Semaphorin 1a-mediated dendritic wiring of the Drosophila mushroom body extrinsic neurons.

SignificanceThe adult Drosophila mushroom body (MB) is one of the most extensively studied neural circuits. However, how its circuit organization is established during development is unclear. In this study, we provide an initial characterization of the assembly process of the extrinsic neurons (dopaminergic neurons and MB output neurons) that target the vertical MB lobes. We probe the cellular mechanisms guiding the neurite targeting of these extrinsic neurons and demonstrate that Semaphorin 1a is required in several MB output neurons for their dendritic innervations to three specific MB lobe zones. Our study reveals several intriguing molecular and cellular principles governing assembly of the MB circuit.

Impaired Filtering and Hyperfocusing: Neural Evidence for Distinct Selective Attention Abnormalities in People with Schizophrenia.

Although schizophrenia is classically thought to involve impaired attentional filtering, people with schizophrenia (PSZ) exhibit a more intense and more exclusive attentional focus than healthy control subjects (HCS) in many tasks. To resolve this contradiction, this functional magnetic resonance imaging study tested the impact of attentional control demands on the modulation of stimulus-induced activation in the fusiform face area and parahippocampal place area when participants (43 PSZ and 43 HCS) were looking for a target face versus house. Stimuli were presented individually, or as face-house overlays that challenged attentional control. Responses were slower for house than face stimuli and when prioritizing houses over faces in overlays, suggesting a difference in salience. Blood-oxygen-level-dependent activity reflected poorer attentional selectivity in PSZ than HCS when attentional control was challenged most, that is, when stimuli were overlaid and the task required detecting the lower-salience house target. By contrast, attentional selectivity was exaggerated in PSZ when control was challenged least, that is, when stimuli were presented sequentially and the task required detecting the higher-salience face target. These findings are consistent with 2 distinct attentional abnormalities in schizophrenia leading to impaired and exaggerated selection under different conditions: attentional control deficits, and hyperfocusing once attention has been directed toward a stimulus.

The requirement of propofol for induction of anesthesia in patients with traumatic brain injury determined using bilateral bispectral index and target controlled infusion - An observational cohort study.

Background and Aims: Patients with traumatic brain injury (TBI) frequently require emergency surgery. There is a paucity of literature with regard to anesthetic requirements in these patients. The aim of the study was to compare the dose of propofol required for induction of anesthesia in patients with different grades of TBI. Material and Methods: This prospective, observational study included patients with mild, moderate, and severe grades of TBI undergoing emergency surgery within 48 h of injury. Bispectral Index (BIS) values were recorded using a bilateral BIS sensor. Anesthesia was induced with a target controlled infusion (TCI) pump. Once BIS reached 40, plasma (Cp) and effect-site (Ce) concentration and total dose of propofol required were noted from the TCI pump. Results: Of the 96 patients recruited, 27, 36, and 33 patients belonged to mild, moderate, and severe TBI (sTBI) groups, respectively. The Ce of propofol in mild, moderate, and sTBI groups was 6 ± 0.9, 5.82 ± 0.98, and 4.48 ± 1.5 µg/mL (P < 0.001), and the dose of propofol required was 1.9 ± 0.2, 1.8 ± 0.4, 1.41 ± 0.5 mg/kg, respectively (P < 0.001). Baseline BIS on the injured side was 80 ± 7.8, 71 ± 9.4, 55 ± 11.6, and on the uninjured side was 89 ± 5.5, 81 ± 8.4, and 65 ± 12 in mild, moderate, and sTBI groups, respectively. Conclusions: The requirement of propofol was reduced in patients with sTBI. The dose of propofol required for induction of anesthesia as determined using Ce was significantly lower only between sTBI and mild TBI and not between patients with sTBI and moderate TBI or between mild and moderate head injury. BIS values were significantly different between the groups (highest in mild TBI and lowest in sTBI) and between normal and injured sides within each group.

