Left and right corticobasal syndrome: comparison of cognitive profiles between metabolic imaging - matched groups.

BACKGROUND: Corticobasal syndrome (CBS) is typically asymmetric. Case reports suggest that left-hemisphere CBS (lhCBS) is associated with major language impairment, and right-hemisphere CBS (rhCBS) is associated with major visuospatial deficits, but no group study has ever verified these observations. In our study, we enrolled 49 patients with CBS, classified them as lhCBS or rhCBS based on asymmetry of hypometabolism on brain FDG-PET and compared their cognitive and behavioural profiles. METHODS: We defined asymmetry of hypometabolism upon visual inspection of qualitative PET images and confirmed it through paired comparison of left- and right-hemisphere FDG uptake values. The two groups were also matched for severity of hypometabolism within the more affected and more preserved hemispheres, to unravel differences in the cognitive profiles ascribable specifically to each hemisphere's functional specializations. All patients were assessed for memory, language, executive and visuospatial deficits, apraxia, neglect, dyscalculia, agraphia and behavioural disturbances. RESULTS: LhCBS (n. 26) and rhCBS (n. 23) patients did not differ for demographics, disease duration and severity of global cognitive impairment. The two cognitive profiles were largely overlapping, with two exceptions: Digit span forward was poorer in lhCBS, and visual neglect was more frequent in rhCBS. CONCLUSIONS: After balancing out patients for hemispheric hypometabolism, we did not confirm worse language or visuospatial deficits in, respectively, lhCBS and rhCBS. However, verbal short-term memory was more impaired in lhCBS, and spatial attention was more impaired in rhCBS. Both of these functions reflect the functional specialization of the left and right fronto-parietal pathways, i.e. of the main loci of neurodegeneration in CBS.

Beyond peripersonal boundaries: insights from crossmodal interactions.

We experience our self as a body located in space. However, how information about self-location is integrated into multisensory processes underlying the representation of the peripersonal space (PPS), is still unclear. Prior studies showed that the presence of visual information related to oneself modulates the multisensory processes underlying PPS. Here, we used the crossmodal congruency effect (CCE) to test whether this top-down modulation depends on the spatial location of the body-related visual information. Participants responded to tactile events on their bodies while trying to ignore a visual distractor presented on the mirror reflection of their body (Self) either in the peripersonal space (Near) or in the extrapersonal space (Far). We found larger CCE when visual events were presented on the mirror reflection in the peripersonal space, as compared to the extrapersonal space. These results suggest that top-down modulation of the multisensory bodily self is only possible within the PPS.

Brain-heart interactions are modulated across the respiratory cycle via interoceptive attention.

Respiration and heartbeat continuously interact within the living organism at many different levels, representing two of the main oscillatory rhythms of the body and providing major sources of interoceptive information to the brain. Despite the modulatory effect of respiration on exteroception and cognition has been recently established in humans, its role in shaping interoceptive perception has been scarcely investigated so far. In two independent studies, we investigated the effect of spontaneous breathing on cardiac interoception by assessing the Heartbeat Evoked Potential (HEP) in healthy humans. In Study 1, we compared HEP activity for heartbeats occurred during inhalation and exhalation in 40 volunteers at rest. We found higher HEP amplitude during exhalation, compared to inhalation, over fronto-centro-parietal areas. This suggests increased brain-heart interactions and improved cortical processing of the heartbeats during exhalation. Further analyses revealed that this effect was moderated by heart rate changes. In Study 2, we tested the respiratory phase-dependent modulation of HEP activity in 20 volunteers during Exteroceptive and Interoceptive conditions of the Heartbeat Detection (HBD) task. In these conditions, participants were requested to tap at each heartbeat, either listened to or felt, respectively. Results showed higher HEP activity and higher detection accuracy at exhalation than inhalation in the Interoceptive condition only. Direct comparisons of Interoceptive and Exteroceptive conditions confirmed stronger respiratory phase-dependent modulation of HEP and accuracy when attention was directed towards the interoceptive stimuli. Moreover, HEP changes during the Interoceptive condition were independent of heart physiology, but were positively correlated with higher detection accuracy at exhalation than inhalation. This suggests a link between optimization of cortical processing of cardiac signals and detection of heartbeats across the respiratory cycle. Overall, we provide data showing that respiration shapes cardiac interoception at the neurophysiological and behavioural levels. Specifically, exhalation may allow attentional shift towards the internal bodily states.

