TMS: Using the Theta-Burst Protocol to Explore Mechanism of Plasticity in Individuals with Fragile X Syndrome and Autism

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.^1,2 Individuals suffering from FXS display abnormalities in the expression of FMR1 - a protein required for typical, healthy neural development.³ Recent data has suggested that the loss of this protein can cause the cortex to be hyperexcitable thereby affecting overall patterns of neural plasticity.^4,5In addition, Fragile X shows a strong comorbidity with autism: in fact, 30% of children with FXS are diagnosed with autism, and 2 - 5% of autistic children suffer from FXS.⁶Transcranial Magnetic Stimulation (a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability via the application of localized magnetic field pulses ^7,8) represents a unique method of exploring plasticity and the manifestations of FXS within affected individuals. More specifically, Theta-Burst Stimulation (TBS), a specific stimulatory protocol shown to modulate cortical plasticity for a duration up to 30 minutes after stimulation cessation in healthy populations, has already proven an efficacious tool in the exploration of abnormal plasticity.^9,10 Recent studies have shown the effects of TBS last considerably longer in individuals on the autistic spectrum - up to 90 minutes.¹¹ This extended effect-duration suggests an underlying abnormality in the brain''s natural plasticity state in autistic individuals - similar to the hyperexcitability induced by Fragile X Syndrome.In this experiment, utilizing single-pulse motor-evoked potentials (MEPs) as our benchmark, we will explore the effects of both intermittent and continuous TBS on cortical plasticity in individuals suffering from FXS and individuals on the Autistic Spectrum.     

Moral Perception and Global Visions

Because moral perception plays an essential role in guiding morally responsible behaviour, agents have a responsibility to develop their capacities in this area. There are several strategies agents can (and should) pursue in order to improve their skills at moral perception. I appeal to insights derived from the work of feminist epistomologists and philosophers of science to argue that feminist approaches to multiculturalism are particularly valuable tools for improving moral perception.     

A Gestalt approach to Gram-negative entry

A major obstacle confronting the discovery and development of new antibacterial agents to combat resistant Gram-negative (GN) organisms is the lack of a rational process for endowing compounds with properties that allow (or promote) entry into the bacterial cytoplasm. The major permeability difference between GN and Gram-positive (GP) bacteria is the GN outer membrane (OM) which is a permeability barrier itself and potentiates efflux pumps that expel compounds. Based on the fact that OM-permeable and efflux-deleted GNs are sensitive to many anti-GP drugs, recent efforts to approach the GN entry problem have focused on ways of avoiding efflux and transiting or compromising the OM, with the tacit assumption that this could allow entry of compounds into the GN cytoplasm. But bypassing the OM and efflux obstacles does not take into account the additional requirement of penetrating the cytoplasmic membrane (CM) whose sieving properties appear to be orthogonal to that of the OM. That is, tailoring compounds to transit the OM may well compromise their ability to enter the cytoplasm. Thus, a Gestalt approach to understanding the chemical requirements for GN entry seems a useful adjunct. This might consist of characterizing compounds which reach the cytoplasm, grouping (or binning) by routes of entry and formulating chemical ‘rules’ for those bins. This will require acquisition of data on large numbers of compounds, using non-activity-dependent methods of measuring accumulation in the cytoplasm.     

Perception of Binaural Cues Develops in Children Who Are Deaf through Bilateral Cochlear Implantation

There are significant challenges to restoring binaural hearing to children who have been deaf from an early age. The uncoordinated and poor temporal information available from cochlear implants distorts perception of interaural timing differences normally important for sound localization and listening in noise. Moreover, binaural development can be compromised by bilateral and unilateral auditory deprivation. Here, we studied perception of both interaural level and timing differences in 79 children/adolescents using bilateral cochlear implants and 16 peers with normal hearing. They were asked on which side of their head they heard unilaterally or bilaterally presented click- or electrical pulse- trains. Interaural level cues were identified by most participants including adolescents with long periods of unilateral cochlear implant use and little bilateral implant experience. Interaural timing cues were not detected by new bilateral adolescent users, consistent with previous evidence. Evidence of binaural timing detection was, for the first time, found in children who had much longer implant experience but it was marked by poorer than normal sensitivity and abnormally strong dependence on current level differences between implants. In addition, children with prior unilateral implant use showed a higher proportion of responses to their first implanted sides than children implanted simultaneously. These data indicate that there are functional repercussions of developing binaural hearing through bilateral cochlear implants, particularly when provided sequentially; nonetheless, children have an opportunity to use these devices to hear better in noise and gain spatial hearing.     

