A multimodal perspective on the composition of cortical oscillations.

An expanding corpus of research details the relationship between functional magnetic resonance imaging (fMRI) measures and neuronal network oscillations. Typically, integrated electroencephalography and fMRI, or parallel magnetoencephalography (MEG) and fMRI are used to draw inference about the consanguinity of BOLD and electrical measurements. However, there is a relative dearth of information about the relationship between E/MEG and the focal networks from which these signals emanate. Consequently, the genesis and composition of E/MEG oscillations requires further clarification. Here we aim to contribute to understanding through a series of parallel measurements of primary motor cortex (M1) oscillations, using human MEG and in vitro rodent local field potentials. We compare spontaneous activity in the ∼10 Hz mu and 15-30 Hz beta frequency ranges and compare MEG signals with independent and integrated layers III and V (LIII/LV) from in vitro recordings. We explore the mechanisms of oscillatory generation, using specific pharmacological modulation with the GABA-A alpha-1 subunit modulator zolpidem. Finally, to determine the contribution of cortico-cortical connectivity, we recorded in vitro M1, during an incision to sever lateral connections between M1 and S1 cortices. We demonstrate that frequency distribution of MEG signals appear have closer statistically similarity with signals from integrated rather than independent LIII/LV laminae. GABAergic modulation in both modalities elicited comparable changes in the power of the beta band. Finally, cortico-cortical connectivity in sensorimotor cortex (SMC) appears to directly influence the power of the mu rhythm in LIII. These findings suggest that the MEG signal is an amalgam of outputs from LIII and LV, that multiple frequencies can arise from the same cortical area and that in vitro and MEG M1 oscillations are driven by comparable mechanisms. Finally, cortico-cortical connectivity is reflected in the power of the SMC mu rhythm

Pyridyl disulfide reaction chemistry : an efficient strategy toward redox-responsive cyclic peptide–polymer conjugates

Cyclic peptide–polymer conjugates are capable of self-assembling into supramolecular polymeric nanotubes driven by the strong multiple hydrogen bonding interactions between the cyclic peptides. In this study, we have engineered responsive nanotubes by introducing a cleavable bond that responds to a reductant utilizing pyridyl disulfide reaction chemistry. Reactions between a cysteine containing cyclic peptide (CP-SH) and pyridyl disulfide containing polymers were initially studied, leading to the quantitative formation of cyclic peptide–polymer conjugates. An asymmetric cyclic peptide–polymer conjugate (PEG-CP-S-S-pPEGA) was then synthesized via orthogonal pyridyl disulfide reaction chemistry and NHS coupling chemistry. The disulfide linker formed by the pyridyl disulfide reaction chemistry was then selectively reduced to thiols in the presence of a reductant, enabling the transition of the conjugates from nonassembling unimers to self-assembled supramolecular polymeric nanotubes. It is anticipated that the pyridyl disulfide reaction chemistry will not only enrich the methodology toward the synthesis of cyclic peptide–polymer conjugates, but also lead to the construction of a new family of redox-responsive cyclic peptide–polymer conjugates and supramolecular polymeric nanotubes with tailored structures and functionalities

Suicide Screening in Primary Care: Use of an Electronic Screener to Assess Suicidality and Improve Provider Follow-Up for Adolescents

Purpose The purpose of this study was to assess the feasibility of using an existing computer decision support system to screen adolescent patients for suicidality and provide follow-up guidance to clinicians in a primary care setting. Predictors of patient endorsement of suicidality and provider documentation of follow-up were examined. Methods A prospective cohort study was conducted to examine the implementation of a CDSS that screened adolescent patients for suicidality and provided follow-up recommendations to providers. The intervention was implemented for patients aged 12–20 years in two primary care clinics in Indianapolis, Indiana. Results The sample included 2,134 adolescent patients (51% female; 60% black; mean age = 14.6 years [standard deviation = 2.1]). Just over 6% of patients screened positive for suicidality. A positive endorsement of suicidality was more common among patients who were female, depressed, and seen by an adolescent−medicine board-certified provider as opposed to general pediatric provider. Providers documented follow-up action for 83% of patients who screened positive for suicidality. Documentation of follow-up action was correlated with clinic site and Hispanic race. The majority of patients who endorsed suicidality (71%) were deemed not actively suicidal after assessment by their provider. Conclusions Incorporating adolescent suicide screening and provider follow-up guidance into an existing computer decision support system in primary care is feasible and well utilized by providers. Female gender and depressive symptoms are consistently associated with suicidality among adolescents, although not all suicidal adolescents are depressed. Universal use of a multi-item suicide screener that assesses recency might more effectively identify suicidal adolescents

