共查询到20条相似文献，搜索用时 31 毫秒
1.
Marta Zamarbide Adele Mossa Pablo Muñoz-Llancao Molly K. Wilkinson Heather L. Pond Adam W. Oaks M. Chiara Manzini 《Neuropsychopharmacology》2019,85(9):760-768
Background
The prevalence of neurodevelopmental disorders is biased toward male individuals, with male-to-female ratios of 2:1 in intellectual disability and 4:1 in autism spectrum disorder. However, the molecular mechanisms of such bias remain unknown. While characterizing a mouse model for loss of the signaling scaffold coiled-coil and C2 domain-containing protein 1A (CC2D1A), which is mutated in intellectual disability and autism spectrum disorder, we identified biochemical and behavioral differences between male and female mice, and explored whether CC2D1A controls male-specific intracellular signaling.Methods
CC2D1A is known to regulate phosphodiesterase 4D (PDE4D), which regulates cyclic adenosine monophosphate (cAMP) signaling. We tested for activation of PDE4D and downstream signaling molecules in the hippocampus of Cc2d1a-deficient mice. We then performed behavioral studies in female mice to analyze learning and memory, and then targeted PDE4D activation with a PDE4D inhibitor to define how changes in cAMP levels affect behavior in male and female mice.Results
We found that in Cc2d1a-deficient male mice PDE4D is hyperactive, leading to a reduction in cAMP response element binding protein signaling, but this molecular deficit is not present in female mice. Cc2d1a-deficient male mice show a deficit in spatial memory, which is not present in Cc2d1a-deficient female mice. Restoring PDE4D activity using an inhibitor rescues cognitive deficits in male mice but has no effect on female mice.Conclusions
Our findings show that CC2D1A regulates cAMP intracellular signaling in a male-specific manner in the hippocampus, leading to male-specific cognitive deficits. We propose that male-specific signaling mechanisms are involved in establishing sex bias in neurodevelopmental disorders. 相似文献2.
Lars I. Eriksson Cecilia Lundholm Kaavya Narasimhalu Rolf Sandin Ya-Ping Jin Margaret Gatz Nancy L. Pedersen 《Alzheimer's & dementia》2019,15(4):534-542
Introduction
We evaluated whether hospitalization with or without surgery increases risk for dementia or Alzheimer's disease.Methods
A clinical sample (843 clinically diagnosed dementia cases; 1686 matched nondemented individuals) was identified from Swedish Twin Registry studies. A register-based sample (4293 cases; 21,465 matched controls) was identified by linkage of Swedish Twin Registry to Swedish Patient Registry records. Apolipoprotein E (APOE) status and within-pair comparisons of dementia discordant twins indicated genetic susceptibility.Results
Nonsurgical hospitalization is associated with greater dementia risk than hospitalization with surgical intervention. In the register sample, thoracic, abdominal, and major orthopedic procedures entailed dementia risk; in the clinical sample, orthopedic alone. Within-pair analyses indicate that associations in part reflect genetic susceptibility in common to hospitalization and dementia. Potential gene-environment interactions were indicated by greater risk due to hospitalization among APOE ε4 noncarriers.Discussion
We confirm hospitalization as a risk factor for dementia, with repeated hospitalizations a more important risk factor than surgery. 相似文献3.
Francesco Di Lorenzo Caterina Motta Sonia Bonnì Nicola Biagio Mercuri Carlo Caltagirone Alessandro Martorana Giacomo Koch 《Brain stimulation》2019,12(1):148-151
Background
Alzheimer's disease (AD) is characterized by a primary impairment of long-term declarative memory caused by deposition of misfolded protein aggregates. Experimental studies showed that AD neuropathological alterations impair synaptic plasticity and memory performance. Transcranial Magnetic Stimulation protocols have been recently introduced to investigate altered mechanisms of cortical plasticity in AD patients.Aim
To investigate relationship between Long-Term Potentiation (LTP)-like cortical plasticity and patients’ neuropsychological performance.Methods
We applied intermittent theta burst stimulation and extensive neuropshycological battery in 75 newly diagnosed AD patients.Results
We found that LTP-like cortical plasticity impairment is selectively associated to a less efficient verbal memory (r?=?0.45; p?=?0.002), but not to other cognitive functions, independently from biomarkers and other demographic and clinical factors.Conclusion
These findings suggest that LTP-like cortical plasticity may represent a neurophysiological surrogate of memory in AD patients by evaluating the weight of pathological changes responsible for cognitive dysfunction. 相似文献4.
