 7 × 5 array of 35 phototransistors is effective in sensing and reproducing the input image by responding to selectively illuminated pixels.

Functional magnetic resonance imaging data for the association between polygenic risk scores for neuroticism and reward-punishment processing.

Neuroticism as a personality trait represents a heritable risk for psychiatric disorders. The polygenic risk score for neuroticism (N-PRS) is used to study genetic vulnerability to neuroticism. The current data present the association of the genetic risk for neuroticism to neural reward-punishment processing using functional magnetic resonance imaging. N-PRS was computed based on the individual's genotype information and a genome-wide association study on the UK Biobank data. While individuals performed a monetary incentive delay task, their neural activations for upcoming incentives (reward: gain, punishment: loss) were measured in blood oxygen level dependent (BOLD) signals during the delay phase. Multivariate ANCOVAs were used to analyze BOLD signals for finding the association between N-PRS and reward-punishment processing by the incentive valence (Related research article: H. Park, K.L. Forthman, R. Kuplicki, T.A. Victor, Tulsa 1000 Investigators, H.W. Yeh, W.K. Thompson, M.P. Paulus, Polygenic risk for neuroticism modulates response to gains and losses in the amygdala and caudate: evidence from a clinical cohort. J. Affect. Disord. 293 (2021) 124-132. https://doi.org/10.1016/j.jad.2021.06.016). These data can be used as reference data for future studies examining the role of the genetic propensity for personality traits in the context of psychiatric disorders.

Neural Processing Dysfunctions During Fear Learning but Not Reward-Related Processing Characterize Depressed Individuals With High Levels of Repetitive Negative Thinking.

BACKGROUND: Repetitive negative thinking (RNT) is a symptom dimension of depression that is associated with a poorer prognosis in terms of higher recurrence, treatment resistance, residual symptoms, and disability. This investigation examined whether RNT is associated with aberrant reward processing and fear learning. METHODS: Very high RNT (VH-RNT) (n = 60) and high RNT (H-RNT) (n = 60) propensity-matched individuals with depression (age, sex, race/ethnicity, income/employment, body mass index, depressive and anxiety symptom severity) participated in this study along with matched healthy comparison volunteers (n = 30). This propensity-matched sample was selected from the larger Tulsa 1000 study. Participants performed two functional magnetic resonance imaging tasks: the monetary incentive delay task probing reward processing and the fear conditioning task probing aversive learning and extinction. RESULTS: Both VH-RNT and H-RNT groups showed lower neural activity than healthy comparison subjects in reward circuitry, including the inferior frontal gyrus (VH-RNT: ß = -1.24, H-RNT: ß = -1.28) and the cerebellum (VH-RNT: ß = -0.93, H-RNT: ß = -1.14). However, individuals with VH-RNT exhibited lower activation than those with H-RNT in central autonomic network components during fear conditioning (ß = -0.84) and continued conditioned responses during early extinction in the postcentral cortex (ß = 0.71). CONCLUSIONS: VH-RNT showed aberrant processing in fear conditioning during both learning and extinction phases compared with H-RNT. These findings demonstrate that dysfunctions of negative valence associated with RNT may be domain specific, which should be taken into account for identifying potential specific targets of intervention.

Ultrasensitive and Selective Field-Effect Transistor-Based Biosensor Created by Rings of MoS2 Nanopores.

The ubiquitous field-effect transistor (FET) is widely used in modern digital integrated circuits, computers, communications, sensors, and other applications. However, reliable biological FET (bio-FET) is not available in real life due to the rigorous requirement for highly sensitive and selective bio-FET fabrication, which remains a challenging task. Here, we report an ultrasensitive and selective bio-FET created by the nanorings of molybdenum disulfide (MoS2) nanopores inspired by nuclear pore complexes. We characterize the nanoring of MoS2 nanopores by scanning transmission electron microscopy, Raman, and X-ray photoelectron spectroscopy spectra. After fabricating MoS2 nanopore rings-based bio-FET, we confirm edge-selective functionalization by the gold nanoparticle tethering test and the change of electrical signal of the bio-FET. Ultrahigh sensitivity of the MoS2 nanopore edge rings-based bio-FET (limit of detection of 1 ag/mL) and high selectivity are accomplished by effective coupling of the aptamers on the nanorings of the MoS2 nanopore edge for cortisol detection. We believe that MoS2 nanopore edge rings-based bio-FET would provide platforms for everyday biosensors with ultrahigh sensitivity and selectivity.

