Natural variation in the maternal and zygotic mRNA complements of the early embryo in Drosophila melanogaster.

BACKGROUND: Maternal gene products supplied to the egg during oogenesis drive the earliest events of development in all metazoans. After the initial stages of embryogenesis, maternal transcripts are degraded as zygotic transcription is activated; this is known as the maternal to zygotic transition (MZT). Recently, it has been shown that the expression of maternal and zygotic transcripts have evolved in the Drosophila genus over the course of 50 million years. However, the extent of natural variation of maternal and zygotic transcripts within a species has yet to be determined. We asked how the maternal and zygotic pools of mRNA vary within and between populations of D. melanogaster. In order to maximize sampling of genetic diversity, African lines of D. melanogaster originating from Zambia as well as DGRP lines originating from North America were chosen for transcriptomic analysis. RESULTS: Generally, we find that maternal transcripts are more highly conserved, and zygotic transcripts evolve at a higher rate. We find that there is more within-population variation in transcript abundance than between populations and that expression variation is highest post- MZT between African lines. CONCLUSIONS: Determining the natural variation of gene expression surrounding the MZT in natural populations of D. melanogaster gives insight into the extent of how a tightly regulated process may vary within a species, the extent of developmental constraint at both stages and on both the maternal and zygotic genomes, and reveals expression changes allowing this species to adapt as it spread across the world.

Neuromodulation in Beta-Band Power Between Movement Execution and Inhibition in the Human Hippocampus.

INTRODUCTION: The hippocampus is thought to be involved in movement, but its precise role in movement execution and inhibition has not been well studied. Previous work with direct neural recordings has found beta-band (13-30 Hz) modulation in both movement execution and inhibition throughout the motor system, but the role of beta-band modulation in the hippocampus during movement inhibition is not well understood. Here, we perform a Go/No-Go reaching task in ten patients with medically refractory epilepsy to study human hippocampal beta-power changes during movement. MATERIALS AND METHODS: Ten epilepsy patients (5 female; ages 21-46) were implanted with intracranial depth electrodes for seizure monitoring and localization. Local field potentials were sampled at 2000 Hz during a Go/No-Go movement task. Comparison of beta-band power between Go and No-Go conditions was conducted using Wilcoxon signed-rank hypothesis testing for each patient. Sub-analyses were conducted to assess differences in the anterior vs posterior contacts, ipsilateral vs contralateral contacts, and male vs female beta-power values. RESULTS: Eight out of ten patients showed significant beta-power decreases during the Go movement response (p < 0.05) compared to baseline. Eight out of ten patients also showed significant beta-power increases in the No-Go condition, occurring in the absence of movement. No significant differences were noted between ipsilateral vs contralateral contacts nor in anterior vs posterior hippocampal contacts. Female participants had a higher task success rate than males and had significantly greater beta-power increases in the No-Go condition (p < 0.001). CONCLUSION: These findings indicate that increases in hippocampal beta power are associated with movement inhibition. To the best of our knowledge, this study is the first to report this phenomenon in the human hippocampus. The beta band may represent a state-change signal involved in motor processing. Future focus on the beta band in understanding human motor and impulse control will be vital.

Primary somatosensory cortex organization for engineering artificial somatosensation.

Somatosensory deficits from stroke, spinal cord injury, or other neurologic damage can lead to a significant degree of functional impairment. The primary (SI) and secondary (SII) somatosensory cortices encode information in a medial to lateral organization. SI is generally organized topographically, with more discrete cortical representations of specific body regions. SII regions corresponding to anatomical areas are less discrete and may represent a more functional rather than topographic organization. Human somatosensory research continues to map cortical areas of sensory processing with efforts primarily focused on hand and upper extremity information in SI. However, research into SII and other body regions is lacking. In this review, we synthesize the current state of knowledge regarding the cortical organization of human somatosensation and discuss potential applications for brain computer interface. In addition to accurate individualized mapping of cortical somatosensation, further research is required to uncover the neurophysiological mechanisms of how somatosensory information is encoded in the cortex.