Zhen Ni Robin F.H. Cash Carolyn Gunraj Eduard Bercovici Mark Hallett Robert Chen 《Brain stimulation》2019,12(1):84-86
Background
Paired associative stimulation (PAS), with stimulus interval of 21.5 or 25?ms, using transcranial magnetic stimulation in the posterior-anterior (PA) current direction, produces a long-term-potentiation-like effect. Stimulation with PA directed current generates both early and late indirect (I)-waves while that in anterior-posterior (AP) current predominantly elicits late I-waves. Short interval intracortical inhibition (SICI) inhibits late I-waves but not early I-waves.Objective
To investigate how cortical inhibition modulates the effects of PAS.Methods
PAS at stimulus interval of 21.5?ms conditioned by SICI (SICI-PAS) was compared to PAS alone with both PA and AP directed currents.Results
PAS with both current directions increased cortical excitability. SICI-PAS increased cortical excitability in the PA but not the AP current direction.Conclusions
Both early and late I-waves circuits can mediate cortical PAS plasticity under different conditions. Plasticity induction with the late but not the early I-wave circuits is blocked by SICI. 相似文献5.
Yen-Feng Lin Albert Vernon Smith Thor Aspelund Rebecca A. Betensky Jordan W. Smoller Vilmundur Gudnason Lenore J. Launer Deborah Blacker 《Alzheimer's & dementia》2019,15(1):65-75
Introduction
We sought to examine the genetic overlap between vascular pathologies and Alzheimer's disease (AD) dementia, and the potential mediating role of vascular pathologies between AD-related genetic variants and late-life cognition.Methods
For 2907 stroke-free older individuals, we examined the association of polygenic risk scores for AD dementia (ADPRSs) with vascular pathologies and with cognition. Mediation analyses addressed whether association between ADPRSs and cognition was mediated by a vascular pathology.Results
ADPRSs were associated with lobar cerebral microbleeds, white matter lesion load, and coronary artery calcification, mostly explained by single nucleotide polymorphisms in the 19q13 region. The effect of ADPRSs on cognition was partially but significantly mediated by cerebral microbleeds, white matter lesions, and coronary artery calcification.Discussion
Our findings provide evidence for genetic overlap, mostly due to apolipoprotein E (APOE) gene, between vascular pathologies and AD dementia. The association between AD polygenic risk and late-life cognition is mediated in part via effects on vascular pathologies. 相似文献6.
W. Robert Bell Yang An Yusuke Kageyama Collin English Gay L. Rudow Olga Pletnikova Madhav Thambisetty Richard O&#x;Brien Abhay R. Moghekar Marilyn S. Albert Peter V. Rabins Susan M. Resnick Juan C. Troncoso 《Alzheimer's & dementia》2019,15(1):8-16
Introduction
Primary age-related tauopathy (PART) is a recently described entity that can cause cognitive impairment in the absence of Alzheimer's disease (AD). Here, we compared neuropathological features, tau haplotypes, apolipoprotein E (APOE) genotypes, and cognitive profiles in age-matched subjects with PART and AD pathology.Methods
Brain autopsies (n = 183) were conducted on participants 85 years and older from the Baltimore Longitudinal Study of Aging and Johns Hopkins Alzheimer's Disease Research Center. Participants, normal at enrollment, were followed with periodic cognitive evaluations until death.Results
Compared with AD, PART subjects showed significantly slower rates of decline on measures of memory, language, and visuospatial performance. They also showed lower APOE ε4 allele frequency (4.1% vs. 17.6%, P = .0046).Discussion
Our observations suggest that PART is separate from AD and its distinction will be important for the clinical management of patients with cognitive impairment and for public health care planning. 相似文献7.
