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Theories of efficient coding propose that the auditory system is optimized for the statistical structure of natural sounds, yet the transformations underlying optimal acoustic representations are not well understood. Using a database of natural sounds including human speech and a physiologically-inspired auditory model, we explore the consequences of peripheral (cochlear) and mid-level (auditory midbrain) filter tuning transformations on the representation of natural sound spectra and modulation statistics. Whereas Fourier-based sound decompositions have constant time-frequency resolution at all frequencies, cochlear and auditory midbrain filters bandwidths increase proportional to the filter center frequency. This form of bandwidth scaling produces a systematic decrease in spectral resolution and increase in temporal resolution with increasing frequency. Here we demonstrate that cochlear bandwidth scaling produces a frequency-dependent gain that counteracts the tendency of natural sound power to decrease with frequency, resulting in a whitened output representation. Similarly, bandwidth scaling in mid-level auditory filters further enhances the representation of natural sounds by producing a whitened modulation power spectrum (MPS) with higher modulation entropy than both the cochlear outputs and the conventional Fourier MPS. These findings suggest that the tuning characteristics of the peripheral and mid-level auditory system together produce a whitened output representation in three dimensions (frequency, temporal and spectral modulation) that reduces redundancies and allows for a more efficient use of neural resources. This hierarchical multi-stage tuning strategy is thus likely optimized to extract available information and may underlies perceptual sensitivity to natural sounds.

Background: Severe energy deficits during military operations, produced by significant increases in exercise and limited dietary intake, result in conditions that degrade lean body mass and lower-body muscle function, which may be mediated by concomitant reductions in circulating testosterone. Methods: We conducted a three-phase, proof-of-concept, single centre, randomised, double-blind, placebo-controlled trial (CinicalTrials.gov, NCT02734238) of non-obese men: 14-d run-in, free-living, eucaloric diet phase; 28-d live-in, 55% exercise- and diet-induced energy deficit phase with (200 mg testosterone enanthate per week, Testosterone, n = 24) or without (Placebo, n = 26) exogenous testosterone; and 14-d recovery, free-living, ad libitum diet phase. Body composition was the primary end point; secondary endpoints included lower-body muscle function and health-related biomarkers. Findings: Following energy deficit, lean body mass increased in Testosterone and remained stable in Placebo, such that lean body mass significantly differed between groups [mean difference between groups (95% CI), 2.5 kg (3.3, 1.6); P

Striatal dopamine dysfunction is associated with the altered top-down modulation of pain processing. The dopamine D2-like receptor family is a potential substrate for such effects due to its primary expression in the striatum, but evidence for this is currently lacking. Here, we investigated the effect of pharmacologically manipulating striatal dopamine D2 receptor activity on the anticipation and perception of acute pain stimuli in humans. Participants received visual cues that induced either certain or uncertain anticipation of two pain intensity levels delivered via a CO2 laser. Rating of the pain intensity and unpleasantness was recorded. Brain activity was recorded with EEG and analysed via source localisation to investigate neural activity during the anticipation and receipt of pain. Participants completed the experiment under three conditions, control (Sodium Chloride), D2 receptor agonist (Cabergoline), and D2 receptor antagonist (Amisulpride), in a repeated-measures, triple-crossover, double-blind study. The antagonist reduced an individuals’ ability to distinguish between low and high pain following uncertain anticipation. The EEG source localisation showed that the agonist and antagonist reduced neural activations in specific brain regions associated with the sensory integration of salient stimuli during the anticipation and receipt of pain. During anticipation, the agonist reduced activity in the right mid-temporal region and the right angular gyrus, whilst the antagonist reduced activity within the right postcentral, right mid-temporal, and right inferior parietal regions. In comparison to control, the antagonist reduced activity within the insula during the receipt of pain, a key structure involved in the integration of the sensory and affective aspects of pain. Pain sensitivity and unpleasantness were not changed by D2R modulation. Our results support the notion that D2 receptor neurotransmission has a role in the top-down modulation of pain.

