Opiate-Induced Suppression of Rat Hypoglossal Motoneuron Activity and Its Reversal by Ampakine Therapy

Background

Hypoglossal (XII) motoneurons innervate tongue muscles and are vital for maintaining upper-airway patency during inspiration. Depression of XII nerve activity by opioid analgesics is a significant clinical problem, but underlying mechanisms are poorly understood. Currently there are no suitable pharmacological approaches to counter opiate-induced suppression of XII nerve activity while maintaining analgesia. Ampakines accentuate α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor responses. The AMPA family of glutamate receptors mediate excitatory transmission to XII motoneurons. Therefore the objectives were to determine whether the depressant actions of μ-opioid receptor activation on inspiratory activity includes a direct inhibitory action at the inspiratory premotoneuron to XII motoneuron synapse, and to identify underlying mechanism(s). We then examined whether ampakines counteract opioid-induced depression of XII motoneuron activity.

Methodology/Principal Findings

A medullary slice preparation from neonatal rat that produces inspiratory-related output in vitro was used. Measurements of inspiratory burst amplitude and frequency were made from XII nerve roots. Whole-cell patch recordings from XII motoneurons were used to measure membrane currents and synaptic events. Application of the μ-opioid receptor agonist, DAMGO, to the XII nucleus depressed the output of inspiratory XII motoneurons via presynaptic inhibition of excitatory glutamatergic transmission. Ampakines (CX614 and CX717) alleviated DAMGO-induced depression of XII MN activity through postsynaptic actions on XII motoneurons.

Conclusions/Significance

The inspiratory-depressant actions of opioid analgesics include presynaptic inhibition of XII motoneuron output. Ampakines counteract μ-opioid receptor-mediated depression of XII motoneuron inspiratory activity. These results suggest that ampakines may be beneficial in countering opiate-induced suppression of XII motoneuron activity and resultant impairment of airway patency.     

The Use of PRV-Bartha to Define Premotor Inputs to Lumbar Motoneurons in the Neonatal Spinal Cord of the Mouse

Background

The neonatal mouse has become a model system for studying the locomotor function of the lumbar spinal cord. However, information about the synaptic connectivity within the governing neural network remains scarce. A neurotropic pseudorabies virus (PRV) Bartha has been used to map neuronal connectivity in other parts of the nervous system, due to its ability to travel trans-neuronally. Its use in spinal circuits regulating locomotion has been limited and no study has defined the time course of labelling for neurons known to project monosynaptically to motoneurons.

Methodology/Principal Findings

Here we investigated the ability of PRV Bartha, expressing green and/or red fluorescence, to label spinal neurons projecting monosynaptically to motoneurons of two principal hindlimb muscles, the tibialis anterior (TA) and gastrocnemius (GC). As revealed by combined immunocytochemistry and confocal microscopy, 24–32 h after the viral muscle injection the label was restricted to the motoneuron pool while at 32–40 h the fluorescence was seen in interneurons throughout the medial and lateral ventral grey matter. Two classes of ipsilateral interneurons known to project monosynaptically to motoneurons (Renshaw cells and cells of origin of C-terminals) were consistently labeled at 40 h post-injection but also a group in the ventral grey matter contralaterally. Our results suggest that the labeling of last order interneurons occurred 8–12 h after motoneuron labeling and we presume this is the time taken by the virus to cross one synapse, to travel retrogradely and to replicate in the labeled cells.

Conclusions/Significance

The study establishes the time window for virally - labelling monosynaptic projections to lumbar motoneurons following viral injection into hindlimb muscles. Moreover, it provides a good foundation for intracellular targeting of the labeled neurons in future physiological studies and better understanding the functional organization of the lumbar neural networks.     

Natural Spike Trains Trigger Short- and Long-Lasting Dynamics at Hippocampal Mossy Fiber Synapses in Rodents

Background

Synapses exhibit strikingly different forms of plasticity over a wide range of time scales, from milliseconds to hours. Studies on synaptic plasticity typically use constant-frequency stimulation to activate synapses, whereas in vivo activity of neurons is irregular.

Methodology/Principal Findings

Using extracellular and whole-cell electrophysiological recordings, we have here studied the synaptic responses at hippocampal mossy fiber synapses in vitro to stimulus patterns obtained from in vivo recordings of place cell firing of dentate gyrus granule cells in behaving rodents. We find that synaptic strength is strongly modulated on short- and long-lasting time scales during the presentation of the natural stimulus trains.

