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BACKGROUND Patient-generated health data (PGHD) are important in the management of several diseases. Although there are limitations, information can be obtained using a wearable device, and time-related information, such as exercise time or sleep time, can also be obtained. Fitbits can be used to acquire sleep onset, sleep offset, total sleep time (TST), and wakefulness after sleep onset (WASO) data, although there are limitations regarding the depth of sleep and satisfaction; therefore, the patient's subjective response is still important information that cannot be replaced. OBJECTIVE To use PGHD related to time, such as sleep, it is necessary to understand the characteristics of the time response recorded by the user; therefore, the characteristics of the user's time perception were analyzed by comparison with wearable data. METHODS Sleep data were acquired for 2 weeks using a Fitbit. Participants' sleep records were collected daily through chatbot conversations while wearing the Fitbit, and the 2 sets of data were statistically compared. RESULTS In total, 736 people aged 30-59 years were recruited, and the sleep data of 550 people who wore Fitbit and responded to the Chat for more than 7 days on the same day were analyzed. Research participants tended to respond to sleep-related times on the hour or 30-min increments, and each participant responded within the range of 60-90 min from the value measured by the Fitbit. However, on average for the participants, the chat responses and the Fitbit data were similar within a difference of approximately 15 min. Regarding sleep onset, the answer was 8 min 33 s±60 min later than that of the Fitbit data, and with respect to sleep offset, the answer was 6 min 39 s±58 min earlier. The participants' actual sleep time (AST) was similar to that obtained by subtracting the WASO from the TST measured by the Fitbit. The AST was 13 min 09 s±86 min longer than the time WASO was subtracted from the Fitbit TST. On days when the participants reported good sleep, they responded 19 min±89min longer on the AST than the Fitbit data. However, for each sleep, the probability that the participant’s AST was within ±30 min of the Fitbit TST-WASO was 55.7%, and the probability that it was within ±60 min was 76.3%. CONCLUSIONS The chatbot sleep response and Fitbit measured time were similar on average and the study participants had a slight tendency to perceive a relatively long sleep time if the answered quality of sleep was good. However, on a participant-by-participant basis, it was difficult to predict participants’ sleep duration responses with the Fitbit data. Individual variations in sleep time perception significantly affect patient response related to sleep, revealing the limitations of objective measures obtained through wearable devices. CLINICALTRIAL KCT0004297

Excitatory projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) drive aversive responses. We used Patch-seq guided multimodal classification to define the structural and functional heterogeneity of the LHA-LHb pathway. Our classification identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles, and projection patterns. We found that genetically-defined LHA-LHb neurons signal distinct aspects of emotional or naturalistic behaviors: Esr1+ LHA-LHb neurons induce aversion, whereas Npy+ LHA-LHb neurons control rearing behavior. Repeated optogenetic drive of Esr1+ LHA-LHb neurons induces a behaviorally persistent aversive state, and large-scale recordings showed a region-specific neural representation of the aversive state in the prelimbic region of the prefrontal cortex. We further found that exposure to unpredictable mild shocks induced a sex-specific sensitivity to develop a stress state in female mice, which was associated with a specific shift in the intrinsic properties of bursting-type Esr1+ LHA-LHb neurons. In summary, we describe the diversity of LHA-LHb neuron types, and provide evidence for the role of Esr1+ neurons in aversion and sexually dimorphic stress sensitivity.

Sleep disturbances are associated with cold hypersensitivity (CH) and characterized by excessive cold sensation in specific body parts and cold thermal discomfort. This study investigated the effects of short-term sleep restriction followed by a recovery phase on subjective health status, inflammation, and lipid metabolism in different types of CH. A total of 118 healthy adults aged 35 to 44 years without sleep disturbances were enrolled. Participants underwent 4-hour sleep restrictions per day for 3 days at a hospital and then returned to their daily lives for 4 days of rest. CH was assessed using a structured questionnaire with eight characteristic symptoms. A questionnaire and blood tests were administered baseline, after sleep restriction, and follow-up to assess cortisol, lipid profiles, and self-reported stress and quality of life (QOL). Participants were divided into CH (44.1%) and non-CH (55.9%) groups. The CH group showed increased stress, impaired QOL, and decreased low-density lipoprotein-cholesterol (LDL-C) levels compared to the non-CH group after sleep restriction. The variance for QOL (effect size = 0.07), subjective stress (effect size = 0.053), and LDL-C (effect size = 0.029) among time points depended on the group. Short-term sleep restriction was associated with deterioration of subjective health and reduced lipid metabolism; such changes were more evident in the CH group. Our findings suggest the need to consider an individual's CH status to assess the clinical risk associated with insufficient sleep.

