BackgroundStandardized neuropsychological testing serves to quantify cognitive impairment in multiple sclerosis (MS) patients. However, the exact mechanism underlying the translation of cognitive dysfunction into difficulties in everyday tasks has remained unclear. To answer this question, we tested if MS patients with intact vs. impaired information processing speed measured by the Symbol Digit Modalities Test (SDMT) differ in their visual search behavior during ecologically valid tasks reflecting everyday activities.MethodsForty-three patients with relapsing-remitting MS enrolled in an eye-tracking experiment consisting of a visual search task with naturalistic images. Patients were grouped into “impaired” and “unimpaired” according to their SDMT performance. Reaction time, accuracy and eye-tracking parameters were measured.ResultsThe groups did not differ regarding age, gender, and visual acuity. Patients with impaired SDMT (cut-off SDMT-z-score < −1.5) performance needed more time to find and fixate the target (q = 0.006). They spent less time fixating the target (q = 0.042). Impaired patients had slower reaction times and were less accurate (both q = 0.0495) even after controlling for patients' upper extremity function. Exploratory analysis revealed that unimpaired patients had higher accuracy than impaired patients particularly when the announced target was in unexpected location (p = 0.037). Correlational analysis suggested that SDMT performance is inversely linked to the time to first fixation of the target only if the announced target was in its expected location (r = −0.498, p = 0.003 vs. r = −0.212, p = 0.229).ConclusionDysfunctional visual search behavior may be one of the mechanisms translating cognitive deficits into difficulties in everyday tasks in MS patients. Our results suggest that cognitively impaired patients search their visual environment less efficiently and this is particularly evident when top-down processes have to be employed.

Aging is accompanied by unisensory decline. To compensate for this, two complementary strategies are potentially relied upon increasingly: first, older adults integrate more information from different sensory organs. Second, according to the predictive coding (PC) model, we form “templates” (internal models or “priors”) of the environment through our experiences. It is through increased life experience that older adults may rely more on these templates compared to younger adults. Multisensory integration and predictive coding would be effective strategies for the perception of near-threshold stimuli, which may however come at the cost of integrating irrelevant information. Both strategies can be studied in multisensory illusions because these require the integration of different sensory information, as well as an internal model of the world that can take precedence over sensory input. Here, we elicited a classic multisensory illusion, the sound-induced flash illusion, in younger (mean: 27 years, N = 25) and older (mean: 67 years, N = 28) adult participants while recording the magnetoencephalogram. Older adults perceived more illusions than younger adults. Older adults had increased pre-stimulus beta-band activity compared to younger adults as predicted by microcircuit theories of predictive coding, which suggest priors and predictions are linked to beta-band activity. Transfer entropy analysis and dynamic causal modeling of pre-stimulus magnetoencephalography data revealed a stronger illusion-related modulation of cross-modal connectivity from auditory to visual cortices in older compared to younger adults. We interpret this as the neural correlate of increased reliance on a cross-modal predictive template in older adults leading to the illusory percept.

In Autism Spectrum Disorders (ASD), impaired response inhibition and lack of adaptation are hypothesized to underlie core ASD symptoms, such as social communication and repetitive, stereotyped behavior. Thus, the aim of the present study was to compare neural correlates of inhibition, post-error adaptation, and reaction time variability in ASD and neuro-typical control (NTC) participants by investigating possible differences in error-related changes of oscillatory MEG activity. Twelve male NTC (mean age 20.3 ± 3.7) and fourteen male patients with ASD (mean age 17.8 ± 2.9) were included in the analysis. Subjects with ASD showed increased error-related reaction time variability. MEG analysis revealed decreased beta power in the ASD group in comparison to the NTC group over the centro-parietal channels in both, the pre-stimulus and post-response interval. In the ASD group, mean centro-parietal beta power negatively correlated with dimensional autism symptoms. In both groups, false alarms were followed by an early increase in temporo-frontal theta to alpha power; and by a later decrease in alpha to beta power at central and posterior sensors. Single trial correlations were additionally studied in the ASD group, who showed a positive correlation of pre-stimulus beta power with post-response theta, alpha, and beta power, particularly after hit trials. On a broader scale, the results deliver important insights into top-down control deficits that may relate to core symptoms observed in ASD.