Erratum to: Functional Brain Organization of Global and Local Visual Perception: An Event-Related Potentials Study

Adult subjects were asked to recognize a hierarchical visual stimulus (a letter) while their attention was drawn to either the global or local level of the stimulus. Event-related potentials (ERP) and behavioral indices (reaction time and percentage of correct responses) were measured. An analysis of behavioral indices showed the global level precedence effect, i.e. the increase in a small letter recognition time when this letter is a part of incongruent stimulus. An analysis of ERP components showed level-related (global vs. local) differences in the timing and topography of the brain organization of perceptual processing and regulatory mechanisms of attention. Visual recognition at the local level was accompanied by (1) stronger activation of the visual associative areas (P _z and T ₆) at the stage of sensory features analysis (P1 ERP component), (2) involvement mainly of inferior temporal cortices of the right hemisphere (T ₆) at the stage of sensory categorization (P2 ERP component), and (3) involvement of prefrontal cortex of the right hemisphere at the stage of selection of the relevant features of the target (N2 ERP component). Visual recognition at the global level was accompanied by (1) pronounced involvement of mechanisms of early sensory selection (N1 ERP component), (2) prevailing activation of parietal cortex of the right hemisphere (P ₄) at the stage of sensory categorization (P2 ERP component) as well as at the stage of the target stimulus identification (P3 ERP component). We suggested that perception of the hierarchical stimulus at the global level is related primarily to the analysis of its spatial features in the dorsal visual system whereas the perception at the local level primarily involves an analysis of the object-related features in the ventral visual system.     

The Influence of Bubbles on the Perception Carbonation Bite

Although many people naively assume that the bite of carbonation is due to tactile stimulation of the oral cavity by bubbles, it has become increasingly clear that carbonation bite comes mainly from formation of carbonic acid in the oral mucosa. In Experiment 1, we asked whether bubbles were in fact required to perceive carbonation bite. Subjects rated oral pungency from several concentrations of carbonated water both at normal atmospheric pressure (at which bubbles could form) and at 2.0 atmospheres pressure (at which bubbles did not form). Ratings of carbonation bite under the two pressure conditions were essentially identical, indicating that bubbles are not required for pungency. In Experiment 2, we created controlled streams of air bubbles around the tongue in mildly pungent CO₂ solutions to determine how tactile stimulation from bubbles affects carbonation bite. Since innocuous sensations like light touch and cooling often suppress pain, we predicted that bubbles might reduce rated bite. Contrary to prediction, air bubbles flowing around the tongue significantly enhanced rated bite, without inducing perceived bite in blank (un-carbonated) solutions. Accordingly, though bubbles are clearly not required for carbonation bite, they may well modulate perceived bite. More generally, the results show that innocuous tactile stimulation can enhance chemogenic pain. Possible physiological mechanisms are discussed.     

Understanding the Development and Perception of Global Health for More Effective Student Education

The concept of “global health” that led to the establishment of the World Health Organization in the 1940s is still promoting a global health movement 70 years later. Today’s global health acts first as a guiding principle for our effort to improve people’s health across the globe. Furthermore, global health has become a branch of science, “global health science,” supporting institutionalized education. Lastly, as a discipline, global health should focus on medical and health issues that: 1) are determined primarily by factors with a cross-cultural, cross-national, cross-regional, or global scope; 2) are local but have global significance if not appropriately managed; and 3) can only be efficiently managed through international or global efforts. Therefore, effective global health education must train students 1) to understand global health status; 2) to investigate both global and local health issues with a global perspective; and 3) to devise interventions to deal with these issues.     

Market Movements: Nongovernmental Organization Strategies to Influence Global Production and Consumption

This article analyzes nongovernmental organization (NGO) "market campaigns" that seek to motivate changes in global consumption and production patterns. Through campaigns targeting products as diverse as paper, shoes, and computers, advocacy groups seek to use existing concerns of consumers to influence producers, and simultaneously, to expand and deepen consumer demand for more sustainable products and services. NGOs deploy both negative information to critique leading brands, and positive information to help build new markets for improved products. Successful market campaigns construct networks of actors that identify points of leverage within global production and trading regimes; coordinate research, exposure, direct action, and negotiations with brands; identify solutions; advance new multi-stakeholder standards and monitoring and certification schemes; build new nongovernmental regulatory institutions; and occasionally attempt to strengthen state regulation. Through an assessment of three market campaigns focused on Staples, Nike, and Dell, this article describes the nature of these campaigns, discusses how they function, assesses their central strategies and tactics, and analyzes whether they are actually having an impact. The article concludes by discussing the relevance and implications of these campaigns for the field of industrial ecology, and how industrial ecology might support future efforts to advance more sustainable production and consumption.     