Brent Wilkinson Oleg V. Evgrafov DongQing Zheng Nicolas Hartel James A. Knowles Nicholas A. Graham Justin K. Ichida Marcelo P. Coba 《Neuropsychopharmacology》2019,85(4):305-316
Background
Disrupted in schizophrenia 1 (DISC1) has been implicated in a number of psychiatric diseases along with neurodevelopmental phenotypes such as the proliferation and differentiation of neural progenitor cells. While there has been significant effort directed toward understanding the function of DISC1 through the determination of its protein-protein interactions within an in vitro setting, endogenous interactions involving DISC1 within a cell type–specific setting relevant to neural development remain unclear.Methods
Using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) genome engineering technology, we inserted an endogenous 3X-FLAG tag at the C-terminus of the canonical DISC1 gene in human induced pluripotent stem cells (iPSCs). We further differentiated these cells and used affinity purification to determine protein-protein interactions involving DISC1 in iPSC-derived neural progenitor cells and astrocytes.Results
We were able to determine 151 novel cell type–specific proteins present in DISC1 endogenous interactomes. The DISC1 interactomes can be clustered into several subcomplexes that suggest novel DISC1 cell-specific functions. In addition, the DISC1 interactome in iPSC-derived neural progenitor cells associates in a connected network containing proteins found to harbor de novo mutations in patients affected by schizophrenia and contains a subset of novel interactions that are known to harbor syndromic mutations in neurodevelopmental disorders.Conclusions
Endogenous DISC1 interactomes within iPSC-derived human neural progenitor cells and astrocytes are able to provide context to DISC1 function in a cell type–specific setting relevant to neural development and enables the integration of psychiatric disease risk factors within a set of defined molecular functions. 相似文献8.
Mascha van &#x;t Wout-Frank M. Tracie Shea Victoria C. Larson Benjamin D. Greenberg Noah S. Philip 《Brain stimulation》2019,12(1):41-43
Background
Facilitating neural activity using non-invasive brain stimulation may improve extinction-based treatments for posttraumatic stress disorder (PTSD).Objective/hypothesis
Here, we examined the feasibility of simultaneous transcranial direct current stimulation (tDCS) application during virtual reality (VR) to reduce psychophysiological arousal and symptoms in Veterans with PTSD.Methods
Twelve Veterans with PTSD received six combat-related VR exposure sessions during sham-controlled tDCS targeting ventromedial prefrontal cortex. Primary outcome measures were changes in skin conductance-based arousal and self-reported PTSD symptom severity.Results
tDCS + VR components were combined without technical difficulty. We observed a significant interaction between reduction in arousal across sessions and tDCS group (p = .03), indicating that the decrease in physiological arousal was greater in the tDCS + VR versus sham group. We additionally observed a clinically meaningful reduction in PTSD symptom severity.Conclusions
This study demonstrates feasibility of applying tDCS during VR. Preliminary data suggest a reduction in psychophysiological arousal and PTSD symptomatology, supporting future studies. 相似文献9.
Eliana Marisa Ramos Deepika Reddy Dokuru Victoria Van Berlo Kevin Wojta Qing Wang Alden Y. Huang Zachary A. Miller Anna M. Karydas Eileen H. Bigio Emily Rogalski Sandra Weintraub Benjamin Rader Bruce L. Miller Maria Luisa Gorno-Tempini Marek-Marsel Mesulam Giovanni Coppola 《Alzheimer's & dementia》2019,15(4):553-560
Introduction
Primary progressive aphasia (PPA) is a neurological syndrome, associated with both frontotemporal dementia and Alzheimer's disease, in which progressive language impairment emerges as the most salient clinical feature during the initial stages of disease.Methods
We screened the main genes associated with Alzheimer's disease and frontotemporal dementia for pathogenic and risk variants in a cohort of 403 PPA cases.Results
In this case series study, 14 (3.5%) cases carried (likely) pathogenic variants: four C9orf72 expansions, nine GRN, and one TARDBP mutation. Rare risk variants, TREM2 R47H and MAPT A152T, were associated with a three- to seven-fold increase in risk for PPA.Discussion
Our results show that while pathogenic variants within the most common dementia genes were rarely associated with PPA, these were found almost exclusively in GRN and C9orf72, suggesting that PPA is more TDP43- than tau-related in our series. This is consistent with the finding that PPA frequency in dominantly inherited dementias is the highest in kindreds with GRN variants. 相似文献10.