Stereotactic Frame-Based Electrode Insertion: The Accuracy of Increasingly Oblique Insertion Angles.

AIM: To investigate the relationship between planned drill approach angle and angular deviation of the stereotactically placed intracranial electrode tips. MATERIAL AND METHODS: Stereotactic electrode implantation was performed in 13 patients with drug resistant epilepsy. A total of 136 electrodes were included in our analysis. Stereotactic targets were planned on pre-operative magnetic resonance imaging (MRI) scans and implantation was carried out using a Cosman-Roberts-Wells stereotactic frame with the Ad-Tech drill guide and electrodes. Post implant electrode angles in the axial, coronal, and sagittal planes were determined from post-operative computerized tomography (CT) scans and compared with planned angles using Bland-Altman plots and linear regression. RESULTS: Qualitative assessment of correlation plots between planned and actual angles demonstrated a linear relationship for axial, coronal, and sagittal planes, with no overt angular deflection for any magnitude of the planned angle. CONCLUSION: The accuracy of CRW frame-based electrode placement using the Ad-Tech drill guide and electrodes is not significantly affected by the magnitude of the planning angle. Based on our results, oblique electrode insertion is a safe and accurate procedure.

Understanding the human conflict processing network: A review of the literature on direct neural recordings during performance of a modified stroop task.

The Stroop Task is a well-known neuropsychological task developed to investigate conflict processing in the human brain. Our group has utilized direct intracranial neural recordings in various brain regions during performance of a modified color-word Stroop Task to gain a mechanistic understanding of non-emotional human conflict processing. The purpose of this review article is to: 1) synthesize our own studies into a model of human conflict processing, 2) review the current literature on the Stroop Task and other conflict tasks to put our research in context, and 3) describe how these studies define a network in conflict processing. The figures presented are reprinted from our prior publications and key publications referenced in the manuscript. We summarize all studies to date that employ invasive intracranial recordings in humans during performance of conflict-inducing tasks. For our own studies, we analyzed local field potentials (LFPs) from patients with implanted stereotactic electroencephalography (SEEG) electrodes, and we observed intracortical oscillation patterns as well as intercortical temporal relationships in the hippocampus, amygdala, and orbitofrontal cortex (OFC) during the cue-processing phase of a modified Stroop Task. Our findings suggest that non-emotional human conflict processing involves modulation across multiple frequency bands within and between brain structures.

A review of neurophysiological effects and efficiency of waveform parameters in deep brain stimulation.

Neurostimulation has diverse clinical applications and potential as a treatment for medically refractory movement disorders, epilepsy, and other neurological disorders. However, the parameters used to program electrodes-polarity, pulse width, amplitude, and frequency-and how they are adjusted have remained largely untouched since the 1970 s. This review summarizes the state-of-the-art in Deep Brain Stimulation (DBS) and highlights the need for further research to uncover the physiological mechanisms of neurostimulation. We focus on studies that reveal the potential for clinicians to use waveform parameters to selectively stimulate neural tissue for therapeutic benefit, while avoiding activating tissue associated with adverse effects. DBS uses cathodic monophasic rectangular pulses with passive recharging in clinical practice to treat neurological conditions such as Parkinson's Disease. However, research has shown that stimulation efficiency can be improved, and side effects reduced, through modulating parameters and adding novel waveform properties. These developments can prolong implantable pulse generator lifespan, reducing costs and surgery-associated risks. Waveform parameters can stimulate neurons based on axon orientation and intrinsic structural properties, providing clinicians with more precise targeting of neural pathways. These findings could expand the spectrum of diseases treatable with neuromodulation and improve patient outcomes.

Theta low-gamma phase amplitude coupling in the human orbitofrontal cortex increases during a conflict-processing task.

