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Facial emotion perception can be studied from the point of view of dynamic systems whose output may depend not only on current input but also on prior history — a phenomenon known as hysteresis. In cognitive neuroscience, hysteresis has been described as positive (perceptual persistence) or negative (fatigue of current percept) depending on whether perceptual switching occurs later or earlier than actual physical stimulus changes. However, its neural correlates remain elusive. We used dynamic transitions between emotional expressions and combined behavioral assessment with functional magnetic resonance imaging (fMRI) to investigate the underlying circuitry of perceptual hysteresis in facial emotion recognition. Our findings revealed the involvement of face-selective visual areas — fusiform face area (FFA) and superior temporal sulcus (STS) — in perceptual persistence as well as the right anterior insula. Moreover, functional connectivity analyses revealed an interplay between the right anterior insula and medial prefrontal cortex, which showed to be dependent on the presence of positive hysteresis. Our results support the hypothesis that high-order regions are involved in perceptual stabilization and decision during perceptual persistence (positive hysteresis) and add evidence to the role of the anterior insula as a hub of sensory information in perceptual decision-making.

Software programming is a modern activity that poses strong challenges to the human brain. The neural mechanisms that support this novel cognitive faculty are still unknown. On the other hand, reading and calculation abilities represent slightly less recent human activities, in which neural correlates are relatively well understood. We hypothesize that calculus and reading brain networks provide joint underpinnings with distinctly weighted contributions which concern programming tasks, in particular concerning error identification. Based on a meta-analysis of the core regions involved in both reading and math and recent experimental evidence on the neural basis of programming tasks, we provide a theoretical account that integrates the role of these networks in program understanding. In this connectivity-based framework, error-monitoring processing regions in the frontal cortex influence the insula, which is a pivotal hub within the salience network, leading into efficient causal modulation of parietal networks involved in reading and mathematical operations. The core role of the anterior insula and anterior midcingulate cortex is illuminated by their relation to performance in error processing and novelty. The larger similarity that we observed between the networks underlying calculus and programming skills does not exclude a more limited but clear overlap with the reading network, albeit with differences in hemispheric lateralization when compared with prose reading. Future work should further elucidate whether other features of computer program understanding also use distinct weights of phylogenetically “older systems” for this recent human activity, based on the adjusting influence of fronto-insular networks. By unraveling the neural correlates of program understanding and bug detection, this work provides a framework to understand error monitoring in this novel complex faculty.

Deficits in mitochondrial function and redox deregulation have been attributed to Huntington's disease (HD), a genetic neurodegenerative disorder largely affecting the striatum. However, whether these changes occur in early stages of the disease and can be detected in vivo is still unclear. In the present study, we analysed changes in mitochondrial function and production of reactive oxygen species (ROS) at early stages and with disease progression. Studies were performed in vivo in human brain by PET using [

Machado-Joseph disease (MJD) or Spinocerebellar ataxia type 3 (SCA3) is the most common form of dominant SCA worldwide. Magnetic Resonance Imaging (MRI) and Proton Magnetic Resonance Spectroscopy (1H-MRS) provide promising non-invasive diagnostic and follow-up tools, also serving to evaluate therapies efficacy. However, pre-clinical studies showing relationship between MRI-MRS based biomarkers and functional performance are missing, which hampers an efficient clinical translation of therapeutics. This study assessed motor behaviour, neurochemical profiles, and morphometry of the cerebellum of MJD transgenic mice and patients aiming at establishing magnetic-resonance-based biomarkers. 1H-MRS and structural MRI measurements of MJD transgenic mice were performed with a 9.4 Tesla scanner, correlated with motor performance on rotarod and compared with data collected from human patients. We found decreased cerebellar white and grey matter and enlargement of the fourth ventricle in both MJD mice and human patients as compared to controls. N-acetylaspartate (NAA), NAA + N-acetylaspartylglutamate (NAA + NAAG), Glutamate, and Taurine, were significantly decreased in MJD mouse cerebellum regardless of age, whereas myo-Inositol (Ins) was increased at early time-points. Lower neurochemical ratios levels (NAA/Ins and NAA/total Choline), previously correlated with worse clinical status in SCAs, were also observed in MJD mice cerebella. NAA, NAA + NAAG, Glutamate, and Taurine were also positively correlated with MJD mice motor performance. Importantly, these 1H-MRS results were largely analogous to those found for MJD in human studies and in our pilot data in human patients. We have established a magnetic resonance-based biomarker approach to monitor novel therapies in preclinical studies and human clinical trials.

