Interhemispheric functional connectivity: an fMRI study in callosotomized patients.

Introduction: Functional connectivity (FC) is defined in terms of temporal correlations between physiological signals, which mainly depend upon structural (axonal) connectivity; it is commonly studied using functional magnetic resonance imaging (fMRI). Interhemispheric FC appears mostly supported by the corpus callosum (CC), although several studies investigating this aspect have not provided conclusive evidence. In this context, patients in whom the CC was resected for therapeutic reasons (split-brain patients) provide a unique opportunity for research into this issue. The present study was aimed at investigating with resting-state fMRI the interhemispheric FC in six epileptic patients who have undergone surgical resection of the CC. Methods: The analysis was performed using fMRI of the Brain Software Library; the evaluation of interhemispheric FC and the recognition of the resting-state networks (RSNs) were performed using probabilistic independent component analysis. Results: Generally, bilateral brain activation was often observed in primary sensory RSNs, while in the associative areas, such as those composing the default mode and fronto-parietal networks, the activation was often unilateral. Discussion: These results suggest that even in the absence of the CC, some interhemispheric communication is still present. This residual FC might be supported through extra-callosal pathways that are likely subcortical, making it possible for some interhemispheric integration. Further studies are needed to confirm these conclusions.

Visual integration across fixation: automatic processes are split but conscious processes remain unified in the split-brain.

The classic view holds that when "split-brain" patients are presented with an object in the right visual field, they will correctly identify it verbally and with the right hand. However, when the object is presented in the left visual field, the patient verbally states that he saw nothing but nevertheless identifies it accurately with the left hand. This interaction suggests that perception, recognition and responding are separated in the two isolated hemispheres. However, there is now accumulating evidence that this interaction is not absolute; for instance, split-brain patients are able to detect and localise stimuli anywhere in the visual field verbally and with either hand. In this study we set out to explore this cross-hemifield interaction in more detail with the split-brain patient DDC and carried out two experiments. The aim of these experiments is to unveil the unity of deliberate and automatic processing in the context of visual integration across hemispheres. Experiment 1 suggests that automatic processing is split in this context. In contrast, when the patient is forced to adopt a conscious, deliberate, approach, processing seemed to be unified across visual fields (and thus across hemispheres). First, we looked at the confidence that DDC has in his responses. The experiment involved a simultaneous "same" versus "different" matching task with two shapes presented either within one hemifield or across fixation. The results showed that we replicated the observation that split brain patients cannot match across fixation, but more interesting, that DDC was very confident in the across-fixation condition while performing at chance-level. On the basis of this result, we hypothesised a two-route explanation. In healthy subjects, the visual information from the two hemifields is integrated in an automatic, unconscious fashion via the intact splenium, and this route has been severed in DDC. However, we know from previous experiments that some transfer of information remains possible. We proposed that this second route (perhaps less visual; more symbolic) may become apparent when he is forced to use a deliberate, consciously controlled approach. In an experiment where he is informed, by a second stimulus presented in one hemifield, what to do with the first stimulus that was presented in the same or the opposite hemifield, we showed that there was indeed interhemispheric transfer of information. We suggest that this two-route model may help in clarifying some of the controversial issues in split-brain research.

Dichotic-listening performance after complete callosotomy: No relief from left-ear extinction by selective attention.

The surgical section of the corpus callosum (callosotomy) has been frequently demonstrated to result in a left-ear extinction in dichotic listening. That is, callosotomy patients report the left-ear stimulus below chance level, resulting in substantially enhanced right-ear advantage (REA) compared with controls. A small number of previous studies also suggest that callosotomy patients can overcome left-ear extinction when the instruction encourages to attend selectively to the left-ear stimulus. In the present case study, we re-examine the role of selective attention in dichotic listening in two patients with complete callosotomy and 40 age- and sex-matched controls. We used the standardised Bergen dichotic-listening paradigm which uses stop-consonant-vowel syllables as stimulus material and includes both a free-report and selective-attention condition. As was predicted, both patients showed a clear left-ear extinction. However, contrasting the earlier reports, we did not find any evidence for a relief from this extinction by selectively attending to the left-ear stimulus. We conclude that previous demonstrations of an attention-improved left-ear recall in callosotomy patients may be attributed to the use of suboptimal dichotic paradigms or residual callosal connectivity, rather than representing a genuine effect of attention.

Functional topography of the corpus callosum as revealed by fMRI and behavioural studies of control subjects and patients with callosal resection.