Objective: To determine whether the performance of multiple sclerosis (MS) patients in the sound-induced flash illusion (SiFi), a multisensory perceptual illusion, would reflect their cognitive impairment. Methods: We performed the SiFi task as well as an extensive neuropsychological testing in 95 subjects [39 patients with relapse-remitting MS (RRMS), 16 subjects with progressive multiple sclerosis (PMS) and 40 healthy control subjects (HC)]. Results: MS patients reported more frequently the multisensory SiFi than HC. In contrast, there were no group differences in the control conditions. Essentially, patients with progressive type of MS continued to perceive the illusion at stimulus onset asynchronies (SOA) that were more than three times longer than the SOA at which the illusion was already disrupted for healthy controls. Furthermore, MS patients' degree of cognitive impairment measured with a broad neuropsychological battery encompassing tests for memory, attention, executive functions, and fluency was predicted by their performance in the SiFi task for the longest SOA of 500 ms. Conclusions: These findings support the notion that MS patients exhibit an altered multisensory perception in the SiFi task and that their susceptibility to the perceptual illusion is negatively correlated with their neuropsychological test performance. Since MS lesions affect white matter tracts and cortical regions which seem to be involved in the transfer and processing of both crossmodal and cognitive information, this might be one possible explanation for our findings. SiFi might be considered as a brief, non-expensive, language- and education-independent screening test for cognitive deficits in MS patients.

Multisensory integration strongly depends on the temporal proximity between two inputs. In the audio-visual domain, stimulus pairs with delays up to a few hundred milliseconds can be perceived as simultaneous and integrated into a unified percept. Previous research has shown that the size of this temporal window of integration can be narrowed by feedback-guided training on an audio-visual simultaneity judgment task. Yet, it has remained uncertain how the neural network that processes audio-visual asynchronies is affected by the training. In the present study, participants were trained on a 2-interval forced choice audio-visual simultaneity judgment task. We recorded their neural activity with magnetoencephalography in response to three different stimulus onset asynchronies (0 ms, each participant’s individual binding window, 300 ms) before, and one day following training. The Individual Window stimulus onset asynchrony condition was derived by assessing each participant’s point of subjective simultaneity. Training improved performance in both asynchronous stimulus onset conditions (300 ms, Individual Window). Furthermore, beta-band amplitude (12–30 Hz) increased from pre-compared to post-training sessions. This increase moved across central, parietal, and temporal sensors during the time window of 80–410 ms post-stimulus onset. Considering the putative role of beta oscillations in carrying feedback from higher to lower cortical areas, these findings suggest that enhanced top-down modulation of sensory processing is responsible for the improved temporal acuity after training. As beta oscillations can be assumed to also preferentially support neural communication over longer conduction delays, the widespread topography of our effect could indicate that training modulates not only processing within primary sensory cortex, but rather the communication within a large-scale network.

Our ability to select relevant information from the environment is limited by the resolution of attention – i.e., the minimum size of the region that can be selected. Neural mechanisms that underlie this limit and its development are not yet understood. Functional magnetic resonance imaging (fMRI) was performed during an object tracking task in 7- and 11-year-old children, and in young adults. Object tracking activated canonical fronto-parietal attention systems and motion-sensitive area MT in children as young as 7 years. Object tracking performance improved with age, together with stronger recruitment of parietal attention areas and a shift from low-level to higher-level visual areas. Increasing the required resolution of spatial attention – which was implemented by varying the distance between target and distractors in the object tracking task – led to activation increases in fronto-insular cortex, medial frontal cortex including anterior cingulate cortex (ACC) and supplementary motor area, superior colliculi, and thalamus. This core circuitry for attentional precision was recruited by all age groups, but ACC showed an age-related activation reduction. Our results suggest that age-related improvements in selective visual attention and in the resolution of attention are characterized by an increased use of more functionally specialized brain regions during the course of development.

The neurophysiological underpinnings of the nonsocial symptoms of autism spectrum disorder (ASD) which include sensory and perceptual atypicalities remain poorly understood. Well-known accounts of less dominant top-down influences and more dominant bottom-up processes compete to explain these characteristics. These accounts have been recently embedded in the popular framework of predictive coding theory. To differentiate between competing accounts, we studied altered information dynamics in ASD by quantifying predictable information in neural signals. Predictable information in neural signals measures the amount of stored information that is used for the next time step of a neural process. Thus, predictable information limits the (prior) information which might be available for other brain areas, for example, to build predictions for upcoming sensory information. We studied predictable information in neural signals based on resting-state magnetoencephalography (MEG) recordings of 19 ASD patients and 19 neurotypical controls aged between 14 and 27 years. Using whole-brain beamformer source analysis, we found reduced predictable information in ASD patients across the whole brain, but in particular in posterior regions of the default mode network. In these regions, epoch-by-epoch predictable information was positively correlated with source power in the alpha and beta frequency range as well as autocorrelation decay time. Predictable information in precuneus and cerebellum was negatively associated with nonsocial symptom severity, indicating a relevance of the analysis of predictable information for clinical research in ASD. Our findings are compatible with the assumption that use or precision of prior knowledge is reduced in ASD patients.