Polygenic risk for neuroticism moderates response to gains and losses in amygdala and caudate: Evidence from a clinical cohort.

BACKGROUND: Neuroticism is a heritable trait that contributes to the vulnerability to depression. We used polygenic risk scores (PRS) to examine genetic vulnerability to neuroticism and its associations with reward/punishment processing in a clinical sample with mood, anxiety, and substance use disorders. It was hypothesized that higher PRS for neuroticism is associated with attenuated neural responses to reward/punishment. METHOD: Four hundred sixty-nine participants were genotyped and their PRSs for neuroticism were computed. Associations between PRS for neuroticism and anticipatory processing of monetary incentives were examined using functional magnetic resonance imaging. RESULTS: Individuals with higher PRS for neuroticism showed less anticipatory activation in the left amygdala and caudate region to incentives regardless of incentive valence. Further, these individuals exhibited altered sensitivity to gain/loss processing in the right anterior insula. Higher PRSs for neuroticism were also associated with reduced processing of gains in the precuneus. LIMITATIONS: The study population consisted of a transdiagnostic sample with dysfunctions in positive and negative valence processing. PRS for neuroticism may be correlated with current clinical symptoms due to the vulnerability to psychiatric disorders. CONCLUSIONS: Greater genetic loading for neuroticism was associated with attenuated anticipatory responsiveness in reward/punishment processing with altered sensitivity to valences. Thus, a higher genetic risk for neuroticism may limit the degree to which positive and/or negative outcomes influence the current mood state, which may contribute to the development of positive and negative affective dysfunctions in individuals with mood, anxiety, and addictive disorders.

Exceptionally Uniform and Scalable Multilayer MoS2 Phototransistor Array Based on Large-Scale MoS2 Grown by RF Sputtering, Electron Beam Irradiation, and Sulfurization.

Two-dimensional molybdenum disulfide (MoS2) has emerged as a promising material for optoelectronic applications because of its superior electrical and optical properties. However, the difficulty in synthesizing large-scale MoS2 films has been recognized as a bottleneck in uniform and reproducible device fabrication and performance. Here, we proposed a radio-frequency magnetron sputter system, and post-treatments of electron beam irradiation and sulfurization to obtain large-scale continuous and high-quality multilayer MoS2 films. Large-area uniformity was confirmed by no deviation of electrical performance in fabricated MoS2 thin-film transistors (TFTs) with an average on/off ratio of 103 and a transconductance of 0.67 nS. Especially, the photoresponsivity of our MoS2 TFT reached 3.7 A W-1, which is a dramatic improvement over that of a previously reported multilayer MoS2 TFT (0.1 A W-1) because of the photogating effect induced by the formation of trap states in the band gap. Finally, we organized a 4 × 4 MoS2 phototransistor array with high photosensitivity, linearity, and uniformity for light detection, which demonstrates the great potential of 2D MoS2 for future-oriented optoelectronic devices.

MoS2 Field-Effect Transistor-Amyloid-ß1-42 Hybrid Device for Signal Amplified Detection of MMP-9.

The detection of circulating protein (CP) is very important for the diagnosis and therapeutics of cancer. Conventional techniques based on a specific antibody-antigen interaction are still lacking because of a shortage of cost effectiveness, complicated sandwich structure and tagging process, and inconsistent detection of CP due to the inherent instability of antibodies. Herein, we demonstrate a hybrid device consisting of two-dimensional (2D) nanoscale molybdenum disulfide (MoS2) field-effect transistor (FET) with an amyloid-ß1-42 (Aß1-42) functionalized surface, which amplifies electric signals of the FET in order to detect matrix metalloproteinase-9 (MMP-9), which is a certain type of CP that degrades Aß1-42. With the hybrid device, we detected the concentrations of MMP-9 in the range from 1 pM to 10 nM. Moreover, using tapping-mode atomic force microscopy and Kelvin probe force microscopy, we verified that the signal amplification corresponding to the MMP-9 concentrations was caused by the reduced length and the decreased surface potential of degraded Aß1-42 due to MMP-9. The hybrid device studied in this paper can be very useful for monitoring MMP-9 activity, as well as serving as a sensing platform for the electrical signal amplification of 2D MoS2 FET-biosensors.

Enhanced Moisture-Reactive Hydrophilic-PTFE-Based Flexible Humidity Sensor for Real-Time Monitoring.