Conclusions/Significance

We conclude that dynamic short- and long-term synaptic plasticity at the hippocampal mossy fiber synapse plays a prominent role in normal synaptic function.     

Temporal Control of Immediate Early Gene Induction by Light

Background

The light-gated cation channel channelrhodopsin-2 (ChR2) is a powerful tool for the optical induction of action potentials in neurons. Mutations of the cysteine 128 (C128) residue have been shown to greatly extend the lifetime of the conducting state of ChR2. However, until now, only subthreshold depolarizations have been reported from C128 mutants.

Methods and Findings

Here we report the induction of long high-frequency spike trains by brief light pulses in ChR2(C128A)-transfected pyramidal cells in hippocampal slice culture. ChR2(C128A)-mediated spike bursts triggered expression of the immediate early gene c-fos in pyramidal neurons. Robust and cell-specific expression of c-Fos protein was detected after a single blue light pulse and depended on action potential firing, but not on synaptic activity. However, photocurrents diminished upon repeated stimulation and limited the number of action potential bursts that could be elicited.

Conclusions

We conclude that the C128A mutant is not suitable for chronic stimulation of neurons, but very useful for light-controlled induction of immediate early genes. This property of ChR2(C128A) could be harnessed to control the expression of proteins under control of the c-fos promoter with precise timing and single cell specificity.     

The Relationship between Respiration-Related Membrane Potential Slow Oscillations and Discharge Patterns in Mitral/Tufted Cells: What Are the Rules?

Background

A slow respiration-related rhythm strongly shapes the activity of the olfactory bulb. This rhythm appears as a slow oscillation that is detectable in the membrane potential, the respiration-related spike discharge of the mitral/tufted cells and the bulbar local field potential. Here, we investigated the rules that govern the manifestation of membrane potential slow oscillations (MPSOs) and respiration-related discharge activities under various afferent input conditions and cellular excitability states.

Methodology and Principal Findings

We recorded the intracellular membrane potential signals in the mitral/tufted cells of freely breathing anesthetized rats. We first demonstrated the existence of multiple types of MPSOs, which were influenced by odor stimulation and discharge activity patterns. Complementary studies using changes in the intracellular excitability state and a computational model of the mitral cell demonstrated that slow oscillations in the mitral/tufted cell membrane potential were also modulated by the intracellular excitability state, whereas the respiration-related spike activity primarily reflected the afferent input. Based on our data regarding MPSOs and spike patterns, we found that cells exhibiting an unsynchronized discharge pattern never exhibited an MPSO. In contrast, cells with a respiration-synchronized discharge pattern always exhibited an MPSO. In addition, we demonstrated that the association between spike patterns and MPSO types appeared complex.

Conclusion

We propose that both the intracellular excitability state and input strength underlie specific MPSOs, which, in turn, constrain the types of spike patterns exhibited.     

Synaptic Plasticity in Medial Vestibular Nucleus Neurons: Comparison with Computational Requirements of VOR Adaptation

Background

Vestibulo-ocular reflex (VOR) gain adaptation, a longstanding experimental model of cerebellar learning, utilizes sites of plasticity in both cerebellar cortex and brainstem. However, the mechanisms by which the activity of cortical Purkinje cells may guide synaptic plasticity in brainstem vestibular neurons are unclear. Theoretical analyses indicate that vestibular plasticity should depend upon the correlation between Purkinje cell and vestibular afferent inputs, so that, in gain-down learning for example, increased cortical activity should induce long-term depression (LTD) at vestibular synapses.

Methodology/Principal Findings

Here we expressed this correlational learning rule in its simplest form, as an anti-Hebbian, heterosynaptic spike-timing dependent plasticity interaction between excitatory (vestibular) and inhibitory (floccular) inputs converging on medial vestibular nucleus (MVN) neurons (input-spike-timing dependent plasticity, iSTDP). To test this rule, we stimulated vestibular afferents to evoke EPSCs in rat MVN neurons in vitro. Control EPSC recordings were followed by an induction protocol where membrane hyperpolarizing pulses, mimicking IPSPs evoked by flocculus inputs, were paired with single vestibular nerve stimuli. A robust LTD developed at vestibular synapses when the afferent EPSPs coincided with membrane hyperpolarisation, while EPSPs occurring before or after the simulated IPSPs induced no lasting change. Furthermore, the iSTDP rule also successfully predicted the effects of a complex protocol using EPSP trains designed to mimic classical conditioning.