Objective. The human orbitofrontal cortex (OFC) is involved in automatic response inhibition and conflict processing, but the mechanism of frequency-specific power changes that control these functions is unknown. Theta and gamma activity have been independently observed in the OFC during conflict processing, while theta-gamma interactions in other brain areas have been noted primarily in studies of memory. Within the OFC, it is possible that theta-gamma phase amplitude coupling (PAC) drives conflict processing. This study aims to characterize the coupled relationship between theta and gamma frequency bands in the OFC during conflict processing using a modified Stroop task.Approach. Eight epilepsy patients implanted with OFC stereotactic electroencephalography electrodes participated in a color-word modified Stroop task. PAC between theta phase and gamma amplitude was assessed to determine the timing and magnitude of neural oscillatory changes. Group analysis was conducted using a non-parametric cluster-permutationt-test on coherence values.Main results.Theta-low gamma (LG) PAC significantly increased in five out of eight patients during successful trials of the incongruent condition compared with the congruent condition. Significant increases in theta-LG PAC were most prominent during cue processing 200-800 ms after cue presentation. On group analysis, trial-averaged mean theta-LG PAC was statistically significantly greater in the incongruent condition compared to the congruent condition (p< 0.001, Cohen'sd= 0.51).Significance.For the first time, we report that OFC theta phase and LG amplitude coupling increases during conflict resolution. Given the delayed onset after cue presentation, OFC theta-LG PAC may contribute to conflict processing after conflict detection and before motor response. This explanation follows the hypothesis that global theta waves modulate local gamma signals. Understanding this relationship within the OFC will help further elucidate the neural mechanisms of human conflict resolution.

Baseline hippocampal beta band power is lower in the presence of movement uncertainty.

Objective.This study aimed to characterize hippocampal neural signatures of uncertainty by measuring beta band power in the period prior to movement cue.Approach. Participants with epilepsy were implanted with hippocampal depth electrodes for stereo electroencephalographic (SEEG) monitoring. Hippocampal beta (13-30 Hz) power changes have been observed during motor tasks such as the direct reach (DR) and Go/No-Go (GNG) tasks. The primary difference between the tasks is the presence of uncertainty about whether movement should be executed. Previous research on cortical responses to uncertainty has found that baseline beta power changes with uncertainty. SEEG data were sampled throughout phases of the DR and GNG tasks. Beta-band power during the fixation phase was compared between the DR and GNG task using a Wilcoxon rank sum test. This unpaired test was also used to analyze response times from cue to task completion between tasks.Main results.Eight patients who performed both reaching tasks were analyzed in this study. Movement response times in the GNG task were on average 210 milliseconds slower than in the DR task. All patients exhibited a significantly increased response latency in the GNG task compared to the DR task (Wilcoxon rank-sum p-value < 0.001). Six out of eight patients demonstrated statistically significant differences in beta power in single hippocampal contacts between the fixation phases of the GNG and DR tasks. At the group level, baseline beta power was significantly lower in the GNG task than in the DR task (Wilcoxon rank-sum p-value < 0.001).Significance. This novel study found that, in the presence of task uncertainty, baseline beta power in the hippocampus is lower than in its absence. This finding implicates movement uncertainty as an important factor in baseline hippocampal beta power during movement preparation.

Amygdaloid theta-band power increases during conflict processing in humans.

The amygdala is a medial temporal lobe structure known to be involved in processing emotional conflict. However, its role in processing non-emotional conflict is not well understood. Previous studies have utilized the Stroop Task to examine brain modulation of humans under the color-word conflict scenario, which is non-emotional conflict processing, and found hippocampal theta-band (4-7 Hz) modulation. This study aims to survey amygdaloid theta power changes during non-emotional conflict processing using intracranial depth electrodes in nine epileptic patients (3 female; age 20-62). All patients were asked to perform a modified Stroop task. During task performance, local field potential (LFP) data was recorded from macro contacts sampled at 2 K Hz and used for analysis. Mean theta power change from baseline was compared between the incongruent and congruent task condition groups using a paired sample t-test. Seven patients were available for analysis after artifact exclusion. In five out of seven patients, statistically significant increases in theta-band power from baseline were noted during the incongruent task condition (paired sample t-test p < 0.001), including one patient exhibiting theta power increases in both task conditions. Average response time was 1.07 s (failure trials) and 1.04 s (success trials). No speed-accuracy tradeoff was noted in this analysis. These findings indicate that human amygdaloid theta-band modulation may play a role in processing non-emotional conflict. It builds directly upon work suggesting that the amygdala processes emotional conflict and provides a neurophysiological mechanism for non-emotional conflict processing as well.

