Maturation-dependent changes in cortical and thalamic activity during sleep slow waves: Insights from a combined EEG-fMRI study.

INTRODUCTION: Studies using scalp EEG have shown that slow waves (0.5-4 Hz), the most prominent hallmark of NREM sleep, undergo relevant changes from childhood to adulthood, mirroring brain structural modifications and the acquisition of cognitive skills. Here we used simultaneous EEG-fMRI to investigate the cortical and subcortical correlates of slow waves in school-age children and determine their relative developmental changes. METHODS: We analyzed data from 14 school-age children with self-limited focal epilepsy of childhood who fell asleep during EEG-fMRI recordings. Brain regions associated with slow-wave occurrence were identified using a voxel-wise regression that also modelled interictal epileptic discharges and sleep spindles. At the group level, a mixed-effects linear model was used. The results were qualitatively compared with those obtained from 2 adolescents with epilepsy and 17 healthy adults. RESULTS: Slow waves were associated with hemodynamic-signal decreases in bilateral somatomotor areas. Such changes extended more posteriorly relative to those in adults. Moreover, the involvement of areas belonging to the default mode network changes as a function of age. No significant hemodynamic responses were observed in subcortical structures. However, we identified a significant correlation between age and thalamic hemodynamic changes. CONCLUSIONS: Present findings indicate that the somatomotor cortex may have a key role in slow-wave expression throughout the lifespan. At the same time, they are consistent with a posterior-to-anterior shift in slow-wave distribution mirroring brain maturational changes. Finally, our results suggest that slow-wave changes may not reflect only neocortical modifications but also the maturation of subcortical structures, including the thalamus.

Mindfulness-based online intervention increases well-being and decreases stress after Covid-19 lockdown.

Mindfulness interventions were shown to be effective in improving well-being and reducing perceived stress in several conditions. These effects were also found in online mindfulness-based training, especially in employees in organizational environments. The aim of this study was to test the effectiveness of an online mindfulness intervention on healthy employees, especially after the first Italian Covid-19 lockdown. Participants in the intervention group underwent an 8-week mindfulness online training program based on the Mindfulness-Based Stress Reduction (MBSR) protocol compared to a control (no-intervention) group. All participants filled in weekly surveys for the whole intervention duration via online questionnaires to measure their habits, mindfulness (FFMQ-15), emotion regulation (ERQ), positive and negative affect (PANAS), depression, anxiety and stress (DASS-21), resilience (RSA) and insomnia (ISI). 69 participants in the intervention group and 63 in the no-treatment control group were considered in the longitudinal analyses. We found significant differences between the intervention and control groups over time in the measures of mindfulness (in particular the nonreactivity subscale), positive affect, depression, and insomnia. Moreover, we found that the frequency of practice and ease perceived in practicing were positively correlated to several indices of well-being (mindfulness, positive affect, cognitive reappraisal) and negatively correlated to several indices of stress (negative affect, depression, anxiety, stress, insomnia, expressive suppression). These results show the importance and effectiveness of online mindfulness training programs to cope with stress among employees, especially after the Covid-19 lockdown.

Cortical and subcortical hemodynamic changes during sleep slow waves in human light sleep.

EEG slow waves, the hallmarks of NREM sleep are thought to be crucial for the regulation of several important processes, including learning, sensory disconnection and the removal of brain metabolic wastes. Animal research indicates that slow waves may involve complex interactions within and between cortical and subcortical structures. Conventional EEG in humans, however, has a low spatial resolution and is unable to accurately describe changes in the activity of subcortical and deep cortical structures. To overcome these limitations, here we took advantage of simultaneous EEG-fMRI recordings to map cortical and subcortical hemodynamic (BOLD) fluctuations time-locked to slow waves of light sleep. Recordings were performed in twenty healthy adults during an afternoon nap. Slow waves were associated with BOLD-signal increases in the posterior brainstem and in portions of thalamus and cerebellum characterized by preferential functional connectivity with limbic and somatomotor areas, respectively. At the cortical level, significant BOLD-signal decreases were instead found in several areas, including insula and somatomotor cortex. Specifically, a slow signal increase preceded slow-wave onset and was followed by a delayed, stronger signal decrease. Similar hemodynamic changes were found to occur at different delays across most cortical brain areas, mirroring the propagation of electrophysiological slow waves, from centro-frontal to inferior temporo-occipital cortices. Finally, we found that the amplitude of electrophysiological slow waves was positively related to the magnitude and inversely related to the delay of cortical and subcortical BOLD-signal changes. These regional patterns of brain activity are consistent with theoretical accounts of the functions of sleep slow waves.