Neural implants that deliver multi-site electrical stimulation to the nervous systems are no longer the last resort but routine treatment options for various neurological disorders. Multi-site electrical stimulation is also widely used to study nervous system function and neural circuit transformations. These technologies increasingly demand dynamic electrical stimulation and closed-loop feedback control for real-time assessment of neural function, which is technically challenging since stimulus-evoked artifacts overwhelm the small neural signals of interest. We report a novel and versatile artifact removal method that can be applied in a variety of settings, from single- to multi-site stimulation and recording and for current waveforms of arbitrary shape and size. The method capitalizes on linear electrical coupling between stimulating currents and recording artifacts, which allows us to estimate a multi-channel linear Wiener filter to predict and subsequently remove artifacts via subtraction. We confirm and verify the linearity assumption and demonstrate feasibility in a variety of recording modalities, including in vitro sciatic nerve stimulation, bilateral cochlear implant stimulation, and multi-channel stimulation and recording between the auditory midbrain and cortex. We demonstrate a vast enhancement in the recording quality with a typical artifact reduction of 25−40 dB. The method is efficient and can be scaled to arbitrary number of stimulus and recording sites, making it ideal for applications in large-scale arrays, closed-loop implants, and high-resolution multi-channel brain-machine interfaces.

The auditory neural code is resilient to acoustic variability and capable of recognizing sounds amongst competing sound sources, yet, the transformations enabling noise robust abilities are largely unknown. We report that a hierarchical spiking neural network (HSNN) optimized to maximize word recognition accuracy in noise and multiple talkers predicts organizational hierarchy of the ascending auditory pathway. Comparisons with data from auditory nerve, midbrain, thalamus and cortex reveals that the optimal HSNN predicts several transformations of the ascending auditory pathway including a sequential loss of temporal resolution and synchronization ability, increasing sparseness, and selectivity. The optimal organizational scheme enhances performance by selectively filtering out noise and fast temporal cues such as voicing periodicity, that are not directly relevant to the word recognition task. An identical network arranged to enable high information transfer fails to predict auditory pathway organization and has substantially poorer performance. Furthermore, conventional single-layer linear and nonlinear receptive field networks that capture the overall feature extraction of the HSNN fail to achieve similar performance. The findings suggest that the auditory pathway hierarchy and its sequential nonlinear feature extraction computations enhance relevant cues while removing non-informative sources of noise, thus enhancing the representation of sounds in noise impoverished conditions.

BackgroundThe Hypotension Prediction Index (the index) software is a machine learning algorithm that detects physiological changes that may lead to hypotension. The original validation used a case control (backwards) analysis that has been suggested to be biased. We therefore conducted a cohort (forwards) analysis and compared this to the original validation technique.MethodsWe conducted a retrospective analysis of data from previously reported studies. All data were analysed identically with 2 different methodologies and receiver operating characteristic curves (ROC) constructed. Both backwards and forwards analyses were performed to examine differences in area under the ROC for HPI and other haemodynamic variables to predict a MAP < 65mmHg for at least 1 minute 5, 10 and 15 minutes in advance.ResultsTwo thousand and twenty-two patients were included in the analysis, yielding 4,152,124 measurements taken at 20 second intervals. The area-under-the-curve for the index predicting hypotension analysed by backward and forward methodologies respectively was 0.957 (95% CI, 0.947-0.964) vs 0.923 (95% CI, 0.912-0.933) 5 minutes in advance, 0.933 (95% CI, 0.924-0.942) vs 0.923 (95% CI, 0.911-0.933) 10 minutes in advance , and 0.929 (95% CI, 0.918-0.938) vs. 0.926 (95% CI, 0.914-0.937) 15 minutes in advance. No other variable had an area-under-the-curve > 0.7 except for MAP. Area-under-the-curve using forward analysis for MAP predicting hypotension 5, 10, and 15 minutes in advance was 0.932 (95% CI, 0.920-0.940), 0.929 (95% CI, 0.918-0.938), and 0.932 (95% CI, 0.921-0.940). The R 2 for the variation in the index due to MAP was 0.77.ConclusionUsing an updated methodology, we found the utility of the HPI index to predict future hypotensive events is high, with an area under the receiver-operating-characteristics curve similar to that of the original validation method.

PURPOSE: To present a case of a pseudoaneurysm of a branch of the left superior gluteal artery (SGA) secondary to lateral wall perforation from an iliac screw and its subsequent evaluation and management. METHODS: Case report. RESULTS: A 67-year-old female with a history of degenerative flatback and scoliosis and pathological fractures of T12 and L1 secondary to osteodisciitis underwent a single0stage L5-S1 ALIF and T9-pelvis posterior instrumented fusion with bilateral dual iliac screw fixation, revision T11-S1 decompression, and T12 and L1 irrigation and debridement and partial corpectomies. During the operation, non-pulsatile bleeding was encountered after creating an initial trajectory for the more proximal of the two left iliac screws. While the initial post-operative course was benign, the patient was readmitted for hypotension and anemia. Computed tomography of the abdomen/pelvis demonstrated a pseudoaneurysm (2.3 cm × 2.1 cm × 2.3 cm) of a branch of the left SGA. Diagnostic angiogram confirmed a pseudoaneurysm off of one of the branches of the left SGA. Endovascular embolization using multiple coils resulted in a complete cessation of blood flow in the pseudoaneurysm. At 2 years follow-up, no symptoms suggestive of recurrence of the pseudoaneurysm were reported. CONCLUSIONS: A pseudoaneurysm of a branch of the left superior gluteal artery as a result of lateral wall perforation from an aberrantly placed iliac screw during an adult spinal deformity operation involving dual screw pelvic fixation is reported. Prompt recognition, multidisciplinary collaboration, and appropriate intervention were key in achieving a successful outcome and preventing further morbidity.