Hippocampal and Orbitofrontal Theta Band Coherence Diminishes During Conflict Resolution.

OBJECTIVE: Coherence between the hippocampus and other brain structures has been shown with the theta frequency (3-8 Hz). Cortical decreases in theta coherence are believed to reflect response accuracy efficiency. However, the role of theta coherence during conflict resolution is poorly understood in noncortical areas. In this study, coherence between the hippocampus and orbitofrontal cortex (OFC) was measured during a conflict resolution task. Although both brain areas have been previously implicated in the Stroop task, their interactions are not well understood. METHODS: Nine patients were implanted with stereotactic electroencephalography contacts in the hippocampus and OFC. Local field potential data were sampled throughout discrete phases of a Stroop task. Coherence was calculated for hippocampal and OFC contact pairs, and coherence spectrograms were constructed for congruent and incongruent conditions. Coherence changes during cue processing were identified using a nonparametric cluster-permutation t test. Group analysis was conducted to compare overall theta coherence changes among conditions. RESULTS: In 6 of 9 patients, decreased theta coherence was observed only during the incongruent condition (P < 0.05). Congruent theta coherence did not change from baseline. Group analysis showed lower theta coherence for the incongruent condition compared with the congruent condition (P < 0.05). CONCLUSIONS: Theta coherence between the hippocampus and OFC decreased during conflict. This finding supports existing theories that theta coherence desynchronization contributes to improved response accuracy and processing efficiency during conflict resolution. The underlying theta coherence observed between the hippocampus and OFC during conflict may be distinct from its previously observed role in memory.

Readmission with venous thromboembolism after surgical treatment by primary cancer site.

BACKGROUND: Venous thromboembolism (VTE) is a common, high-mortality condition among surgical cancer patients. Comprehensive analyses of VTE among postoperative cancer patients are lacking. We sought to determine the association between readmission with VTE and primary cancer diagnosis in a nationwide database at 90- and 180-days after initial admission for cancer surgery. METHODS: Retrospective analyses of post-surgical cancer patients readmitted with VTE were conducted using data from the Nationwide Readmissions Database (NRD) (2010-2014). Multivariate logistic regression models adjusting for patient and hospital factors were used to determine 90- and 180-day readmission rates for VTE by cancer type. Patient factors associated with readmission were also examined. RESULTS: Among a sample of 535,992 cancer patients undergoing tumor resection, readmission with VTE occurred in 1.7% within 90-days and 2.3% within 180-days. Patients readmitted for VTE experienced a 7% mortality rate. Highest rates of VTE readmission at 180 days occurred in brain (6.7%), pancreatic (5.6%), and respiratory and intrathoracic cancers (4.4%). Using pancreatic cancer as reference, brain cancer had the highest odds of readmission at 180-days (OR 2.23, 95% CI [1.95-2.55]). CONCLUSION: Readmission with VTE among surgical cancer patients occurred in 2.3% of patients within 180 days. Among cancer types, primary brain cancer was independently associated with readmission with VTE.

Beta-band modulation in the human hippocampus during a conflict response task.

