Effects of aging on the response of single neurons to amplitude-modulated noise in primary auditory cortex of rhesus macaque

Temporal envelope processing is critical for speech comprehension, which is known to be affected by normal aging. Whereas the macaque is an excellent animal model for human cerebral cortical function, few studies have investigated neural processing in the auditory cortex of aged, nonhuman primates. Therefore, we investigated age-related changes in the spiking activity of neurons in primary auditory cortex (A1) of two aged macaque monkeys using amplitude-modulated (AM) noise and compared these responses with data from a similar study in young monkeys (Yin P, Johnson JS, O'Connor KN, Sutter ML. J Neurophysiol 105: 582–600, 2011). For each neuron, we calculated firing rate (rate code) and phase-locking using phase-projected vector strength (temporal code). We made several key findings where neurons in old monkeys differed from those in young monkeys. Old monkeys had higher spontaneous and driven firing rates, fewer neurons that synchronized with the AM stimulus, and fewer neurons that had differential responses to AM stimuli with both a rate and temporal code. Finally, whereas rate and temporal tuning functions were positively correlated in young monkeys, this relationship was lost in older monkeys at both the population and single neuron levels. These results are consistent with considerable evidence from rodents and primates of an age-related decrease in inhibition throughout the auditory pathway. Furthermore, this dual coding in A1 is thought to underlie the capacity to encode multiple features of an acoustic stimulus. The apparent loss of ability to encode AM with both rate and temporal codes may have consequences for stream segregation and effective speech comprehension in complex listening environments.

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Effects of GABAA kinetics on cortical population activity: computational studies and physiological confirmations

Voltage-sensitive dye (VSD) imaging produces an unprecedented real-time and high-resolution mesoscopic signal to measure the cortical population activity. We have previously shown that the neuronal compartments contributions to the signal are dynamic and stimulus-dependent (Chemla S, Chavane F. Neuroimage 53: 420–438, 2010). Moreover, the VSD signal can also be strongly affected by the network state, such as in anesthetized vs. awake preparations. Here, we investigated the impact of the network state, through GABA_A receptors modulation, on the VSD signal using a computational approach. We therefore systematically measured the effect of the GABA_A-mediated inhibitory postsynaptic potentials (IPSPs) decay time constant (_G) on our modeled VSD response to an input stimulus of increasing strength. Our simulations suggest that _G strongly modulates the dynamics of the VSD signal, affecting the amplitude, input response function, and the transient balance of excitation and inhibition. We confirmed these predictions experimentally on awake and anesthetized monkeys, comparing VSD responses to drifting gratings stimuli of various contrasts. Lastly, one in vitro study has suggested that GABA_A receptors may also be directly affected by the VSDs themselves (Mennerick S, Chisari M, Shu H, Taylor A, Vasek M, Eisenman L, Zorumski C. J Neurosci 30: 2871–2879, 2010). Our modeling approach suggests that the type of modulation described in this study would actually have a negligible influence on the population response. This study highlights that functional results acquired with different techniques and network states must be compared with caution. Biophysical models are proposed here as an adequate tool to delineate the domain of VSD data interpretation.

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Failure to suppress low-frequency neuronal oscillatory activity underlies the reduced effectiveness of random patterns of deep brain stimulation

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established treatment for the motor symptoms of Parkinson's disease (PD). However, the mechanisms of action of DBS are unknown. Random temporal patterns of DBS are less effective than regular DBS, but the neuronal basis for this dependence on temporal pattern of stimulation is unclear. Using a rat model of PD, we quantified the changes in behavior and single-unit activity in globus pallidus externa and substantia nigra pars reticulata during high-frequency STN DBS with different degrees of irregularity. Although all stimulus trains had the same average rate, 130-Hz regular DBS more effectively reversed motor symptoms, including circling and akinesia, than 130-Hz irregular DBS. A mixture of excitatory and inhibitory neuronal responses was present during all stimulation patterns, and mean firing rate did not change during DBS. Low-frequency (7–10 Hz) oscillations of single-unit firing times present in hemiparkinsonian rats were suppressed by regular DBS, and neuronal firing patterns were entrained to 130 Hz. Irregular patterns of DBS less effectively suppressed 7- to 10-Hz oscillations and did not regularize firing patterns. Random DBS resulted in a larger proportion of neuron pairs with increased coherence at 7–10 Hz compared with regular 130-Hz DBS, which suggested that long pauses (interpulse interval >50 ms) during random DBS facilitated abnormal low-frequency oscillations in the basal ganglia. These results suggest that the efficacy of high-frequency DBS stems from its ability to regularize patterns of neuronal firing and thereby suppress abnormal oscillatory neural activity within the basal ganglia.

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In vivo analysis of cerebellar Purkinje cell activity in SCA2 transgenic mouse model

Cerebellar Purkinje cells (PCs) are primarily affected in many spinocerebellar ataxias (SCA). In this study we investigated functional activity of PCs in transgenic mouse model of SCA2, a polyglutamine neurodegenerative hereditary disorder. In our studies we used extracellular single-unit recording method to compare spontaneous activity of PCs in age-matched wild-type mice and SCA2-58Q transgenic mice. We discovered that the fraction of PCs with bursting and an irregular pattern of spontaneous activity dramatically increases in aged SCA2-58Q mice compared with wild-type littermates. Small-conductance calcium-activated potassium (SK) channels play an important role in determining firing rate of PCs. Indeed, we demonstrated that intraperitoneal (IP) injection of SK channel inhibitor NS8593 induces an irregular pattern of PC activity in wild-type mice. Furthermore, we demonstrated that IP injection of SK channel-positive modulator chlorzoxazone (CHZ) decreases spontaneous firing rate of cerebellar PCs. Finally, we have shown that IP injections with CHZ normalize firing activity of cerebellar PCs from aging SCA2-58Q mice. We propose that alterations in PC firing patterns is one of potential causes of ataxic symptoms in SCA2 and in other SCAs and that positive modulators of SK channels can be used to normalize activity of PCs and alleviate ataxic phenotype in patients with SCA.