The concept of a topographical map of the corpus callosum (CC), the main interhemispheric commissure, has emerged from human lesion studies and from anatomical tracing investigations in other mammals. Over the last few years, a rising number of researchers have been reporting functional magnetic resonance imaging (fMRI) activation in also the CC. This short review summarizes the functional and behavioral studies performed in groups of healthy subjects and in patients undergone to partial or total callosal resection, and it is focused on the work conducted by the authors. Functional data have been collected by diffusion tensor imaging and tractography (DTI and DTT) and functional magnetic resonance imaging (fMRI), both techniques allowing to expand and refine our knowledge of the commissure. Neuropsychological test were also administered, and simple behavioral task, as imitation perspective and mental rotation ability, were analyzed. These researches added new insight on the topographic organization of the human CC. By combining DTT and fMRI it was possible to observe that the callosal crossing points of interhemispheric fibers connecting homologous primary sensory cortices, correspond to the CC sites where the fMRI activation elicited by peripheral stimulation was detected. In addition, CC activation during imitation and mental rotation performance was also reported. These studies demonstrated the presence of specific callosal fiber tracts that cross the commissure in the genu, body, and splenium, at sites showing fMRI activation, consistently with cortical activated areas. Altogether, these findings lend further support to the notion that the CC displays a functional topographic organization, also related to specific behavior.

Neuronal nitric oxide synthase positive neurons in the human corpus callosum: a possible link with the callosal blood-oxygen-level dependent (BOLD) effect.

Brain functions have been investigated in the past decades via the blood-oxygen-level dependent (BOLD) effect using functional magnetic resonance imaging. One hypothesis explaining the BOLD effect involves the Nitric Oxide (NO) gaseous neurotransmitter, possibly released also by cells in the corpus callosum (CC). The eventual presence of NO releasing neurons and/or glial cells in the CC can be assessed by immunohistochemistry. Serial sections both from paraffin-embedded and frozen samples of CC obtained from adult human brains autopsy were studied with immunohistochemistry and immunofluorescence analysis, using an antibody against the neuronal isoform of Nitric Oxide Synthase (nNOS), the enzyme synthetizing the NO. The staining revealed the presence of many nNOS-immunopositive cells in the CC, shown to be neurons with immunofluorescence. Neuronal NOS-positive neurons presented different morphologies, were more numerous 4 mm apart from the midline, and displayed a peak in the body of the CC. In some cases, they were located at the upper boundary of the CC, more densely packed in the proximity of the callosal arterioles. The significant presence of nNOS-immunopositive neurons within the commissure suggests their probable role in the CC neurovascular regulation in the adult brain and could explain the BOLD effect detected in human CC.

Scattered Tubular Cells Markers in Macula Densa of Normal Human Adult Kidney.

BACKGROUND: The scattered tubular cells (STCs) are a population of resident progenitor tubular cells with expansion, self-renewal and epithelial differentiation abilities. Although these cells are localized within the proximal (PTs) and distal (DTs) tubules in a normal adult kidney, their presence has never been demonstrated in human macula densa (MD). The purpose of the present study is to describe the presence of STCs in MD using specific markers such as prominin-1 (CD133), cytokeratin 7 (KRT7) and vimentin (VIM). METHODS: We analyzed two sets of three consecutive serial sections for each sample. The first sections of each set were immunostained for nNOS to identify MD, the second sections were immune-stained for CD133 (specific STCs marker) while the third sections were analyzed for KRT7 (another STCs specific marker) and VIM (that stains the basal pole of the STCs) in the first and second sets, respectively, in order to study the co-expression of KRT7 and VIM with the CD133 marker. RESULTS: CD133 was localized in some MD cells and in the adjacent DT cells. Moreover, CD133 was detected in the parietal epithelial cells of Bowman's capsule and in some proximal tubules (PT). KRT7-positive cells were identified in MD and adjacent DT cells, while KRT7 positivity was mostly confined in both DT and collecting ducts (CD) in the other areas of the renal parenchyma. CD133 and KRT7 were co-expressed in some MD and adjacent DT cells. Some of the latter cells were positive both for CD133 and VIM. CD133 was always localized in the apical part of the cells, whereas the VIM expression was evident only in the cellular basal pole. Although some cells of MD expressed VIM or CD133, none of them co-expressed VIM and CD133. CONCLUSIONS: The presence of STCs was demonstrated in human adult MD, suggesting that this structure has expansion, self-renewal and epithelial differentiation abilities, similar to all other parts of renal tubules.