The local and long-range connectivity of cortical neurons are considered instrumental to the functional repertoire of the cortical region in which they reside. In cortical networks, distinct cell types build local circuit structures enabling computational operations. Computations in the medial prefrontal cortex (mPFC) are thought to be central to cognitive operation, including decision-making and memory. We used a retrograde trans-synaptic rabies virus system to generate brain-wide maps of the input to excitatory neurons as well as three inhibitory interneuron subtypes in the mPFC. On the global scale the input patterns were found to be mainly cell type independent, with quantitative differences in key brain regions, including the basal forebrain. Mapping of the local mPFC network revealed high connectivity between the different subtypes of interneurons. The connectivity mapping gives insight into the information that the mPFC processes and the structural architecture underlying the mPFC's unique functions.

Postmenopausal women have a higher prevalence of hypertension compared to premenopausal women. Hypertension is a risk factor for cardiovascular diseases, the prevalence of which is ever increasing. This study investigated the effects of long-term acupuncture on lowering the blood pressure of postmenopausal women with prehypertension and stage 1 hypertension. Participants were 122 postmenopausal women aged less than 65 years, diagnosed with prehypertension or stage 1 hypertension (systolic blood pressure 120–159 mmHg or diastolic blood pressure 80–99 mmHg). We used a propensity score-matched design. The experimental group (n = 61) received acupuncture for four weeks every six months over a period of two years. The control group (n = 61) received no intervention. An Analysis of covariance (ANCOVA) was performed for the primary efficacy analysis. Relative risk ratios were used to compare group differences in treatment effects. Acupuncture significantly reduced the participants’ diastolic blood pressure (−9.92 mmHg, p &lt, 0.001) and systolic blood pressure (−10.34 mmHg, 0.001) from baseline to follow-up. The results indicate that acupuncture alleviates hypertension in postmenopausal women, reducing their risk of developing cardiovascular diseases and improving their health and quality of life.

Studies in rats, monkeys, and humans have found action-value signals in multiple regions of the brain. These findings suggest that action-value signals encoded in these brain structures bias choices toward higher expected rewards. However, previous estimates of action-value signals might have been inflated by serial correlations in neural activity and also by activity related to other decision variables. Here, we applied several statistical tests based on permutation and surrogate data to analyze neural activity recorded from the striatum, frontal cortex, and hippocampus. The results show that previously identified action-value signals in these brain areas cannot be entirely accounted for by concurrent serial correlations in neural activity and action value. We also found that neural activity related to action value is intermixed with signals related to other decision variables. Our findings provide strong evidence for broadly distributed neural signals related to action value throughout the brain.

