Neurofeedback training of executive function in autism spectrum disorder: distinct effects on brain activity levels and compensatory connectivity changes.

BACKGROUND: Deficits in executive function (EF) are consistently reported in autism spectrum disorders (ASD). Tailored cognitive training tools, such as neurofeedback, focused on executive function enhancement might have a significant impact on the daily life functioning of individuals with ASD. We report the first real-time fMRI neurofeedback (rt-fMRI NF) study targeting the left dorsolateral prefrontal cortex (DLPFC) in ASD. METHODS: Thirteen individuals with autism without intellectual disability and seventeen neurotypical individuals completed a rt-fMRI working memory NF paradigm, consisting of subvocal backward recitation of self-generated numeric sequences. We performed a region-of-interest analysis of the DLPFC, whole-brain comparisons between groups and, DLPFC-based functional connectivity. RESULTS: The ASD and control groups were able to modulate DLPFC activity in 84% and 98% of the runs. Activity in the target region was persistently lower in the ASD group, particularly in runs without neurofeedback. Moreover, the ASD group showed lower activity in premotor/motor areas during pre-neurofeedback run than controls, but not in transfer runs, where it was seemingly balanced by higher connectivity between the DLPFC and the motor cortex. Group comparison in the transfer run also showed significant differences in DLPFC-based connectivity between groups, including higher connectivity with areas integrated into the multidemand network (MDN) and the visual cortex. CONCLUSIONS: Neurofeedback seems to induce a higher between-group similarity of the whole-brain activity levels (including the target ROI) which might be promoted by changes in connectivity between the DLPFC and both high and low-level areas, including motor, visual and MDN regions.

Standard Doses of Cholecalciferol Reduce Glucose and Increase Glutamine in Obesity-Related Hypertension: Results of a Randomized Trial.

In arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication. The defined endpoint was the assessment of circulating metabolites using a nuclear magnetic resonance-based metabolomics approach. Univariate and multivariate analyses were used to evaluate the systemic metabolic alterations caused by cholecalciferol. In comparison with normotensive controls, hypertensive patients presented overall decreased expression of several amino acids (p < 0.05), including amino acids with ketogenic and glucogenic properties as well as aromatic amino acids. Following cholecalciferol supplementation, increases were observed in glutamine (p < 0.001) and histidine levels (p < 0.05), with several other amino acids remaining unaffected. Glucose (p < 0.05) and acetate (p < 0.05) decreased after 24 weeks in the group taking the supplement, and changes in the saturation of fatty acids (p < 0.05) were also observed, suggesting a role of liposoluble vitamin D in lipid metabolism. Long-term cholecalciferol supplementation in chronically obese and overweight hypertensives induced changes in the blood serum metabolome, which reflected systemic metabolism and may have fostered a new microenvironment for cell proliferation and biology. Of note, the increased availability of glutamine may be relevant for the proliferation of different T-cell subsets.

The Effects of Tryptamine Psychedelics in the Brain: A meta-Analysis of Functional and Review of Molecular Imaging Studies.

There is an increasing interest in the neural effects of psychoactive drugs, in particular tryptamine psychedelics, which has been incremented by the proposal that they have potential therapeutic benefits, based on their molecular mimicry of serotonin. It is widely believed that they act mainly through 5HT2A receptors but their effects on neural activation of distinct brain systems are not fully understood. We performed a quantitative meta-analysis of brain imaging studies to investigate the effects of substances within this class (e.g., LSD, Psilocybin, DMT, Ayahuasca) in the brain from a molecular and functional point of view. We investigated the question whether the changes in activation patterns and connectivity map into regions with larger 5HT1A/5HT2A receptor binding, as expected from indolaemine hallucinogens (in spite of the often reported emphasis only on 5HT2AR). We did indeed find that regions with changed connectivity and/or activation patterns match regions with high density of 5HT2A receptors, namely visual BA19, visual fusiform regions in BA37, dorsal anterior and posterior cingulate cortex, medial prefrontal cortex, and regions involved in theory of mind such as the surpramarginal gyrus, and temporal cortex (rich in 5HT1A receptors). However, we also found relevant patterns in other brain regions such as dorsolateral prefrontal cortex. Moreover, many of the above-mentioned regions also have a significant density of both 5HT1A/5HT2A receptors, and available PET studies on the effects of psychedelics on receptor occupancy are still quite scarce, precluding a metanalytic approach. Finally, we found a robust neuromodulatory effect in the right amygdala. In sum, the available evidence points towards strong neuromodulatory effects of tryptamine psychedelics in key brain regions involved in mental imagery, theory of mind and affective regulation, pointing to potential therapeutic applications of this class of substances.