Global Motion Percept Mediated through Integration of Barber Poles Presented in Bilateral Visual Hemifields

How is motion information that has been obtained through multiple viewing apertures integrated to form a global motion percept? We investigated the mechanisms of motion integration across apertures in two hemifields by presenting gratings through two rectangles (that form the dual barber poles) and recording the perceived direction of motion by human observers. To this end, we presented dual barber poles in conditions with various inter-component distances between the apertures and evaluated the degree to which the hemifield information was integrated by measuring the magnitude of the perceived barber pole illusion. Surprisingly, when the inter-component distance between the two apertures was short, the perceived direction of motion of the dual barber poles was similar to that of a single barber pole formed by the concatenation of the two component barber poles, indicating motion integration is achieved through a simple concatenation mechanism. We then presented dual barber poles in which the motion and contour properties of the two component barber poles differed to characterize the constraints underlying cross-hemifield integration. We found that integration is achieved only when phase, speed, wavelength, temporal frequency, and duty cycle are identical in the two barber poles, but can remain robust when the contrast of the two component barber poles differs substantially. We concluded that a motion stimulus presented in bilateral hemifields tends to be integrated to yield a global percept with a substantial tolerance for spatial distance and contrast difference.     

背景噪声对人感知声音时间信息的影响

对声音时间信息的分辨在人和动物感知声音信息的过程中至关重要.在自然声环境中,声音信息总处于一定的噪声背景下.文章以间隔探测阈值为指标测定了人对纯音和噪声的间隔探测阈值,以及持续噪声背景对间隔探测阈值的影响.声音信号采用1000～10000 Hz的纯音信号和白噪声信号,声音强度为70 dB SPL.背景噪声为持续白噪声,强度分别为45、55、65 dB SPL.结果表明,对纯音信号,随着背景噪声强度增加,间隔探测阈值有升高的趋势.对噪声信号来说,45、55 dB SPL的背景噪声对噪声信号的间隔探测阈值无显著影响,但65 dB SPL的背景噪声使间隔探测阈值显著升高.研究结果提示,背景噪声能够在一定程度上影响人对声音时间信息的感知,影响的程度与背景噪声的强度有关.     

Sympathectomy Does Not Influence Experimental Itch and Cutaneous Temperature Perception Thresholds

The effect of endoscopic thoracic sympathectomy on experimentally histamineinduced itch was studied in seven patients, all of whom were suffering from palmar hyperhidrosis; cutaneous warm, cold, and heat pain perception thresholds were also studied in five of these seven patients. Surgery was effective in abolishing palmar sweating in all patients. No significant differences were seen in itch, flare, wheal, or thermal perception thresholds following sympathectomy as compared to the preoperative period. These findings suggest that the sympathetic system may be of limited importance for somatosensory perception in healthy humans during normal conditions.     

营养液对植物影响的数学模型的全局稳定性

营养液的合理调配,对促进植物早熟、生长,抗干旱,防虫害具有重要意义.本文根据营养液和植物生长规律的关系,建立了营养液浓度-植物生长量的数学模型.通过比较原理,得到模型有界正解的存在性,进而利用特征值法、Liapunov函数法对模型的动力学特性进行分析.证明了模型平衡点的存在性,并讨论其稳定性,得到系统正平衡点的全局稳定性,为现实的无土栽培管理提供理论依据.     

Influence of Rhythmic Grouping on Duration Perception: A Novel Auditory Illusion

This study investigated a potential auditory illusion in duration perception induced by rhythmic temporal contexts. Listeners with or without musical training performed a duration discrimination task for a silent period in a rhythmic auditory sequence. The critical temporal interval was presented either within a perceptual group or between two perceptual groups. We report the just-noticeable difference (difference limen, DL) for temporal intervals and the point of subjective equality (PSE) derived from individual psychometric functions based on performance of a two-alternative forced choice task. In musically untrained individuals, equal temporal intervals were perceived as significantly longer when presented between perceptual groups than within a perceptual group (109.25% versus 102.5% of the standard duration). Only the perceived duration of the between-group interval was significantly longer than its objective duration. Musically trained individuals did not show this effect. However, in both musically trained and untrained individuals, the relative difference limens for discriminating the comparison interval from the standard interval were larger in the between-groups condition than in the within-group condition (7.3% vs. 5.6% of the standard duration). Thus, rhythmic grouping affected sensitivity to duration changes in all listeners, with duration differences being harder to detect at boundaries of rhythm groups than within rhythm groups. Our results show for the first time that temporal Gestalt induces auditory duration illusions in typical listeners, but that musical experts are not susceptible to this effect of rhythmic grouping.     