BACKGROUND Mobile health (mHealth) is a major source of health management systems. Moreover, the demand for mHealth, which is in need of change due to the COVID-19 pandemic, is increasing worldwide. Accordingly, interest in health care in everyday life and the importance of mHealth are growing. OBJECTIVE We developed the MibyeongBogam (MBBG) app that evaluates the user’s subhealth status via a smartphone and provides a health management method based on that user’s subhealth status for use in everyday life. Subhealth is defined as a state in which the capacity to recover to a healthy state is declined, but without the presence of clinical disease. The objective of this study was to compare the awareness and status of subhealth after the use of the MBBG app between intervention and control groups, and to evaluate the app’s practicality. METHODS This study was a prospective, open-label, parallel group, randomized controlled trial. The study was conducted at two hospitals in Korea with 150 healthy people in their 30s and 40s, at a 1:1 allocation ratio. Participants visited the hospital three times as follows: preintervention, intermediate visit 6 weeks after the intervention, and final visit 12 weeks after the intervention. Key endpoints were measured at the first visit before the intervention and at 12 weeks after the intervention. The primary outcome was the awareness of subhealth, and the secondary outcomes were subhealth status, health-promoting behaviors, and motivation to engage in healthy behaviors. RESULTS The primary outcome, subhealth awareness, tended to slightly increase for both groups after the uncompensated intervention, but there was no significant difference in the score between the two groups (intervention group: mean 23.69, SD 0.25 vs control group: mean 23.1, SD 0.25; P=.09). In the case of secondary outcomes, only some variables of the subhealth status showed significant differences between the two groups after the intervention, and the intervention group showed an improvement in the total scores of subhealth (P=.03), sleep disturbance (P=.02), depression (P=.003), anger (P=.01), and anxiety symptoms (P=.009) compared with the control group. CONCLUSIONS In this study, the MBBG app showed potential for improving the health, especially with regard to sleep disturbance and depression, of individuals without particular health problems. However, the effects of the app on subhealth awareness and health-promoting behaviors were not clearly evaluated. Therefore, further studies to assess improvements in health after the use of personalized health management programs provided by the MBBG app are needed. The MBBG app may be useful for members of the general public, who are not diagnosed with a disease but are unable to lead an optimal daily life due to discomfort, to seek strategies that can improve their health. CLINICALTRIAL Clinical Research Information Service KCT0003488; https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=14379

Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies the expression of cortical gamma rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband gamma power. Increased baseline broadband gamma is also a prominent characteristic in schizophrenia, and a hallmark of network alterations induced by N-methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine. It has been questioned if enhanced broadband gamma power is a true rhythm, and if rhythmic PV inhibition is involved or not. It has been suggested that asynchronous and increased firing activities underlie broadband power increases spanning the gamma band. Using mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that local LFP (local field potential) oscillations and neuronal activity with decreased synchronicity generate increases in prefrontal broadband gamma power. Specifically, reduced spike time precision of both local PV interneurons and wide-spiking (WS) excitatory neurons contribute to increased firing rates, and spectral leakage of spiking activity (spike “contamination”) affecting the broadband gamma band. Desynchronization was evident at multiple time scales, with reduced spike-LFP entrainment, reduced cross-frequency coupling, and fragmentation of brain states. While local application of S(+)-ketamine in wildtype mice triggered network desynchronization and increases in broadband gamma power, our investigations suggest that disparate mechanisms underlie increased power of broadband gamma caused by genetic alteration of PV interneurons, and ketamine-induced power increases in broadband gamma. Our studies, thus, confirm that broadband gamma increases can arise from asynchronous activities, and demonstrate that long-term deficiency of PV inhibition can be a contributor.

Background: Insomnia and hypertension are diseases with a high prevalence and a known association with each other. Sihogayonggolmoryeo-tang (SYM) is an herbal medicine traditionally used for the treatment of insomnia disorder concurrent with hypertension. However, no scientific clinical evidence exists supporting the effects of SYM on these disorders. This study aims to explore the feasibility, effectiveness, and safety of SYM for the treatment of insomnia disorder with concurrent prehypertension or stage 1 hypertension. Methods: A prospective, randomized, wait-list controlled, parallel, pilot clinical trial has been designed for a study to be conducted in Daejeon, Republic of Korea. Thirty insomnia disorder patients with prehypertension or stage 1 hypertension will be randomly assigned to a SYM or wait-list group at a 1:1 ratio. The SYM group will be administered SYM granules twice a day for 4 weeks and followed-up for 2 weeks while the wait-list group will not receive SYM granules. All participants in both groups will be given brochures with instructions for maintaining sleep hygiene and lifestyle modifications to reduce hypertension. Data will be collected at baseline and at 2, 4, and 6 weeks after allocation. The primary outcome is the Insomnia Severity Index score at 4 weeks post-treatment. The secondary outcomes will consist of the Pittsburgh Sleep Quality Index, sleep diary, systolic and diastolic blood pressure, brachial-ankle pulse wave velocity, ankle-brachial index, atherosclerosis biomarkers, the Hospital Anxiety and Depression Scale, the 5-level EuroQol-5 dimensions, and the Patient Global Impression of Change. Adverse events and laboratory test results will be monitored to assess the safety. Data will be recorded in electronic case report forms and analyzed using SPSS Statistics, Version 24.0. Discussion: This is the first clinical trial to explore the effectiveness and safety of SYM for the treatment of insomnia disorder concurrent with prehypertension or stage 1 hypertension. The results of this study can form the foundation for a future multicenter, large-scale, confirmatory clinical trial. Trial registration: Clinical Research Information Service, KCT0005001 (registered on May 8, 2020).