Reductions in perceived stress following Transcendental Meditation practice are associated with increased brain regional connectivity at rest.

Transcendental Meditation (TM) is defined as a mental process of transcending using a silent mantra. Previous work showed that relatively brief period of TM practice leads to decreases in stress and anxiety. However, whether these changes are subserved by specific morpho-functional brain modifications (as observed in other meditation techniques) is still unclear. Using a longitudinal design, we combined psychometric questionnaires, structural and resting-state functional magnetic resonance imaging (RS-fMRI) to investigate the potential brain modifications underlying the psychological effects of TM. The final sample included 19 naïve subjects instructed to complete two daily 20-min TM sessions, and 15 volunteers in the control group. Both groups were evaluated at recruitment (T0) and after 3 months (T1). At T1, only meditators showed a decrease in perceived anxiety and stress (t(18) = 2.53, p = 0.02), which correlated negatively with T1-T0 changes in functional connectivity among posterior cingulate cortex (PCC), precuneus and left superior parietal lobule. Additionally, TM practice was associated with increased connectivity between PCC and right insula, likely reflecting changes in interoceptive awareness. No structural changes were observed in meditators or control subjects. These preliminary findings indicate that beneficial effects of TM may be mediated by functional brain changes that take place after a short practice period of 3 months.

Modality-independent encoding of individual concepts in the left parietal cortex.

The organization of semantic information in the brain has been mainly explored through category-based models, on the assumption that categories broadly reflect the organization of conceptual knowledge. However, the analysis of concepts as individual entities, rather than as items belonging to distinct superordinate categories, may represent a significant advancement in the comprehension of how conceptual knowledge is encoded in the human brain. Here, we studied the individual representation of thirty concrete nouns from six different categories, across different sensory modalities (i.e., auditory and visual) and groups (i.e., sighted and congenitally blind individuals) in a core hub of the semantic network, the left angular gyrus, and in its neighboring regions within the lateral parietal cortex. Four models based on either perceptual or semantic features at different levels of complexity (i.e., low- or high-level) were used to predict fMRI brain activity using representational similarity encoding analysis. When controlling for the superordinate component, high-level models based on semantic and shape information led to significant encoding accuracies in the intraparietal sulcus only. This region is involved in feature binding and combination of concepts across multiple sensory modalities, suggesting its role in high-level representation of conceptual knowledge. Moreover, when the information regarding superordinate categories is retained, a large extent of parietal cortex is engaged. This result indicates the need to control for the coarse-level categorial organization when performing studies on higher-level processes related to the retrieval of semantic information.

Are Supramodality and Cross-Modal Plasticity the Yin and Yang of Brain Development? From Blindness to Rehabilitation.

Research in blind individuals has primarily focused for a long time on the brain plastic reorganization that occurs in early visual areas. Only more recently, scientists have developed innovative strategies to understand to what extent vision is truly a mandatory prerequisite for the brain's fine morphological architecture to develop and function. As a whole, the studies conducted to date in sighted and congenitally blind individuals have provided ample evidence that several "visual" cortical areas develop independently from visual experience and do process information content regardless of the sensory modality through which a particular stimulus is conveyed: a property named supramodality. At the same time, lack of vision leads to a structural and functional reorganization within "visual" brain areas, a phenomenon known as cross-modal plasticity. Cross-modal recruitment of the occipital cortex in visually deprived individuals represents an adaptative compensatory mechanism that mediates processing of non-visual inputs. Supramodality and cross-modal plasticity appears to be the "yin and yang" of brain development: supramodal is what takes place despite the lack of vision, whereas cross-modal is what happens because of lack of vision. Here we provide a critical overview of the research in this field and discuss the implications that these novel findings have for the development of educative/rehabilitation approaches and sensory substitution devices (SSDs) in sensory-impaired individuals.

Congenital blindness affects diencephalic but not mesencephalic structures in the human brain.