武陵源世界遗产地声景感知及影响感知的要素研究

保护地的声景具有重要价值。声景感知是衡量保护地声景质量的有效工具之一。声景感知受到声景环境、声源构成、主导音等要素影响,也会对人们环境感知的可接受度、情绪等方面产生影响。已有对城市和乡村环境中主导音、听觉对视觉及情绪影响等方面的研究,但对保护地中声景感知及影响感知的要素研究较为缺乏。以武陵源世界遗产地的声景为对象,通过听音实验,相关性分析、对比分析得出武陵源声景的总体特点。可知武陵源声环境中导游喇叭和谈话的声音是感知频率高且接受度最低的声源,因而在保护管理中应予以重视和控制。武陵源世界遗产地内乡村环境中的鸟鸣、流水等自然声源的可接受度要高于武陵源中纯自然环境中的同等声源的可接受度。在低噪声环境下,高感知频率的声源与主导音不一致,即被感知频率高的声源不一定是主导音。并通过相关性分析,得出声景与情绪感知与性格之间存在相关性,且不同声景环境中的自然声源均能使性格“内向安静”和“易焦虑的人”感到“放松”“舒适”和“多样丰富”。最后,基于上述结论,提出了对武陵源声景价值认知的策略和保护管理的建议。     

Global perception depends on coherent work of bilateral visual cortices: Transcranial magnetic stimulation (TMS) studies

Previous research suggests that the right and left hemispheres dominate global and local perception of hierarchical patterns, respectively. The current work examined whether global perception of hierarchical stimuli requires coherent work of bilateral visual cortices using transcranial magnetic stimulation (TMS). Subjects discriminated global or local properties of compound letters in Experiment 1. Reaction times were recorded when single-pulse real TMS or sham TMS was delivered over the left or right visual cortex. While a global precedence effect (i.e., faster responses to global than local targets and stronger global-to-local interference than the reverse) was observed, TMS decreased global-to-local interference whereas increased local-to-global interference. Experiment 2 ruled out the possibility that the effects observed in Experiment 1 resulted from perceptual learning. Experiment 3 used compound shapes and observed TMS effect similar to that in Experiment 1. Moreover, TMS also slowed global RTs whereas speeded up local RTs in Experiment 3. Finally, the TMS effects observed in Experiments 1 and 3 did not differ between the conditions when TMS was applied over the left and right hemispheres. The results support a coherence hypothesis that global perception of compound stimuli depends upon the coherent work of bilateral visual cortices.     

Contradictory Behavioral Biases Result from the Influence of Past Stimuli on Perception

Biases such as the preference of a particular response for no obvious reason, are an integral part of psychophysics. Such biases have been reported in the common two-alternative forced choice (2AFC) experiments, where participants are instructed to compare two consecutively presented stimuli. However, the principles underlying these biases are largely unknown and previous studies have typically used ad-hoc explanations to account for them. Here we consider human performance in the 2AFC tone frequency discrimination task, utilizing two standard protocols. In both protocols, each trial contains a reference stimulus. In one (Reference-Lower protocol), the frequency of the reference stimulus is always lower than that of the comparison stimulus, whereas in the other (Reference protocol), the frequency of the reference stimulus is either lower or higher than that of the comparison stimulus. We find substantial interval biases. Namely, participants perform better when the reference is in a specific interval. Surprisingly, the biases in the two experiments are opposite: performance is better when the reference is in the first interval in the Reference protocol, but is better when the reference is second in the Reference-Lower protocol. This inconsistency refutes previous accounts of the interval bias, and is resolved when experiments statistics is considered. Viewing perception as incorporation of sensory input with prior knowledge accumulated during the experiment accounts for the seemingly contradictory biases both qualitatively and quantitatively. The success of this account implies that even simple discriminations reflect a combination of sensory limitations, memory limitations, and the ability to utilize stimuli statistics.     

Global perception depends on coherent work of bilateral visual cortices: Transcranial magnetic stimulation (TMS) studies

Previous research suggests that the right and left hemispheres dominate global and local perception of hierarchical patterns, respectively. The current work examined whether global perception of hierarchi-cal stimuli requires coherent work of bilateral visual cortices using transcranial magnetic stimulation (TMS). Subjects discriminated global or local properties of compound letters in Experiment 1. Reaction times were recorded when single-pulse real TMS or sham TMS was delivered over the left or right visual cortex. While a global precedence effect (i.e., faster responses to global than local targets and stronger global-to-local interference than the reverse) was observed, TMS decreased global-to-local interference whereas increased local-to-global interference. Experiment 2 ruled out the possibility that the effects observed in Experiment 1 resulted from perceptual learning. Experiment 3 used compound shapes and observed TMS effect similar to that in Experiment 1. Moreover, TMS also slowed global RTs whereas speeded up local RTs in Experiment 3. Finally, the TMS effects observed in Experiments 1 and 3 did not differ between the conditions when TMS was applied over the left and right hemispheres. The results support a coherence hypothesis that global perception of compound stimuli depends upon the co-herent work of bilateral visual cortices.