Identification and characterization of the novel bioactive compounds from microalgae and cyanobacteria for pharmaceutical and nutraceutical applications.

Microalgae and cyanobacteria (blue-green algae) are used as food by humans. They have gained a lot of attention in recent years because of their potential applications in biotechnology. Microalgae and cyanobacteria are good sources of many valuable compounds, including important biologically active compounds with antiviral, antibacterial, antifungal, and anticancer activities. Under optimal growth condition and stress factors, algal biomass produce varieties of potential bioactive compounds. In the current review, bioactive compounds production and their remarkable applications such as pharmaceutical and nutraceutical applications along with processes involved in identification and characterization of the novel bioactive compounds are discussed. Comprehensive knowledge about the exploration, extraction, screening, and trading of bioactive products from microalgae and cyanobacteria and their pharmaceutical and other applications will open up new avenues for drug discovery and bioprospecting.

The effect of prone positioning on surgical pleth index in patients undergoing spine surgery under general anesthesia - A prospective observational study.

Background and Aims: Surgical Pleth Index (SPI) provides an objective assessment of nociception - anti-nociception balance but is influenced by multiple confounders. The effect of change of position on SPI, has not been studied extensively. The aim of the study was to observe the effect of prone positioning on SPI and its correlation with hemodynamic variables, in patients undergoing lumbar and thoracic spine surgery. Material and Methods: This prospective observational pilot study included 14 patients. In addition to hemodynamic monitoring, SPI, entropy and pulse pressure variability (PPV) were monitored. Propofol and Fentanyl infusions were used for maintenance of anesthesia. The patients were made prone on bolsters and all the variables were recorded every 5 minutes in supine position and after making prone for 20 minutes, before and after incision, muscle splitting and laminectomy. Results: Comparing the last value of the variables in the supine position with those immediately after making prone, SPI increased by 16.36 units (P = 0.003), followed by gradual reduction over the next 20 minutes. Mean arterial pressure and heart rate increased transiently (Pvalue = 0.028 and 0.025, respectively) without any significant change in PPV. Surgical incision also led to a significant increase in SPI. Conclusion: Prone positioning leads to significant increase in SPI, probably due to increased sympathetic tone.

Transsaccadic visual perception of foveal compared to peripheral environmental changes.

The maintenance of stable visual perception across eye movements is hypothesized to be aided by extraretinal information (e.g., corollary discharge [CD]). Previous studies have focused on the benefits of this information for perception at the fovea. However, there is little information on the extent that CD benefits peripheral visual perception. Here we systematically examined the extent that CD supports the ability to perceive transsaccadic changes at the fovea compared to peripheral changes. Human subjects made saccades to targets positioned at different amplitudes (4° or 8°) and directions (rightward or upward). On each trial there was a reference point located either at (fovea) or 4° away (periphery) from the target. During the saccade the target and reference disappeared and, after a blank period, the reference reappeared at a shifted location. Subjects reported the perceived shift direction, and we determined the perceptual threshold for detection and estimate of the reference location. We also simulated the detection and location if subjects solely relied on the visual error of the shifted reference experienced after the saccade. The comparison of the reference location under these two conditions showed that overall the perceptual estimate was approximately 53% more accurate and 30% less variable than estimates based solely on visual information at the fovea. These values for peripheral shifts were consistently lower than that at the fovea: 34% more accurate and 9% less variable. Overall, the results suggest that CD information does support stable visual perception in the periphery, but is consistently less beneficial compared to the fovea.

People with schizophrenia show enhanced cognitive costs of maintaining a single item in working memory.