While there is ample evidence that the structure and function of visual cortical areas are affected by early visual deprivation, little is known of how early blindness modifies subcortical relay and association thalamic nuclei, as well as mesencephalic structures. Therefore, in the present multicenter study, we used MRI to measure volume of the superior and inferior colliculi, as well as of the thalamic nuclei relaying sensory and motor information to the neocortex, parcellated according to atlas-based thalamo-cortical connections, in 29 individuals with congenital blindness of peripheral origin (17 M, age 35.7 ± 14.3 years) and 29 sighted subjects (17 M, age 31.9 ± 9.0). Blind participants showed an overall volume reduction in the left (p = 0.008) and right (p = 0.007) thalami, as compared to the sighted individuals. Specifically, the lateral geniculate (i.e., primary visual thalamic relay nucleus) was 40% reduced (left: p = 4 × 10(-6), right: p < 1 × 10(-6)), consistent with findings from animal studies. In addition, associated thalamic nuclei that project to temporal (left: p = 0.005, right: p = 0.005), prefrontal (left: p = 0.010, right: p = 0.014), occipital (left: p = 0.005, right: p = 0.023), and right premotor (p = 0.024) cortical regions were also significantly reduced in the congenitally blind group. Conversely, volumes of the relay nuclei directly involved in auditory, motor, and somatosensory processing were not affected by visual deprivation. In contrast, no difference in volume was observed in either the superior or the inferior colliculus between the two groups. Our findings indicate that visual loss since birth leads to selective volumetric changes within diencephalic, but not mesencephalic, structures. Both changes in reciprocal cortico-thalamic connections or modifications in the intrinsic connectivity between relay and association nuclei of the thalamus may contribute to explain these alterations in thalamic volumes. Sparing of the superior colliculi is in line with their composite, multisensory projections, and with their not exclusive visual nature.

Spatial imagery relies on a sensory independent, though sensory sensitive, functional organization within the parietal cortex: a fMRI study of angle discrimination in sighted and congenitally blind individuals.

Although vision offers distinctive information to space representation, individuals who lack vision since birth often show perceptual and representational skills comparable to those found in sighted individuals. However, congenitally blind individuals may result in impaired spatial analysis, when engaging in 'visual' spatial features (e.g., perspective or angle representation) or complex spatial mental abilities. In the present study, we measured behavioral and brain responses using functional magnetic resonance imaging in sighted and congenitally blind individuals during spatial imagery based on a modified version of the mental clock task (e.g., angle discrimination) and a simple recognition control condition, as conveyed across distinct sensory modalities: visual (sighted individuals only), tactile and auditory. Blind individuals were significantly less accurate during the auditory task, but comparable-to-sighted during the tactile task. As expected, both groups showed common neural activations in intraparietal and superior parietal regions across visual and non-visual spatial perception and imagery conditions, indicating the more abstract, sensory independent functional organization of these cortical areas, a property that we named supramodality. At the same time, however, comparisons in brain responses and functional connectivity patterns across experimental conditions demonstrated also a functional lateralization, in a way that correlated with the distinct behavioral performance in blind and sighted individuals. Specifically, blind individuals relied more on right parietal regions, mainly in the tactile and less in the auditory spatial processing. In sighted, spatial representation across modalities relied more on left parietal regions. In conclusions, intraparietal and superior parietal regions subserve supramodal spatial representations in sighted and congenitally blind individuals. Differences in their recruitment across non-visual spatial processing in sighted and blind individuals may be related to distinctive behavioral performance and/or mental strategies adopted when they deal with the same spatial representation as conveyed through different sensory modalities.

Beyond motor scheme: a supramodal distributed representation in the action-observation network.

The representation of actions within the action-observation network is thought to rely on a distributed functional organization. Furthermore, recent findings indicate that the action-observation network encodes not merely the observed motor act, but rather a representation that is independent from a specific sensory modality or sensory experience. In the present study, we wished to determine to what extent this distributed and 'more abstract' representation of action is truly supramodal, i.e. shares a common coding across sensory modalities. To this aim, a pattern recognition approach was employed to analyze neural responses in sighted and congenitally blind subjects during visual and/or auditory presentation of hand-made actions. Multivoxel pattern analyses-based classifiers discriminated action from non-action stimuli across sensory conditions (visual and auditory) and experimental groups (blind and sighted). Moreover, these classifiers labeled as 'action' the pattern of neural responses evoked during actual motor execution. Interestingly, discriminative information for the action/non action classification was located in a bilateral, but left-prevalent, network that strongly overlaps with brain regions known to form the action-observation network and the human mirror system. The ability to identify action features with a multivoxel pattern analyses-based classifier in both sighted and blind individuals and independently from the sensory modality conveying the stimuli clearly supports the hypothesis of a supramodal, distributed functional representation of actions, mainly within the action-observation network.