In the later stages of addiction, automatized processes play a prominent role in guiding drug-seeking and drug-taking behavior. However, little is known about the neural correlates of automatized drug-taking skills and drugrelated action knowledge in humans. We employed functional magnetic resonance imaging (fMRI) while smokers and non-smokers performed an orientation affordance task, where compatibility between the hand used for a behavioral response and the spatial orientation of a priming stimulus leads to shorter reaction times resulting from activation of the corresponding motor representations. While non-smokers exhibited this behavioral effect only for control objects, smokers showed the affordance effect for both control and smoking-related objects. Furthermore, smokers exhibited reduced fMRI activation for smoking-related as compared to control objects for compatible stimulus-response pairings in a sensorimotor brain network consisting of the right primary motor cortex, supplementary motor area, middle occipital gyrus, left fusiform gyrus and bilateral cingulate gyrus. In the incompatible condition, we found higher fMRI activation in smokers for smoking-related as compared to control objects in the right primary motor cortex, cingulate gyrus, and left fusiform gyrus. This suggests that the activation and performance of deeply embedded, automatized drug-taking schemata employ less brain resources. This might reduce the threshold for relapsing in individuals trying to abstain from smoking. In contrast, the interruption or modification of already triggered automatized action representations require increased neural resources.

Addiction is a significant health burden with a major impact on society. Its neural underpinnings have been extensively studied in animal experiments and human neuroimaging studies, which have demonstrated that during addiction various reorganizational processes hijack the reward and habit systems. Thus, subcortical and cortical brain regions become involved in pathological learning and maintenance of incentive values and automatized actions, which consequently contribute to the emergence and persistence of addiction. Reward-related processes that are affected predominantly during early stages of addiction comprise the ventral tegmental area, ventral and dorsomedial striatum, amygdala, hippocampus, orbitofrontal/medial prefrontal cortex, anterior cingulate cortex, and insula. Habit-related mechanisms are under the control of a more complex network including interconnections between the ventral tegmental area, ventral and dorsolateral striatum, parts of the amygdala, and cortical regions such as premotor and motor cortex, parietal and inferior/middle temporal cortex, as well as the cerebellum.

Visuo-haptic integration contributes essentially to object shape recognition. Although there has been a considerable advance in elucidating the neural underpinnings of multisensory perception, it is still unclear whether seeing an object and exploring it with the dominant hand elicits the same brain response as compared to the non-dominant hand. Using fMRI to measure brain activation in right-handed participants, we found that for both left- and right-hand stimulation the left lateral occipital complex (LOC) and anterior cerebellum (aCER) were involved in visuo-haptic integration of familiar objects. These two brain regions were then further investigated in another study, where unfamiliar, novel objects were presented to a different group of right-handers. Here the left LOC and aCER were more strongly activated by bimodal than unimodal stimuli only when the left but not the right hand was used. A direct comparison indicated that the multisensory gain of the fMRI activation was significantly higher for the left than the right hand. These findings are in line with the principle of "inverse effectiveness", implying that processing of bimodally presented stimuli is particularly enhanced when the unimodal stimuli are weak. This applies also when right-handed subjects see and simultaneously touch unfamiliar objects with their non-dominant left hand. Thus, the fMRI signal in the left LOC and aCER induced by visuo-haptic stimulation is dependent on which hand was employed for haptic exploration.

Previous studies investigating mild cognitive impairment (MCI) have focused primarily on cognitive, memory, attention, and executive function deficits. There has been relatively little research on the perceptual deficits people with MCI may exhibit. This is surprising given that it has been suggested that sensory and cognitive functions share a common cortical framework [1]. In the following study, we presented the sound-induced flash illusion (SiFi) to a group of participants with mild cognitive impairment (MCI) and healthy controls (HC). The SiFi is an audio-visual illusion whereby two-beeps and one-flash are presented. Participants tend to perceive two flashes when the time-interval between the auditory beeps is small [2, 3]. Participants with MCI perceived significantly more illusions compared to HC over longer auditory time-intervals. This suggests that MCIs integrate more (arguably irrelevant) audiovisual information compared to HCs. By incorporating perceptual tasks into a clinical diagnosis it may be possible to gain a more comprehensive understanding into the disease, as well as provide a more accurate diagnose to those who may have a language impairment.