A multimodal perspective on the composition of cortical oscillations:frontiers in human neuroscience

An expanding corpus of research details the relationship between functional magnetic resonance imaging (fMRI) measures and neuronal network oscillations. Typically, integratedelectroencephalography(EEG) and fMRI,orparallel magnetoencephalography (MEG) and fMRI are used to draw inference about the consanguinity of BOLD and electrical measurements. However, there is a relative dearth of information about the relationship between E/MEG and the focal networks from which these signals emanate. Consequently, the genesis and composition of E/MEG oscillations requires further clarification. Here we aim to contribute to understanding through a series of parallel measurements of primary motor cortex (M1) oscillations, using human MEG and in-vitro rodent local field potentials. We compare spontaneous activity in the ~10Hz mu and 15-30Hz beta frequency ranges and compare MEG signals with independent and integrated layers III and V(LIII/LV) from in vitro recordings. We explore the mechanisms of oscillatory generation, using specific pharmacological modulation with the GABA-A alpha-1 subunit modulator zolpidem. Finally, to determine the contribution of cortico-cortical connectivity, we recorded in-vitro M1, during an incision to sever lateral connections between M1 and S1 cortices. We demonstrate that frequency distribution of MEG signals appear have closer statistically similarity with signals from integrated rather than independent LIII/LV laminae. GABAergic modulation in both modalities elicited comparable changes in the power of the beta band. Finally, cortico-cortical connectivity in sensorimotor cortex (SMC) appears to directly influence the power of the mu rhythm in LIII. These findings suggest that the MEG signal is an amalgam of outputs from LIII and LV, that multiple frequencies can arise from the same cortical area and that in vitro and MEG M1 oscillations are driven by comparable mechanisms. Finally, corticocortical connectivity is reflected in the power of the SMC mu rhythm. © 2013 Ronnqvist, Mcallister, Woodhall, Stanford and Hall

Bradykinesia Is Driven by Cumulative Beta Power During Continuous Movement and Alleviated by Gabaergic Modulation in Parkinson's Disease

Spontaneous and "event-related" motor cortex oscillations in the beta (15-30 Hz) frequency range are well-established phenomena. However, the precise functional significance of these features is uncertain. An understanding of the specific function is of importance for the treatment of Parkinson's disease (PD), where attenuation of augmented beta throughout the motor network coincides with functional improvement. Previous research using a discrete movement task identified normalization of elevated spontaneous beta and postmovement beta rebound following GABAergic modulation. Here, we explore the effects of the gamma-aminobutyric acid type A modulator, zolpidem, on beta power during the performance of serial movement in 17 (15M, 2F; mean age, 66 ± 6.3 years) PD patients, using a repeated-measures, double-blinded, randomized, placebo-control design. Motor symptoms were monitored before and after treatment, using time-based Unified Parkinson's Disease Rating Scale measurements and beta oscillations in primary motor cortex (M1) were measured during a serial-movement task, using magnetoencephalography. We demonstrate that a cumulative increase in M1 beta power during a 10-s tapping trial is reduced following zolpidem, but not placebo, which is accompanied by an improvement in movement speed and efficacy. This work provides a clear mechanism for the generation of abnormally elevated beta power in PD and demonstrates that perimovement beta accumulation drives the slowing, and impaired initiation, of movement. These findings further indicate a role for GABAergic modulation in bradykinesia in PD, which merits further exploration as a therapeutic target.Peer reviewe

Oscillatory beta activity mediates neuroplastic effects of motor cortex stimulation in humans

Continuous theta burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation protocol that can inhibithumanmotor cortex (M1) excitability and impair movement for ≤1 h. While offering valuable insights into brain function and potential therapeutic benefits, these neuroplastic effects are highly variable between individuals. The source of this variability, and the electrophysiological mechanisms underlying the inhibitory after-effects, are largely unknown. In this regard, oscillatory activity at beta frequency (15-35 Hz) is of particular interest as it is elevated in motor disorders such as Parkinson's disease and modulated during the generation of movements. Here, we used a source-level magnetoencephalography approach to investigate the hypothesis that the presence of neuroplastic effects following cTBS is associated with concurrent changes in oscillatory M1 beta activity. M1 cortices were localized with a synthetic aperture magnetometry beamforming analysis of visually cued index finger movements. Virtual electrode analysis was used to reconstruct the spontaneous and movement-related oscillatory activity in bilateral M1 cortices, before and from 10 to 45 min after cTBS. We demonstrate that 40 s of cTBS applied over left M1 reduced corticospinal excitability in the right index finger of 8/16 participants. In these responder participants only, cTBS increased the power of the spontaneous beta oscillations in stimulated M1 and delayed reaction times in the contralateral index finger. No further changes were observed in the latency or power of movement-related beta oscillations. These data provide insights into the electrophysiological mechanisms underlying cTBS-mediated impairment of motor function and demonstrate the association between spontaneous oscillatory beta activity in M1 and the inhibition of motor function. © 2013 the authors