Hypoglycaemic and Antioxidant Properties of Acrocomia aculeata (Jacq.) Lodd Ex Mart. Extract Are Associated with Better Vascular Function of Type 2 Diabetic Rats.

Oxidative stress is involved in the metabolic dysregulation of type 2 diabetes (DM2). Acrocomia aculeata (Aa) fruit pulp has been described for the treatment of several diseases, and recently we have proved that its leaves have phenolic compounds with a marked antioxidant effect. We aimed to assess whether they can improve metabolic, redox and vascular functions in DM2. Control Wistar (W-Ctrl) and non-obese type 2 diabetic Goto-Kakizaki (GK-Ctrl) rats were treated for 30 days with 200 mg.kg-1 aqueous extract of Aa (EA-Aa) (Wistar, W-EA-Aa/GK, GK-EA-Aa). EA-Aa was able to reduce fasting glycaemia and triglycerides of GK-EA-Aa by improving proteins related to glucose and lipid metabolism, such as GLUT-4, PPARγ, AMPK, and IR, when compared to GK-Ctrl. It also improved viability of 3T3-L1 pre-adipocytes exposed by H2O2. EA-Aa also increased the levels of catalase in the aorta and kidney, reduced oxidative stress and increased relaxation of the aorta in GK-treated rats in relation to GK-Ctrl, in addition to the protective effect against oxidative stress in HMVec-D cells. We proved the direct antioxidant potential of the chemical compounds of EA-Aa, the increase in antioxidant defences in a tissue-specific manner and hypoglycaemic properties, improving vascular function in type 2 diabetes. EA-Aa and its constituents may have a therapeutic potential for the treatment of DM2 complications.

Training the social brain: Clinical and neural effects of an 8-week real-time functional magnetic resonance imaging neurofeedback Phase IIa Clinical Trial in Autism.

LAY ABSTRACT: Neurofeedback is an emerging therapeutic approach in neuropsychiatric disorders. Its potential application in autism spectrum disorder remains to be tested. Here, we demonstrate the feasibility of real-time functional magnetic resonance imaging volitional neurofeedback in targeting social brain regions in autism spectrum disorder. In this clinical trial, autism spectrum disorder patients were enrolled in a program with five training sessions of neurofeedback. Participants were able to control their own brain activity in this social brain region, with positive clinical and neural effects. Larger, controlled, and blinded clinical studies will be required to confirm the benefits.

Frontoparietal microstructural damage mediates age-dependent working memory decline in face and body information processing: Evidence for dichotomic hemispheric bias mechanisms.

Age-associated damage in the microstructure of frontally-based connections (e.g. genu of the corpus callosum and superior longitudinal fasciculus) is believed to lead to impairments in processing speed and executive function. Using mediation analysis, we tested the potential contribution of callosal and frontoparietal association tracts to age-dependent effects on cognition/executive function as measured with 1-back working memory tasks for visual stimulus categories (i.e. faces and non-emotional bodies) in a group of 55 healthy adults (age range 23-79 years). Constrained spherical deconvolution-based tractography was employed to reconstruct the genu/prefrontal section of the corpus callosum (GCC) and the central/second branch of the superior longitudinal fasciculus (CB-SLF). Age was associated with (i) reductions in fractional anisotropy (FA) in the GCC and in the right and left CB-SLF and (iii) decline in visual object category processing. Mediation analysis revealed that microstructural damage in right hemispheric CB-SLF is associated with age-dependent decline in face processing likely reflecting the stimulus-specific/holistic nature of face processing within dedicated/specialized frontoparietal routes. By contrast, microstructural damage in left hemispheric CB-SLF associated with age-dependent decline in non-emotional body processing, consistent with the more abstract nature of non-emotional body categories. In sum, our findings suggest that frontoparietal microstructural damage mediates age-dependent decline in face and body information processing in a manner that reflects the hemispheric bias of holistic vs. abstract nature of face and non-emotional body category processing.