Humans and other animals effortlessly identify natural sounds and categorize them into behaviorally relevant categories. Yet, the acoustic features and neural transformations that enable sound recognition and the formation of perceptual categories are largely unknown. Here, using multichannel neural recordings in the auditory midbrain of unanesthetized female rabbits, we first demonstrate that neural ensemble activity in the auditory midbrain displays highly structured correlations that vary with distinct natural sound stimuli. These stimulus-driven correlations can be used to accurately identify individual sounds using single-response trials, even when the sounds do not differ in their spectral content. Combining neural recordings and an auditory model, we then show how correlations between frequency-organized auditory channels can contribute to discrimination of not just individual sounds but sound categories. For both the model and neural data, spectral and temporal correlations achieved similar categorization performance and appear to contribute equally. Moreover, both the neural and model classifiers achieve their best task performance when they accumulate evidence over a time frame of approximately 1-2 seconds, mirroring human perceptual trends. These results together suggest that time-frequency correlations in sounds may be reflected in the correlations between auditory midbrain ensembles and that these correlations may play an important role in the identification and categorization of natural sounds.

Cognitive stimulation therapy (CST) is widely used with people with dementia, but there is no evidence of its efficacy in mild cognitive impairment or dementia in Parkinson’s disease (PD-MCI; PDD) or dementia with Lewy bodies (DLB). We aimed to explore the impact of ‘CST-PD’, which is home-based, individualized CST adapted for this population. In a single-blind, randomized controlled exploratory pilot trial (RCT), we randomized 76 participant–dyads [PD-MCI ( n = 15), PDD ( n = 40), DLB ( n = 21) and their care partners] to CST-PD or treatment as usual (TAU). CST-PD involves home-based cognitively stimulating and engaging activities delivered by a trained care partner. Exploratory outcomes at 12 weeks included cognition (Addenbrooke’s Cognitive Evaluation; ACE-III), neuropsychiatric symptoms and function. In care partners, we assessed burden, stress and general health status. Relationship quality and quality of life were assessed in both dyad members. At 12 weeks, the ACE-III showed a nonstatistically significant improvement in the CST-PD group compared with the TAU group, although neuropsychiatric symptoms increased significantly in the former. In contrast, care partners’ quality of life ( d = 0.16) and relationship quality (‘satisfaction’, d = 0.01; ‘positive interaction’, d = 0.55) improved significantly in the CST-PD group, and care burden ( d = 0.16) and stress ( d = 0.05) were significantly lower. Qualitative findings in the CST-PD recipients revealed positive ‘in the moment’ responses to the intervention, supporting the quantitative results. In conclusion, care-partner-delivered CST-PD may improve a range of care-partner outcomes that are important in supporting home-based care. A full-scale follow-up RCT to evaluate clinical and cost effectiveness is warranted.

Accurately resolving frequency components in sounds is essential for sound recognition, yet there is little direct evidence for how frequency selectivity is preserved or newly created across auditory structures. We demonstrate that prepotentials (PPs) with physiological properties resembling presynaptic potentials from broadly tuned brainstem inputs can be recorded concurrently with postsynaptic action potentials in inferior colliculus (IC). These putative brainstem inputs (PBIs) are broadly tuned and exhibit delayed and spectrally interleaved excitation and inhibition not present in the simultaneously recorded IC neurons (ICNs). A sharpening of tuning is accomplished locally at the expense of spike-timing precision through nonlinear temporal integration of broadband inputs. A neuron model replicates the finding and demonstrates that temporal integration alone can degrade timing precision while enhancing frequency tuning through interference of spectrally in- and out-of-phase inputs. These findings suggest that, in contrast to current models that require local inhibition, frequency selectivity can be sharpened through temporal integration, thus supporting an alternative computational strategy to quickly refine frequency selectivity.