Conclusions

These results, in strong support of theoretical predictions, suggest that the cerebellum alters the strength of vestibular synapses on MVN neurons through hetero-synaptic, anti-Hebbian iSTDP. Since the iSTDP rule does not depend on post-synaptic firing, it suggests a possible mechanism for VOR adaptation without compromising gaze-holding and VOR performance in vivo.     

The Neuropsychology of Starvation: Set-Shifting and Central Coherence in a Fasted Nonclinical Sample

Objectives

Recent research suggests certain neuropsychological deficits occur in anorexia nervosa (AN). The role of starvation in these deficits remains unclear. Studies of individuals without AN can elucidate our understanding of the effect of short-term starvation on neuropsychological performance.

Methods

Using a within-subjects repeated measures design, 60 healthy female participants were tested once after fasting for 18 hours, and once when satiated. Measures included two tasks to measure central coherence and a set-shifting task.

Results

Fasting exacerbated set-shifting difficulties on a rule-change task. Fasting was associated with stronger local and impaired global processing, indicating weaker central coherence.

Conclusions

Models of AN that propose a central role for set-shifting difficulties or weak central coherence should also consider the impact of short-term fasting on these processes.     

Axons Amplify Somatic Incomplete Spikes into Uniform Amplitudes in Mouse Cortical Pyramidal Neurons

Background

Action potentials are the essential unit of neuronal encoding. Somatic sequential spikes in the central nervous system appear various in amplitudes. To be effective neuronal codes, these spikes should be propagated to axonal terminals where they activate the synapses and drive postsynaptic neurons. It remains unclear whether these effective neuronal codes are based on spike timing orders and/or amplitudes.

Methodology/Principal Findings

We investigated this fundamental issue by simultaneously recording the axon versus soma of identical neurons and presynaptic vs. postsynaptic neurons in the cortical slices. The axons enable somatic spikes in low amplitude be enlarged, which activate synaptic transmission in consistent patterns. This facilitation in the propagation of sequential spikes through the axons is mechanistically founded by the short refractory periods, large currents and high opening probability of axonal voltage-gated sodium channels.

Conclusion/Significance

An amplification of somatic incomplete spikes into axonal complete ones makes sequential spikes to activate consistent synaptic transmission. Therefore, neuronal encoding is likely based on spike timing order, instead of graded analogues.     

Quantal glutamate release is essential for reliable neuronal encodings in cerebral networks

Background

The neurons and synapses work coordinately to program the brain codes of controlling cognition and behaviors. Spike patterns at the presynaptic neurons regulate synaptic transmission. The quantitative regulations of synapse dynamics in spike encoding at the postsynaptic neurons remain unclear.

Methodology/Principal Findings

With dual whole-cell recordings at synapse-paired cells in mouse cortical slices, we have investigated the regulation of synapse dynamics to neuronal spike encoding at cerebral circuits assembled by pyramidal neurons and GABAergic ones. Our studies at unitary synapses show that postsynaptic responses are constant over time, such as glutamate receptor-channel currents at GABAergic neurons and glutamate transport currents at astrocytes, indicating quantal glutamate release. In terms of its physiological impact, our results demonstrate that the signals integrated from quantal glutamatergic synapses drive spike encoding at GABAergic neurons reliably, which in turn precisely set spike encoding at pyramidal neurons through feedback inhibition.

Conclusion/Significance

Our studies provide the evidences for the quantal glutamate release to drive the spike encodings precisely in cortical circuits, which may be essential for programming the reliable codes in the brain to manage well-organized behaviors.     

Experience-Driven Axon Retraction in the Pharmacologically Inactivated Visual Cortex Does Not Require Synaptic Transmission

Background

Experience during early postnatal development plays an important role in the refinement of specific neural connections in the brain. In the mammalian visual system, altered visual experiences induce plastic adaptation of visual cortical responses and guide rearrangements of afferent axons from the lateral geniculate nucleus. Previous studies using visual deprivation demonstrated that the afferents serving an open eye significantly retract when cortical neurons are pharmacologically inhibited by applying a γ-aminobutyric acid type A receptor agonist, muscimol, whereas those serving a deprived eye are rescued from retraction, suggesting that presynaptic activity can lead to the retraction of geniculocortical axons in the absence of postsynaptic activity. Because muscimol application suppresses the spike activity of cortical neurons leaving transmitter release intact at geniculocortical synapses, local synaptic interaction may underlie the retraction of active axons in the inhibited cortex.