Inhibitory interneurons expressing parvalbumin (PV) are central to cortical network dynamics, generation of γ oscillations, and cognition. Dysfunction of PV interneurons disrupts cortical information processing and cognitive behavior. Brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (trkB) signaling regulates the maturation of cortical PV interneurons but is also implicated in their adult multidimensional functions. Using a novel viral strategy for cell-type-specific and spatially restricted expression of a dominant-negative trkB (trkB.DN), we show that BDNF/trkB signaling is essential to the integrity and maintenance of prefrontal PV interneurons in adult male and female mice. Reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) resulted in deficient PV inhibition and increased baseline local field potential (LFP) activity in a broad frequency band. The altered network activity was particularly pronounced during increased activation of the prefrontal network and was associated with changed dynamics of local excitatory neurons, as well as decreased modulation of the LFP, abnormalities that appeared to generalize across stimuli and brain states. In addition, our findings link reduced BDNF/trkB signaling in prefrontal PV interneurons to increased aggression. Together our investigations demonstrate that BDNF/trkB signaling in PV interneurons in the adult mPFC is essential to local network dynamics and cognitive behavior. Our data provide direct support for the suggested association between decreased trkB signaling, deficient PV inhibition, and altered prefrontal circuitry. SIGNIFICANCE STATEMENT Brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (trkB) signaling promotes the maturation of inhibitory parvalbumin (PV) interneurons, neurons central to local cortical dynamics, γ rhythms, and cognition. Here, we used a novel viral approach for reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) to establish the role of BDNF/trkB signaling in adult prefrontal network activities. Reduced BDNF/trkB signaling caused pronounced morphologic alterations, reduced PV inhibition, and deficient prefrontal network dynamics. The altered network activity appeared to manifest across stimuli and brain states and was associated with aberrant local field potential (LFP) activities and increased aggression. The results demonstrate that adult BDNF/trkB signaling is essential to PV inhibition and prefrontal circuit function and directly links BDNF/trkB signaling to network integrity in the adult brain.

Inhibitory interneurons expressing parvalbumin (PV) in the prefrontal cortex (PFC) are central to excitatory/inhibitory (E/I) balance, generation of gamma oscillations, and cognition. Dysfunction of PV interneurons disrupts information processing and cognitive behavior. Tyrosine receptor kinase B (trkB) signaling is known to regulate the differentiation and maturation of cortical PV interneurons during development, but is also suggested to be involved in the activity and network functions of PV interneurons in the adult brain. Using a novel viral strategy for cell-type and region-specific expression of a dominant negative trkB in adult mice, we show that reduced trkB signaling in PV interneurons in the PFC leads to pronounced morphological, physiological, and behavioral changes. Our results provide evidence for a critical role of trkB signaling in the function of PV interneurons in the adult brain, local network activities central to prefrontal circuit dynamics, and cognitive behavior.