BACKGROUND: Working memory (WM) deficits are seen as a core deficit in schizophrenia, implicated in the broad cognitive impairment seen in the illness. Here we examine the impact of WM storage of a single item on the operation of other cognitive systems. METHODS: We studied 37 healthy controls (HCS) and 43 people with schizophrenia (PSZ). Each trial consisted of a sequence of two potential target stimuli, T1 and T2. T1 was a letter presented for 100 ms. After delays of 100-800 ms, T2 was presented. T2 was a 1 or a 2 and required a speeded response. In one condition, subjects were instructed to ignore T1 but respond to T2. In another condition, they were required to report T1 after making their speeded response to T2 (i.e. to make a speeded T2 response while holding T1 in WM). RESULTS: PSZ were dramatically slowed at responding to T2 when T1 was held in WM. A repeated measures ANOVA yielded main effects of group, delay, and condition with a group by condition interaction (p's < 0.001). Across delays, the slowing of the T2 response when required to hold T1 in memory, relative to ignoring T1, was nearly 3 times higher in PSZ than HCS (633 v. 219 ms). CONCLUSIONS: Whereas previous studies have focused on reduced storage capacity, the present study found that PSZ are impaired at performing tasks while they are successfully maintaining a single item in WM. This may play a role in the broad cognitive impairment seen in PSZ.

Quantifying the spatial extent of the corollary discharge benefit to transsaccadic visual perception.

Extraretinal information, such as corollary discharge (CD), is hypothesized to help compensate for saccade-induced visual input disruptions. However, support for this hypothesis is largely for one-dimensional transsaccadic visual changes, with little comprehensive information on the spatial characteristics. Here we systematically mapped the two-dimensional extent of this compensation by quantifying the insensitivity to different displacement metrics. Human subjects made saccades to targets positioned at different amplitudes (4° or 8°) and directions (rightward, oblique, or upward). After the saccade the initial target disappeared and, after a blank period, reappeared at a shifted location-a collinear, diagonal, or orthogonal displacement. Subjects reported the perceived shift direction, and we determined the displacement detection based on the perceptual judgments. The two-dimensional insensitivity fields resulting from the perceptual thresholds had spatial features similar to the saccadic eye movement variability: 1) scaled with movement amplitude, 2) oriented (less sensitive to the change) along the saccade vector, and 3) approximately constant in shape when normalized by movement amplitude. In addition, comparing the postsaccadic perceptual estimate of the presaccadic target location to that based solely on the postsaccade visual error showed that overall the perceptual estimate was approximately 50% more accurate and 35% less variable than estimates based solely on this visual information. However, this relationship was not uniform: The benefit of extraretinal information was observed largely for displacements with a component parallel to the saccade vector. These results suggest a graded use of extraretinal information when forming the postsaccadic perceptual evaluation of transsaccadic environmental changes.

ECG contamination of EEG signals: effect on entropy.

Entropy™ is a proprietary algorithm which uses spectral entropy analysis of electroencephalographic (EEG) signals to produce indices which are used as a measure of depth of hypnosis. We describe a report of electrocardiographic (ECG) contamination of EEG signals leading to fluctuating erroneous Entropy values. An explanation is provided for mechanism behind this observation by describing the spread of ECG signals in head and neck and its influence on EEG/Entropy by correlating the observation with the published Entropy algorithm. While the Entropy algorithm has been well conceived, there are still instances in which it can produce erroneous values. Such erroneous values and their cause may be identified by close scrutiny of the EEG waveform if Entropy values seem out of sync with that expected at given anaesthetic levels.

The effect of saccade metrics on the corollary discharge contribution to perceived eye location.