Objective. Identify the role of beta-band (13-30 Hz) power modulation in the human hippocampus during conflict processing.Approach. We investigated changes in the spectral power of the beta band (13-30 Hz) as measured by depth electrode leads in the hippocampus during a modified Stroop task in six patients with medically refractory epilepsy. Previous work done with direct electrophysiological recordings in humans has shown hippocampal theta-band (3-8 Hz) modulation during conflict processing. Local field potentials sampled at 2 k Hz were used for analysis and a non-parametric cluster-permutationt-test was used to identify the time period and frequency ranges of significant power change during cue processing (i.e. post-stimulus, pre-response).Main results. In five of the six patients, we observe a statistically significant increase in hippocampal beta-band power during successful conflict processing in the incongruent trial condition (cluster-based correction for multiple comparisons,p< 0.05). There was no significant beta-band power change observed during the cue-processing period of the congruent condition in the hippocampus of these patients.Significance. The beta-power changes during conflict processing represented here are consistent with previous studies suggesting that the hippocampus plays a role in conflict processing, but it is the first time that the beta band has been shown to be involved in humans with direct electrophysiological evidence. We propose that beta-band modulation plays a role in successful conflict detection and automatic response inhibition in the human hippocampus as studied during a conflict response task.

Evolution of larval segment position across 12 Drosophila species.

Many developmental traits that are critical to the survival of the organism are also robust. These robust traits are resistant to phenotypic change in the face of variation. This presents a challenge to evolution. In this article, we asked whether and how a well-established robust trait, Drosophila segment patterning, changed over the evolutionary history of the genus. We compared segment position scaled to body length at the first-instar larval stage among 12 Drosophila species. We found that relative segment position has changed many times across the phylogeny. Changes were frequent, but primarily small in magnitude. Phylogenetic analysis demonstrated that rates of change in segment position are variable along the Drosophila phylogenetic tree, and that these changes can occur in short evolutionary timescales. Correlation between position shifts of segments decreased as the distance between two segments increased, suggesting local control of segment position. The posterior-most abdominal segment showed the highest magnitude of change on average, had the highest rate of evolution between species, and appeared to be evolving more independently as compared to the rest of the segments. This segment was exceptionally elongated in the cactophilic species in our dataset, raising questions as to whether this change may be adaptive.

Readmission following inpatient stereotactic radiosurgery for brain tumors.

BACKGROUND: Stereotactic radiosurgery (SRS) is indicated for a spectrum of brain tumors and is often an outpatient procedure, though severe disease may precipitate inpatient treatment. Readmission following inpatient SRS for brain tumors is not well understood. OBJECTIVES: To characterize rate, associative factors, and predictors of SRS readmission. METHODS: Retrospective analysis of inpatients treated with SRS for brain neoplasms was conducted (2010-2014 Nationwide Readmissions Database). Diagnoses upon readmission were characterized. Associations with 30-day readmission were identified using multivariate analyses. RESULTS: Of 2,553 patients undergoing SRS, 390 were readmitted (15.3%) within 30 days. Leading readmission diagnoses were infectious or embolic. Neurological readmissions of intracerebral hemorrhage (2.1%) and cerebral edema (1.5%) were rare. Malignant tumors (OR=1.60, p=0.007) and discharge to facility (OR=1.41, p=0.004) were associated with readmission. CONCLUSION: Inpatients receiving SRS for brain tumors have a 15.3% 30-day readmission rate. Neurologic readmissions were rare, underscoring the neurological safety of SRS, even in sick inpatients.

Increased complication and mortality among non-index hospital readmissions after brain tumor resection is associated with low-volume readmitting hospitals.