Error monitoring is the metacognitive process by which we are able to detect and signal our errors once a response has been made. Monitoring when the outcome of our actions deviates from the intended goal is crucial for behavior, learning, and the development of higher-order social skills. Here, we explored the neuronal substrates of error monitoring during the integration of facial expression cues using electroencephalography (EEG). Our goal was to investigate the signatures of error monitoring before and after a response execution dependent on the integration of facial cues. We followed the hypothesis of midfrontal theta as a robust neuronal marker of error monitoring since it has been consistently described as a mechanism to signal the need for cognitive control. Also, we hypothesized that EEG frequency-domain components might bring advantage to study error monitoring in complex scenarios as it carries information from locked and non-phase-locked signals. A challenging go/no-go saccadic paradigm was applied to elicit errors: integration of facial emotional signals and gaze direction was required to solve it. EEG data were acquired from twenty healthy participants and analyzed at the level of theta band activity during response preparation and execution. Although theta modulation has been consistently demonstrated during error monitoring, it is still unclear how early it starts to occur. We found theta power differences at midfrontal channels between correct and error trials. Theta was higher immediately after erroneous responses. Moreover, before response initiation we observed the opposite: lower theta preceding errors. These results suggest theta band activity not only as an index of error monitoring, which is needed to enhance cognitive control, but also as a requisite for success. This study adds to previous evidence for the role of theta band in error monitoring processes by revealing error-related patterns even before response execution in complex tasks, and using a paradigm requiring the integration of facial expression cues.

While dynamic ocular motor abnormalities (e.g., gaze-evoked nystagmus (GEN), low optokinetic nystagmus (OKN), pursuit and vestibulo-ocular reflex (VOR) gains, and dysmetric saccades) have been shown to be potential biomarkers in spinocerebellar ataxia type 3 (SCA3), the value of static abnormalities (e.g., convergent [esodeviation] and divergent strabismus [exodeviation]) is unknown. Moreover, studies on dynamic abnormalities in SCA3 usually do not take into account the existence of potential abduction-adduction asymmetries in patients with degenerative ataxia. Thirty-eight patients with genetically confirmed SCA3 (24 females; mean age ± SD, 49.8± 12.2 years) and 22 healthy controls (12 females, p = 0.589; mean age ± SD, 50.7± 12.5 years, p = 0.651) underwent clinical and video-oculographic assessment. A p value 0.002 (between- and within-group analyses) and 0.001 (correlation analysis) was considered significant. Patients showed larger esodeviation at distance (p 0.001), became more esodeviated in lateral gaze (p 0.001), and their near exodeviation correlated with scale for the assessment and rating of ataxia (SARA) score (p = 0.004). Pursuit, OKN, and VOR gains were lower in patients, both for their adducting and abducting components (p 0.001). Saccades showed higher velocities (p 0.001), abducting saccades showed lower amplitude (p 0.001), and adducting saccades tended to show greater vertical bias (p = 0.018) in patients. Abducting saccades showed relatively lower velocity (p 0.001) and lower amplitude (p = 0.015) than abducting saccades within patients. All dynamic ocular motor abnormalities except saccades correlated with SARA score, CAG repeat number, and/or disease duration (p 0.001). Static and dynamic ocular motor abnormalities are potential biomarkers in SCA3. SCA3 studies using saccades should take into account the existence of potential abduction-adduction asymmetries.

Several studies highlighted the role of insula on several functions and in sexual behavior. This exploratory study examines the relationships among genital responses, brain responses, and eye movements, to disentangle the role played by the anterior and posterior insula during different stages of male sexual response and during visual attention to sexual stimuli. In 19 healthy men, fMRI, eye movement, and penile tumescence data were collected during a visual sexual stimulation task. After a whole-brain analysis comparing neutral and sexual clips and confirming a role for the bilateral insulae, we selected two bilateral seed regions in anterior and posterior insula for functional connectivity analysis. Single-ROI-GLMs were run for the FC target regions. Single-ROI-GLMs were performed based on areas to which participants fixate: "Faces", "Genitals," and "Background" with the contrast "Genitals > Faces". Single-ROI-GLMs with baseline, onset, and sustained PT response for the sexual clips were performed. We found stronger effects for the posterior than the anterior insula. In the target regions of the posterior insula, we found three different pathways: the first involved in visual attention, onset of erection, and sustained erection; the second involved only in the onset of erection, and the third limited to sustained erection. ispartof: SCIENTIFIC REPORTS vol:10 issue:1 ispartof: location:England status: published