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Large-scale imaging of cortical dynamics during sensory perception and behavior

Sensory-driven behaviors engage a cascade of cortical regions to process sensory input and generate motor output. To investigate the temporal dynamics of neural activity at this global scale, we have improved and integrated tools to perform functional imaging across large areas of cortex using a transgenic mouse expressing the genetically encoded calcium sensor GCaMP6s, together with a head-fixed visual discrimination behavior. This technique allows imaging of activity across the dorsal surface of cortex, with spatial resolution adequate to detect differential activity in local regions at least as small as 100 μm. Imaging during an orientation discrimination task reveals a progression of activity in different cortical regions associated with different phases of the task. After cortex-wide patterns of activity are determined, we demonstrate the ability to select a region that displayed conspicuous responses for two-photon microscopy and find that activity in populations of individual neurons in that region correlates with locomotion in trained mice. We expect that this paradigm will be a useful probe of information flow and network processing in brain-wide circuits involved in many sensory and cognitive processes.

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Muscle fatigue increases beta-band coherence between the firing times of simultaneously active motor units in the first dorsal interosseous muscle

Synchronization between the firing times of simultaneously active motor units (MUs) is generally assumed to increase during fatiguing contractions. To date, however, estimates of MU synchronization have relied on indirect measures, derived from surface electromyographic (EMG) interference signals. This study used intramuscular coherence to investigate the correlation between MU discharges in the first dorsal interosseous muscle during and immediately following a submaximal fatiguing contraction, and after rest. Coherence between composite MU spike trains, derived from decomposed surface EMG, were examined in the delta (1–4 Hz), alpha (8–12 Hz), beta (15–30 Hz), and gamma (30–60 Hz) frequency band ranges. A significant increase in MU coherence was observed in the delta, alpha, and beta frequency bands postfatigue. In addition, wavelet coherence revealed a tendency for delta-, alpha-, and beta-band coherence to increase during the fatiguing contraction, with subjects exhibiting low initial coherence values displaying the greatest relative increase. This was accompanied by an increase in MU short-term synchronization and a decline in mean firing rate of the majority of MUs detected during the sustained contraction. A model of the motoneuron pool and surface EMG was used to investigate factors influencing the coherence estimate. Simulation results indicated that changes in motoneuron inhibition and firing rates alone could not directly account for increased beta-band coherence postfatigue. The observed increase is, therefore, more likely to arise from an increase in the strength of correlated inputs to MUs as the muscle fatigues.

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Membrane–plate transition in leaves as an influence on dietary selectivity and tooth form

Publication date: Available online 3 June 2016
Source:Journal of Human Evolution
Author(s): Mauricio G. Talebi, Enrico A. Sala, Barbara Carvalho, Giovanna M. Villani, Peter W. Lucas, Adam van Casteren
Primates need accurate sensory signals about food quality to forage efficiently. Current evidence suggests that they target leaf foods based on color at long-range, reinforcing this with post-ingestive sensations relating to leaf toughness evoked during chewing. Selection against tough leaves effectively selects against high fiber content, which in turn gives a greater opportunity of acquiring protein. Here we consider a novel intermediate mechanical factor that could aid a folivore: leaves may transform mechanically from membranes (sheets that cannot maintain their shape under gravitational loads and thus 'flop') early on in development into plates (that can maintain their shape) as they mature. This transformation can be detected visually. Mechanical tests on two species of leaf eaten by southern muriqui monkeys (Brachyteles arachnoides) in Southern Atlantic Forest, Brazil, support a membrane-to-plate shift in turgid leaves during their development. A measure of this mechanical transition, termed lambda (λ), was found to correlate with both leaf color and toughness, thus supporting a potential role in leaf selection. Muriquis appear to select membranous leaves, but they also eat leaves that are plate-like. We attribute this to the degree of cresting of their molar teeth. A dietary choice restricted to membranous leaves might typify the type of 'fallback' leaf that even frugivorous primates will target because membranes of low toughness are relatively easily chewed. This may be relevant to the diets of hominins because these lack the bladed postcanine teeth seen in mammals with a specialized folivorous diet. We suggest that mammals with such dental adaptations can consume tougher leaf 'plates' than others.



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A Comparison of Benefit Limits in Mental Health

Abstract

This study provides insight to policy makers and stakeholders on how three types of benefits limits on Medicaid-covered mental health services might affect access for consumers diagnosed with severe mental illness. The study used a retrospective cohort design with data for Medicaid-covered, community-based mental health services provided in Ohio during fiscal year 2010. Log-binomial regression was used for the analysis. Results indicate that limits compared have significant, varying consequences based on Medicaid coverage and diagnoses. When constraining Medicaid costs, policy makers should consider how limits will disrupt care and include clinicians in discussions prior to implementation.

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Patient Activation and Mental Health Care Experiences Among Women Veterans

Abstract

We utilized a nationally representative survey of women veteran primary care users to examine associations between patient activation and mental health care experiences. A dose–response relationship was observed, with odds of high quality ratings significantly greater at each successive level of patient activation. Higher activation levels were also significantly associated with preference concordant care for gender-related preferences (use of female providers, women-only settings, and women-only groups as often as desired). Results add to the growing literature documenting better health care experiences among more activated patients, and suggest that patient activation may play an important role in promoting engagement with mental health care.

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Mental Health Clinicians’ Participation in Web-Based Training for an Evidence Supported Intervention: Signs of Encouragement and Trouble Ahead

Abstract

Comprehensive scalable clinician training is needed to increase the impact of evidence-supported psychotherapies. This study was designed to ascertain clinician participation in different low-cost training activities, what predicts their training participation, and how participation can be increased. The study enrolled 163 clinicians. Of these, 105 completed a follow-up survey and 20 completed a more in-depth qualitative interview. Some activities (web training) attracted greater participation than others (e.g., discussion boards, role playing). Key findings include the desirability of self-paced learning and the flexibility it afforded practicing clinicians. However, some found the lack of accountability insurmountable. Many desired in-person training as a way to introduce accountability and motivation. While low-cost, relevant, self-paced learning appeals to practicing clinicians, it may need to be combined with opportunities for in-person training and accountability mechanisms in order to encourage large numbers of clinicians to complete training.