Method and Findings

New studies reported here determined whether experience-driven axon retraction can occur in the visual cortex inactivated by blocking synaptic inputs. We inactivated the primary visual cortex of kittens by suppressing synaptic transmission with cortical injections of botulinum neurotoxin type E, which cleaves a synaptic protein, SNAP-25, and blocks transmitter release, and examined the geniculocortical axon morphology in the animals with normal vision and those deprived of vision binocularly. We found that afferent axons in the animals with normal vision showed a significant retraction in the inactivated cortex, as similarly observed in the muscimol-treated cortex, whereas the axons in the binocularly deprived animals were preserved.

Conclusions

Therefore, the experience-driven axon retraction in the inactivated cortex can proceed in the absence of synaptic transmission. These results suggest that presynaptic mechanisms play an important role in the experience-driven refinement of geniculocortical axons.     

US News and World Report Cancer Hospital Rankings: Do They Reflect Measures of Research Productivity?

Context

Prior research has faulted the US News and World Report hospital specialty rankings for excessive reliance on reputation, a subjective measure of a hospital''s performance.

Objective

To determine whether and to what extent reputation correlates with objective measures of research productivity among cancer hospitals.

Design

A retrospective observational study.

Setting

Automated search of NIH Reporter, BioEntrez, BioMedline and Clinicaltrials.gov databases.

Participants

The 50 highest ranked cancer hospitals in 2013''s US News and World Report Rankings.

Exposure

We ascertained the number of NCI funded grants, and the cumulative funds received by each cancer center. Additionally, we identified the number of phase I, phase II, and phase III studies published and indexed in MEDLINE, and registered at clinicaltrials.gov. All counts were over the preceding 5 years. For published articles, we summed the impact factor of the journals in which they appeared. Trials were attributed to centers on the basis of the affiliation of the lead author or study principal investigator.

Main Outcome

Correlation coefficients from simple and multiple linear regressions for measures of research productivity and a center''s reputation.

Results

All measures of research productivity demonstrated robust correlation with reputation (mean r-squared  = 0.65, median r-squared = 0.68, minimum r-squared = .41, maximum r-squared = 0.80). A multivariable model showed that 93% of the variation in reputation is explained by objective measures.

Conclusion

Contrary to prior criticism, the majority of reputation, used in US News and World Rankings, can be explained by objective measures of research productivity among cancer hospitals.     

Influence of different envelope maskers on signal recognition and neuronal representation in the auditory system of a grasshopper

Background

Animals that communicate by sound face the problem that the signals arriving at the receiver often are degraded and masked by noise. Frequency filters in the receiver''s auditory system may improve the signal-to-noise ratio (SNR) by excluding parts of the spectrum which are not occupied by the species-specific signals. This solution, however, is hardly amenable to species that produce broad band signals or have ears with broad frequency tuning. In mammals auditory filters exist that work in the temporal domain of amplitude modulations (AM). Do insects also use this type of filtering?

Principal Findings

Combining behavioural and neurophysiological experiments we investigated whether AM filters may improve the recognition of masked communication signals in grasshoppers. The AM pattern of the sound, its envelope, is crucial for signal recognition in these animals. We degraded the species-specific song by adding random fluctuations to its envelope. Six noise bands were used that differed in their overlap with the spectral content of the song envelope. If AM filters contribute to reduced masking, signal recognition should depend on the degree of overlap between the song envelope spectrum and the noise spectra. Contrary to this prediction, the resistance against signal degradation was the same for five of six masker bands. Most remarkably, the band with the strongest frequency overlap to the natural song envelope (0–100 Hz) impaired acceptance of degraded signals the least. To assess the noise filter capacities of single auditory neurons, the changes of spike trains as a function of the masking level were assessed. Increasing levels of signal degradation in different frequency bands led to similar changes in the spike trains in most neurones.

Conclusions

There is no indication that auditory neurones of grasshoppers are specialized to improve the SNR with respect to the pattern of amplitude modulations.     