TAS1R3 and TAS2R38 Polymorphisms Affect Sweet Taste Perception: An Observational Study on Healthy and Obese Subjects.

Background: The inter-individual differences in taste perception find a possible rationale in genetic variations. We verified whether the presence of four different single nucleotide polymorphisms (SNPs) in genes encoding for bitter (TAS2R38; 145G > C; 785T > C) and sweet (TAS1R3; −1572C > T; −1266C > T) taste receptors influenced the recognition of the basic tastes. Furthermore, we tested if the allelic distribution of such SNPs varied according to BMI and whether the associations between SNPs and taste recognition were influenced by the presence of overweight/obesity. Methods: DNA of 85 overweight/obese patients and 57 normal weight volunteers was used to investigate the SNPs. For the taste test, filter paper strips were applied. Each of the basic tastes (sweet, sour, salty, bitter) plus pure rapeseed oil, and water were tested. Results: Individuals carrying the AV/AV diplotype of the TAS2R38 gene (A49P G/G and V262 T/T) were less sensitive to sweet taste recognition. These alterations remained significant after adjustment for gender and BMI. Moreover, a significant decrease in overall taste recognition associated with BMI and age was found. There was no significant difference in allelic distribution for the investigated polymorphisms between normal and overweight/obese patients. Conclusions: Our findings suggest that overall taste recognition depends on age and BMI. In the total population, the inter-individual ability to identify the sweet taste at different concentrations was related to the presence of at least one genetic variant for the bitter receptor gene but not to the BMI.

Neuronal nitric oxyde synthase positive neurons in human indusium griseum.

The study was designed to analyze the nNOS positive neurons present in the indusium griseum by describing their distribution and morphology. To this purpose, sagittal serial sections from paraffin or frozen autopsy specimens of corpus callosum including the overlying indusium griseum were processed by immunohistochemistry and immunofluorescence, using an antibody against the neuronal form of the enzyme nitric oxyde synthase. To test the specificity of the antibody used, Western Blot was performed in the indusium griseum of the same specimens. The stainings revealed the presence of many neuronal nitric oxyde synthase-immunopositive neurons in human indusium griseum, located along both rostral-caudal and medio-lateral directions. In particular, they were more numerous 1 mm apart from the midline, and their number peaked over the body of the corpus callosum. They showed different morphologies; in some cases, they were located at the boundary between indusium griseum and corpus callosum, more densely packed in proximity to the pial arteries penetrating into the corpus callosum. The significant presence and distribution of neuronal nitric oxyde synthase-immunopositive neurons suggests that indusium griseum likely plays a functional role in the neurovascular regulation within the corpus callosum. Schematic representation of human adult IG and the neurovascular unit originating from sopracallosal artery (Sca) that branches into smaller arterioles (Br) (created in PowerPoint). The arterioles cross the three layers of IG (layers I, II and III) and penetrate into the CC separated from IG by the Virchow-Robin space (VRs). As the arterioles go deeper, this space disappears and the vascular basement membrane comes into direct contact with the astrocytic end-feets (intracallosal arterioles and capillaries). nNOS-immunopositive neurons (nNOSIP N) surround the arterioles and control the vasomotore tone secreting nitric oxyde (NO). Two morphological types of nNOSIP N can be appreciated by the use of different colors: fusiform (blue) and ovoidal (pink). Also NeuN-immunopositive neurons (N) and many astrocytes (As) are present, more numerous in IG than in CC.

The functional characterization of callosal connections.

The brain operates through the synaptic interaction of distant neurons within flexible, often heterogeneous, distributed systems. Histological studies have detailed the connections between distant neurons, but their functional characterization deserves further exploration. Studies performed on the corpus callosum in animals and humans are unique in that they capitalize on results obtained from several neuroscience disciplines. Such data inspire a new interpretation of the function of callosal connections and delineate a novel road map, thus paving the way toward a general theory of cortico-cortical connectivity. Here we suggest that callosal axons can drive their post-synaptic targets preferentially when coupled to other inputs endowing the cortical network with a high degree of conditionality. This might depend on several factors, such as their pattern of convergence-divergence, the excitatory and inhibitory operation mode, the range of conduction velocities, the variety of homotopic and heterotopic projections and, finally, the state-dependency of their firing. We propose that, in addition to direct stimulation of post-synaptic targets, callosal axons often play a conditional driving or modulatory role, which depends on task contingencies, as documented by several recent studies.

Revisiting the attentional bias in the split brain.