Background Physical symptoms such as fatigue, pain, digestive problems, and sleep disturbances are chief reasons individuals seek primary care, as they affect health-related quality of life. We investigated the associations between various combinations of these common symptoms and individuals’ health-related quality of life. Methods This large-scale survey study of 1100 Koreans aged ≥19 years was conducted in 2017 using multi-stage stratified sampling based on region, sex, and age. Data were collected using questionnaires administered face-to-face; then, a linear regression analysis was performed to assess how the symptoms were related to participants’ health-related quality of life. Complex symptoms were defined as co-occurrence of two or more of the four symptoms—fatigue, pain, digestive problems, and sleep disturbances. Results The most frequently observed stand-alone symptom was fatigue, while the most common combination was fatigue and pain. When examined individually, fatigue, digestive problems, and sleep disturbances were closely associated with mental health-related quality of life, and pain was associated with physical health-related quality of life. Complex symptoms were also related to health-related quality of life. Lower physical health-related quality of life was strongly associated when fatigue and pain or all four symptoms were co-occurring, and the lowest mental health-related quality of life was seen when all four symptoms were present, after adjusting for all variables. Conclusions Symptoms can be present in various combinations and are significantly associated with health-related quality of life. Extra attention should be given to patterns accompanying fatigue and pain and to those involving more symptoms. This elucidated the characteristics of symptoms that affect the health-related quality of life of South Korean adults.

Electrophysiological recording and optogenetic control of neuronal activity in behaving animals have been integral to the elucidation of how neurons and circuits modulate network activity in the encoding and causation of behavior. However, most current electrophysiological methods require substantial economical investments and prior expertise. Further, the inclusion of optogenetics with electrophysiological recordings in freely moving animals adds complexity to the experimental design. Expansion of the technological repertoire across laboratories, research institutes, and countries, demands open access to high-quality devices that can be built with little prior expertise from easily accessible parts of low cost. We here present an affordable, truly easy-to-assemble micro-drive for electrophysiology in combination with optogenetics in freely moving rodents. The DMCdrive is particularly suited for reliable recordings of neurons and network activities over the course of weeks, and simplify optical tagging and manipulation of neurons in the recorded brain region. The highly functional and practical drive design has been optimized for accurate tetrode movement in brain tissue, and remarkably reduced build time. We provide a complete overview of the drive design, its assembly and use, and proof-of-principle demonstration of recordings paired with cell-type-specific optogenetic manipulations in the prefrontal cortex (PFC) of freely moving transgenic mice and rats.

Introduction Prolonged fatigue is common among adults, yet only a small percentage of affected individuals seek medical attention. Following findings that complementary and alternative medicine can be effective strategies for improving fatigue, we evaluated the effect of an herbal tea regimen on prolonged fatigue. Methods In this pilot randomized controlled trial, participants with prolonged fatigue were randomly allocated to either a tea (n = 20) or control (n = 20) group. The tea group consumed herbal tea consisting of Astragali Radix, Angelicae gigantis Radix, and Zizyphi Fructus twice daily for 4 weeks, whereas the control group received no intervention. Outcomes were assessed at baseline and 4 and 8 weeks. The primary outcome was fatigue severity, measured using the Chalder Fatigue Scale. Secondary outcomes included sleep quality, depression symptoms, and quality of life. Results Among the 40 individuals screened, 35 completed the study. Fatigue severity was significantly lower in the tea group than the control group at 4 weeks, and within the tea group, fatigue severity and sleep quality improved at the 4- and 8-week follow-ups vs. baseline in the tea group. Depression also significantly improved in the tea group at 8 weeks. There were no changes within the control group on any measure. Conclusion The findings suggest that our herbal tea formulation reduces fatigue severity and improves sleep quality in adults with prolonged fatigue.

The local and long-range connectivity of cortical neurons are considered instrumental to the functional repertoire of the cortical region in which they reside. In cortical networks, distinct cell types build local circuit structures enabling computational operations. Computations in the medial prefrontal cortex (mPFC) are thought to be central to cognitive operation, including decision-making and memory. We used a retrograde trans-synaptic rabies virus system to generate brain-wide maps of the input to excitatory neurons as well as three inhibitory interneuron subtypes in the mPFC. On the global scale the input patterns were found to be mainly cell type independent, with quantitative differences in key brain regions, including the basal forebrain. Mapping of the local mPFC network revealed high connectivity between the different subtypes of interneurons. The connectivity mapping gives insight into the information that the mPFC processes and the structural architecture underlying the mPFC's unique functions.