Synaptic responses evoked by tactile stimuli in Purkinje cells in mouse cerebellar cortex Crus II in vivo

Background

Sensory stimuli evoke responses in cerebellar Purkinje cells (PCs) via the mossy fiber-granule cell pathway. However, the properties of synaptic responses evoked by tactile stimulation in cerebellar PCs are unknown. The present study investigated the synaptic responses of PCs in response to an air-puff stimulation on the ipsilateral whisker pad in urethane-anesthetized mice.

Methods and Main Results

Thirty-three PCs were recorded from 48 urethane-anesthetized adult (6–8-week-old) HA/ICR mice by somatic or dendritic patch-clamp recording and pharmacological methods. Tactile stimulation to the ipsilateral whisker pad was delivered by an air-puff through a 12-gauge stainless steel tube connected with a pressurized injection system. Under current-clamp conditions (I = 0), the air-puff stimulation evoked strong inhibitory postsynaptic potentials (IPSPs) in the somata of PCs. Application of SR95531, a specific GABA_A receptor antagonist, blocked IPSPs and revealed stimulation-evoked simple spike firing. Under voltage-clamp conditions, tactile stimulation evoked a sequence of transient inward currents followed by strong outward currents in the somata and dendrites in PCs. Application of SR95531 blocked outward currents and revealed excitatory postsynaptic currents (EPSCs) in somata and a temporal summation of parallel fiber EPSCs in PC dendrites. We also demonstrated that PCs respond to both the onset and offset of the air-puff stimulation.

Conclusions

These findings indicated that tactile stimulation induced asynchronous parallel fiber excitatory inputs onto the dendrites of PCs, and failed to evoke strong EPSCs and spike firing in PCs, but induced the rapid activation of strong GABA_A receptor-mediated inhibitory postsynaptic currents in the somata and dendrites of PCs in the cerebellar cortex Crus II in urethane-anesthetized mice.     

The amplitude and phase responses of the firing rates of some motoneuron models

A vertebrate motoneuron receives an enormous amount of synaptic activity from descending pathways, from spinal cord interneurons and directly from mechanoreceptor afferents. The intrinsic characteristics of the motoneuron will determine how its output spike train will encode the activities of all its inputs. Therefore, the essence of the intrinsic motoneuron characteristics should be well studied and modelled if the roles of the motoneuron as a processing or encoding element are to be well understood. Mathematical models of motoneurons have been described in the literature and tested mostly under static conditions. To increase the reality of the validation of such models, the objective of the present work is to test a few selected models described in the literature using sinusoidal injected current of different frequencies. The resulting frequency responses are compared with data available in the literature from cat type F motoneurons. Discrepancies between some of the models' responses and real motoneuron data suggest that improvements are needed in the modelling of the afterhyperpolarization mechanism.     

Netrin signaling breaks the equivalence between two identified zebrafish motoneurons revealing a new role of intermediate targets

Background

We previously showed that equivalence between two identified zebrafish motoneurons is broken by interactions with identified muscle fibers that act as an intermediate target for the axons of these motoneurons. Here we investigate the molecular basis of the signaling interaction between the intermediate target and the motoneurons.

Principal Findings

We provide evidence that Netrin 1a is an intermediate target-derived signal that causes two equivalent motoneurons to adopt distinct fates. We show that although these two motoneurons express the same Netrin receptors, their axons respond differently to Netrin 1a encountered at the intermediate target. Furthermore, we demonstrate that when Netrin 1a is knocked down, more distal intermediate targets that express other Netrins can also function to break equivalence between these motoneurons.

Significance

Our results suggest a new role for intermediate targets in breaking neuronal equivalence. The data we present reveal that signals encountered during axon pathfinding can cause equivalent neurons to adopt distinct fates. Such signals may be key in diversifying a neuronal population and leading to correct circuit formation.     

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

Background

Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials.

Objective

To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD.

Design

A 24-week randomised, controlled, double-blind, parallel-group, multi-country study.

Participants

179 drug-naïve mild AD patients who participated in the Souvenir II study.

Intervention

Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks.

Outcome

In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance.

Results

The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance.

Conclusions

The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions.

Trial registration

Dutch Trial Register NTR1975.     

Long-Term Plasticity Is Proportional to Theta-Activity

Background

Theta rhythm in the hippocampal formation is a main feature of exploratory behaviour and is believed to enable the encoding of new spatial information and the modification of synaptic weights. Cyclic changes of dentate gyrus excitability during theta rhythm are related to its function, but whether theta epochs per se are able to alter network properties of dentate gyrus for long time-periods is still poorly understood.