Previous research has revealed a strong right bias in allocation of attention in split brain subjects, suggesting that a pathological attention bias occurs not only after unilateral (usually right-hemispheric) damage but also after functional disconnection of intact right-hemispheric areas involved in allocation of attention from those in the left hemisphere. Here, we investigated the laterality bias in spatial attention, as measured with the greyscales task, in two split-brain subjects (D.D.C. and D.D.V.) who had undergone complete callosotomy. The greyscales task requires participants to judge the darker (or brighter) of two left-right mirror-reversed luminance gradients under conditions of free viewing, and offers an efficient means of quantifying pathological attentional biases in patients with unilateral lesions. As predicted, the results of the two split-brain subjects revealed a pathological rightward bias in allocation of attention, suggesting strong dependence on a single hemisphere (the left) in spatial attention, which is opposite to what one expects from people with intact commissures, and is remarkable in that it occurs in free viewing. In that sense both split-brain patients are behaving as though the brain is indeed split, especially in D.D.C. who had undergone partial resection of the anterior commissure in addition to complete callosotomy, whereas the anterior commissure is still intact in D.D.V. The findings support the view that the commissural pathways play a significant role in integration of attentional processes across cerebral hemispheres.

Role of corpus callosum in sleep spindle synchronization and coupling with slow waves.

Sleep spindles of non-REM sleep are transient, waxing-and-waning 10-16 Hz EEG oscillations, whose cortical synchronization depends on the engagement of thalamo-cortical loops. However, previous studies in animal models lacking the corpus callosum due to agenesis or total callosotomy and in humans with agenesis of the corpus callosum suggested that cortico-cortical connections may also have a relevant role in cortical (inter-hemispheric) spindle synchronization. Yet, most of these works did not provide direct quantitative analyses to support their observations. By studying a rare sample of callosotomized, split-brain patients, we recently demonstrated that the total resection of the corpus callosum is associated with a significant reduction in the inter-hemispheric propagation of non-REM slow waves. Interestingly, sleep spindles are often temporally and spatially grouped around slow waves (0.5-4 Hz), and this coordination is thought to have an important role in sleep-dependent learning and memory consolidation. Given these premises, here we set out to investigate whether total callosotomy may affect the generation and spreading of sleep spindles, as well as their coupling with sleep slow waves. To this aim, we analysed overnight high-density EEG recordings (256 electrodes) collected in five patients who underwent total callosotomy due to drug-resistant epilepsy (age 40-53, two females), three non-callosotomized neurological patients (age 44-66, two females), and in a sample of 24 healthy adult control subjects (age 20-47, 13 females). Individual sleep spindles were automatically detected using a validated algorithm and their properties and topographic distributions were computed. All analyses were performed with and without a regression-based adjustment accounting for inter-subject age differences. The comparison between callosotomized patients and healthy subjects did not reveal systematic variations in spindle density, amplitude or frequency. However, callosotomized patients were characterized by a reduced spindle duration, which could represent the result of a faster desynchronization of spindle activity across cortical areas of the two hemispheres. In contrast with our previous findings regarding sleep slow waves, we failed to detect in callosotomized patients any clear, systematic change in the inter-hemispheric synchronization of sleep spindles. In line with this, callosotomized patients were characterized by a reduced extension of the spatial association between temporally coupled spindles and slow waves. Our findings are consistent with a dependence of spindles on thalamo-cortical rather than cortico-cortical connections in humans, but also revealed that, despite their temporal association, slow waves and spindles are independently regulated in terms of topographic expression.

Hypoxia-induced expression of neuronal nitric oxide synthase in astrocytes of human corpus callosum.

Nitric oxide (NO) is a gaseous neurotransmitter largely diffused in the brain; among other functions, it regulates the cerebral blood flow in response to hypoxia. NO can be synthetized by three different isoforms of the enzyme NO synthase: neuronal (nNOS), typical of neurons, endothelial and inducible. The aim of this study was to assess nNOS expression in human corpus callosum (CC) astrocytes, and its relationship with the hypoxia duration. Autoptic samples of CC from adult human subjects have been processed with immunohistochemistry and immunofluorescence using antibodies anti-nNOS and anti-glial fibrillary acidic protein (GFAP), the astrocyte marker. Results demonstrated for the first time the presence of nNOS-immunopositive astrocytes in the human CC. In particular, nNOS-positive astrocytes were absent in subjects deceased after a short hypoxia; their number and labeling intensity, however, increased with hypoxia prolongation. Neuronal NOS immunopositivity of CC astrocytes seems thus related to the hypoxia duration and the consequent brain damage.