Feng Zhang Rujia Zhong Song Li Zhenfa Fu Renfei Wang Tianxiao Wang Zhili Huang Weidong Le 《Alzheimer's & dementia》2019,15(4):590-597
Objective
The present work aims to evaluate the significance of sleep disturbance and electroencephalogram (EEG) alteration in the early stage of Alzheimer's disease (AD).Background and Rationale
Sleep disturbance is common in patients with AD. It is not known if it can occur at the early stage of AD and if EEG recording may help identify the early sign of the disease.Historical Evolution
Sleep disturbance in AD has generally been considered as late consequence of the neurodegenerative process. A growing body of evidence has suggested that the sleep disturbance may occur at the early stage of AD.Updated Hypothesis
Based on the previous epidemiologic studies and our recent findings, we propose that sleep disturbance may play an important role in the development of AD. Sleep EEG changes may serve as a valuable early sign for AD in the prepathological stage.Early Experimental Data
Our data suggested that AβPPswe/PS1ΔE9 transgenic AD mice at preplaque stage (3 and 4 months of age) exhibited different profile of sleep architecture and sleep EEG, which preceded the cognitive deficit and AD neuropathology.Future Experiments and Validation Studies
Future experiments should focus on sleep EEG changes in patients with mild cognitive impairment and early stage of AD. Follow-up studies in high-risk population of the elderly are equally important. In addition, the exact molecular mechanism underlying the sleep disturbance should be thoroughly investigated.Major Challenges for the Hypothesis
Studies on human participants with early stage of AD, especially the follow-up studies on the presymptomatic elderly in a large population, are difficult and time-consuming.Linkage to Other Major Theories
Our hypothesis may link previous theories to establish a bidirectional relationship between sleep disorders and AD, which may finally form a new schematic mechanism to understand the disease pathogenesis and disease progression. 相似文献11.
Dalia Khammash Molly Simmonite Thad A. Polk Stephan F. Taylor Sean K. Meehan 《Brain stimulation》2019,12(3):702-704
Background
Transcranial magnetic stimulation (TMS) is a non-invasive method to stimulate localized brain regions. Despite widespread use in motor cortex, TMS is seldom performed in sensory areas due to variable, qualitative metrics.Objective
Assess the reliability and validity of tracing phosphenes, and to investigate the stimulation parameters necessary to elicit decreased visual cortex excitability with paired-pulse TMS at short inter-stimulus intervals.Methods
Across two sessions, single and paired-pulse recruitment curves were derived by having participants outline elicited phosphenes and calculating resulting average phosphene sizes.Results
Phosphene size scaled with stimulus intensity, similar to motor cortex. Paired-pulse recruitment curves demonstrated inhibition at lower conditioning stimulus intensities than observed in motor cortex. Reliability was high across sessions.Conclusions
TMS-induced phosphenes are a valid and reliable tool for measuring cortical excitability and inhibition in early visual areas. Our results also provide appropriate stimulation parameters for measuring short-latency intracortical inhibition in visual cortex. 相似文献12.