Leakage Current Mechanisms in SiGe HBTs Fabricated Using Selective and Nonselective Epitaxy

SiGe heterojunction bipolar transistors (HTBs) have been fabricated using selective epitaxy for the Si collector, followed in the same growth step by nonselective epitaxy for the p+ SiGe base and n-Si emitter cap. DC electrical characteristics are compared with cross-section TEM images to identify the mechanisms and origins of leakage currents associated with the epitaxy in two different types of transistor . In the first type, the polysilicon emitter is smaller than the collector active area, so that the extrinsic base implant penetrates into the single-crystal Si and SiGe around the perimeter of the emitter and the polycrystalline Si and SiGe exrtrinsic base. In these transistors, the Bummel plots are near-ideal and there is no evidence of emitter/collector leakage. In the second type, the collector active area is smaller than the polysilicon emitter, so the extrinsic base implant only penetrates into the polysilicon extrinsic base. In these transistors, the leakage currents observed depend on the base doping level. In transistors with a low doped base, emitter/collector and emitter/base leakage is observed, whereas in transistors with a high doped base only emitter/base leakage is observed. The emitter/collector leakage is explained by punch through o fhte base caused by thinning of the SiGe base at the emitter perimeter. The emitter/base leakeage is shown to be due to Poole-Frenkel mechanism and is explained by penetration of the emitter/base depletion region into the p+ polysilicon extrinsic base at the emitter periphery. Variable collector/base reverse leakage currents are observed and a variety of mechanisms are observed, including Shockley-Read-Hall recombination, trap assisted tunneling, Poole Frenkel and band to band tunneling. These result s are explained by the presence of polysilicon grains on the sidewalls of the field oxide at the collector perimeter

Are working memory and glutamate concentrations involved in early-life stress and severity of psychosis?

Objective Occurrences of early‐life stress (ELS) are associated with the severity of psychotic symptoms and working memory (WM) deficits in patients with psychosis (PSY). This study investigated potential mediation roles of WM behavioral performance and glutamate concentrations in prefrontal brain regions on the association between ELS and psychotic symptom severity in PSY. Method Forty‐seven patients with PSY (established schizophrenia, n = 30; bipolar disorder, n = 17) completed measures of psychotic symptom severity. In addition, data on ELS and WM performance were collected in both patients with PSY and healthy controls (HC; n = 41). Resting‐state glutamate concentrations in the bilateral dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) were also assessed with proton magnetic resonance spectroscopy for both PSY and HC groups. t tests, analyses of variance, and regression analyses were utilized. Results Participants with PSY reported significantly more ELS occurrences and showed poorer WM performance than HC. Furthermore, individuals with PSY displayed lower glutamate concentrations in the left DLPFC than HC. Neither ELS nor WM performance were predictive of severity of psychotic symptoms in participants with PSY. However, we found a significant negative correlation between glutamate concentrations in the left DLPFC and ELS occurrence in HC only. Conclusion In individuals with PSY, the current study found no evidence that the association between ELS and psychotic symptoms is mediated by WM performance or prefrontal glutamate concentrations. In HC, the association between ELS experience and glutamate concentrations may indicate a neurometabolite effect of ELS that is independent of an illness effect in psychosis

Collaboration between Science and Religious Education teachers in Scottish Secondary schools

The article reports on quantitative research that examines: (1) the current practice in collaboration; and (2) potential for collaboration between Science and Religious Education teachers in a large sample of Scottish secondary schools. The authors adopt and adapt three models (conflict; concordat and consonance) to interrogate the relationship between science and religion (and the perceived relation between these two subjects in schools) (Astley and Francis 2010). The findings indicate that there is evidence of limited collaboration and, in a few cases, a dismissive attitude towards collaboration (conflict and concordat and very weak consonance). There is, however, evidence of a genuine aspiration for greater collaboration among many teachers (moving towards a more robust consonance model). The article concludes by discussing a number of key factors that must be realised for this greater collaboration to be enacted

On Hirschman and log-Sobolev inequalities in mu-deformed Segal-Bargmann analysis

We consider a deformation of Segal-Bargmann space and its transform. We study L^p properties of this transform and obtain entropy-entropy inequalities (Hirschman) and entropy-energy inequalities (log-Sobolev) that generalize the corresponding known results in the undeformed theory.Comment: 42 pages, 3 figure