Singularity and consciousness: A neuropsychological contribution.

In common sense experience based on introspection, consciousness is singular. There is only one 'me' and that is the one that is conscious. This means that 'singularity' is a defining aspect of 'consciousness'. However, the three main theories of consciousness, Integrated Information, Global Workspace and Recurrent Processing theory, are generally not very clear on this issue. These theories have traditionally relied heavily on neuropsychological observations and have interpreted various disorders, such as anosognosia, neglect and split-brain as impairments in conscious awareness without any reference to 'the singularity'. In this review, we will re-examine the theoretical implications of these impairments in conscious awareness and propose a new way how to conceptualize consciousness of singularity. We will argue that the subjective feeling of singularity can coexist with several disunified conscious experiences. Singularity awareness may only come into existence due to environmental response constraints. That is, perceptual, language, memory, attentional and motor processes may largely proceed unintegrated in parallel, whereas a sense of unity only arises when organisms need to respond coherently constrained by the affordances of the environment. Next, we examine from this perspective psychiatric disorders and psycho-active drugs. Finally, we present a first attempt to test this hypothesis with a resting state imaging experiment in a split-brain patient. The results suggest that there is substantial coherence of activation across the two hemispheres. These data show that a complete lesioning of the corpus callosum does not, in general, alter the resting state networks of the brain. Thus, we propose that we have separate systems in the brain that generate distributed conscious. The sense of singularity, the experience of a 'Me-ness', emerges in the interaction between the world and response-planning systems, and this leads to coherent activation in the different functional networks across the cortex.

Is the Imitative Competence an Asymmetrically Distributed Function?

This study reconsiders behavioral and functional data from studies investigating the anatomical imitation (AI) and the related mental rotation (MR) competence, carried out by our group in healthy subjects, with intact interhemispheric connections, and in split-brain patients, completely or partially lacking callosal connections. The results strongly point to the conclusion that AI and MR competence requires interhemispheric communication, mainly occurring through the corpus callosum, which is the largest white matter structure in the human brain. The results are discussed in light of previous studies and of future implications.

Integrity of Corpus Callosum Is Essential for theCross-Hemispheric Propagation of Sleep Slow Waves:A High-Density EEG Study in Split-Brain Patients.

The slow waves of non-rapid eye movement (NREM) sleep reflect experience-dependent plasticity and play a direct role in the restorative functions of sleep. Importantly, slow waves behave as traveling waves, and their propagation is assumed to occur through cortico-cortical white matter connections. In this light, the corpus callosum (CC) may represent the main responsible for cross-hemispheric slow-wave propagation. To verify this hypothesis, we performed overnight high-density (hd)-EEG recordings in five patients who underwent total callosotomy due to drug-resistant epilepsy (CPs; two females), in three noncallosotomized neurologic patients (NPs; two females), and in a sample of 24 healthy adult subjects (HSs; 13 females). In all CPs slow waves displayed a significantly reduced probability of cross-hemispheric propagation and a stronger inter-hemispheric asymmetry. In both CPs and HSs, the incidence of large slow waves within individual NREM epochs tended to differ across hemispheres, with a relative overall predominance of the right over the left hemisphere. The absolute magnitude of this asymmetry was greater in CPs relative to HSs. However, the CC resection had no significant effects on the distribution of slow-wave origin probability across hemispheres. The present results indicate that CC integrity is essential for the cross-hemispheric traveling of slow waves in human sleep, which is in line with the assumption of a direct relationship between white matter integrity and slow-wave propagation. Our findings also revealed a residual cross-hemispheric slow-wave propagation that may rely on alternative pathways, including cortico-subcortico-cortical loops. Finally, these data indicate that the lack of the CC does not lead to differences in slow-wave generation across brain hemispheres.SIGNIFICANCE STATEMENT The slow waves of NREM sleep behave as traveling waves, and their propagation has been suggested to reflect the integrity of white matter cortico-cortical connections. To directly assess this hypothesis, here we investigated the role of the corpus callosum in the cortical spreading of NREM slow waves through the study of a rare population of totally callosotomized patients. Our results demonstrate a causal role of the corpus callosum in the cross-hemispheric traveling of sleep slow waves. Additionally, we found that callosotomy does not affect the relative tendency of each hemisphere at generating slow waves. Incidentally, we also found that slow waves tend to originate more often in the right than in the left hemisphere in both callosotomized and healthy adult individuals.

Split-Brain: What We Know Now and Why This is Important for Understanding Consciousness.