Peptide-lipid nanoconstructs act site-specifically towards glioblastoma growth impairment.

Ultra-small nanostructured lipid carriers (usNLCs) have been hypothesized to promote site-specific glioblastoma (GB) drug delivery. Envisioning a multitarget purpose towards tumor cells and microenvironment, a surface-bioconjugated usNLC prototype is herein presented. The comeback of co-delivery by repurposing atorvastatin and curcumin, as complementary therapy, was unveiled and characterized, considering colloidal properties, stability, and drug release behavior. Specifically, the impact of the surface modification of usNLCs with hyaluronic acid (HA) conjugates bearing the cRGDfK and H7k(R2)2 peptides, and folic acid (FA) on GB cells was sequentially evaluated, in terms of cytotoxicity, internalization, uptake mechanism and hemolytic character. As proof-of-principle, the biodistribution, tolerability, and efficacy of the nanocarriers were assessed, the latter in GB-bearing mice through magnetic resonance imaging and spectroscopy. The hierarchical modification of the usNLCs promotes a preferential targeting behavior to the brain, while simultaneously sparing the elimination by clearance organs. Moreover, usNLCs were found to be well tolerated by mice and able to impair tumor growth in an orthotopic xenograft model, whereas for mice administered with the non-encapsulated therapeutic compounds, tumor growth exceeded 181% in the same period. Relevant biomarkers extracted from metabolic spectroscopy were ultimately identified as a potential tumor signature.

How much of the BOLD-fMRI signal can be approximated from simultaneous EEG data: relevance for the transfer and dissemination of neurofeedback interventions.

OBJECTIVE: fMRI-based neurofeedback (NF) interventions represent the method of choice for the neuromodulation of localized brain areas. Although we have already validated an fMRI-NF protocol targeting the facial expressions processing network (FEPN), its dissemination is hampered by the economical and logistical constraints of fMRI-NF interventions, which may be however surpassed by transferring it to EEG setups, due to their low cost and portability. One of the major challenges of this procedure is then to reconstruct the BOLD-fMRI signal measured at the FEPN using only EEG signals. Because these types of approaches have been poorly explored so far, here we systematically investigated the extent at which the BOLD-fMRI signal recorded from the FEPN during a fMRI-NF protocol could be reconstructed from the simultaneously recorded EEG signal. APPROACH: Several features from both scalp and source spaces (the latter estimated using continuous EEG source imaging) were extracted and used as predictors in a regression problem using random forests. Furthermore, three different approaches to deal with the hemodynamic delay of the BOLD signal were tested. The resulting models were compared with the only approach already proposed in the literature that uses spectral features and considers different time delays. MAIN RESULTS: The combination of linear and non-linear features (particularly the largest Lyapunov exponent and entropy measures) projected into the source space, spatially filtered by independent component analysis (ICA) and convolved with multiple HRF functions peaking at different latencies, increases significantly the reconstruction accuracy (defined as the correlation between the measured and approximated BOLD signal) from 20% (direct comparison with the method used in the current literature) to 56%. SIGNIFICANCE: With this pipeline, a more accurate reconstruction of the BOLD signal can be obtained, which will positively impact the transfer of fMRI-based neurofeedback interventions to EEG setups, and more importantly, their dissemination and efficacy in modulating the activity of the desired brain areas.

Self-Modulation of Premotor Cortex Interhemispheric Connectivity in a Real-Time Functional Magnetic Resonance Imaging Neurofeedback Study Using an Adaptive Approach.