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Locking Away “Recidivism”

Abstract

The etymology of the word recidivism is explored as is its use in the psychiatric literature and other areas. This paper revisits a proposal to stop using the word to describe hospital readmission and substance use relapse since the origin of the word and predominant meaning reflect crime and acts that offend society. Public policy makers and leaders should be careful to not misuse the word and unwittingly stigmatize persons with mental illness and substance use disorders.

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Retraction Note: Computerized Performance Monitoring Systems: Learning and Living with its Limitations

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Future Research on Psychotherapy Practice in Usual Care

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The Expanding Relevance of Routinely Collected Outcome Data for Mental Health Care Decision Making

Abstract

Evidence shows that routine outcome monitoring (ROM) and feedback using standardized measurement tools enhances the outcomes of individual patients. When outcome data from a large number of patients and clinicians are collected, patterns can be tracked and comparisons can be made at multiple levels. Variability in skills and outcomes among clinicians and service settings has been documented, and the relevance of ROM for decision making is rapidly expanding alongside the transforming health care landscape. In this article, we highlight several developing core implications of ROM for mental health care, and frame points of future work and discussion.

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Does the Hospital Predict Readmission? A Multi-level Survival Analysis Approach

Abstract

Time to psychiatric rehospitalization was predicted for a sample of 1473 Medicaid-insured youth in Illinois in 2005 and 2006. A multi-level model statistical strategy was employed to account for the fact that youth days to rehospitalization were nested within hospital and to test the hypothesis that hospitals would vary significantly in return rates, controlling for individual-level (e.g., symptom, demographic) variables. Hospitals did not vary significantly in days to rehospitalization. At the individual-level, level of externalizing behavior and residential treatment placement predicted a faster return to the hospital. These results support the perspective that hospital outcomes are best operationalized using variables tied more directly to the inpatient episode (e.g., LOS, reductions in acuity).

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Projected Spending on Psychotropic Medications 2013–2020

Abstract

Spending on psychotropic medications has grown rapidly in recent decades. Using national data on drug expenditures, patent expirations, future drug development and expert interviews, we project that spending will grow more slowly over the period 2012–2020. The average annual increase is projected to be just 3.0 % per year, continuing the steady deceleration in recent years. The main drivers of this expected deceleration include slower development of new drugs, upcoming patent expirations which will lower prices, and payers' growing ability to manage utilization and promote generic use. The slowdown will relieve some cost pressures on payers, particularly Medicare and Medicaid.

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An Economic Evaluation of a Weight Loss Intervention Program for People with Serious Mental Illnesses Taking Antipsychotic Medications

Abstract

Individuals with serious mental illnesses suffer from obesity and cardiometabolic diseases at high rates, and antipsychotic medications exacerbate these conditions. While studies have shown weight loss and lifestyle interventions can be effective in this population, few have assessed intervention cost-effectiveness. We present results from a 12-month randomized controlled trial that reduced weight, fasting glucose, and medical hospitalizations in intervention participants. Costs per participant ranged from $4365 to $5687. Costs to reduce weight by one kilogram ranged from $1623 to $2114; costs to reduce fasting glucose by 1 mg/dL ranged from $467 to $608. Medical hospitalization costs were reduced by $137,500.

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Socio-contextual Determinants of Research Evidence Use in Public-Youth Systems of Care

Abstract

Recent efforts have been devoted to understanding the conditions by which research evidence use (REU) is facilitated from the perspective of system leaders in the context of implementing evidence-based child mental health interventions. However, we have limited understanding of the extent to which outer contextual factors influence REU. Outer contextual factors for 37 counties in California were gathered from public records in 2008; and child welfare, juvenile justice, and mental health system leaders' perceptions of their REU were measured via a web-based survey from 2010 to 2012. Results showed that leaders with higher educational attainment and in counties with lower expenditures on inpatient mental health services were significantly associated with higher REU. Positive relationships between gathering research evidence and racial minority concentration and poverty at the county level were also detected. Results underscore the need to identify the organizational and socio-political factors by which mental health services and resources meet client demands that influence REU, and to recruit and retain providers with a graduate degree to negotiate work demands and interpret research evidence.

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Online Information Searches and Help Seeking for Mental Health Problems in Urban China

Abstract

In recent years, the Internet has emerged as an alternative information source on mental health problems. Yet, the profile of the typical Internet help seeker is to be determined. Based on data from a household survey of 2558 Beijing residents, the study investigates online information searches and help seeking for mental health problems. Multinomial logistic regressions are estimated for respondents' access to the Internet, and mental-health-related information searches and help seeking on the Internet for the whole community sample and the most psychologically distressed subsample. The study identifies a digital divide in online help seeking for mental health issues based on age, migration and hukou status, and socio-economic factors. Youth and high socio-economic status are significant predictors of Internet access and use. Among the whole community sample, rural-to-urban migrants are less likely to have access to the Internet and search information or seek help online. Among the most psychologically distressed subsample, urban-to-urban migrants are significantly more likely to have access to the Internet and search information or seek help online. Given the shortage of mental health professionals in China, online information dissemination and guided self-help, if properly designed, could offer a means to reach large numbers of individuals in a cost-effective manner.

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Unpacking Clinical Supervision in Transitional and Permanent Supportive Housing: Scrutiny or Support?

Abstract

Behavioral health organizations use clinical supervision to ensure professional development and practice quality. This qualitative study examined 35 service coordinators' perspectives on supervision in two distinct supportive housing program types (permanent and transitional). Thematic analysis of in-depth interviews yielded three contrast themes: support versus scrutiny, planned versus impromptu time, and housing first versus treatment first. Supervisory content and format resulted in differential perceptions of supervision, thereby influencing opportunities for learning. These findings suggest that unpacking discrete elements of supervision enactment in usual care settings can inform implementation of recovery-oriented practice.