Kyoko Ohashi Carl M. Anderson Elizabeth A. Bolger Alaptagin Khan Cynthia E. McGreenery Martin H. Teicher 《Neuropsychopharmacology》2019,85(8):690-702
Background
Childhood maltreatment is a major risk factor for psychopathology. However, some maltreated individuals appear remarkably resilient to the psychiatric effects while manifesting the same array of brain abnormalities as maltreated individuals with psychopathology. Hence, a critical aim is to identify compensatory brain alterations that enable resilient individuals to maintain mental well-being despite alterations in stress-susceptible regions.Methods
Network models were constructed from diffusion tensor imaging and tractography in physically healthy unmedicated 18- to 25-year-old participants (N = 342, n = 192 maltreated) to develop network-based explanatory models.Results
First, we determined that susceptible and resilient individuals had the same alterations in global fiber stream network architecture using two different definitions of resilience: 1) no lifetime history of Axis I or II disorders, and 2) no clinically significant symptoms of anxiety, depression, anger-hostility, or somatization. Second, we confirmed an a priori hypothesis that right amygdala nodal efficiency was lower in asymptomatic resilient than in susceptible participants or control subjects. Third, we identified eight other nodes with reduced nodal efficiency in resilient individuals and showed that nodal efficiency moderated the relationship between maltreatment and psychopathology. Fourth, we found that models based on global network architecture and nodal efficiency could delineate group membership (control, susceptible, resilient) with 75%, 82%, and 80% cross-validated accuracy.Conclusions
Together these findings suggest that sparse fiber networks with increased small-worldness following maltreatment render individuals vulnerable to psychopathology if abnormalities occur in specific nodes, but that decreased ability of certain nodes to propagate information throughout the network mitigates the effects and leads to resilience. 相似文献13.
Kumar B. Rajan Jennifer Weuve Lisa L. Barnes Robert S. Wilson Denis A. Evans 《Alzheimer's & dementia》2019,15(1):1-7
Introduction
The trends in prevalence and incidence of Alzheimer's disease (AD) dementia remain uncertain.Methods
A sample of 2794 participants with a clinical diagnosis for AD dementia were included.Results
The 2010 census standardized prevalence of AD dementia was 14.5% (95% CI = 13.7–15.3), and annual incidence was 2.3% (1.7–2.9). Both prevalence and incidence showed substantial variation over time, but no secular trends. The prevalence of AD dementia did not change significantly from 14.6% (95% CI = 13.0, 16.2) in 1994–1997 to 14.7% (95% CI = 13.2, 16.2) in 2010–2012 (P = .84). The annual incidence of AD dementia was 2.8% (95% CI = 2.2, 3.2) in 1998–2000 and 2.2% (95% CI = 1.6, 2.8) in 2004–2006 (P = .20) and remained steady in 2010–2012. The prevalence and incidence among African Americans were approximately twice than those among European Americans.Conclusions
The prevalence and incidence of AD dementia showed substantial variation between 1994 and 2012, but no secular trend. 相似文献14.
Alan M. Smith Joseph J. King Paul R. West Michael A. Ludwig Elizabeth L.R. Donley Robert E. Burrier David G. Amaral 《Neuropsychopharmacology》2019,85(4):345-354
Background
Autism spectrum disorder (ASD) is behaviorally and biologically heterogeneous and likely represents a series of conditions arising from different underlying genetic, metabolic, and environmental factors. There are currently no reliable diagnostic biomarkers for ASD. Based on evidence that dysregulation of branched-chain amino acids (BCAAs) may contribute to the behavioral characteristics of ASD, we tested whether dysregulation of amino acids (AAs) was a pervasive phenomenon in individuals with ASD. This is the first article to report results from the Children’s Autism Metabolome Project (CAMP), a large-scale effort to define autism biomarkers based on metabolomic analyses of blood samples from young children.Methods
Dysregulation of AA metabolism was identified by comparing plasma metabolites from 516 children with ASD with those from 164 age-matched typically developing children recruited into the CAMP. ASD subjects were stratified into subpopulations based on shared metabolic phenotypes associated with BCAA dysregulation.Results
We identified groups of AAs with positive correlations that were, as a group, negatively correlated with BCAA levels in ASD. Imbalances between these two groups of AAs identified three ASD-associated amino acid dysregulation metabotypes. The combination of glutamine, glycine, and ornithine amino acid dysregulation metabotypes identified a dysregulation in AA/BCAA metabolism that is present in 16.7% of the CAMP subjects with ASD and is detectable with a specificity of 96.3% and a positive predictive value of 93.5% within the ASD subject cohort.Conclusions
Identification and utilization of metabotypes of ASD can lead to actionable metabolic tests that support early diagnosis and stratification for targeted therapeutic interventions. 相似文献15.