Recent studies have reported on the feasibility of real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) training. Although modulation of blood oxygenation level-dependent signal of single brain regions in rt-fMRI NF is a well established technique, the same does not hold true for modulation of connectivity. Self-modulation of interregional connectivity is a potential alternative in clinical neuroscience applications, since long-range functional dysconnectivity is being increasingly recognized as a mechanism underlying neuropsychiatric disorders. In this study, a framework was designed to train participants to self-regulate, in real time, interhemispheric functional connectivity between bilateral premotor cortices. To this end, participants use a novel adaptive motor imagery task, with gradual frequency variation preventing activity plateaus and subsequent decreases in correlation of activity (three NF runs). Participants were able to upregulate and maintain interhemispheric connectivity using such adaptive approach, as measured by correlation analysis. Modulation was achieved by simultaneous volitional control of activity in premotor areas. Activation patterns in the downregulation condition led to significantly lower correlation values than those observed in the upregulation condition, in the first two NF runs. Comparison between runs with and without feedback showed enhanced activation in key reward, executive function, and cognitive control regions, suggesting NF promotes reward and the development of goal-directed behavior. This proof-of-principle study suggests that functional connectivity feedback can be used for volitional self-modulation of neuronal connectivity. Functional connectivity-based NF could serve as a possible therapeutic tool in diseases related to the impairment of interhemispheric connectivity, particularly in the context to motor training after stroke.

Targeting dynamic facial processing mechanisms in superior temporal sulcus using a novel fMRI neurofeedback target.

The superior temporal sulcus (STS) encompasses a complex set of regions involved in a wide range of cognitive functions. To understand its functional properties, neuromodulation approaches such brain stimulation or neurofeedback can be used. We investigated whether the posterior STS (pSTS), a core region in the face perception and imagery network, could be specifically identified based on the presence of dynamic facial expressions (and not just on simple motion or static face signals), and probed with neurofeedback. Recognition of facial expressions is critically impaired in autism spectrum disorder, making this region a relevant target for future clinical neurofeedback studies. We used a stringent localizer approach based on the contrast of dynamic facial expressions against static neutral faces plus moving dots. The target region had to be specifically responsive to dynamic facial expressions instead of mere motion and/or the presence of a static face. The localizer was successful in selecting this region across subjects. Neurofeedback was then performed, using this region as a target, with two novel feedback rules (mean or derivative-based, using visual or auditory interfaces). Our results provide evidence that a facial expression-selective cluster in pSTS can be identified and may represent a suitable target for neurofeedback approaches, aiming at social and emotional cognition. These findings highlight the presence of a highly selective region in STS encoding dynamic aspects of facial expressions. Future studies should elucidate its role as a mechanistic target for neurofeedback strategies in clinical disorders of social cognition such as autism.

Age-related differences in event-related potentials and pupillary responses in cued reaction time tasks.

Deficits in the noradrenergic system are associated with age-related cognitive decline, yet how healthy aging influences the functional properties of this arousal system is still poorly understood. We addressed this question in humans using pupillometry, a well-established indicator of activity levels in the locus coeruleus (LC), the main noradrenergic center in the brain. We recorded the pupillogram and the electroencephalogram of 36 young and 39 older adults, while they were engaged in cued reaction time tasks known to elicit LC responses in monkeys. Event-related potentials (ERPs) revealed significant group differences. Older adults showed higher cortical activation during preparatory processes reflected in enhanced cue-evoked frontocentral ERPs and reduced parietal ERPs at the time of the motor response. In contrast, the amplitude of the task-related pupillary responses did not show a significant group effect. Our findings suggest that aging-related changes in cortical processing during motor preparation and execution, as documented by electroencephalogram, are not accompanied by changes in the amplitude of activation of the LC, as documented by pupillography.

A Novel Biomarker of Compensatory Recruitment of Face Emotional Imagery Networks in Autism Spectrum Disorder.

Imagery of facial expressions in Autism Spectrum Disorder (ASD) is likely impaired but has been very difficult to capture at a neurophysiological level. We developed an approach that allowed to directly link observation of emotional expressions and imagery in ASD, and to derive biomarkers that are able to classify abnormal imagery in ASD. To provide a handle between perception and action imagery cycles it is important to use visual stimuli exploring the dynamical nature of emotion representation. We conducted a case-control study providing a link between both visualization and mental imagery of dynamic facial expressions and investigated source responses to pure face-expression contrasts. We were able to replicate the same highly group discriminative neural signatures during action observation (dynamical face expressions) and imagery, in the precuneus. Larger activation in regions involved in imagery for the ASD group suggests that this effect is compensatory. We conducted a machine learning procedure to automatically identify these group differences, based on the EEG activity during mental imagery of facial expressions. We compared two classifiers and achieved an accuracy of 81% using 15 features (both linear and non-linear) of the signal from theta, high-beta and gamma bands extracted from right-parietal locations (matching the precuneus region), further confirming the findings regarding standard statistical analysis. This robust classification of signals resulting from imagery of dynamical expressions in ASD is surprising because it far and significantly exceeds the good classification already achieved with observation of neutral face expressions (74%). This novel neural correlate of emotional imagery in autism could potentially serve as a clinical interventional target for studies designed to improve facial expression recognition, or at least as an intervention biomarker.