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Treatment Efficacy of Integrative Family and Systems Treatment (I-FAST) With and Without Consultation: The Role of Model Training in the Sustainability of Evidence-Based Family Treatments

Abstract

This study examined the efficacy of the Integrative Family and Systems Treatment (I-FAST) training model that seeks to support development of model expertise within the agency in the context of facilitating the sustainability of evidence-based family treatment within community mental health settings. A quasi-experimental design was used to examine treatment outcomes of I-FAST among agencies that received ongoing Consultation and agencies that received No Consultation upon completion of I-FAST training. χ ² analyses and independent samples t test analyses showed that there were no significant differences between the two groups on clients who had achieved reliable change on Problem Severity and Functioning based on parents' assessments. Significance of this study is discussed in the context of the role of evidence-based family therapy (EBFT) training in facilitating its sustainability in community mental health settings.

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The Healthy Immigrant Effect on Mental Health: Determinants and Implications for Mental Health Policy in Spain

Abstract

Since the mid-1990s, Spain has started to receive a great number of migrant populations. The migration process can have a significantly negative impact on mental health of immigrant population and, consequently, generate implications for the delivery of mental health services. The aim of this article is to provide empirical evidence to demonstrate that the mental health of immigrants in Spain deteriorates the longer they are resident in the country. An empirical approach to this relationship is carried out with data from the National Survey of Health of Spain 2011–2012 and poisson and negative binomial models. Results show that immigrants who reside <10 years in Spain appear to be in a better state of mental health than that observed for the national population. Studying health disparities in the foreign population and its evolution are relevant to ensure the population's access to health services and care. The need for further research is especially true in the case of the immigrant population's mental health in Spain because there is scant evidence available on their situation.

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Characteristics of Successful and Unsuccessful Mental Health Referrals of Refugees

Abstract

In this community based participatory research study, we explored key characteristics of mental health referrals of refugees using stories of providers collected through an on-line survey. Ten coders sorted 60 stories of successful referrals and 34 stories of unsuccessful referrals into domains using the critical incident technique. Principal components analysis yielded categories of successful referrals that included: active care coordination, establishing trust, proactive resolution of barriers, and culturally responsive care. Unsuccessful referrals were characterized by cultural barriers, lack of care coordination, refusal to see refugees, and system and language barriers. Recommendations for training and policy are discussed.

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Erratum to: Moderate and Vigorous Intensity Exercise During Pregnancy and Gestational Weight Gain in Women with Gestational Diabetes

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Spatiotemporal expression pattern of the zebrafish aquaporin 8 family during early developmental stages

Publication date: Available online 3 June 2016
Source:Gene Expression Patterns
Author(s): Soonil Koun, Jun-Dae Kim, Myungchull Rhee, Myoung-Jin Kim, Tae-Lin Huh
Aquaporin 8 (Aqp 8) is a transmembrane protein that is selectively permeated by water and some small solutes, and physiologically contributes to acid-base equilibrium in the gastrointestinal tract. Here, we described the characterization and spatiotemporal expression pattern of zebrafish aqp8 (zaqp8) gene family, including zaqp8a.1, zaqp8a.2, and zaqp8b, during the early developmental stages. The expression of zaqp8a.1 started first in the lateral plate mesoderm at the 12-somite stage (ss) and then expanded sequentially to the dorsal aorta, intersegmental blood vessels and then to the dorsal longitudinal anastomotic vessel at 24 h post fertilization (hpf). At 28 hpf, expression of zaqp8a.1 was also detected in the embryonic heart tube. Four days post fertilization (dpf), strong zaqp8a.1 expression was detected in the gastrointestinal tract and liver. By 72 hpf, the expression of zaqp8a.2 was first detected in the primitive gut region but not detected in the liver. The expression of zaqp8b was first detected in the intermediate mesoderm at 10 ss. From 24 hpf to 6 dpf, the proximal convoluted segment of the embryonic kidney was marked by zaqp8b expression Overall, these differential expression patterns of aqp8a.1, aqp8a.2, and aqp8b suggest that they possibly play distinct roles throughout the embryonic development by controlling or maintaining organ-specific cellular water homeostasis. Our study provides new evidence that organogenesis requires differential roles of Aqp8 proteins in zebrafish.



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The effects of accumulated muscle fatigue on the mechanomyographic waveform: implications for injury prediction

Abstract

Purpose

Muscle fatigue has been identified as a risk factor for spontaneous muscle injuries in sport. However, few studies have investigated the accumulated effects of muscle fatigue on human muscle contractile properties. This study aimed to determine whether repeated bouts of exercise inducing acute fatigue leads to longer-term fatigue-related changes in muscle contractile properties.

Methods

Maximum voluntary contraction (MVC), electromyographic (EMG) and mechanomyographic (MMG) measures were recorded in the biceps brachii of 11 participants for 13 days, before and after a maximally fatiguing exercise protocol. The exercise protocol involved participants repetitively lifting a weight (concentric contractions only) equal to 40 % MVC, until failure.

Results

A significant (p < 0.05) acute pre- to post-exercise decline of biceps brachii MVC and median power frequency (MPF) was observed each day, whilst no difference existed between pre-exercise MVC or MPF values on subsequent days (days 2–13). However, decreases in number of lift repetitions and in pre-exercise MMG values of muscle belly displacement, contraction velocity and half-relaxation velocity were observed through to day 13.

Conclusions

Whilst MVC and MPF measures resolved by the following day's test session, MMG measures indicated an ongoing decrement in muscle performance through days 2–13 consistent with the decline in lift repetitions observed. These results suggest that MMG may be more sensitive in detecting accumulated muscle fatigue than the 'gold standard' measures of MVC/MPF. Considering that muscle fatigue leads to injury, the on-going monitoring of MMG derived contractile properties of muscles in athletes may aid in the prediction of fatigued-induced muscle injury.