Sensen Song Anna Zilverstand Wenjun Gui Hui-jie Li Xiaolin Zhou 《Brain stimulation》2019,12(3):606-618
Background
Brain stimulation interventions are increasingly used to reduce craving and consumption in individuals with drug addiction or excessive eating behavior. However, the efficacy of these novel treatments and whether effect sizes are affected by the length of the intervention has not been comprehensively evaluated.Objective
A meta-analytical approach was employed to evaluate the effectiveness of non-invasive excitatory brain stimulation [transcranial Direct Current Stimulation (tDCS) and high-frequency repetitive Transcranial Magnetic Stimulation (rTMS)] targeted at dorsolateral prefrontal cortex (dlPFC) for reducing craving and consumption levels in drug and eating addiction, including both single- and multi-session protocols.Methods
After a comprehensive literature search, 48 peer-reviewed studies (1095 participants in total) were included in the current meta-analysis. We computed Hedge's g as a conservative measure for evaluating effect sizes.Results
Random effects analyses revealed a small effect of neuromodulation interventions on craving and a medium effect on consumption, favoring active over sham stimulation. These effects did not differ across the different populations investigated (alcohol, nicotine, illicit drugs, eating addictions) or by the used technique (rTMS/tDCS, left/right hemisphere). Multi-session protocols showed a larger effect size for reducing craving and consumption than single-session protocols, with a positive linear association between the number of sessions or administered pulses and craving reduction, indicating a dose-response effect.Conclusions
Our results provide compelling evidence that novel non-invasive brain stimulation targeted at dlPFC reduces craving and consumption levels (providing the first meta-analytical evidence for the latter effect in drug addiction), with larger effects in multi-session as compared to single-session interventions. 相似文献16.
Natalie Schaworonkow Jochen Triesch Ulf Ziemann Christoph Zrenner 《Brain stimulation》2019,12(1):110-118
Background
Corticospinal excitability depends on the current brain state. The recent development of real-time EEG-triggered transcranial magnetic stimulation (EEG-TMS) allows studying this relationship in a causal fashion. Specifically, it has been shown that corticospinal excitability is higher during the scalp surface negative EEG peak compared to the positive peak of μ-oscillations in sensorimotor cortex, as indexed by larger motor evoked potentials (MEPs) for fixed stimulation intensity.Objective
We further characterize the effect of μ-rhythm phase on the MEP input-output (IO) curve by measuring the degree of excitability modulation across a range of stimulation intensities. We furthermore seek to optimize stimulation parameters to enable discrimination of functionally relevant EEG-defined brain states.Methods
A real-time EEG-TMS system was used to trigger MEPs during instantaneous brain-states corresponding to μ-rhythm surface positive and negative peaks with five different stimulation intensities covering an individually calibrated MEP IO curve in 15 healthy participants.Results
MEP amplitude is modulated by μ-phase across a wide range of stimulation intensities, with larger MEPs at the surface negative peak. The largest relative MEP-modulation was observed for weak intensities, the largest absolute MEP-modulation for intermediate intensities. These results indicate a leftward shift of the MEP IO curve during the μ-rhythm negative peak.Conclusion
The choice of stimulation intensity influences the observed degree of corticospinal excitability modulation by μ-phase. Lower stimulation intensities enable more efficient differentiation of EEG μ-phase-defined brain states. 相似文献17.
Sina Kohl Ricci Hannah Lorenzo Rocchi Camilla L. Nord John Rothwell Valerie Voon 《Neuropsychopharmacology》2019,85(4):355-363
Background
The ability to stop a suboptimal response is integral to decision making and is commonly impaired across psychiatric disorders. Cortical paired associative stimulation (cPAS) is a form of transcranial magnetic stimulation in which paired pulses can induce plasticity at cortical synapses. Here we used cPAS protocols to target cortico-cortical and cortico-subcortical networks by using different intervals between the paired pulses in an attempt to modify response inhibition.Methods
A total of 25 healthy volunteers underwent four cPAS sessions in random order 1 week apart: right inferior frontal cortex (IFC) stimulation preceding right presupplementary motor area (pre-SMA) stimulation by 10 or 4 ms and pre-SMA stimulation preceding IFC stimulation by 10 or 4 ms. Subjects were tested on the stop signal task along with the delay discounting task as control at baseline (randomized across sessions and cPAS protocol) and after each cPAS session.Results
The stop signal reaction time showed a main effect of cPAS condition when controlling for age (F3,57 = 4.05, p = .01). Younger subjects had greater impairments in response inhibition when the pre-SMA pulse preceded the IFC pulse by 10 ms. In older individuals, response inhibition improved when the IFC pulse preceded the pre-SMA pulse by 4 ms. There were no effects on delay discounting.Conclusions
cPAS modified response inhibition through age-dependent long-term potentiation and depression-like plasticity mechanisms via putative cortico-cortical and cortico-subcortical networks. We show for the first time the capacity for cPAS to modify a cognitive process highly relevant to psychiatric disorders. 相似文献18.