The human visual system is constantly processing multiple and often conflicting sensory cues to make perceptual decisions. Given the nonlinear nature of emotion recognition, this often leads to different percepts of the same physical facial expression. Moreover, the state of the emotion recognition system might depend on the trajectory of temporal context, potentially leading to a phenomenon known as perceptual hysteresis. Here, we aimed to explore temporal context-related mechanisms underlying perceptual hysteresis during emotion recognition. We hypothesized that dependence on recent perceptual experience might reveal important clues about the role of short-term memory on the perception of emotional stimuli. Behavioral data were acquired using reality-based, changing emotion expressions morphed from a source to a target emotion with different valences, always passing through a neutral expression. Participants identified the onset and offset of what they perceived as the neutral expression interval. Our results showed that current perception of emotional expression is affected by recent temporal context, thus revealing perceptual hysteresis. We also found a relation between recent perceptual history effects and stimulus emotional Content: The positive valence of the stimulus emotional content appeared to abolish perceptual history effects, whereas negatively loaded stimuli induced clear short-term memory effects and positive hysteresis. Our findings show direct competition between recent perceptual experience and stimulus emotional content during decision making, which affects the formation of current percepts in emotion recognition.

Software programming is a complex and relatively recent human activity, involving the integration of mathematical, recursive thinking and language processing. The neural correlates of this recent human activity are still poorly understood. Error monitoring during this type of task, requiring the integration of language, logical symbol manipulation and other mathematical skills, is particularly challenging. We therefore aimed to investigate the neural correlates of decision-making during source code understanding and mental manipulation in professional participants with high expertise. The present fMRI study directly addressed error monitoring during source code comprehension, expert bug detection and decision-making. We used C code, which triggers the same sort of processing irrespective of the native language of the programmer. We discovered a distinct role for the insula in bug monitoring and detection and a novel connectivity pattern that goes beyond the expected activation pattern evoked by source code understanding in semantic language and mathematical processing regions. Importantly, insula activity levels were critically related to the quality of error detection, involving intuition, as signalled by reported initial bug suspicion, prior to final decision and bug detection. Activity in this salience network (SN) region evoked by bug suspicion was predictive of bug detection precision, suggesting that it encodes the quality of the behavioral evidence. Connectivity analysis provided evidence for top-down circuit “reutilization” stemming from anterior cingulate cortex (BA32), a core region in the SN that evolved for complex error monitoring such as required for this type of recent human activity. Cingulate (BA32) and anterolateral (BA10) frontal regions causally modulated decision processes in the insula, which in turn was related to activity of math processing regions in early parietal cortex. In other words, earlier brain regions used during evolution for other functions seem to be reutilized in a top-down manner for a new complex function, in an analogous manner as described for other cultural creations such as reading and literacy. Electronic supplementary material The online version of this article (10.1007/s11682-018-9885-1) contains supplementary material, which is available to authorized users.

This study aimed to explore the differential role of the frontoparietal network in processing different visual object categories, matched for difficulty level, during a 1-back paradigm. To achieve this goal, we first mapped the effort-related frontoparietal saliency network, by contrasting activation elicited by face, object, place, body and verbal stimulus categories, which were matched for performance level, and speed of processing, with difficult scrambled stimuli. We then computed the weight of object predictors on that specific network, using an independent orthogonal analysis. Overall, our results demonstrated that face (and to some extent also places) stimuli were associated with lower processing load in regions of the frontoparietal network comparing to other visual categories, suggesting that face/place processing does require to a much smaller extent the recruitment of the frontoparietal control network than any other object categories. Thus, face detection and place detection seem to be routed in specific neuronal systems that readily encode the holistic nature of this type of objects. We conclude that the more limited recruitment of frontoparietal networks reflects the automaticity of face and place processing and their smaller dependence on general capacity limits.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder showing predominant brainstem involvement, characterized by marked slowing of rapid eye movements (saccades), particularly along the vertical plane. While the contribution of the brainstem damage for the saccadic disturbance in PSP has been extensively studied, much less is known about its cortical and subcortical pathomechanisms. We measured reflexive (prosaccades) and voluntary (antisaccades) saccades in the vertical and horizontal plane in PSP patients (n=8) and controls (n=10) in an eye tracking study, followed by the measurement of blood oxygenation-level dependent (BOLD) activation (PSP, n=6; controls, n=10) during similar saccade paradigms. Behaviorally, PSP patients evidenced slower and lower amplitude prosaccades (horizontal and vertical) and lower amplitude antisaccades (vertical) than controls. Functionally, patients showed decreased frontostriatal BOLD activation during prosaccades (horizontal and vertical) and antisaccades (vertical), relative to controls. Additionally, PSP patients showed less default mode network (DMN) deactivation than controls for all types of saccades. Within groups, controls showed no BOLD differences between horizontal and vertical prosaccades while PSP patients demonstrated greater DMN deactivation during vertical prosaccades. Both groups evidenced greater DMN deactivation during vertical antisaccades when compared to their horizontal counterpart and patients further showed relative frontostriatal BOLD hypoactivity during vertical antisaccades. We found fMRI evidence of frontostriatal hypoactivity in PSP patients relative to controls, especially during vertical saccades. These new findings highlight the impact of cortical impairment in saccadic disturbance of PSP.