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Forearm muscle oxidative capacity index predicts sport rock-climbing performance

Abstract

Rock-climbing performance is largely dependent on the endurance of the forearm flexors. Recently, it was reported that forearm flexor endurance in elite climbers is independent of the ability to regulate conduit artery (brachial) blood flow, suggesting that endurance is not primarily dependent on the ability of the brachial artery to deliver oxygen, but rather the ability of the muscle to perfuse and use oxygen, i.e., skeletal muscle oxidative capacity.

Purpose

The aim of the study was to determine whether an index of oxidative capacity in the flexor digitorum profundus (FDP) predicts the best sport climbing red-point grade within the last 6 months. Participants consisted of 46 sport climbers with a range of abilities.

Methods

Using near-infrared spectroscopy, the oxidative capacity index of the FDP was assessed by calculating the half-time for tissue oxygen resaturation (O₂HTR) following 3–5 min of ischemia.

Results

Linear regression, adjusted for age, sex, BMI, and training experience, revealed a 1-s decrease in O₂HTR was associated with an increase in red-point grade by 0.65 (95 % CI 0.35–0.94, Adj R ²  = 0.53).

Conclusions

Considering a grade of 0.4 separated the top four competitors in the 2015 International Federation Sport Climbing World Cup, this finding suggests that forearm flexor oxidative capacity index is an important determinant of rock-climbing performance.

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Modulation of Brain Criticality via Suppression of EEG Long-Range Temporal Correlations (LRTC) in a Closed-Loop Neurofeedback Stimulation

Publication date: Available online 3 June 2016
Source:Clinical Neurophysiology
Author(s): Stavros I. Dimitriadis, David Linden




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Intrauterine exposition to smoking and autonomic nervous system function during sleep

Publication date: Available online 3 June 2016
Source:Clinical Neurophysiology
Author(s): Magda Lahorgue Nunes




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Long-term Effectiveness of Intensive Therapy in Chronic Stroke

Background. While recent clinical trials involving robot-assisted therapy have failed to show clinically significant improvement versus conventional therapy, it is possible that a broader strategy of intensive therapy—to include robot-assisted rehabilitation—may yield clinically meaningful outcomes. Objective. To test the immediate and sustained effects of intensive therapy (robot-assisted therapy plus intensive conventional therapy) on outcomes in a chronic stroke population. Methods. A multivariate mixed-effects model adjusted for important covariates was established to measure the effect of intensive therapy versus usual care. A total of 127 chronic stroke patients from 4 Veterans Affairs medical centers were randomized to either robot-assisted therapy (n = 49), intensive comparison therapy (n = 50), or usual care (n = 28), in the VA-ROBOTICS randomized clinical trial. Patients were at least 6 months poststroke, of moderate-to-severe upper limb impairment. The primary outcome measure was the Fugl-Meyer Assessment at 12 and 36 weeks. Results. There was significant benefit of intensive therapy over usual care on the Fugl-Meyer Assessment at 12 weeks with a mean difference of 4.0 points (95% CI = 1.3-6.7); P = .005; however, by 36 weeks, the benefit was attenuated (mean difference 3.4; 95% CI = –0.02 to 6.9; P = .05). Subgroup analyses showed significant interactions between treatment and age, treatment and time since stroke. Conclusions. Motor benefits from intensive therapy compared with usual care were observed at 12 and 36 weeks posttherapy; however, this difference was attenuated at 36 weeks. Subgroups analysis showed that younger age, and a shorter time since stroke were associated with greater immediate and long-term improvement of motor function.

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Effects of Exercise on Falls, Balance, and Gait Ability in Parkinsons Disease: A Meta-analysis

Postural instability and falls are complex and disabling features of Parkinson's disease (PD) and respond poorly to anti-Parkinsonian medication. There is an imperative need to evaluate the effectiveness of exercise interventions in enhancing postural stability and decreasing falls in the PD population. The objectives of our study were to determine the effects of exercise training on the enhancement of balance and gait ability and reduction in falls for people with PD and to investigate potential factors contributing to the training effects on balance and gait ability of people with PD. We included 25 randomized control trials of a moderate methodological quality in our meta-analysis. The trials examined the effects of exercise training on balance and gait ability and falls against no intervention and placebo intervention. The results showed positive effects of exercise intervention on enhancing balance and gait performance (Hedges' g = 0.303 over the short-term in 24 studies and 0.419 over the long-term in 12 studies; P < .05) and reducing the fall rate (rate ratio = 0.485 over the short-term in 4 studies and 0.413 over the long-term in 5 studies; P < .05). The longest follow-up duration was 12 months. There was no evidence that training decreased the number of fallers over the short- or long-term (P > .05). The results of our metaregression and subgroup analysis showed that facility-based training produced greater training effects on improving PD participants' balance and gait ability (P < .05). The findings support the application of exercise training to improve balance and gait ability and prevent falls in people with PD.

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Influence of Spinal Cord Integrity on Gait Control in Human Spinal Cord Injury

Background. Clinical trials in spinal cord injury (SCI) primarily rely on simplified outcome metrics (ie, speed, distance) to obtain a global surrogate for the complex alterations of gait control. However, these assessments lack sufficient sensitivity to identify specific patterns of underlying impairment and to target more specific treatment interventions. Objective. To disentangle the differential control of gait patterns following SCI beyond measures of time and distance. Methods. The gait of 22 individuals with motor-incomplete SCI and 21 healthy controls was assessed using a high-resolution 3-dimensional motion tracking system and complemented by clinical and electrophysiological evaluations applying unbiased multivariate analysis. Results. Motor-incomplete SCI patients showed varying degrees of spinal cord integrity (spinal conductivity) with severe limitations in walking speed and altered gait patterns. Principal component (PC) analysis applied on all the collected data uncovered robust coherence between parameters related to walking speed, distortion of intralimb coordination, and spinal cord integrity, explaining 45% of outcome variance (PC 1). Distinct from the first PC, the modulation of gait-cycle variables (step length, gait-cycle phases, cadence; PC 2) remained normal with respect to regained walking speed, whereas hip and knee ranges of motion were distinctly altered with respect to walking speed (PC 3). Conclusions. In motor-incomplete SCI, distinct clusters of discretely controlled gait parameters can be discerned that refine the evaluation of gait impairment beyond outcomes of walking speed and distance. These findings are specifically different from that in other neurological disorders (stroke, Parkinson) and are more discrete at targeting and disentangling the complex effects of interventions to improve walking outcome following motor-incomplete SCI.