A whole brain longitudinal study in the YAC128 mouse model of Huntington's disease shows distinct trajectories of neurochemical, structural connectivity and volumetric changes.

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.

Unisensory and multisensory Self-referential stimulation of the lower limb: An exploratory fMRI study on healthy subjects.

BACKGROUND: The holistic view of the person is the essence of the physiotherapy. Knowledge of approaches that develop the whole person promotes better patient outcomes. Multisensory Self-referential stimulation, more than a unisensory one, seems to produce a holistic experience of the Self ("Core-Self"). OBJECTIVES: (1) To analyze the somatotopic brain activation during unisensory and multisensorial Self-referential stimulus; and (2) to understand if the areas activated by multisensorial Self-referential stimulation are the ones responsible for the "Core-Self." METHODS: An exploratory functional magnetic resonance imaging (fMRI) study was performed with 10 healthy subjects, under the stimulation of the lower limbs with three Self-referential stimuli: unisensory auditory-verbal, unisensory tactile-manual, and multisensory, applying the unisensory stimuli simultaneously. RESULTS: Unisensory stimulation elicits bilateral activations of the temporoparietal junction (TPJ), of the primary somatosensory cortex (S1), of the primary motor cortex (BA4), of the premotor cortex (BA6) and of BA44; multisensory stimulation also elicits activity in TPJ, BA4, and BA6, and when compared with unisensory stimuli, activations were found in: (1) Cortical and subcortical midline structures-BA7 (precuneus), BA9 (medial prefrontal cortex), BA30 (posterior cingulated), superior colliculum and posterior cerebellum; and (2) Posterior lateral cortex-TPJ, posterior BA13 (insula), BA19, and BA37. Bilateral TPJ is the one that showed the biggest activation volume. CONCLUSION: This specific multisensory stimulation produces a brain activation map in regions that are responsible for multisensory Self-processing and may represent the Core-Self. We recommend the use of this specific multisensory stimulation as a physiotherapy intervention strategy that might promote the Self-reorganization.

Functional Neuroimaging in Obesity Research.

Functional neuroimaging is beginning to yield valuable insights into the neurobiological underpinnings of the effects of obesity on neural circuits. Functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) studies have been used to identify aberrant activation patterns in regions implicated in reward (e.g., striatum, orbitofrontal cortex, insula), emotion and memory (e.g., amygdala, hippocampus), sensory and motor processing (e.g., insula, precentral gyrus), and cognitive control and attention (e.g., prefrontal cortex, cingulate) in obese individuals. Although a great amount of research using these techniques has already unveiled the influence of different neural response patterns on obesogenic behaviors, in this chapter we will, otherwise, try to highlight the effects of obesity on specific neuronal circuits and discuss recent developments in fMRI-based neurofeedback approaches as an alternative in obesity treatment.

Pure visual imagery as a potential approach to achieve three classes of control for implementation of BCI in non-motor disorders.