Background The success of translational research depends on how well animal models mimic the pathophysiology of the human phenotype, and on the identification of disease mechanisms such as enhanced glycation. Methods Here, we studied cardiac MRI and metabolic phenotypes in human type 2 diabetes (N = 106; 55 patients+51 controls) and animal models with distinct levels of fat diet and end glycation products, to model the role of these factors in the cardiac phenotype. We included four groups of rats, designed to evaluate the role of lipid load and glucotoxicity in cardiac function and to correlate these with the cardiac phenotype observed in humans. We also aimed to assess into which extent phenotypes were related to specific risk factors. Results Stroke Volume (SV) and Peak Filling Rate (PFR) measures were similarly discriminative both in humans and animal models, particularly when enhanced glycation was present. Factorial analysis showed that reduction of multidimensionality into common main explanatory factors, in humans and animals, revealed components that equally explained the variance of cardiac phenotypes (87.62% and 83.75%, respectively). One of the components included, both in humans and animals, SV, PFR and peak ejection rate (PER). The other components included in both humans and animals are the following: ESV (end systolic volume), left ventricular mass (LVM) and ejection fraction (EF). These components were useful for between group discrimination. Conclusions We conclude that animal models of enhanced glycation and human type 2 diabetes share a striking similarity of cardiac phenotypic components and relation with metabolic changes, independently of fact content in the diet, which reinforces the role of glucose dysmetabolism in left ventricular dysfunction and provides a potentially useful approach for translational research in diabetes, in particular when testing new therapies early on during the natural history of this condition.

The study of the physiological effects underlying brain response to transcranial magnetic stimulation is important to understand its impact on neurorehabilitation. We aim to analyze the impact of a transcranial magnetic stimulation protocol, the continuous theta burst (cTBS), on human neurophysiology, particularly on contralateral motor rhythms. cTBS was applied in 20 subjects over the primary motor cortex. We recorded brain electrical activity pre- and post-cTBS with electroencephalography both at rest and while performing motor tasks, to evaluate changes in brain oscillatory patterns such as mu and beta rhythms. Moreover, we measured motor-evoked potentials before and after cTBS to assess its impact on brain's excitability. On the hemisphere contralateral to the protocol, we did observe a significant increase in mu (p = 0.027) and beta (p = 0.006) rhythms from pre- to post-cTBS, at the beginning of arm elevation. The topology of action planning and motor execution suggests that cTBS produced an inhibitory effect that propagated to the contralateral hemisphere, thereby precluding the expected/desired excitation for therapy purposes. This novel approach provides support for the notion that this protocol induces inhibitory changes in contralateral motor rhythms, by decreasing desynchronization, contradicting the ipsilateral inhibition vs. contralateral disinhibition hypothesis. Our results have implications for personalized cTBS usage as a rehabilitation intervention, suggesting that an unexpected propagation of inhibition can occur.

This study aims to investigate the relationship between structural changes in the retina and white matter in the brain, in early Alzheimer's disease (AD). Twenty-three healthy controls (mean age = 63.4±7.5 years) and seventeen AD patients (mean age = 66.5±6.6 years) were recruited for this study. By combining two imaging techniques-optical coherence tomography and diffusion tensor imaging (DTI)-the association between changes in the thickness of individual retinal layers and white matter dysfunction in early AD was assessed. Retinal layers were segmented, and thickness measurements were obtained for each layer. DTI images were analyzed with a quantitative data-driven approach to evaluating whole-brain diffusion metrics, using tract-based spatial statistics. Diffusion metrics, such as fractional anisotropy, are markers for white matter integrity. Multivariate and partial correlation analyses evaluating the association between individual retinal layers thickness and diffusion metrics were performed. We found that axial diffusivity, indexing axonal integrity, was significantly reduced in AD (p = 0.016, Cohen's d = 1.004) while in the retina, only a marginal trend for significance was found for the outer plexiform layer (p = 0.084, Cohen's d = 0.688). Furthermore, a positive association was found in the AD group between fractional anisotropy and the inner nuclear layer thickness (p < 0.05, r = 0.419, corrected for multiple comparisons by controlling family-wise error rate). Our findings suggest that axonal damage in the brain dominates early on in this condition and shows an association with retinal structural integrity already at initial stages of AD. These findings are consistent with an early axonal degeneration mechanism in AD.