The structure-guided design of chloride-conducting channelrhodopsins has illuminated mechanisms underlying ion selectivity of this remarkable family of light-activated ion channels. The first generation of chloride-conducting channelrhodopsins, guided in part by development of a structure-informed electrostatic model for pore selectivity, included both the introduction of amino acids with positively charged side chains into the ion conduction pathway and the removal of residues hypothesized to support negatively charged binding sites for cations. Engineered channels indeed became chloride selective, reversing near −65 mV and enabling a new kind of optogenetic inhibition; however, these first-generation chloride-conducting channels displayed small photocurrents and were not tested for optogenetic inhibition of behavior. Here we report the validation and further development of the channelrhodopsin pore model via crystal structure-guided engineering of next-generation light-activated chloride channels (iC++) and a bistable variant (SwiChR++) with net photocurrents increased more than 15-fold under physiological conditions, reversal potential further decreased by another ∼15 mV, inhibition of spiking faithfully tracking chloride gradients and intrinsic cell properties, strong expression in vivo, and the initial microbial opsin channel-inhibitor–based control of freely moving behavior. We further show that inhibition by light-gated chloride channels is mediated mainly by shunting effects, which exert optogenetic control much more efficiently than the hyperpolarization induced by light-activated chloride pumps. The design and functional features of these next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition, confirm fundamental predictions of the ion selectivity model, and further elucidate electrostatic and steric structure–function relationships of the light-gated pore.

The Supplementary Information is available in the online version of this Publisher Correction.

The cortico-basal ganglia network has been proposed to consist of parallel loops serving distinct functions. However, it is still uncertain how the content of processed information varies across different loops and how it is related to the functions of each loop. We investigated this issue by comparing neuronal activity in the dorsolateral (sensorimotor) and dorsomedial (associative) striatum, which have been linked to habitual and goal-directed action selection, respectively, in rats performing a dynamic foraging task. Both regions conveyed significant neural signals for the animal's goal choice and its outcome. Moreover, both regions conveyed similar levels of neural signals for action value before the animal's goal choice and chosen value after the outcome of the animal's choice was revealed. However, a striking difference was found in the persistence of neural signals for the animal's chosen action. Signals for the animal's goal choice persisted in the dorsomedial striatum until the outcome of the animal's next goal choice was revealed, whereas they dissipated rapidly in the dorsolateral striatum. These persistent choice signals might be used for causally linking temporally discontiguous responses and their outcomes in the dorsomedial striatum, thereby contributing to its role in goal-directed action selection.

The Republic of Korea (ROK) has enjoyed rapid economic growth and development over the last 30 years. Rapid increases in energy use—especially petroleum, natural gas, and electricity, and especially in the industrial and transport sectors—have fueled the ROK's economic growth, but with limited fossil fuel resources of its own, the result has been that the ROK is almost entirely dependent on energy imports. The article that follows summarizes the recent trends in the ROK energy sector, including trends in energy demand and supply, and trends in economic, demographic, and other activities that underlie trends in energy use. The ROK has been experiencing drastic changes in its energy system, mainly induced by industrial, supply security, and environmental concerns, and energy policies in the ROK have evolved over the years to address such challenges through measures such as privatization of energy-sector activities, emphases on enhancing energy security through development of energy efficiency, nuclear power, and renewable energy, and a related focus on reducing greenhouse gas emissions. The assembly of a model for evaluating energy futures in the ROK (ROK2010 LEAP) is described, and results of several policy-based scenarios focused on different levels of nuclear energy utilization are described, and their impacts on of energy supply and demand in the ROK through the year 2030 are explored, along with their implications for national energy security and long-term policy plans. Nuclear power continues to hold a crucial position in the ROK's energy policy, but aggressive expansion of nuclear power alone, even if possible given post-Fukushima global concerns, will not be sufficient to attain the ROK's “green economy” and greenhouse gas emissions reduction goals.

Combined heat and power (CHP) and district heating (DH) promotion policies are based on the assumption of high energy efficiencies. In the last two decades, however, there has been a big increase in energy efficiencies of combined-cycle gas power plants (CCs) including CHPs and gas-condensing boilers. This study tries to verify the validity of the assumption of high energy efficiency of DH. The experience in the agglomeration of Seoul shows that DH in combination with large modern CHPs is not more energy efficient but substantially more expensive compared to individual gas heating by efficient condensing boilers in combination with CCs. We argue that the Korean government should review its CHP/DH support programs and abandon the so-called heat supply monopoly for DH operators in newly developed residential areas. Such a policy intervention only distorts the space heating market and wastes valuable financial resources. Furthermore, the public should be properly informed on energy efficiency as well as energy- and system-related costs of various heat supply systems. In the light of the present improvements in the performance of gas-condensing boilers and CCs, the validity of the assumption of high energy efficiency of CHP/DH in other countries has to be reviewed.