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Responsiveness of the Neuromuscular Recovery Scale During Outpatient Activity-Dependent Rehabilitation for Spinal Cord Injury

Background. The Neuromuscular Recovery Scale (NRS) was developed by researchers and clinicians to functionally classify people with spinal cord injury (SCI) by measuring functionally relevant motor tasks without compensation. Previous studies established strong interrater and test-retest reliability and validity of the scale. Objective. To determine responsiveness of the NRS, a version including newly added upper-extremity items, in an outpatient rehabilitation setting. Methods. Assessments using the NRS and 6 other instruments were conducted at enrollment and discharge from a locomotor training program for 72 outpatients with SCI classified as American Spinal Injury Association Impairment Scale grades A to D (International Standards for Neurological Classification of Spinal Cord Injury). Mixed-model t statistics for instruments were calculated and adjusted for confounding factors (eg, sample size, demographic variables) for all patients and subgroups stratified by injury level and/or severity. The resulting adjusted response means (ARMs) and 95% confidence intervals (CIs) were used to determine responsiveness, and significant differences between instruments were identified with pairwise comparisons. Results. The NRS was significantly responsive for SCI outpatients (ARM = 1.05; CI = 0.75-1.35). Changes in motor function were detected across heterogeneous groups. Regardless of injury level or severity, the responsiveness of the NRS was equal to, and often significantly exceeded, the responsiveness of other instruments. Conclusions. The NRS is a responsive measure that detects change in motor function during outpatient neurorehabilitation for SCI. There is potential utility for its application in randomized controlled trials and as a measure of clinical recovery across diverse SCI populations.

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Exercise Training and Cognitive Rehabilitation: A Symbiotic Approach for Rehabilitating Walking and Cognitive Functions in Multiple Sclerosis?

The current review develops a rationale and framework for examining the independent and combined effects of exercise training and cognitive rehabilitation on walking and cognitive functions in persons with multiple sclerosis (MS). To do so, we first review evidence for improvements in walking and cognitive outcomes with exercise training and cognitive rehabilitation in MS. We then review evidence regarding cognitive–motor coupling and possible cross-modality transfer effects of exercise training and cognitive rehabilitation. We lastly present a macro-level framework for considering mechanisms that might explain improvements in walking and cognitive dysfunction with exercise and cognitive rehabilitation individually and combined in MS. We conclude that researchers should consider examining the effects of exercise training and cognitive rehabilitation on walking, cognition, and cognitive–motor interactions in MS and the possible physiological and central mechanisms for improving these functions.

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An RCT to Treat Learning Impairment in Traumatic Brain Injury: The TBI-MEM Trial

Objective. To examine the efficacy of the modified Story Memory Technique (mSMT) to improve learning (ie, acquisition) and memory in participants with TBI. The mSMT is a behavioral intervention that teaches context and imagery to facilitate learning within 10 sessions over 5 weeks. Methods. A total of 69 participants with moderate-severe Traumatic Brain Injury (TBI), 35 in the treatment group and 34 in the placebo control group, completed this double-blind, placebo-controlled randomized clinical trial. A baseline neuropsychological assessment was administered, including questionnaires assessing everyday memory. Repeat assessments were conducted immediately posttreatment and 6 months following treatment. Participants in the treatment group were randomly assigned to a booster session or a non–booster session group after completion of treatment with the mSMT to examine the efficacy of monthly booster sessions in facilitating the treatment effect over time. Results. The treatment group demonstrated significant improvement on a prose memory task relative to the placebo group posttreatment (² = 0.064 medium effect). Similar results were noted on objective measures of everyday memory, specifically prospective memory (Cohen's w = 0.43, medium effect), and family report of disinhibition in daily life (² = 0.046, medium effect). Conclusion. The mSMT is effective for improving learning and memory in TBI. Classification of evidence. Based on widely accepted classification systems for treatment study design, this study provides class I evidence that the mSMT behavioral intervention improves both objective memory and everyday memory in persons with TBI over 5 weeks. Thus, this study extends the evidence for efficacy of the treatment protocol to a sample of persons with TBI.

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Enhanced Neurobehavioral Outcomes of Action Observation Prosthesis Training

Background. Previous studies have demonstrated improved neurobehavioral outcomes when prosthesis users learn task-specific behaviors by imitating movements of prosthesis users (matched limb) compared with intact limbs (mismatched limb). Objective. This study is the first to use a unique combination of neurophysiological and task performance methods to investigate prosthetic device training strategies from a cognitive motor control perspective. Intact nonamputated prosthesis users (NAPUs) donned specially adapted prosthetic devices to simulate the wrist and forearm movement that persons with transradial limb loss experience. The hypothesis is that NAPUs trained with matched limb imitation would show greater engagement of parietofrontal regions and reduced movement variability compared with their counterparts trained with a mismatched limb. Methods. Training elapsed over 3 days comprised alternating periods of video demonstration observation followed by action imitation. At the beginning and end of the training protocol, participants performed a cued movement paradigm while electroencephalography and electrogoniometry data were collected to track changes in cortical activity and movement variability, respectively. Results. Matched limb participants showed greater engagement of motor-related areas while mismatched limb participants showed greater engagement of the parietooccipital system. Matched limb participants also showed lower movement variability. Conclusions. These results indicate that the type of limb imitated influences neural and behavioral strategies for novel prosthetic device usage. This finding is important, as customary prosthetic rehabilitation with intact therapists involves mismatched limb imitation that may exacerbate challenges in adapting to new motor patterns demanded by prosthesis use.