Saccadic behaviour ranges from reflexive (e.g., prosaccade) to goal oriented voluntary movements (e.g., antisaccade). Behavioural asymmetries between vertical and horizontal saccades have been described both in normal individuals (greater delay of vertical prosaccades) and in disease states such as Parkinson's disease (PD) (prosaccades are short and antisaccades are delayed, especially in the vertical plane, possibly due to a frontostriatal deficit). Importantly, the cortical mechanisms for the generation of vertical saccades are largely unknown, both in health and disease, when compared with their horizontal counterpart. Moreover, studies exploring saccadic neural correlates and putative compensatory mechanisms at a functional level in PD are scarce. We investigated horizontal and vertical prosaccades and antisaccades in an eye tracking paradigm in 19 PD patients off medication and 22 healthy controls, followed by a block-design functional Magnetic Resonance Imaging (fMRI) study, consisting of two runs (prosaccade, antisaccade) of 6 blocks each (3 vertical, 3 horizontal). While saccade metrics were not significantly different between groups, PD showed left frontal underactivation during horizontal prosaccades and right parietal overactivation during horizontal and vertical prosaccades and horizontal antisaccades. Moreover, controls showed greater deactivation of the default-mode network (DMN) during antisaccades. Vertical prosaccades were associated with greater right frontal and cerebellar activity in controls, and cuneus hypoactivity in PD. Vertical antisaccades were associated with greater DMN deactivation in both groups and left frontal hypoactivity in PD. Putative functional compensatory changes in the right parietal cortex in PD patients may help to keep saccadic behaviour at the same level as the healthy controls. We provide first time evidence showing that functional cortical asymmetries between vertical and horizontal saccades occur distinctively in PD patients and healthy controls.

Objective Electroencephalographic biomarkers have been widely investigated in autism, in the search for diagnostic, prognostic and therapeutic outcome measures. Here we took advantage of the information available in temporal oscillatory patterns evoked by simple perceptual decisions to investigate whether stimulus dependent oscillatory signatures can be used as potential biomarkers in autism spectrum disorder (ASD). Methods We studied an extensive set of stimuli (9 categories of faces) and performed data driven classification (Support vector machine, SVM) of ASD vs. Controls with features based on the EEG power responses. We carried out an extensive time-frequency and synchrony analysis of distinct face categories requiring different processing mechanisms in terms of non-holistic vs. holistic processing. Results We found that the neuronal oscillatory responses of low gamma frequency band, locked to photographic and abstract two-tone (Mooney) face stimulus presentation are decreased in ASD vs. the control group. We also found decreased time-frequency (TF) responses in the beta band in ASD after 350 ms, possibly related to motor preparation. On the other hand, synchrony in the 30–45 Hz band showed a distinct spatial pattern in ASD. These power changes enabled accurate classification of ASD with an SVM approach. SVM accuracy was approximately 85%. ROC curves showed about 94% AUC (area under the curve). Combination of Mooney and Photographic face stimuli evoked features enabled a better separation between groups, reaching an AUC of 98.6%. Conclusion We identified a relative decrease in EEG responses to face stimuli in ASD in the beta (15–30 Hz; >350 ms) and gamma (30–45 Hz; 55–80 Hz; 50–350 ms) frequency ranges. These can be used as input of a machine learning approach to separate between groups with high accuracy. Significance Future studies can use EEG time-frequency patterns evoked by particular types of faces as a diagnostic biomarker and potentially as outcome measures in therapeutic trials.

Positron emission tomography (PET) neuroimaging with the Pittsburgh Compound_B (PiB) is widely used to assess amyloid plaque burden. Standard quantification approaches normalize PiB-PET by mean cerebellar gray matter uptake. Previous studies suggested similar pons and white-matter uptake in Alzheimer's disease (AD) and healthy controls (HC), but lack exhaustive comparison of normalization across the three regions, with data-driven diagnostic classification. We aimed to compare the impact of distinct reference regions in normalization, measured by data-driven statistical analysis, and correlation with cerebrospinal fluid (CSF) amyloid β (Aβ) species concentrations. 243 individuals with clinical diagnosis of AD, HC, mild cognitive impairment (MCI) and other dementias, from the Biomarkers for Alzheimer's/Parkinson's Disease (BIOMARKAPD) initiative were included. PiB-PET images and CSF concentrations of Aβ38, Aβ40 and Aβ42 were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF Aβ concentrations were calculated. Normalization by cerebellar gray matter and pons yielded identical classification accuracy of AD (accuracy-96%, sensitivity-96%, specificity-95%), and significantly higher than Aβ concentrations (best accuracy 91%). Normalization by the white-matter showed decreased extent of statistically significant multivoxel patterns and was the only method not outperforming CSF biomarkers, suggesting statistical inferiority. Aβ38 and Aβ40 correlated negatively with PiB-PET images normalized by the white-matter, corroborating previous observations of correlations with non-AD-specific subcortical changes in white-matter. In general, when using the pons as reference region, higher voxel-wise group differences and stronger correlation with Aβ42, the Aβ42/Aβ40 or Aβ42/Aβ38 ratios were found compared to normalization based on cerebellar gray matter., Highlights • Direct multivariate comparison of distinct reference regions in normalization of PET amyloid markers • Using the pons as ROI, higher voxel-wise group differences emerge • Using the pons as ROIs stronger correlation with Aβ42, the Aβ42/Aβ40 or Aβ42/Aβ38 ratios were found. • Evidence for statistical inferiority of CSF biomarkers • Aβ38 and Aβ40 correlated negatively with PiB-PET white-matter normalized images.