Corollary discharge (CD) is hypothesized to provide the movement information (direction and amplitude) required to compensate for the saccade-induced disruptions to visual input. Here, we investigated to what extent these conveyed metrics influence perceptual stability in human subjects with a target-displacement detection task. Subjects made saccades to targets located at different amplitudes (4°, 6°, or 8°) and directions (horizontal or vertical). During the saccade, the target disappeared and then reappeared at a shifted location either in the same direction or opposite to the movement vector. Subjects reported the target displacement direction, and from these reports we determined the perceptual threshold for shift detection and estimate of target location. Our results indicate that the thresholds for all amplitudes and directions generally scaled with saccade amplitude. Additionally, subjects on average produced hypometric saccades with an estimated CD gain <1. Finally, we examined the contribution of different error signals to perceptual performance, the saccade error (movement-to-movement variability in saccade amplitude) and visual error (distance between the fovea and the shifted target location). Perceptual judgment was not influenced by the fluctuations in movement amplitude, and performance was largely the same across movement directions for different magnitudes of visual error. Importantly, subjects reported the correct direction of target displacement above chance level for very small visual errors (<0.75°), even when these errors were opposite the target-shift direction. Collectively, these results suggest that the CD-based compensatory mechanisms for visual disruptions are highly accurate and comparable for saccades with different metrics.

Prognostic value of FOUR and GCS scores in determining mortality in patients with traumatic brain injury.

BACKGROUND: The Glasgow Coma Scale (GCS) is considered the gold standard for assessment of unconsciousness in patients with traumatic brain injury (TBI) against which other scales are compared. To overcome the disadvantages of GCS, the Full Outline Of Unresponsiveness (FOUR) score was proposed. We aimed to compare the predictability of FOUR score and GCS for early mortality, after moderate and severe TBI. METHODS: This is a prospective observational study of patients with moderate and severe TBI. Both FOUR and GCS scores were determined at admission. The primary outcome was mortality at the end of 2 weeks of injury. RESULTS: A total of 138 (117 males) patients were included in the study. Out of these, 17 (12.3 %) patients died within 2 weeks of injury. The mean GCS and FOUR scores were 9.5 (range, 3-13) and 11 (0-16), respectively. The total GCS and FOUR scores were significantly lower in patients who did not survive. At a cut-off score of 7 for FOUR score, the AUC was 0.97, with sensitivity of 97.5 and specificity of 88.2 % (p < 0.0001). For GCS score, AUC was 0.95, with sensitivity of 98.3 % and specificity of 82.4 % with cut-off score of 6 (p < 0.0001). The correlation coefficient was 0.753 (p < 0.001) between the GCS and FOUR scores. CONCLUSIONS: The predictive value of the FOUR score on admission of patients with TBI is no better than the GCS score.

Incidence and risk factors for oxygen desaturation during recovery from modified electroconvulsive therapy: A prospective observational study.

BACKGROUND AND AIMS: Electroconvulsive therapy (ECT) is an established modality of treatment for severe psychiatric illnesses. Among the various complications associated with ECT, oxygen desaturation is often under reported. None of the previous studies has evaluated the predictive factors for oxygen desaturation during ECT. The objective of this study was to evaluate the incidence of oxygen desaturation during recovery from anesthesia for modified ECT and evaluate its risk factors in a large sample. MATERIALS AND METHODS: All patients aged above 15 years who were prescribed a modified ECT for their psychiatric illness over 1 year were prospectively included in this observational study. The association between age, body mass index (BMI), doses of thiopentone and suxamethonium, stimulus current, ECT session number, pre- and post-ECT heart rate and mean arterial pressure, seizure duration, and pre- and post ECT oxygen saturation, was systematically studied. RESULTS: The incidence of oxygen desaturation was 29% (93/316 patients). Seizure duration and BMI were found to be significantly correlated with post ECT desaturation. CONCLUSION: In this prospective observational study, the incidence of oxygen desaturation during recovery from anesthesia for ECT was high. The study identified obesity and duration of seizure as the independent predictors of this complication. This knowledge is likely to help in identifying and optimizing such patients before subsequent ECT sessions.

Martial Arts: Orthopaedic Injuries and Related Biomechanics.