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Short-Duration and Intensive Training Improves Long-Term Reaching Performance in Individuals With Chronic Stroke

Previous studies have shown that multiple sessions of reach training lead to long-term improvements in movement time and smoothness in individuals post-stroke. Yet such long-term training regimens are often difficult to implement in actual clinical settings. In this study, we evaluated the long-term and generalization effects of short-duration and intensive reach training in 16 individuals with chronic stroke and mild to moderate impairments. Participants performed 2 sessions of unassisted intensive reach training, with 600 movements per session, and with display of performance-based feedback after each movement. The participants' trunks were restrained with a belt to avoid compensatory movements. Training resulted in significant and durable (1 month) improvements in movement time (20.4% on average) and movement smoothness (22.7% on average). The largest improvements occurred in individuals with the largest initial motor impairments. In addition, training induced generalization to nontrained targets, which persisted in 1-day and in 1-month retention tests. Finally, there was a significant improvement in the Box and Block test from baseline to 1-month retention test (23% on average). Thus, short-duration and intensive reach training can lead to generalized and durable benefits in individuals with chronic stroke and mild to moderate impairments.

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Prefrontal Cortex Activation While Walking Under Dual-Task Conditions in Stroke: A Multimodal Imaging Study

Background. Walking while performing another task (eg, talking) is challenging for many stroke survivors, yet its neural basis are not fully understood. Objective. To investigate prefrontal cortex activation and its relationship to gait measures while walking under single-task (ST) and dual-task (DT) conditions (ie, walking while simultaneously performing a cognitive task) in stroke survivors. Methods. We acquired near-infrared spectroscopy (NIRS) data from the prefrontal cortex during treadmill walking in ST and DT conditions in chronic stroke survivors and healthy controls. We also acquired functional magnetic resonance imaging (fMRI) and NIRS during simulated walking under these conditions. Results. NIRS revealed increased oxygenated hemoglobin concentration in DT-walking compared with ST-walking for both groups. For simulated walking, NIRS showed a significant effect of group and group x task, being greater on both occasions, in stroke survivors. A greater increase in brain activation observed from ST to DT walking/ simulated walking was related to a greater change in motor performance in stroke survivors. fMRI revealed increased activity during DT relative to ST conditions in stroke patients in areas including the inferior temporal gyri, superior frontal gyri and cingulate gyri bilaterally, and the right precentral gyrus. The DT-related increase in fMRI activity correlated with DT-related change in behavior in stroke participants in the bilateral inferior temporal gyrus, left cingulate gyrus, and left frontal pole. Conclusion. Our results provide novel evidence that enhanced brain activity changes relate to dual task motor decrements.

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Inpatient walking activity to predict readmission in older adults

Publication date: Available online 2 June 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Steve R. Fisher, James E. Graham, Kenneth J. Ottenbacher, Rachel Deer, Glenn V. Ostir
ObjectiveTo compare the 30-day readmission predictive power of in-hospital walking activity and in-hospital activities of daily living (ADL) in older acutely ill patients. In addition, we sought to identify preliminary walking thresholds that could support the targeting of interventions aimed at minimizing rehospitalizations.DesignProspective, observational clinical cohort study. Step counts during hospitalization were assessed via accelerometry. ADL function was assessed within 48 hours of admission.SettingAcute care hospital.ParticipantsOne hundred and sixty-four ambulatory persons aged 65 and older admitted to the hospital from the community with an acute medical illness.InterventionNA.Main Outcome MeasuresReadmission back to the index hospital (yes vs. no) within 30 days of discharge.ResultsTwenty-six patients (15.8%) were readmitted within 30 days of discharge. Walking activity during hospitalization was more strongly and significantly associated with 30-day readmission (OR: 0.90; CI: 0.82-0.98) than ADL function (OR: 0.45; CI: 0.14-1.45) after adjusting for relevant readmission risk factors. The predictive accuracy (area under the curve) was highest for models that included walking activity and changed little with the addition of ADLs. A walking threshold of 275 steps or more per day identified patients at reduced 30-day readmission risk.ConclusionWalking activity was a stronger predictor of readmission than ADLs. Monitoring patient activity during hospitalization may provide clinicians with valuable information on early readmission risk not captured by measures of ADLs. Further study is needed to replicate these findings and monitor walking activity post hospitalization to further advance our understanding of readmission risk.



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Cerebral oxidative metabolism is decreased with extreme apnea in humans; impact of hypercapnia

Abstract

Prolonged apnea in humans is reflected in progressive hypoxemia and hypercapnia. Here, we explore the cerebral metabolic responses under extreme hypoxia and hypercapnia associated with prolonged apnea. We hypothesized that the cerebral metabolic rate for oxygen (CMRO₂) will be reduced near the termination of apnea, attributed in part to the hypercapnia. Fourteen elite apnea-divers performed a maximal apnea (range: 3:36 to 7:26 min) under dry laboratory-conditions. In a subset study with the same divers, the impact of hypercapnia on cerebral metabolism was determined using varying levels of hypercapnic breathing, in the background of similar hypoxia. In both studies the CMRO₂ was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-internal jugular venous oxygen content difference. Non-oxidative cerebral metabolism was calculated from the ratio of oxygen and carbohydrate (lactate and glucose) metabolism. The CMRO₂ was reduced by ∼29% (P < 0.01, Cohen's d = 1.18) near the termination of apnea when compared to baseline, but non-oxidative metabolism remained unaltered. In the subset study, in similar backgrounds of hypoxia (arterial O₂ tension: ∼38.4 mmHg), severe hypercapnia (arterial CO₂ tension: ∼58.7 mmHg), but not mild-hypercapnia (arterial CO₂ tension: ∼46.3 mmHg), depressed the CMRO₂ (∼17%, P = 0.04, Cohen's d = 0.87). Similarly to the apnea, there was no change in the non-oxidative metabolism. These data indicate that hypercapnia can in part explain the reduction in CMRO₂ near apnea breakpoint. This hypercapnic-induced oxygen conservation may protect the brain against severe hypoxemia associated with prolonged apnea.