C.M. Warren K.D. Tona L. Ouwerkerk J. van Paridon F. Poletiek Henk van Steenbergen J.A. Bosch S. Nieuwenhuis 《Brain stimulation》2019,12(3):635-642
Background
Transcutaneous vagus nerve stimulation (tVNS) is a new, non-invasive technique being investigated as an intervention for a variety of clinical disorders, including epilepsy and depression. It is thought to exert its therapeutic effect by increasing central norepinephrine (NE) activity, but the evidence supporting this notion is limited.Objective
In order to test for an impact of tVNS on psychophysiological and hormonal indices of noradrenergic function, we applied tVNS in concert with assessment of salivary alpha amylase (SAA) and cortisol, pupil size, and electroencephalograph (EEG) recordings.Methods
Across three experiments, we applied real and sham tVNS to 61 healthy participants while they performed a set of simple stimulus-discrimination tasks. Before and after the task, as well as during one break, participants provided saliva samples and had their pupil size recorded. EEG was recorded throughout the task. The target for tVNS was the cymba conchae, which is heavily innervated by the auricular branch of the vagus nerve. Sham stimulation was applied to the ear lobe.Results
P3 amplitude was not affected by tVNS (Experiment 1A: N?=?24; Experiment 1B: N?=?20; Bayes factor supporting null model?=?4.53), nor was pupil size (Experiment 2: N?=?16; interaction of treatment and time: p?=?.79). However, tVNS increased SAA (Experiments 1A and 2: N?=?25) and attenuated the decline of salivary cortisol compared to sham (Experiment 2: N?=?17), as indicated by significant interactions involving treatment and time (p?=?.023 and p?=?.040, respectively).Conclusion
These findings suggest that tVNS modulates hormonal indices but not psychophysiological indices of noradrenergic function. 相似文献19.
Rosa Capozzo Celeste Sassi Monia B. Hammer Simona Arcuti Chiara Zecca Maria R. Barulli Rosanna Tortelli J. Raphael Gibbs Cynthia Crews Davide Seripa Francesco Carnicella Claudia Dell&#x;Aquila Marco Rossi Filippo Tamma Francesco Valluzzi Bruno Brancasi Francesco Panza Andrew B. Singleton Giancarlo Logroscino 《Alzheimer's & dementia》2017,13(8):858-869
Introduction
We investigated the clinical differences between familial and sporadic frontotemporal dementia (FTD), screening for mutations in known FTD genes.Methods
We diagnosed 22 affected individuals belonging to eight families and 43 sporadic cases with FTD in Apulia, Southern Italy, in 2 years. Mutations in common causative FTD genes (GRN, MAPT, VCP, and TARDBP) and C9ORF72 expansions were screened.Results
Behavioral variant of FTD was the most common clinical subtype (50% and 69% in familial and sporadic cases, respectively). Social conduct impairment/disinhibition, loss of insight, and inflexibility were the most frequent clinical features observed at onset. One new mutation was identified in GRN in family A.Discussion
Disease onset in sporadic FTD was more frequently characterized by a clustering of behavioral symptoms with apathy and loss of personal hygiene. Mutations in common causative FTD genes are not a major cause of familial and sporadic FTD in the Southern Italian population. 相似文献20.
Mohamed Abdulkadir Carol A. Mathews Jeremiah M. Scharf Dongmei Yu Jay A. Tischfield Gary A. Heiman Pieter J. Hoekstra Andrea Dietrich 《Neuropsychopharmacology》2019,85(4):298-304