Martial arts are various systems of combat skills encompassing striking and grappling. Many styles have evolved into modern sports, and some have been included in the Olympics. The physicality of these can predispose practitioners to musculoskeletal injuries, such as anterior cruciate ligament ruptures; patellar, shoulder, or elbow instabilities; extremity fractures; and hand and spine injuries, which have been studied both clinically and biomechanically. The most common injury related to longer time loss from participation is an anterior cruciate ligament rupture. Higher injury incidence is associated with a higher level of experience and competition. Orthopaedic management of martial arts injuries should reflect the specific needs of each martial artist and the biomechanics of motions common to each style. Full-contact practitioners may benefit from broader surgical indications and special attention to the choice and positioning of implants; nonsurgical treatment may be appropriate for certain pediatric or noncontact practitioners. Approximately 60% of martial artists can return to the preinjury level of participation after a major injury. Injury prevention and rehabilitation programs should optimize neuromotor control and core engagement to ensure proper body mechanics. Gradual incorporation of martial arts movement into the postoperative physical therapy curriculum can benefit physical progress and help gain confidence toward full participation.

Variational mode decomposition-based EEG analysis for the classification of disorders of consciousness.

Aberrant alterations in any of the two dimensions of consciousness, namely awareness and arousal, can lead to the emergence of disorders of consciousness (DOC). The development of DOC may arise from more severe or targeted lesions in the brain, resulting in widespread functional abnormalities. However, when it comes to classifying patients with disorders of consciousness, particularly utilizing resting-state electroencephalogram (EEG) signals through machine learning methods, several challenges surface. The non-stationarity and intricacy of EEG data present obstacles in understanding neuronal activities and achieving precise classification. To address these challenges, this study proposes variational mode decomposition (VMD) of EEG before feature extraction along with machine learning models. By decomposing preprocessed EEG signals into specified modes using VMD, features such as sample entropy, spectral entropy, kurtosis, and skewness are extracted across these modes. The study compares the performance of the features extracted from VMD-based approach with the frequency band-based approach and also the approach with features extracted from raw-EEG. The classification process involves binary classification between unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS), as well as multi-class classification (coma vs. UWS vs. MCS). Kruskal-Wallis test was applied to determine the statistical significance of the features and features with a significance of p < 0.05 were chosen for a second round of classification experiments. Results indicate that the VMD-based features outperform the features of other two approaches, with the ensemble bagged tree (EBT) achieving the highest accuracy of 80.5% for multi-class classification (the best in the literature) and 86.7% for binary classification. This approach underscores the potential of integrating advanced signal processing techniques and machine learning in improving the classification of patients with disorders of consciousness, thereby enhancing patient care and facilitating informed treatment decision-making.

Imaging CaLexA and TRIC Signals in the Dissected Fly Central Nervous System.

Calcium-dependent nuclear import of LexA (CaLexA) and transcriptional reporter of intracellular calcium (TRIC) are transcription-based genetically encoded calcium indicators (transcriptional GECIs). When expressed in neurons, CaLexA and TRIC report neuronal activity by converting intracellular calcium levels into transcription activities and, subsequently, reporter gene expression. CaLexA and TRIC have been used successfully in many studies to label neurons associated with particular behaviors, regulated by internal states, or evoked by specific sensory inputs. This protocol details procedures for generating flies expressing genetic components of CaLexA and TRIC in specific neurons, performing immunostaining to label CaLexA and TRIC signals, and quantifying the signals using an open-source imaging analysis software.

Transcriptional Genetically Encoded Calcium Indicators in Drosophila.

Knowing which neurons are active during behavior is a crucial step toward understanding how nervous systems work. Neuronal activation is generally accompanied by an increase in intracellular calcium levels. Therefore, intracellular calcium levels are widely used as a proxy for neuronal activity. Many types of synthetic components and bioluminescent or fluorescent proteins that report transient and long-term changes in intracellular calcium levels have been developed over the past 60 years. Calcium indicators that enable imaging of the dynamic activity of a large ensemble of neurons in behaving animals have revolutionized the field of neuroscience. Among these, transcription-based genetically encoded calcium indicators (transcriptional GECIs) have proven easy to use and do not depend on sophisticated imaging systems, offering unique advantages over other types of calcium indicators. Here, we describe the two currently available fly transcriptional GECIs-calcium-dependent nuclear import of LexA (CaLexA) and transcriptional reporter of intracellular calcium (TRIC)-and review studies that have used them. In the accompanying protocol, we present step-by-step details for generating CaLexA- and TRIC-ready flies and for imaging CaLexA and TRIC signals in dissected brains after experimental manipulations of intact free-moving flies.

