Expectation violations enhance neuronal encoding of sensory information in mouse primary visual cortex.

The response of cortical neurons to sensory stimuli is shaped both by past events (adaptation) and the expectation of future events (prediction). Here we employed a visual stimulus paradigm with different levels of predictability to characterise how expectation influences orientation selectivity in the primary visual cortex (V1) of male mice. We recorded neuronal activity using two-photon calcium imaging (GCaMP6f) while animals viewed sequences of grating stimuli which either varied randomly in their orientations or rotated predictably with occasional transitions to an unexpected orientation. For single neurons and the population, there was significant enhancement in the gain of orientation-selective responses to unexpected gratings. This gain-enhancement for unexpected stimuli was prominent in both awake and anaesthetised mice. We implemented a computational model to demonstrate how trial-to-trial variability in neuronal responses were best characterised when adaptation and expectation effects were combined.

Hippocampus-Prefrontal Coupling Regulates Recognition Memory for Novelty Discrimination.

Recognition memory provides the ability to distinguish familiar from novel objects and places, and is important for recording and updating events to guide appropriate behavior. The hippocampus (HPC) and medial prefrontal cortex (mPFC) have both been implicated in recognition memory, but the nature of HPC-mPFC interactions, and its impact on local circuits in mediating this process is not known. Here we show that novelty discrimination is accompanied with higher theta activity (4-10 Hz) and increased c-Fos expression in both these regions. Moreover, theta oscillations were highly coupled between the HPC and mPFC during recognition memory retrieval for novelty discrimination, with the HPC leading the mPFC, but not during initial learning. Principal neurons and interneurons in the mPFC responded more strongly during recognition memory retrieval compared with learning. Optogenetic silencing of HPC input to the mPFC disrupted coupled theta activity between these two structures, as well as the animals' (male Sprague Dawley rats) ability to differentiate novel from familiar objects. These results reveal a key role of monosynaptic connections between the HPC and mPFC in novelty discrimination via theta coupling and identify neural populations that underlie this recognition memory-guided behavior.SIGNIFICANCE STATEMENT Many memory processes are highly dependent on the interregional communication between the HPC and mPFC via neural oscillations. However, how these two brain regions coordinate their oscillatory activity to engage local neural populations to mediate recognition memory for novelty discrimination is poorly understood. This study revealed that the HPC and mPFC theta oscillations and their temporal coupling is correlated with recognition memory-guided behavior. During novel object recognition, the HPC drives mPFC interneurons to effectively reduce the activity of principal neurons. This study provides the first evidence for the requirement of the HPC-mPFC pathway to mediate recognition memory for novelty discrimination and describes a mechanism for how this memory is regulated.

State-Dependent Changes in Perception and Coding in the Mouse Somatosensory Cortex.

An animal's behavioral state is reflected in the dynamics of cortical population activity and its capacity to process sensory information. To better understand the relationship between behavioral states and information processing, mice are trained to detect varying amplitudes of whisker-deflection under two-photon calcium imaging. Layer 2/3 neurons in the vibrissal primary somatosensory cortex are imaged across different behavioral states, defined based on detection performance (low to high-state) and pupil diameter. The neurometric curve in each behavioral state mirrors the corresponding psychometric performance, with calcium signals predictive of the animal's choice. High behavioral states are associated with lower network synchrony, extending over shorter cortical distances. The decrease in correlation across neurons in high state results in enhanced information transmission capacity at the population level. The observed state-dependent changes suggest that the coding regime within the first stage of cortical processing may underlie adaptive routing of relevant information through the sensorimotor system.

Measurement invariance across gender and age groups, validity and reliability of the Chinese version of the short-form supportive care needs survey questionnaire (SCNS-SF34).

BACKGROUND: Despite the wide use of the Short-Form Supportive Care Needs Survey Questionnaire (SCNS-SF34), the measurement invariance of the SCNS-SF34 across the main groups-gender and age-which might be of interest in the application of the instrument has never been confirmed. To provide an accurate assessment tool to evaluate the unmet needs of Chinese cancer patients, the present study aimed to assess the measurement invariance of the SCNS-SF34 across gender and age groups and to assess the validity and reliability of the Chinese version of the SCNS-SF34. METHODS: The SCNS-SF34 was administrated to 1106 Chinese cancer patients. Other instruments included the Memorial Symptom Assessment Scale-Short Form (MSAS-SF), the Short-Form-12 Health Survey version 2 (SF-12 v2) and the Hospital Anxiety and Depression Scale (HADS). Factor structure, internal construct validity, convergent validity, known-group validity and internal consistency were assessed. RESULTS: Our data fit the original five-factor model. Multi-group confirmatory factor analysis indicated measurement invariance across age and gender groups. The domains of the SCNS-SF34 had moderate correlations with the corresponding domains of the MSAS-SF, the SF-12 v2 and the HADS, which supported convergent validity. Of the 34 items, 33 had an item-total correlation that was corrected for an overlap of > 0.4 to support the internal construct validity. The SCNS-SF34 aptly differentiated patients by age and gender. The Cronbach's alpha coefficient ranged from 0.64 to 0.87. CONCLUSIONS: We confirm the measurement invariance of the Chinese version of the SCNS-SF34 across gender and age group. It is a valid and reliable tool for evaluating the needs of Chinese patients with cancer.