Summary While signatures of attention have been extensively studied in sensory systems, the neural sources and computations responsible for top-down control of attention are largely unknown. Using chronic recordings in mice, we found that fast-spiking parvalbumin (FS-PV) interneurons in medial prefrontal cortex (mPFC) uniformly show increased and sustained firing during goal-driven attentional processing, correlating to the level of attention. Elevated activity of FS-PV neurons on the timescale of seconds predicted successful execution of behavior. Successful allocation of attention was characterized by strong synchronization of FS-PV neurons, increased gamma oscillations, and phase locking of pyramidal firing. Phase-locked pyramidal neurons showed gamma-phase-dependent rate modulation during successful attentional processing. Optogenetic silencing of FS-PV neurons deteriorated attentional processing, while optogenetic synchronization of FS-PV neurons at gamma frequencies had pro-cognitive effects and improved goal-directed behavior. FS-PV neurons thus act as a functional unit coordinating the activity in the local mPFC circuit during goal-driven attentional processing., Graphical Abstract, Highlights • Increased firing of mPFC PV interneurons is a signature of top-down attention • Attention is characterized by synchronization of mPFC PV neurons and elevated gamma • Local pyramidal neurons show gamma-phase-dependent rate modulation during attention • Synchronization of mPFC PV neurons at gamma frequencies has pro-cognitive effects, A combination of electrophysiology and optogenetic manipulations reveal that inhibitory parvalbumin interneurons and gamma oscillations are central to prefrontal cortex's control of attention.

Newly experienced events are often remembered together with how rewarding the experiences are personally. Although the hippocampus is a candidate structure where subjective values are integrated with other elements of episodic memory, it is uncertain whether and how the hippocampus processes value-related information. We examined how activity of dorsal CA1 and dorsal subicular neurons in rats performing a dynamic foraging task was related to reward values that were estimated using a reinforcement learning model. CA1 neurons carried significant signals related to action values before the animal revealed its choice behaviorally, indicating that the information on the expected values of potential choice outcomes was available in CA1. Moreover, after the outcome of the animal's goal choice was revealed, CA1 neurons carried robust signals for the value of chosen action and they temporally overlapped with the signals related to the animal's goal choice and its outcome, indicating that all the signals necessary to evaluate the outcome of an experienced event converged in CA1. On the other hand, value-related signals were substantially weaker in the subiculum. These results suggest a major role of CA1 in adding values to experienced events during episodic memory encoding. Given that CA1 neuronal activity is modulated by diverse attributes of an experienced event, CA1 might be a place where all the elements of episodic memory are integrated.

The striatum is thought to play a crucial role in value-based decision making. Although a large body of evidence suggests its involvement in action selection as well as action evaluation, underlying neural processes for these functions of the striatum are largely unknown. To obtain insights on this matter, we simultaneously recorded neuronal activity in the dorsal and ventral striatum of rats performing a dynamic two-armed bandit task, and examined temporal profiles of neural signals related to animal's choice, its outcome, and action value. Whereas significant neural signals for action value were found in both structures before animal's choice of action, signals related to the upcoming choice were relatively weak and began to emerge only in the dorsal striatum ∼200 ms before the behavioral manifestation of the animal's choice. In contrast, once the animal revealed its choice, signals related to choice and its value increased steeply and persisted until the outcome of animal's choice was revealed, so that some neurons in both structures concurrently conveyed signals related to animal's choice, its outcome, and the value of chosen action. Thus, all the components necessary for updating values of chosen actions were available in the striatum. These results suggest that the striatum not only represents values associated with potential choices before animal's choice of action, but might also update the value of chosen action once its outcome is revealed. In contrast, action selection might take place elsewhere or in the dorsal striatum only immediately before its behavioral manifestation.