OBJECTIVE: The achievement of multiple instances of control with the same type of mental strategy represents a way to improve flexibility of brain-computer interface (BCI) systems. Here we test the hypothesis that pure visual motion imagery of an external actuator can be used as a tool to achieve three classes of electroencephalographic (EEG) based control, which might be useful in attention disorders. APPROACH: We hypothesize that different numbers of imagined motion alternations lead to distinctive signals, as predicted by distinct motion patterns. Accordingly, a distinct number of alternating sensory/perceptual signals would lead to distinct neural responses as previously demonstrated using functional magnetic resonance imaging (fMRI). We anticipate that differential modulations should also be observed in the EEG domain. EEG recordings were obtained from twelve participants using three imagery tasks: imagery of a static dot, imagery of a dot with two opposing motions in the vertical axis (two motion directions) and imagery of a dot with four opposing motions in vertical or horizontal axes (four directions). The data were analysed offline. MAIN RESULTS: An increase of alpha-band power was found in frontal and central channels as a result of visual motion imagery tasks when compared with static dot imagery, in contrast with the expected posterior alpha decreases found during simple visual stimulation. The successful classification and discrimination between the three imagery tasks confirmed that three different classes of control based on visual motion imagery can be achieved. The classification approach was based on a support vector machine (SVM) and on the alpha-band relative spectral power of a small group of six frontal and central channels. Patterns of alpha activity, as captured by single-trial SVM closely reflected imagery properties, in particular the number of imagined motion alternations. SIGNIFICANCE: We found a new mental task based on visual motion imagery with potential for the implementation of multiclass (3) BCIs. Our results are consistent with the notion that frontal alpha synchronization is related with high internal processing demands, changing with the number of alternation levels during imagery. Together, these findings suggest the feasibility of pure visual motion imagery tasks as a strategy to achieve multiclass control systems with potential for BCI and in particular, neurofeedback applications in non-motor (attentional) disorders.

Control of Brain Activity in hMT+/V5 at Three Response Levels Using fMRI-Based Neurofeedback/BCI.

A major challenge in brain-computer interface (BCI) research is to increase the number of command classes and levels of control. BCI studies often use binary control level approaches (level 0 and 1 of brain activation for each class of control). Different classes may often be achieved but not different levels of activation for the same class. The increase in the number of levels of control in BCI applications may allow for larger efficiency in neurofeedback applications. In this work we test the hypothesis whether more than two modulation levels can be achieved in a single brain region, the hMT+/V5 complex. Participants performed three distinct imagery tasks during neurofeedback training: imagery of a stationary dot, imagery of a dot with two opposing motions in the vertical axis and imagery of a dot with four opposing motions in vertical or horizontal axes (imagery of 2 or 4 motion directions). The larger the number of motion alternations, the higher the expected hMT+/V5 response. A substantial number (17 of 20) of participants achieved successful binary level of control and 12 were able to reach even 3 significant levels of control within the same session, confirming the whole group effects at the individual level. With this simple approach we suggest that it is possible to design a parametric system of control based on activity modulation of a specific brain region with at least 3 different levels. Furthermore, we show that particular imagery task instructions, based on different number of motion alternations, provide feasible achievement of different control levels in BCI and/or neurofeedback applications.

Visual motion imagery neurofeedback based on the hMT+/V5 complex: evidence for a feedback-specific neural circuit involving neocortical and cerebellar regions.

OBJECTIVE: Current approaches in neurofeedback/brain-computer interface research often focus on identifying, on a subject-by-subject basis, the neural regions that are best suited for self-driven modulation. It is known that the hMT+/V5 complex, an early visual cortical region, is recruited during explicit and implicit motion imagery, in addition to real motion perception. This study tests the feasibility of training healthy volunteers to regulate the level of activation in their hMT+/V5 complex using real-time fMRI neurofeedback and visual motion imagery strategies. APPROACH: We functionally localized the hMT+/V5 complex to further use as a target region for neurofeedback. An uniform strategy based on motion imagery was used to guide subjects to neuromodulate hMT+/V5. MAIN RESULTS: We found that 15/20 participants achieved successful neurofeedback. This modulation led to the recruitment of a specific network as further assessed by psychophysiological interaction analysis. This specific circuit, including hMT+/V5, putative V6 and medial cerebellum was activated for successful neurofeedback runs. The putamen and anterior insula were recruited for both successful and non-successful runs. SIGNIFICANCE: Our findings indicate that hMT+/V5 is a region that can be modulated by focused imagery and that a specific cortico-cerebellar circuit is recruited during visual motion imagery leading to successful neurofeedback. These findings contribute to the debate on the relative potential of extrinsic (sensory) versus intrinsic (default-mode) brain regions in the clinical application of neurofeedback paradigms. This novel circuit might be a good target for future neurofeedback approaches that aim, for example, the training of focused attention in disorders such as ADHD.

Feature analysis for correlation studies of simultaneous EEG-fMRI data: A proof of concept for neurofeedback approaches.

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.

To perceive or not perceive: the role of gamma-band activity in signaling object percepts.

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.