High-frequency activity (HFA) is believed to subserve a functional role in cognition, but these patterns are often not accessible to scalp EEG recordings. Intracranial studies provide a unique opportunity to link the all-encompassing range of high-frequency patterns with holistic perception. We tested whether the functional topography of HFAs (up to 250Hz) is related to perceptual decision-making. Human intracortical data were recorded (6 subjects; >250channels) during an ambiguous object-recognition task. We found a spatial topography of HFAs reflecting processing anterior dorsal and ventral streams, linked to decision independently of the type of processed object/stimulus category. Three distinct regional fingerprints could be identified, with lower gamma frequency patterns (

It remains an outstanding question whether gamma‐band oscillations reflect unitary cognitive processes within the same task. EEG/MEG studies do lack the resolution or coverage to address the highly debated question whether single gamma activity patterns are linked with multiple cognitive modules or alternatively each pattern associates with a specific cognitive module, within the same coherent perceptual task. One way to disentangle these issues would be to provide direct identification of their sources, by combining different techniques. Here, we directly examined these questions by performing simultaneous EEG/fMRI using an ambiguous perception paradigm requiring holistic integration. We found that distinct gamma frequency sub‐bands reflect different neural substrates and cognitive mechanisms when comparing object perception states vs. no categorical perception. A low gamma sub‐band (near 40 Hz) activity was tightly related to the decision making network, and in particular the anterior insula. A high gamma sub‐band (∼60 Hz) could be linked to early visual processing regions. The demonstration of a clear functional topography for distinct gamma sub‐bands within the same task shows that distinct gamma‐band modulations underlie sensory processing and perceptual decision mechanisms. Hum Brain Mapp 35:5219–5235, 2014. 2014 Wiley Periodicals, Inc.

Localized neurodevelopmental defects provide an opportunity to study structure-function correlations in the human nervous system. This unique multimodal case report of epileptogenic dysplasia in the visual cortex allowed exploring visual function across distinct pathways in retinotopic regions and the dorsal stream, in relation to fMRI retinotopic mapping and spike triggered BOLD responses. Pre-surgical EEG/video monitoring, MRI/DTI, EEG/fMRI, PET and SPECT were performed to characterize structure/function correlations in this patient with a very early lesion onset. In addition, we included psychophysical methods (assessing parvo/konio and magnocellular pathways) and retinotopic mapping. We could identify dorsal stream impairment (with extended contrast sensitivity deficits within the input magno system contrasting with more confined parvocellular deficits) with disrupted active visual field input representations in regions neighboring the lesion. Simultaneous EEG/fMRI identified perilesional and retinotopic bilaterally symmetric BOLD deactivation triggered by interictal spikes, which matched the contralateral spread of magnocellular dysfunction revealed in the psychophysical tests. Topographic changes in retinotopic organization further suggested long term functional effects of abnormal electrical discharges during brain development. We conclude that fMRI based visual field cortical mapping shows evidence for retinotopic dissociation between magno and parvocellular function well beyond striate cortex, identifiable in high level dorsal visual representations around visual area V3A which is consistent with the effects of epileptic spike triggered negative BOLD.

The identification and interpretation of facial expressions is an important feature of social cognition. This characteristic is often impaired in various neurodevelopmental disorders. Recent therapeutic approaches to intervene in social communication impairments include neurofeedback (NF). In this study, we present a NF real-time functional Magnetic Resonance Imaging (rt-fMRI), combined with electroencephalography (EEG) to train social communication skills. In this sense, we defined the right Superior Temporal Sulcus as our target region-of-interest. To analyze the correlation between the fMRI regions of interest and the EEG data, we transposed the sources located at the nearest cortical location to the target region. We extracted a set of 75 features from EEG segments and performed a correlation analysis with the brain activations extracted from rt-fMRI in the right pSTS region. The finding of significant correlations of simultaneously measured signals in distinct modalities (EEG and fMRI) is promising. Future studies should address whether the observed correlation levels between local brain activity and scalp measures are sufficient to implement NF approaches.