ObjectivesCell-free hemoglobin (CFH) is a potent mediator of endothelial dysfunction, organ injury, coagulopathy, and immunomodulation in hemolysis. These mechanisms have been demonstrated in patients with sepsis, hemoglobinopathies, and those receiving transfusions. However, less is known about the role of CFH in the pathophysiology of trauma, despite the release of equivalent levels of free hemoglobin.Data sourcesOvid MEDLINE, Embase, Web of Science Core Collection, and BIOSIS Previews were searched up to January 21, 2023, using key terms related to free hemoglobin and trauma.Data extractionTwo independent reviewers selected studies focused on hemolysis in trauma patients, hemoglobin breakdown products, hemoglobin-mediated injury in trauma, transfusion, sepsis, or therapeutics.Data synthesisData from the selected studies and their references were synthesized into a narrative review.ConclusionsFree hemoglobin likely plays a role in endothelial dysfunction, organ injury, coagulopathy, and immune dysfunction in polytrauma. This is a compelling area of investigation as multiple existing therapeutics effectively block these pathways.

The emergence of immersive VR technology in K-12 educational spaces has created a need for research examining the affordances and constraints of this technology for student learning. The current study uses a case-study methodology to illustrate K-12 secondary science teachers' perceived affordances and constraints of using immersive VR tools to develop maker-centered learning experiences which align with curricular goals following a professional development experience. Findings suggest teachers were able to design student-centered maker learning experiences using immersive VR devices that addressed K-12 science content. In addition, participants discovered ways to overcome reported challenges, and develop teaching artifacts as well. This study offers a model for teacher educators in this area, examples of curriculum aligned learning activities, and provides a foundation for future research on integration of VR in K-12 contexts.

Using a longitudinal national educational dataset, data science methods were applied to explain students' educational trajectories and determine the most predictive variables in STEM degree attainment. Challenging the notion of the STEM pipeline, an Alternative Pathways to STEM (APS) model was proposed. Using a foundation of Social Cognitive Career Theory, academic, demographic, and economic variables were selected for analysis and Imbalanced dataset and random forest data analytic techniques were implemented. Results supported the consideration of the Alternate Pathways to STEM model given the varied educational pathways identified throughout STEM matriculation. Additionally, multiple academic variables, except for career interest, were found to be most predictive of STEM graduation, while demographic and economic variables were not significant. These findings have important implications for recruiting STEM students and increasing STEM graduation rates. Additional research is recommended using these data extraction and analysis methodologies on other datasets to further test the efficacy of the Alternative Pathways to STEM model.

This study introduces Indigenous Case Study (ICS) as a methodology poised to foster decolonized and anti-racist spaces. ICS is a weaving of TribalCrit, critical and Indigenous methodological approaches, and considers contemporary and historical contexts, simultaneously. In the current manuscript, ICS helps reimage campuses through revised policies and practices that work toward the creation of decolonized and inclusive institutions for Native students and communities. ICS allows for deeper analyses as we interrogate the dissonance between university president's statements about race and inclusion, institutional policies and practices, and the experiences of Native students as shared through student stories. We explore historical documents, president speeches, campus events, individual interviews, and researcher auto-narratives in Sharing Circles over the course of five years. The findings situate historical and contemporary campus contexts as we reveal five manifestations of oppression experienced by Native students: exploitation, marginalization, powerlessness, cultural imperialism, and violence. ICS provides circular and methodical methods that offer the opportunity to think in more complex ways as we offer findings and discussions on the cultivation of decolonized and anti-racist spaces.

To communicate effectively animals need to detect temporal vocalization cues that vary over several orders of magnitude in their amplitude and frequency content. This large range of temporal cues is evident in the power-law scale-invariant relationship between the power of temporal fluctuations in sounds and the sound modulation frequency (f). Though various forms of scale invariance have been described for natural sounds, the origins and implications of scale invariant phenomenon remain unknown. Using animal vocalization sequences, including continuous human speech, and a stochastic model of temporal amplitude fluctuations we demonstrate that temporal acoustic edges are the primary acoustic cue accounting for the scale invariant phenomenon. The modulation spectrum of vocalization sequences and the model both exhibit a dual regime lowpass structure with a flat region at low modulation frequencies and scale invariant 1/f2 trend for high modulation frequencies. Moreover, we find a time-frequency tradeoff between the average vocalization duration of each vocalization sequence and the cutoff frequency beyond which scale invariant behavior is observed. These results indicate that temporal edges are universal features responsible for scale invariance in vocalized sounds. This is significant since temporal acoustic edges are salient perceptually and the auditory system could exploit such statistical regularities to minimize redundancies and generate compact neural representations of vocalized sounds.