OBJECTIVE: Fragmentation of care following craniotomy for tumor resection is increasingly common with the regionalization of neurosurgery. Hospital readmission to a hospital (non-index) other than the one from which patients received their original care (index) has been associated with increases in both morbidity and mortality for cancer patients. The impact of non-index readmission after surgical management of brain tumors has not previously been evaluated. The authors set out to determine rates of non-index readmission following craniotomy for tumor resection and evaluated outcomes following index and non-index readmissions. METHODS: Retrospective analyses of data from cases involving resection of a primary brain tumor were conducted using data from the Nationwide Readmissions Database (NRD) for 2010-2014. Multivariate logistic regression was used to evaluate the independent association of patient and hospital factors with readmission to an index versus non-index hospital. Further analysis evaluated association of non-index versus index hospital readmission with mortality and major complications during readmission. Effects of readmission hospital procedure volume on mortality and morbidity were evaluated in post hoc analysis. RESULTS: In a total of 17,459 unplanned readmissions, 84.4% patients were readmitted to index hospitals and 15.6% to non-index hospitals. Patient factors associated with increased likelihood of non-index readmission included older age (75+: OR 1.44, 95% CI 1.19-1.75), elective index admission (OR 1.19, 95% CI 1.08-1.30), increased Elixhauser comorbidity score ≥2 (OR 1.18, 95% CI 1.01-1.37), and malignant tumor diagnosis (OR 1.32, 95% CI 1.19-1.45) (all p < 0.04). Readmission to a non-index facility was associated with a 28% increase in major complications (OR 1.28, 95% CI 1.14-1.43, p < 0.001) and 21% increase in mortality (OR 1.21, 95% CI 1.02-1.44, p = 0.032) in initial analysis. Following a second multivariable logistic regression analysis including the readmitting hospital characteristics, low procedure volume of a readmitting facility was significantly associated with non-index readmission (p < 0.001). Readmission to a lower-procedure-volume facility was associated with a 46%-75% increase in mortality (OR 1.46-1.75, p < 0.005) and a 21%-35% increase in major complications (OR 1.21-1.34, p < 0.005). Following adjustment for volume at a readmitting facility, admission to a non-index facility was no longer associated with mortality (OR 0.90, 95% CI 0.71-1.14, p = 0.378) or major complications (OR 1.09, CI 0.94-1.26, p = 0.248). CONCLUSIONS: Of patient readmissions following brain tumor resection, 15.6% occur at a non-index facility. Low procedure volume is a confounder for non-index analysis and is associated with an increased likelihood of major complications and mortality, as compared to readmission to high-procedure-volume hospitals. Further studies should evaluate interventions targeting factors associated with unplanned readmission.

Nonindex Readmission After Ruptured Brain Aneurysm Treatment Is Associated with Higher Morbidity and Repeat Readmission.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) requires complex multidisciplinary care. After initial treatment (index hospital), readmission to a different hospital (nonindex) can compromise quality of care, resulting in increased morbidity. We aimed to evaluate factors associated with nonindex readmission and evaluate association of nonindex hospital readmission on outcomes in patients with ruptured aneurysm. METHODS: Readmissions within 90 days after aSAH treatment were identified in the 2010-2014 Nationwide Readmissions Database. Multivariable logistic regression identified patient and hospital characteristics associated with nonindex readmission. Separate multivariable models determined increased morbidity or risk of second readmission for nonindex readmissions. RESULTS: A total of 9254 patients who underwent treatment of ruptured aneurysms from 2010 to 2014 were identified. Of these, 1985 (21.5%) were readmitted within 90 days. Three hundred and fifty-five of these readmissions (17.9%) occurred to nonindex hospitals. Patients that were discharged to a skilled nursing or other facility (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.27-2.28]) had higher odds of nonindex readmission, whereas patients with private insurance were associated with lower odds of nonindex readmission (OR, 0.65; 95% CI, 0.46-0.92). Patients readmitted to a nonindex (vs. index) hospital were associated with increased likelihood of major complications (OR, 1.71; 95% CI, 1.18-2.48) and second readmissions (OR, 1.51; 95% CI, 1.17-1.96). CONCLUSIONS: After treatment of a ruptured cerebral aneurysm, 17.9% of readmissions occurred at a nonindex hospital. These patients were at increased risk for major complications or subsequent readmissions, which may be because of care fragmentation. Interventions aimed at improving continuity of care may reduce higher morbidity associated with nonindex readmission.