Saccadic intrusions are involuntary saccades that interrupt fixation and are usually conjugate between eyes.1 Although saccadic intrusions may be seen in healthy individuals, they also accompany certain neurologic disorders (usually manifesting higher frequency or amplitude) including cerebellar disease.2 We present a patient with spinocerebellar ataxia type 3 (SCA3) with an uncommon monocular/disconjugate alternating type of saccadic intrusion.

Human interaction and physical environmental factors are part of the stimuli presented to laboratory animals everyday, influencing their behaviour and physiology and contributing to their welfare. Certain environmental conditions and routine procedures in the animal facility might induce stress responses and when the animal is unable to maintain its homeostasis in the presence of a particular stressor, the animal's wellbeing is threatened. This review article summarizes several published studies on the impact of environmental factors such as light, noise, cage cleaning and in-house transport on welfare and stress of laboratory rats. The behaviour and physiological responses of laboratory rats to different environmental housing conditions and routine procedures are reviewed. Recommendations on the welfare of laboratory rats and refinements in experimental design are discussed and how these can influence and improve the quality of scientific data.

It has been hypothesized that neural synchrony underlies perceptual coherence. The hypothesis of loss of central perceptual coherence has been proposed to be at the origin of abnormal cognition in autism spectrum disorders and Williams syndrome, a neurodevelopmental disorder linked with autism, and a clearcut model for impaired central coherence. We took advantage of this model of impaired holistic processing to test the hypothesis that loss of neural synchrony plays a separable role in visual integration using EEG and a set of experimental tasks requiring coherent integration of local elements leading to 3-D face perception. A profound reorganization of brain activity was identified. Neural synchrony was reduced across stimulus conditions, and this was associated with increased amplitude modulation at 25–45 Hz. This combination of a dramatic loss of synchrony despite increased oscillatory activity is strong evidence that synchrony underlies central coherence. This is the first time, to our knowledge, that dissociation between amplitude and synchrony is reported in a human model of impaired perceptual coherence, suggesting that loss of phase coherence is more directly related to disruption of holistic perception.

Williams syndrome (WS) is a clinical model of dorsal stream vulnerability and impaired visual integration. However, little is still known about the neurophysiological correlates of perceptual integration in this condition. We have used a 3D structure-from-motion (SFM) integrative task to characterize the neuronal underpinnings of 3D perception in WS and to probe whether gamma oscillatory patterns reflect changed holistic perception. Coherent faces were parametrically modulated in 3D depth (three different depth levels) to vary levels of stimulus ambiguity. We have found that the electrophysiological (EEG/ERP) correlates of such holistic percepts were distinct across groups. Independent component analysis demonstrated the presence of a novel component with a late positivity around 200 ms that was absent in controls. Source localization analysis of ERP signals showed a posterior occipital shift in WS and reduced parietal dorsal stream sources. Interestingly, low gamma-band oscillations (20-40 Hz) induced by this 3D perceptual integration task were significantly stronger and sustained during the stimulus presentation in WS whereas high gamma-band oscillations (60-90 Hz) were reduced in this clinical model of impaired visual coherence, as compared to controls. These observations suggest that dorsal stream processing of 3D SFM stimuli has distinct neural correlates in WS and different cognitive strategies are employed by these patients to reach visual coherence. Importantly, we found evidence for the presence of different sub-bands (20-40 Hz/60-90 Hz) within the gamma range which can be dissociated concerning the respective role on the coherent percept formation, both in typical and atypical development.

A current challenge in cognitive neuroscience is to provide an explicit separation of the neural correlates of abstract global decision variables from sensory and integrative ones. In particular, the insular cortex and the adjacent frontal operculum seem to have a crucial but still unclear role in evidence accumulation and decision signaling in perceptual decision-making tasks. Here, we have used a visual decision-making paradigm based on the detection of ambiguous two-tone (Mooney) face stimuli to assess the emergence of holistic percepts. These are constructed using global gestalt rules and not by gradual spatiotemporal increases in sensory evidence. Our paradigm (neurochronometric approach) enabled the experimental separation between multiple cognitive components in perceptual decision validated by both model-driven and data-driven analysis. This strategy allowed for the functional dissection of operculo-insular networks into task related complexes such as anterior (accumulator), middle (decision) and posterior (somatosensory/sensorimotor). We conclude that global perceptual integration based on holistic rules requires a distributed operculo-insular network.