Reinforcement learning theories postulate that actions are chosen to maximize a long-term sum of positive outcomes based on value functions, which are subjective estimates of future rewards. In simple reinforcement learning algorithms, value functions are updated only by trial-and-error, whereas they are updated according to the decision-maker's knowledge or model of the environment in model-based reinforcement learning algorithms. To investigate how animals update value functions, we trained rats under two different free-choice tasks. The reward probability of the unchosen target remained unchanged in one task, whereas it increased over time since the target was last chosen in the other task. The results show that goal choice probability increased as a function of the number of consecutive alternative choices in the latter, but not the former task, indicating that the animals were aware of time-dependent increases in arming probability and used this information in choosing goals. In addition, the choice behavior in the latter task was better accounted for by a model-based reinforcement learning algorithm. Our results show that rats adopt a decision-making process that cannot be accounted for by simple reinforcement learning models even in a relatively simple binary choice task, suggesting that rats can readily improve their decision-making strategy through the knowledge of their environments.

Purpose : To evaluate the diagnostic accuracy of non-invasive coronary angiography by electron beam tomog-raphy(EBT) for the depiction of coronary artery stenosis, as compared with conventional coronary angiogra-phy. Materials and Methods : In 20 patients with no history of coronary artery disease, EBT (Imatron C-150) study was performed with EKG-gating. Forty images were obtained in each patient from the pulmonary trunk to the cardiac base at 80% R-R interval, and data were reconstructed into a three-dimensional coronary angiography. The interval between conventional coronary arteriograpy and EBT was less than 30 (mean, 9) days. Coronary arteries were divided into seven segments, and stenosis was defined as a narrowing of the luminal diameter of the coronary artery of more than 50 %. The results of EBT and of conventional angiography were compared for diagnostic accuracy. Results : Conventional argiography revealed significant stenosis of the coronary artery in 12 of the 20 patients, while the use of three-dimensional coronary angiography by EBT revealed this in 16. The sensitivity and speci-ficity of EBT were relatively high in the depiction of stenosis in the proximal left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA) and middle LAD, but low sensitivity in the middle LCx and RCA. In the left main coronary artery, sensitivity was 50%. The sensitivity, specificity, accuracy, and pos-itive and negative predictive values for the depiction of coronary artery stenosis with three-dimensional coro-nary arteriography by EBT were 79%, 95 %, 93 %, 71%, and 97 %, respectively. Conclusion: Three-dimensional coronary angiography by EBT is a non-invasive diagnostic modality for the de-piction of proximal epicardial coronary artery stenosis and appears to be useful for excluding the probability of ischemic heart disease in a selected patient group.

SummaryWe investigated how different subregions of rodent prefrontal cortex contribute to value-based decision making, by comparing neural signals related to animal's choice, its outcome, and action value in orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) of rats performing a dynamic two-armed bandit task. Neural signals for upcoming action selection arose in the mPFC, including the anterior cingulate cortex, only immediately before the behavioral manifestation of animal's choice, suggesting that rodent prefrontal cortex is not involved in advanced action planning. Both OFC and mPFC conveyed signals related to the animal's past choices and their outcomes over multiple trials, but neural signals for chosen value and reward prediction error were more prevalent in the OFC. Our results suggest that rodent OFC and mPFC serve distinct roles in value-based decision making and that the OFC plays a prominent role in updating the values of outcomes expected from chosen actions.

CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report that inhibiting the generation of progeny by a subclass of pericytes led to decreased fibrosis and extracellular matrix deposition after spinal cord injury in mice. Regeneration of raphespinal and corticospinal tract axons was enhanced and sensorimotor function recovery improved following spinal cord injury in animals with attenuated pericyte-derived scarring. Using optogenetic stimulation, we demonstrate that regenerated corticospinal tract axons integrated into the local spinal cord circuitry below the lesion site. The number of regenerated axons correlated with improved sensorimotor function recovery. In conclusion, attenuation of pericyte-derived fibrosis represents a promising therapeutic approach to facilitate recovery following CNS injury.