Temporal cueing enhances neuronal and behavioral discrimination performance in rat whisker system.

Since sensory systems operate with a finite quantity of processing resources, an animal would benefit from prioritizing processing of sensory stimuli within a time window that is expected to provide key information. This behavioral manifestation of such prioritization is known as attention. Here, we investigate attention with temporal cueing and its neuronal correlates in the rat primary vibrissal somatosensory (vS1) cortex. Rats were trained in a simple whisker vibration detection task. A vibration was presented at one of two spatial locations (left or right), sometimes after an unknown time interval and sometimes after receiving an auditory cue. The auditory cue provided temporal but not spatial information about the vibration. We found that for all rats ( n = 6), the auditory cue consistently enhanced detection of the vibration stimulus. Neuronal activity in vS1 cortex reflected the observed behavioral enhancement from temporal cueing with single units responded differentially to the whisker vibration stimulus when it was temporally predicted by the auditory cue, exhibiting an enhanced signal-to-noise ratio. Our findings indicate that rats are capable of prioritizing processing within a specified time window and provide evidence that the primary sensory cortex may participate in the temporal allocation of resources. NEW & NOTEWORTHY We demonstrate a novel paradigm of temporal cueing in rats. In a two-alternative whisker detection task, an auditory cue provided information about the timing of the stimulus but not the correct choice. In the presence of cue, detection was faster and more accurate, and neuronal activity from the primary somatosensory cortex revealed enhanced representation of vibrations. These results thus establish the rat as an alternative model organism to primates for studying temporal attention.

Sensory Prioritization in Rats: Behavioral Performance and Neuronal Correlates.

Operating with some finite quantity of processing resources, an animal would benefit from prioritizing the sensory modality expected to provide key information in a particular context. The present study investigated whether rats dedicate attentional resources to the sensory modality in which a near-threshold event is more likely to occur. We manipulated attention by controlling the likelihood with which a stimulus was presented from one of two modalities. In a whisker session, 80% of trials contained a brief vibration stimulus applied to whiskers and the remaining 20% of trials contained a brief change of luminance. These likelihoods were reversed in a visual session. When a stimulus was presented in the high-likelihood context, detection performance increased and was faster compared with the same stimulus presented in the low-likelihood context. Sensory prioritization was also reflected in neuronal activity in the vibrissal area of primary somatosensory cortex: single units responded differentially to the whisker vibration stimulus when presented with higher probability compared with lower probability. Neuronal activity in the vibrissal cortex displayed signatures of multiplicative gain control and enhanced response to vibration stimuli during the whisker session. In conclusion, rats allocate priority to the more likely stimulus modality and the primary sensory cortex may participate in the redistribution of resources. SIGNIFICANCE STATEMENT: Detection of low-amplitude events is critical to survival; for example, to warn prey of predators. To formulate a response, decision-making systems must extract minute neuronal signals from the sensory modality that provides key information. Here, we identify the behavioral and neuronal correlates of sensory prioritization in rats. Rats were trained to detect whisker vibrations or visual flickers. Stimuli were embedded in two contexts in which either visual or whisker modality was more likely to occur. When a stimulus was presented in the high-likelihood context, detection was faster and more reliable. Neuronal recording from the vibrissal cortex revealed enhanced representation of vibrations in the prioritized context. These results establish the rat as an alternative model organism to primates for studying attention.

Comprehensive proteomic profiling identifies serum proteomic signatures for detection of hepatocellular carcinoma and its subtypes.

BACKGROUND: Detection of hepatocellular carcinoma (HCC) in patients with chronic liver disease (CLD) is difficult. We investigated the use of comprehensive proteomic profiling of sera to differentiate HCC from CLD. METHODS: Proteomes in sera from 20 CLD patients with alpha-fetoprotein (AFP) <500 microg/L (control group) and 38 HCC patients (disease group) were profiled by anion-exchange fractionation (first dimension), two types (IMAC3 copper and WCX2) of ProteinChip Arrays (second dimension), and time-of-flight mass spectrometry (third dimension). Bioinformatic tests were used to identify tumor-specific proteomic features and to estimate the values of the tumor-specific proteomic features in the diagnosis of HCC. Cross-validation was performed, and we also validated the models with pooled sera from the control and disease groups, serum from a CLD patient with AFP >500 microg/L, and postoperative sera from two HCC patients. RESULTS: Among 2384 common serum proteomic features, 250 were significantly different between the HCC and CLD cases. Two-way hierarchical clustering differentiated HCC and CLD cases. Most HCC cases with advanced disease were clustered together and formed two subgroups that contained significantly more cases with lymph node invasion or distant metastasis. For differentiation of HCC and CLD by an artificial network (ANN), the area under the ROC curve was 0.91 (95% confidence interval, 0.82-1.01; P <0.0005) for all cases and 0.954 (95% confidence interval, 0.881-1.027; P <0.0005) for cases with nondiagnostic serum AFP (<500 microg/L). At a specificity of 90%, the sensitivity was 92%. Both cluster analysis and ANN correctly classified the pooled serum samples, the CLD serum sample with increased AFP, and the HCC patient in complete remission. CONCLUSION: Tumor-specific proteomic signatures may be useful for detection and classification of hepatocellular cancers.