Recently, the discussion regarding the consequences of cutting the corpus callosum ("split-brain") has regained momentum (Corballis, Corballis, Berlucchi, & Marzi, Brain, 141(6), e46, 2018; Pinto et al., Brain, 140(5), 1231-1237, 2017a; Pinto, Lamme, & de Haan, Brain, 140(11), e68, 2017; Volz & Gazzaniga, Brain, 140(7), 2051-2060, 2017; Volz, Hillyard, Miller, & Gazzaniga, Brain, 141(3), e15, 2018). This collective review paper aims to summarize the empirical common ground, to delineate the different interpretations, and to identify the remaining questions. In short, callosotomy leads to a broad breakdown of functional integration ranging from perception to attention. However, the breakdown is not absolute as several processes, such as action control, seem to remain unified. Disagreement exists about the responsible mechanisms for this remaining unity. The main issue concerns the first-person perspective of a split-brain patient. Does a split-brain harbor a split consciousness or is consciousness unified? The current consensus is that the body of evidence is insufficient to answer this question, and different suggestions are made with respect to how future studies might address this paucity. In addition, it is suggested that the answers might not be a simple yes or no but that intermediate conceptualizations need to be considered.

Normal human macula densa morphology and cell turnover: A histological, ultrastructural, and immunohistochemical investigation.

The aim was to analyze the morphology of normal human macula densa (MD), evaluate the cells that may be responsible for its turnover, and collect quantitative data. Of four samples of normal human renal tissue, two were embedded in resin to measure the longitudinal extension and examine the ultrastructure of the MD, the other two were embedded in paraffin to study apoptosis and cell proliferation. The MD is composed of a monolayer tissue about 40 µm long, which includes 35-40 cells arranged in overlapping rows. Ultrastructurally, MD cells show two polarized portions: an apical end, with sensory features, and a basolateral aspect, with paracrine function. MD cells are connected apically by tight junctions, with/without adherens junctions, which form a barrier between the distal tubule lumen and the interstitium. Cells in degeneration, often associated with macrophages, and undifferentiated cells were found in the MD and adjacent distal tubule. A filamentous mat previously described in proximal tubule scattered tubular cells (STCs) was detected in the basal cytoplasm in undifferentiated cells. The tissue was consistently negative for the proliferation marker Ki67 and for the apoptotic markers caspase-3 and caspase-9. This work confirms our earlier morphological findings and provides new data: (a) MD cells display both apical adherens and tight junctions, the latter forming a tubulo-mesangial barrier; (b) the MD is a monolayer made up of about 40 cells arranged in rows; (c) the simultaneous presence of degenerating (8-13%) and undifferentiated (4-13%) cells reminiscent of STCs suggests a non-negligible cell turnover.

A Study on the Relationship between Type 2 Diabetes and Taste Function in Patients with Good Glycemic Control.

Type 2 diabetes mellitus (T2DM) has a very high impact on quality of life as it is characterized by disabling complications. There is little evidence about taste alterations in diabetes. Since many individual factors are involved in the onset of diabetes, the purpose of our study is to search a possible link between diabetes and individual taste function. Thirty-two participants with T2DM and 32 volunteers without T2DM (healthy controls) were recruited. Four concentrations of each of the four basic tastes (sweet, sour, salty, bitter), and pure rapeseed oil and water, were applied with cotton pads to the protruded tongue, immediately posterior to its first third, either to the left or right side. The results showed significant differences between groups in the ability to recognize sour, bitter, sweet, and water. Taste scores were lower in subjects with T2DM than in healthy controls, and an age-related decline in taste function was found. The taste function reduction associated with T2DM was not related to gender, disease duration, and glycemic control. In conclusion, it can be hypothesized that a general alteration of taste function can lead patients with type 2 diabetes to search for foods richer in sugars, as in a vicious circle, thus decreasing the likelihood of remission of diabetes mellitus.

Maria Montessori and Neuroscience: The Trailblazing Insights of an Exceptional Mind.

This comment presents Maria Montessori (1870-1952) and highlights that her child-centered method of education is based on brilliant intuitions, which were confirmed by neuroscience research many decades later, such as the distinction of three critical periods in children's psychobiological development; the importance of the environment in supporting cerebral development and in promoting learning, as well as of affective stimulation in psychological growth and maturation; the specific neural structure of humans that specifically enables the acquisition of a language; the vital role of fine object manipulation in neuropsychological development, and of the physical exercise in brain and nervous system development.