Evidence of a direct influence between the thalamus and hMT+ independent of V1 in the human brain as measured by fMRI.

In the present study we employed Conditional Granger Causality (CGC) and Coherence analysis to investigate whether visual motion-related information reaches the human middle temporal complex (hMT+) directly from the Lateral Geniculate Nucleus (LGN) of the thalamus, by-passing the primary visual cortex (V1). Ten healthy human volunteers underwent brain scan examinations by functional magnetic resonance imaging (fMRI) during two optic flow experiments. In addition to the classical LGN-V1-hMT+ pathway, our results showed a significant direct influence of the blood oxygenation level dependent (BOLD) signal recorded in LGN over that in hMT+, not mediated by V1 activity, which strongly supports the existence of a bilateral pathway that connects LGN directly to hMT+ and serves visual motion processing. Furthermore, we evaluated the relative latencies among areas functionally connected in the processing of visual motion. Using LGN as a reference region, hMT+ exhibited a statistically significant earlier peak of activation as compared to V1. In conclusion, our findings suggest the co-existence of an alternative route that directly links LGN to hMT+, bypassing V1. This direct pathway may play a significant functional role for the faster detection of motion and may contribute to explain persistence of unconscious motion detection in individuals with severe destruction of primary visual cortex (blindsight).

Do we really need vision? How blind people "see" the actions of others.

Observing and learning actions and behaviors from others, a mechanism crucial for survival and social interaction, engages the mirror neuron system. To determine whether vision is a necessary prerequisite for the human mirror system to develop and function, we used functional magnetic resonance imaging to compare brain activity in congenitally blind individuals during the auditory presentation of hand-executed actions or environmental sounds, and the motor pantomime of manipulation tasks, with that in sighted volunteers, who additionally performed a visual action recognition task. Congenitally blind individuals activated a premotor-temporoparietal cortical network in response to aurally presented actions that overlapped both with mirror system areas found in sighted subjects in response to visually and aurally presented stimuli, and with the brain response elicited by motor pantomime of the same actions. Furthermore, the mirror system cortex showed a significantly greater response to motor familiar than to unfamiliar action sounds in both sighted and blind individuals. Thus, the mirror system in humans can develop in the absence of sight. The results in blind individuals demonstrate that the sound of an action engages the mirror system for action schemas that have not been learned through the visual modality and that this activity is not mediated by visual imagery. These findings indicate that the mirror system is based on supramodal sensory representations of actions and, furthermore, that these abstract representations allow individuals with no visual experience to interact effectively with others.

Imagery and spatial processes in blindness and visual impairment.

The objective of this review is to examine and evaluate recent findings on cognitive functioning (in particular imagery processes) in individuals with congenital visual impairments, including total blindness, low-vision and monocular vision. As one might expect, the performance of blind individuals in many behaviours and tasks requiring imagery can be inferior to that of sighted subjects; however, surprisingly often this is not the case. Interestingly, there is evidence that the blind often employ different cognitive mechanisms than sighted subjects, suggesting that compensatory mechanisms can overcome the limitations of sight loss. Taken together, these studies suggest that the nature of perceptual input on which we commonly rely strongly affects the organization of our mental processes. We also review recent neuroimaging studies on the neural correlates of sensory perception and mental imagery in visually impaired individuals that have cast light on the plastic functional reorganization mechanisms associated with visual deprivation.

The effect of visual experience on the development of functional architecture in hMT+.

We investigated whether the visual hMT+ cortex plays a role in supramodal representation of sensory flow, not mediated by visual mental imagery. We used functional magnetic resonance imaging to measure neural activity in sighted and congenitally blind individuals during passive perception of optic and tactile flows. Visual motion-responsive cortex, including hMT+, was identified in the lateral occipital and inferior temporal cortices of the sighted subjects by response to optic flow. Tactile flow perception in sighted subjects activated the more anterior part of these cortical regions but deactivated the more posterior part. By contrast, perception of tactile flow in blind subjects activated the full extent, including the more posterior part. These results demonstrate that activation of hMT+ and surrounding cortex by tactile flow is not mediated by visual mental imagery and that the functional organization of hMT+ can develop to subserve tactile flow perception in the absence of any visual experience. Moreover, visual experience leads to a segregation of the motion-responsive occipitotemporal cortex into an anterior subregion involved in the representation of both optic and tactile flows and a posterior subregion that processes optic flow only.