The relation of gamma-band synchrony to holistic perception in which concerns the effects of sensory processing, high level perceptual gestalt formation, motor planning and response is still controversial. To provide a more direct link to emergent perceptual states we have used holistic EEG/ERP paradigms where the moment of perceptual “discovery” of a global pattern was variable. Using a rapid visual presentation of short-lived Mooney objects we found an increase of gamma-band activity locked to perceptual events. Additional experiments using dynamic Mooney stimuli showed that gamma activity increases well before the report of an emergent holistic percept. To confirm these findings in a data driven manner we have further used a support vector machine classification approach to distinguish between perceptual vs. non perceptual states, based on time-frequency features. Sensitivity, specificity and accuracy were all above 95%. Modulations in the 30–75 Hz range were larger for perception states. Interestingly, phase synchrony was larger for perception states for high frequency bands. By focusing on global gestalt mechanisms instead of local processing we conclude that gamma-band activity and synchrony provide a signature of holistic perceptual states of variable onset, which are separable from sensory and motor processing.

Huntington's disease (HD) is a neurodegenerative disorder causing cognitive and motor impairments, evolving to death within 15-20 years after symptom onset. We previously established a mouse model with the entire human HD gene containing 128 CAG repeats (YAC128) which accurately recapitulates the natural history of the human disease. Defined time points in this natural history enable the understanding of longitudinal trajectories from the neurochemical and structural points of view using non-invasive high-resolution multi-modal imaging. Accordingly, we designed a longitudinal structural imaging (MRI and DTI) and spectroscopy (1H-MRS) study in YAC128, at 3, 6, 9 and 12 months of age, at 9.4 T. Structural analysis (MRI/DTI), confirmed that the striatum is the earliest affected brain region, but other regions were also identified through connectivity analysis (pre-frontal cortex, hippocampus, globus pallidus and thalamus), suggesting a striking homology with the human disease. Importantly, we found for the first time, a negative correlation between striatal and hippocampal changes only in YAC128. In fact, the striatum showed accelerated volumetric decay in HD, as opposed to the hippocampus. Neurochemical analysis of the HD striatum suggested early neurometabolic alterations in neurotransmission and metabolism, with a significant increase in striatal GABA levels, and specifically anticorrelated levels of N-acetyl aspartate and taurine, suggesting that the later is homeostatically adjusted for neuroprotection, as neural loss, indicated by the former, is progressing. These results provide novel insights into the natural history of HD and prove a valuable role for longitudinal multi-modal panels of structural and metabolite/neurotransmission in the YAC128 model.

Blood-brain barrier (BBB) disruption is a common feature in neurodegenerative diseases. However, BBB integrity has not been assessed in spinocerebellar ataxias (SCAs) such as Machado-Joseph disease/SCA type 3 (MJD/SCA3), a genetic disorder, triggered by polyglutamine-expanded ataxin-3. To investigate that, BBB integrity was evaluated in a transgenic mouse model of MJD and in human post-mortem brain tissues.Firstly, we investigated the BBB permeability in MJD mice by: i) assessing the extravasation of the Evans blue (EB) dye and blood-borne proteins (e.g fibrinogen) in the cerebellum by immunofluorescence, and ii) in vivo Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI). The presence of ataxin-3 aggregates in brain blood vessels and the levels of tight junction (TJ)-associated proteins were also explored by immunofluorescence and western blotting. Human brain samples were used to confirm BBB permeability by evaluating fibrinogen extravasation, co-localization of ataxin-3 aggregates with brain blood vessels and neuroinflammation.In the cerebellum of the mouse model of MJD, there was a 5-fold increase in EB accumulation when compared to age-matched controls. Moreover, vascular permeability displayed a 13-fold increase demonstrated by DCE-MRI. These results were validated by the 2-fold increase in fibrinogen extravasation in transgenic animals comparing to controls. Interestingly, mutant ataxin-3 aggregates were detected in cerebellar blood vessels of transgenic mice, accompanied by alterations of TJ-associated proteins in cerebellar endothelial cells, namely a 29% decrease in claudin-5 oligomers and a 10-fold increase in an occludin cleavage fragment. These results were validated in post-mortem brain samples from MJD patients as we detected fibrinogen extravasation across BBB, the presence of ataxin-3 aggregates in blood vessels and associated microgliosis.Altogether, our results prove BBB impairment in MJD/SCA3. These findings contribute for a better understanding of the disease mechanisms and opens the opportunity to treat MJD with medicinal products that in normal conditions would not cross the BBB.