Studying Healthy Psychosislike Experiences to Improve Illness Prediction.

Importance: Distinguishing delusions and hallucinations from unusual beliefs and experiences has proven challenging. Observations: The advent of neural network and generative modeling approaches to big data offers a challenge and an opportunity; healthy individuals with unusual beliefs and experiences who are not ill may raise false alarms and serve as adversarial examples to such networks. Conclusions and Relevance: Explicitly training predictive models with adversarial examples should provide clearer focus on the features most relevant to casehood, which will empower clinical research and ultimately diagnosis and treatment.

Sustained attention deficits in schizophrenia: Effect of memory load on the Identical Pairs Continuous Performance Test.

Background: Sustained attention and vigilance impairments are well documented in people with schizophrenia (PSZ). The processes implicated in this impairment remain unclear. Here we investigated whether vigilance performance varied as a function of working memory load, and also examined the role of attentional lapsing that might arise from a loss of task set resulting in mind wandering. Method: We examined Continuous Performance Test Identical Pairs (CPT-IP) data from a cumulative sample of 247 (PSZ) and 238 healthy control (HC) participants collected over a series of studies. Results: PSZ performed more poorly that HC across conditions with signal/noise discrimination (d') decreasing with increasing working memory load across both groups However, there was a significant interaction of group and load suggesting that performance of PSZ was more negatively impacted by increasing load. We also found that PSZ has a significantly higher rate of attention lapsing than did HC. Discussion: Our results suggest that difficulties maintaining task set and working memory limitations are implicated in the impairments observed on the Identical Pairs CPT. Difficulties with task set maintenance appear to explain the majority of between-group variance, with a more subtle impact of increasing working memory load.

Postoperative delayed neurocognitive recovery: Evaluation of its incidence and correlation with intraoperative cerebral desaturation - A prospective observational study.

BACKGROUND: Delayed neurocognitive recovery (DNR) is commonly seen in patients in the postoperative period. Literature has shown that monitoring cerebral desaturation intraoperatively can predict the development of DNR in elderly patients undergoing surgery in prone position. This prospective observational study was conducted in patients of all ages, with the primary objective to determine the incidence of DNR and its correlation with cerebral oximetry. The secondary objectives were to determine if intraoperative cerebral desaturation influenced the neuropsychometric variables from preoperative to postoperative period. METHODS: This study included 61 patients, aged > 18 years undergoing spinal surgery in prone position. An evening before surgery and at 48 h postoperatively, patients were subjected to neuropsychological examination; Hindi Mental State Examination, Colour Trail Test 1 (CTT 1), CTT 2, Auditory Verbal Learning (AVLT) tests conducted by principal investigator (PI). DNR was defined as a 20% change in any of the test scores from the baseline. rSO2 was recorded bilaterally every 10 min throughout surgery by an independent person. Cerebral desaturation was defined as a 20% drop in rSO2 from the control value. RESULTS: The incidence of DNR was 24.6%. The duration of anesthesia and cerebral desaturation were found to be independently predictive of DNR, with each hour of anesthesia causing a two-fold increase in the chances of development DNR (P = 0.019) and presence of cerebral desaturation causing a 6-fold increase (P = 0.039). CTT 1 and CTT 2 tests had significantly larger increase in test scores in the postoperative period, in patients with cerebral desaturation. CONCLUSION: Duration of anesthesia and cerebral desaturation were factors predictive of the development of DNR in patients undergoing spine surgery in prone position.