In this article, we review a recent paper by Stevenson et al. (J Neurosci 34: 691-697, 2014). This paper illustrates the need to present different forms of stimuli in order to characterize the perceptual abilities of people with autism spectrum disorder (ASD). Furthermore, we will discuss their behavioral results and offer an opposing viewpoint to the suggested neuronal drivers of ASD.

32 In this article, we review the paper Multisensory Temporal Integration in Autism Spectrum 33 Disorders, by Stevenson et al. (2014). This paper illustrates the need to present different forms of 34 stimuli in order to characterize the perceptual abilities of people with autism spectrum disorder (ASD). 35 Furthermore, we will discuss their behavioral results and offer an opposing viewpoint to the suggested 36 neuronal drivers of ASD. 37

Human neuroimaging studies suggest that neural cue reactivity is strongly associated with indices of drug use, including addiction severity and treatment success. However, little is known about factors that modulate cue reactivity. The goal of this review, in which we survey published fMRI and PET studies on drug cue reactivity in cocaine, alcohol, and tobacco cigarette users, is to highlight major factors that modulate brain reactivity to drug cues. First, we describe cue reactivity paradigms used in neuroimaging research and outline the brain circuits that underlie cue reactivity. We then discuss major factors that have been shown to modulate cue reactivity and review specific evidence as well as outstanding questions related to each factor. Building on previous model-building reviews on the topic, we then outline a simplified model that includes the key modulatory factors and a tentative ranking of their relative impact. We conclude with a discussion of outstanding challenges and future research directions, which can inform future neuroimaging studies as well as the design of treatment and prevention programs.

The most common form of synaesthesia is grapheme colour synaesthesia. However, rarer forms of synaesthesia also exist, such as word gustatory and olfactory gustatory synaesthesia, whereby a word or smell will induce a specific. In this study we describe a single individual (LJ) who experiences a concurrent olfactory stimulus when presented with congruent visual images. For some visual stimuli, he perceives a strong and automatic olfactory percept, which has existed throughout his life. In this study, we explore whether his experiences are a new form of synaesthesia or simply vivid imagery. Unlike other forms of synaesthesia, the concurrent odour is congruent to the visual inducer. For example, a photograph of dress shoes will elicit the smell of leather. We presented LJ and several control participants with 75 images of everyday objects. Their task was to indicate the strength of any perceived odours induced by the visual images. LJ rated several of the images as inducing a concurrent odour, while controls did not have any such percept. Images that LJ reported as inducing the strongest odours were used, along with colour-matched control images, in the context of an fMRI experiment. Participants were given a one-back task to maintain attention. A block-design odour localizer was presented to localize the piriform cortex (primary olfactory cortex). We found an increased BOLD response in the piriform cortex for the odour-inducing images compared to the control images in LJ. There was no difference in BOLD response between these two stimulus types in the control participants. A subsequent olfactory imagery task did not elicit enhanced activity in the piriform cortex in LJ, suggesting his perceptual experiences may not be based on olfactory imagery.

The car dependence of people living in contemporary cities is a major concern for policy makers, who often find it difficult to persuade people into more sustainable transport modes. By contrast, recent insights from neuroscience have shown that a broad spectrum of behaviors can become habitual and, thus, resistant to change. Here, we outline the potential of collaboration between neuroscience and human geography aiming at a better understanding of habits that determine everyday commuting routines.

The McGurk-effect (McGurk and MacDonald, 1976) is a robust illusion which is broadly studied in the context of audiovisual integration. In the illusion, auditory speech perception is modified by discrepant visual lip-movements when presented synchronously, leading to a third, not physically present percept. There is an ongoing debate as to whether the percept is integrated early in the sensory system or if it is susceptible to cognitive intervention. Here, the McGurk-effect was studied using gender congruency (face/voice stimuli) as the cognitive intervention to address the question of integration. We first investigated changes in prevalence and reaction times due to perceived gender discrepancy during the McGurk-percept. In the second experiment, neural correlates of the gender discrepant McGurk-percept were studied using fMRI. We did not find differences in reaction times or accuracy between gender congruent or incongruent stimuli. Thus it appears the McGurk-percept itself is unaffected by gender incongruent stimuli on a behavioural level. In the fMRI experiment, we found the superior temporal gyrus to reveal a significantly increased activity when the McGurk-effect is perceived as compared to non-McGurk trials, but no effect in this area was found for gender congruency. However, a 2 × 2 whole brain ANOVA revealed a significant interaction in the face identity processing area (fusiform gyrus) as well as inferior parietal gyrus and superior colliculus. We suggest a mechanism, allowing a stable illusory percept in the gender discrepant McGurk-percept to be facilitated. To our knowledge this is the first study to demonstrate on a neural level that gender congruency affects processing of the McGurk-effect.