Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans

Because of attentional limitations, the human visual system can process for awareness and response only a fraction of the input received. Lesion and functional imaging studies have identified frontal, temporal, and parietal areas as playing a major role in the attentional control of visual processing, but very little is known about how these areas interact to form a dynamic attentional network. We hypothesized that the network communicates by means of neural phase synchronization, and we used magnetoencephalography to study transient long-range interarea phase coupling in a well studied attentionally taxing dual-target task (attentional blink). Our results reveal that communication within the fronto-parieto-temporal attentional network proceeds via transient long-range phase synchronization in the beta band. Changes in synchronization reflect changes in the attentional demands of the task and are directly related to behavioral performance. Thus, we show how attentional limitations arise from the way in which the subsystems of the attentional network interact. The human brain faces an inestimable task of reducing a potentially overloading amount of input into a manageable flow of information that reflects both the current needs of the organism and the external demands placed on it. This task is accomplished via a ubiquitous construct known as “attention,” whose mechanism, although well characterized behaviorally, is far from understood at the neurophysiological level. Whereas attempts to identify particular neural structures involved in the operation of attention have met with considerable success (1-5) and have resulted in the identification of frontal, parietal, and temporal regions, far less is known about the interaction among these structures in a way that can account for the task-dependent successes and failures of attention. The goal of the present research was, thus, to unravel the means by which the subsystems making up the human attentional network communicate and to relate the temporal dynamics of their communication to observed attentional limitations in humans. A prime candidate for communication among distributed systems in the human brain is neural synchronization (for review, see ref. 6). Indeed, a number of studies provide converging evidence that long-range interarea communication is related to synchronized oscillatory activity (refs. 7-14; for review, see ref. 15). To determine whether neural synchronization plays a role in attentional control, we placed humans in an attentionally demanding task and used magnetoencephalography (MEG) to track interarea communication by means of neural synchronization. In particular, we presented 10 healthy subjects with two visual target letters embedded in streams of 13 distractor letters, appearing at a rate of seven per second. The targets were separated in time by a single distractor. This condition leads to the “attentional blink” (AB), a well studied dual-task phenomenon showing the reduced ability to report the second of two targets when an interval <500 ms separates them (16-18). Importantly, the AB does not prevent perceptual processing of missed target stimuli but only their conscious report (19), demonstrating the attentional nature of this effect and making it a good candidate for the purpose of our investigation. Although numerous studies have investigated factors, e.g., stimulus and timing parameters, that manipulate the magnitude of a particular AB outcome, few have sought to characterize the neural state under which “standard” AB parameters produce an inability to report the second target on some trials but not others. We hypothesized that the different attentional states leading to different behavioral outcomes (second target reported correctly or not) are characterized by specific patterns of transient long-range synchronization between brain areas involved in target processing. Showing the hypothesized correspondence between states of neural synchronization and human behavior in an attentional task entails two demonstrations. First, it needs to be demonstrated that cortical areas that are suspected to be involved in visual-attention tasks, and the AB in particular, interact by means of neural synchronization. This demonstration is particularly important because previous brain-imaging studies (e.g., ref. 5) only showed that the respective areas are active within a rather large time window in the same task and not that they are concurrently active and actually create an interactive network. Second, it needs to be demonstrated that the pattern of neural synchronization is sensitive to the behavioral outcome; specifically, the ability to correctly identify the second of two rapidly succeeding visual targets

Gender differences in the sensitivity to negative stimuli:cross-modal affective priming study

Background: There is evidence showing that men and women differ with regard to the processing of emotional information. However, the mechanisms behind these differences are not fully understood. Method: The sample comprised of 275 (167 female) right-handed, healthy participants, recruited from the community. We employed a customized affective priming task, which consisted of three subtests, differing in the modality of the prime (face, written word, and sound). The targets were always written words of either positive or negative valence. The priming effect was measured as reaction time facilitation in conditions where both prime and target were emotional (of the same positive or negative valence) compared with conditions where the emotional targets were preceded by neutral primes. Results: The priming effect was observed across all three modalities, with an interaction of gender by valence: the priming effect in the emotionally negative condition in male participants was stronger compared with females. This was accounted for by the differential priming effect within the female group where priming was significantly smaller in the emotionally negative conditions compared with the positive conditions. The male participants revealed a comparable priming effect across both the emotionally negative and positive conditions. Conclusion: Reduced priming in negative conditions in women may reflect interference processes due to greater sensitivity to negative valence of stimuli. This in turn could underlie the gender-related differences in susceptibility to emotional disorders.

A potentially scalable method for the harvesting of hMSCs from microcarriers

The use of hMSCs for allogeneic therapies requiring lot sizes of billions of cells will necessitate large-scale culture techniques such as the expansion of cells on microcarriers in bioreactors. Whilst much research investigating hMSC culture on microcarriers has focused on growth, much less involves their harvesting for passaging or as a step towards cryopreservation and storage. A successful new harvesting method has recently been outlined for cells grown on SoloHill microcarriers in a 5L bioreactor [1]. Here, this new method is set out in detail, harvesting being defined as a two-step process involving cell 'detachment' from the microcarriers' surface followed by the 'separation' of the two entities. The new detachment method is based on theoretical concepts originally developed for secondary nucleation due to agitation. Based on this theory, it is suggested that a short period (here 7min) of intense agitation in the presence of a suitable enzyme should detach the cells from the relatively large microcarriers. In addition, once detached, the cells should not be damaged because they are smaller than the Kolmogorov microscale. Detachment was then successfully achieved for hMSCs from two different donors using microcarrier/cell suspensions up to 100mL in a spinner flask. In both cases, harvesting was completed by separating cells from microcarriers using a Steriflip® vacuum filter. The overall harvesting efficiency was >95% and after harvesting, the cells maintained all the attributes expected of hMSC cells. The underlying theoretical concepts suggest that the method is scalable and this aspect is discussed too. © 2014 The Authors.

Differential activation in temporal, cingulate and prefrontal cortices during response inhibition in bipolar disorder

Background: Increased impulsivity and aberrant response inhibition have been observed in bipolar disorder (BD). This study examined the functional abnormalities and underlying neural processes during response inhibition in BD, and its relationship to impulsivity. Methods: We assessed impulsivity using the Barratt Impulsiveness Scale (BIS) and, using functional magnetic resonance imaging (fMRI), measured neural activity in response to an Affective Go-NoGo Task, consisting of emotional facial stimuli (fear, happy, anger faces) and non-emotional control stimuli (neutral female and male faces) in euthymic BD (n=23) and healthy individuals (HI; n=25). Results: BD patients were significantly more impulsive, yet did not differ from HI on accuracy or reaction time on the emotional go/no-go task. Comparing neural patterns of activation when processing emotional Go versus emotional NoGo trials yielded increased activation in BD within temporal and cingulate cortices and within prefrontal-cortical regions in HI. Furthermore, higher BIS scores for BD were associated with slower reaction times, and indicative of compensatory cognitive strategies to counter increased impulsivity. Conclusions: These findings illustrate cognition-emotion interference in BD and the observed differences in neural activation indicate potentially altered emotion modulation. Increased activation in brain regions previously shown in emotion regulation and response inhibition tasks could represent a disease-specific marker for BD