Methodology/Principal Findings

We used low-frequency stimulation protocols that amplify the power of endogenous theta oscillations, in order to estimate the plasticity effect of endogenous theta oscillations on a population level. We found that stimulation-induced augmentation of the theta rhythm is linked to a subsequent increase of neuronal excitability and decrease of the synaptic response. This EPSP-to-Spike uncoupling is related to an increased postsynaptic spiking on the positive phases of theta frequency oscillations. Parallel increase of the field EPSP slope and the population spike occurs only after concurrent pre- and postsynaptic activation. Furthermore, we observed that long-term potentiation (>24 h) occurs in the dentate gyrus of freely behaving adult rats after phasic activity of entorhinal afferents in the theta-frequency range. This plasticity is proportional to the field bursting activity of granule cells during the stimulation, and may comprise a key step in spatial information transfer. Long-term potentiation of the synaptic component occurs only when the afferent stimulus precedes the evoked population burst, and is input-specific.

Conclusions/Significance

Our data confirm the role of the dentate gyrus in filtering information to the subsequent network during the activated state of the hippocampus.     

Dynamic Eye Tracking Based Metrics for Infant Gaze Patterns in the Face-Distractor Competition Paradigm

Objective

To develop new standardized eye tracking based measures and metrics for infants’ gaze dynamics in the face-distractor competition paradigm.

Method

Eye tracking data were collected from two samples of healthy 7-month-old (total n = 45), as well as one sample of 5-month-old infants (n = 22) in a paradigm with a picture of a face or a non-face pattern as a central stimulus, and a geometric shape as a lateral stimulus. The data were analyzed by using conventional measures of infants’ initial disengagement from the central to the lateral stimulus (i.e., saccadic reaction time and probability) and, additionally, novel measures reflecting infants gaze dynamics after the initial disengagement (i.e., cumulative allocation of attention to the central vs. peripheral stimulus).

Results

The results showed that the initial saccade away from the centrally presented stimulus is followed by a rapid re-engagement of attention with the central stimulus, leading to cumulative preference for the central stimulus over the lateral stimulus over time. This pattern tended to be stronger for salient facial expressions as compared to non-face patterns, was replicable across two independent samples of 7-month-old infants, and differentiated between 7 and 5 month-old infants.

Conclusion

The results suggest that eye tracking based assessments of infants’ cumulative preference for faces over time can be readily parameterized and standardized, and may provide valuable techniques for future studies examining normative developmental changes in preference for social signals.

Significance

Standardized measures of early developing face preferences may have potential to become surrogate biomarkers of neurocognitive and social development.     

Do Post Discharge Phone Calls Improve Care Transitions? A Cluster-Randomized Trial

Importance

The transition from hospital to home can expose patients to adverse events during the post discharge period. Post discharge care including phone calls may provide support for patients returning home but the impact on care transitions is unknown.

Objective

To examine the effect of a 72-hour post discharge phone call on the patient''s transition of care experience.

Design

Cluster-randomized control trial.

Setting

Urban, academic medical center.

Participants

General medical patients age 18 and older discharged home after hospitalization.

Main Outcomes and Measures

Primary outcome measure was the Care Transition Measure (CTM-3) score, a validated measure of the quality of care transitions. Secondary measures included self-reported adherence to medication and follow up plans, and 30-day composite of emergency department (ED) visits and hospital readmission.

Results

328 patients were included in the study over an 6-month period. 114 (69%) received a post discharge phone call, and 214 of all patients in the study completed the follow outcome survey (65% response rate). A small difference in CTM-3 scores was observed between the intervention and control groups (1.87 points, 95% CI 0.47–3.27, p = 0.01). Self-reported adherence to treatment plans, ED visits, and emergency readmission rates were similar between the two groups (odds ratio 0.57, 95% CI 0.13–2.45, 1.20, 95% CI 0.61–2.37, and 1.18, 95% CI 0.53–2.61, respectively).

Conclusions and Relevance

A single post discharge phone call had a small impact on the quality of care transitions and no effect on hospital utilization. Higher intensity post discharge support may be required to improve the patient experience upon returning home.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01580774","term_id":"NCT01580774"}}NCT01580774