Flexible sensors connected to cell phones are a promising technology that can aid in continuously monitoring signals in our daily lives, such as an individual's health status and information from buildings, farms, and industry. Among such signals, real-time humidity monitoring is crucial to a comfortable life, as human bodies, plants, and industrial environments require appropriate humidity to be maintained. We propose a hydrophilic polytetrafluoroethylene (H-PTFE)-based flexible humidity sensor integrated with readout circuitry, wireless communication, and a mobile battery. To enhance its sensitivity, linearity, and reliability, treatment with sodium hydroxide implements additional hydroxyl (OH) groups, which further enhance the sensitivity, create a strong linearity with respect to variations in relative humidity, and produce a relatively free hysteresis. Furthermore, to create robust mechanical stability, cyclic upward bending was performed for up to 3000 cycles. The overall electrical and mechanical results demonstrate that the flexible real-time H-PTFE humidity sensor system is suitable for applications such as wearable smart devices.

Label-Free and Recalibrated Multilayer MoS2 Biosensor for Point-of-Care Diagnostics.

Molybdenum disulfide (MoS2) field-effect transistor (FET)-based biosensors have attracted significant attention as promising candidates for highly sensitive, label-free biomolecule detection devices. In this paper, toward practical applications of biosensors, we demonstrate reliable and quantitative detection of a prostate cancer biomarker using the MoS2 FET biosensor in a nonaqueous environment by reducing nonspecific molecular binding events and realizing uniform chemisorption of anti-PSA onto the MoS2 surface. A systematic and statistical study on the capability of the proposed device is presented, and the biological binding events are directly confirmed and characterized through intensive structural and electrical analysis. Our proposed biosensor can reliably detect various PSA concentrations with a limit of 100 fg/mL. Moreover, rigorous theoretical simulations provide a comprehensive understanding of the operating mechanism of the MoS2 FET biosensors, and further suggests the enhancement of the sensitivity through engineering device design parameters.

Two-dimensional layered MoS2 biosensors enable highly sensitive detection of biomolecules.

We present a MoS2 biosensor to electrically detect prostate specific antigen (PSA) in a highly sensitive and label-free manner. Unlike previous MoS2-FET-based biosensors, the device configuration of our biosensors does not require a dielectric layer such as HfO2 due to the hydrophobicity of MoS2. Such an oxide-free operation improves sensitivity and simplifies sensor design. For a quantitative and selective detection of PSA antigen, anti-PSA antibody was immobilized on the sensor surface. Then, introduction of PSA antigen, into the anti-PSA immobilized sensor surface resulted in a lable-free immunoassary format. Measured off-state current of the device showed a significant decrease as the applied PSA concentration was increased. The minimum detectable concentration of PSA is 1 pg/mL, which is several orders of magnitude below the clinical cut-off level of ~4 ng/mL. In addition, we also provide a systematic theoretical analysis of the sensor platform - including the charge state of protein at the specific pH level, and self-consistent channel transport. Taken together, the experimental demonstration and the theoretical framework provide a comprehensive description of the performance potential of dielectric-free MoS2-based biosensor technology.

The formation of source memory under distraction.

BACKGROUND: It is vital to select and process relevant information while restraining irrelevant information for successful retrieval. When multiple streams of information are concurrently present, the ability to overcome distraction is very crucial for processing relevant information. Despite its significance, the neural mechanism of successful memory formation under distraction remains unclear, especially with memory for associations. The present fMRI study investigated the effect of distraction due to irrelevant stimuli in source memory. METHODS: In the MR scanner, participants studied an item and perceptual context with no distractor, a letter-distractor, or a word-distractor. Following the study phase, a source recognition test was administered in which participants were instructed to judge the study status of the test items and context of studied items. Participants' encoding activity was back-sorted by later source recognition to find the influence of distractors in subsequent memory effects. RESULTS: Source memory with distractors recruited greater encoding activity in the left dorsolateral prefrontal cortex, and the bilateral inferior temporal gyrus/fusiform cortex, along with the left posterior hippocampus. However, enhanced activity in the left anterior ventrolateral prefrontal cortex and the left parahippocampal cortex predicted successful source memory regardless of the presence of a distractor. CONCLUSIONS: These findings of subsequent memory effects suggest that strong binding of the item-context associations, as well as resistance to interference, may have greater premium in the formation of successful source memory of pictures under distraction. Further, attentional selection to the relevant target seems to play a major role in contextual binding under distraction by enhancing the viability of memory representations from interference effects of distractors.