This article is protected by copyright. All rights reserved

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A novel set-up for the ex vivo analysis of mechanical properties of mouse aortic segments stretched at physiological pressure and frequency

Abstract

Cyclic stretch is a major contributor of vascular function. However, isolated mouse aortas are frequently studied at low stretch frequency or even isometric conditions. Pacing experiments in rodents and humans show that arterial compliance is stretch frequency-dependent. The Rodent Oscillatory Tension Set-up to study Arterial Compliance is an in-house developed organ bath set-up that clamps aortic segments to imposed preloads at physiological rates up to 600 bpm. The technique enables us to derive pressure-diameter loops and assess biomechanical properties of the segment. To validate the applicability of this set-up we aimed to confirm the effects of distension pressure and vascular smooth muscle tone on arterial stiffness. At physiological stretch frequency (10 Hz), Peterson modulus (293 (10) mmHg) for wild-type mouse aorta increased 22% upon a rise in pressure from 80–120 mmHg to 100–140 mmHg, while, at normal pressure, Ep increased 80% upon maximal contraction of the vascular smooth muscle cells. We further validated the method using a mouse model with a mutation in the Fibrillin-1 gene and an endothelial nitric oxide synthase knock-out model. Both models are known to have increased arterial stiffness, and this was confirmed using the set-up. To our knowledge, this is the first set-up that facilitates the study of biomechanical properties of mouse aortic segments at physiological stretch frequency and pressure. We believe that this set-up can contribute to a better understanding of how cyclic stretch frequency, amplitude and active vessel wall components influence arterial stiffening.

This article is protected by copyright. All rights reserved

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IOP-details

Publication date: July 2016
Source:International Journal of Psychophysiology, Volume 105





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Editorial Board

Publication date: July 2016
Source:International Journal of Psychophysiology, Volume 105





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Instructions to Authors

Publication date: July 2016
Source:International Journal of Psychophysiology, Volume 105





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Genetic influences on phase synchrony of brain oscillations supporting response inhibition

Publication date: Available online 2 June 2016
Source:International Journal of Psychophysiology
Author(s): Viktor Müller, Andrey P. Anokhin, Ulman Lindenberger
Phase synchronization of neuronal oscillations is a fundamental mechanism underlying cognitive processing and behavior, including context-dependent response production and inhibition. Abnormalities in neural synchrony can lead to abnormal information processing and contribute to cognitive and behavioral deficits in neuropsychiatric disorders. However, little is known about genetic and environmental contributions to individual differences in cortical oscillatory dynamics underlying response inhibition. This study examined heritability of event-related phase synchronization of brain oscillations in 302 young female twins including 94 MZ and 57 DZ pairs performing a cued Go/No-Go version of the Continuous Performance Test (CPT). We used the Phase Locking Index (PLI) to assess inter-trial phase clustering (synchrony) in several frequency bands in two time intervals after stimulus onset (0–300 and 301–600ms). Response inhibition (i.e., successful response suppression in No-Go trials) was characterized by a transient increase in phase synchronization of delta- and theta-band oscillations in the fronto-central midline region. Genetic analysis showed significant heritability of the phase locking measures related to response inhibition, with 30 to 49% of inter-individual variability being accounted for by genetic factors. This is the first study providing evidence for heritability of task-related neural synchrony. The present results suggest that PLI can serve as an indicator of genetically transmitted individual differences in neural substrates of response inhibition.



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International Organization of Psychophysiology - Details

Publication date: June 2016
Source:International Journal of Psychophysiology, Volume 104





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Editorial Board

Publication date: June 2016
Source:International Journal of Psychophysiology, Volume 104





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Instructions ot Authors

Publication date: June 2016
Source:International Journal of Psychophysiology, Volume 104





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The homozygous R504C mutation in MTO1 gene is responsible for ONCE syndrome

Abstract

We report clinical and biochemical finding from three unrelated patients presenting ONCE (Optic Neuropathy, Cardiomyopathy and Encephalopathy with lactic acidosis and combined OXPHOS deficiency) syndrome. Whole-exome sequencing (WES) of the three patients and the healthy sister of one of them were used to identify the carry gene. Clinical and biochemical findings were used to filter variants, and molecular, in silico and genetic studies were performed to characterize the candidate variants. Mitochondrial DNA (mtDNA) defects involving mutations, deletions or depletion were discarded, whereas WES uncovered a double homozygous mutation in the MTO1 gene (NM_001123226:c.1510C>T, p.R504C, and c.1669G>A, p.V557M) in two of the patients and the homozygous mutation p.R504C in the other. Therefore, our data confirm p.R504C as pathogenic mutation responsible of ONCE syndrome, and p.V557M as a rare polymorphic variant.

The R504C mutation in MTO1 gene is the responsible of ONCE syndrome (Optic Neuropathy, Cardiomyopathy and Encephalopathy with lactic acidosis and combined OXPHOS deficiency) and V557M is a rare polymorphic variant

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Analysis of CCM1 expression uncovers novel minor-form exons and variable splicing patterns

Abstract

Cerebral cavernous malformations (CCM) are vascular lesions, which occur sporadically or following an autosomal dominant inheritance pattern with variable expression and incomplete penetrance. Three genes have been associated with the disease (CCM1, CCM2 and CCM3). CCM1 has been reported to express atypical transcripts in addition to alternative splicing of non-coding exons. Here, we report the identification of novel alternative splicing events in the CCM1 gene. 5′RACE analysis revealed several transcription start sites, novel exons located in introns 2 and 7, and a larger exon 13. The 5′UTR CCM1 region showed at least eight splicing variants which were differentially transcribed. The results shown here expand our knowledge of CCM1 gene expression, which seems to be more complex than previously reported. The novel minor-form exons herein described should be considered in molecular diagnosis of CCM. These findings support new functional transcript sequences that could be considered in the pathogenesis and variable clinical penetrance of Krit1-linked CCMs.

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