Clinical and metabolic imaging features of late-onset and early-onset posterior cortical atrophy.

BACKGROUND AND PURPOSE: Late-onset (LO) and early-onset (EO) dementia show neurobiological and clinical differences. Clinical and 18 fluoro-deoxy-glucose positron emission tomography (FDG-PET) features of LO and EO posterior cortical atrophy (LO_PCA, EO_PCA), the visual variant of Alzheimer's disease (AD), were compared. LO_PCA patients were also compared with a group of patients with LO typical AD (tAD). METHODS: Thirty-seven LO_PCA patients (onset age ≥ 65 years), 29 EO_PCA patients and 40 tAD patients who all underwent a standard neuropsychological battery were recruited; PCA patients were also assessed for the presence of posterior signs and symptoms. Brain FDG-PET was available in 32 LO_PCA cases, 23 EO_PCA cases and all tAD cases, and their scans were compared with scans from 30 healthy elderly controls. Within the entire PCA sample FDG uptake was also correlated with age at onset as a continuous variable. RESULTS: The main difference between the two PCA groups was a higher prevalence of Bálint-Holmes symptoms in EO cases, which was associated with the presence of severe bilateral occipito-temporo-parietal hypometabolism, whilst LO_PCA patients showed reduction of FDG uptake mainly in the right posterior regions. The latter group also showed mesial temporal hypometabolism, similarly to the tAD group, although with a right rather than left lateralization. Correlation analysis confirmed the association between older age and decreased limbic metabolism and between younger age and decreased left parietal metabolism. CONCLUSIONS: The major involvement of the temporal cortex in LO cases and of the parietal cortex in EO cases reported previously within the AD spectrum holds true also for the visual variant of AD.

Brand new norms for a good old test: Northern Italy normative study of MiniMental State Examination.

AIM: Mini-Mental State Examination (MMSE) is one of the most used tests for the screening of global cognition in patients with neurological and medical disorders. Norms for the Italian version of the test were published in the 90 s; more recent norms were published in 2020 for Southern Italy only. In the present study, we computed novel adjustment coefficients, equivalent scores and cut-off value for Northern Italy (Lombardia and Veneto) and Italian speaking Switzerland. METHODS: We recruited 361 healthy young and old (range: 20-95 years) individuals of both sexes (men: 156, women: 205) and from different educational levels (range: 4-22 years). Neuropsychiatric disorders and severe medical conditions were excluded with a questionnaire and cognitive deficits and were ruled out with standardized neuropsychological tests assessing the main cognitive domains. We used a slightly modified version of MMSE: the word 'fiore' was replaced with 'pane' in verbal recalls to reduce the common interference error 'casa, cane, gatto'. The effect of socio-demographic features on performance at MMSE was assessed via multiple linear regression, with test raw score as dependent variable and sex, logarithm of 101-age and square root of schooling as predictors. RESULTS: Mean raw MMSE score was 28.8 ± 1.7 (range: 23-30). Multiple linear regression showed a significant effect of all socio-demographic variables and reported a value of R2 = 0.26. The new cut off was ≥ 26 /30. CONCLUSION: We provide here updated norms for a putatively more accurate version of Italian MMSE, produced in a Northern population but potentially valid all over Italy.

Two independent and primitive envelopes of the bilobate nucleus of comet 67P.

The factors shaping cometary nuclei are still largely unknown, but could be the result of concurrent effects of evolutionary and primordial processes. The peculiar bilobed shape of comet 67P/Churyumov-Gerasimenko may be the result of the fusion of two objects that were once separate or the result of a localized excavation by outgassing at the interface between the two lobes. Here we report that the comet's major lobe is enveloped by a nearly continuous set of strata, up to 650 metres thick, which are independent of an analogous stratified envelope on the minor lobe. Gravity vectors computed for the two lobes separately are closer to perpendicular to the strata than those calculated for the entire nucleus and adjacent to the neck separating the two lobes. Therefore comet 67P/Churyumov-Gerasimenko is an accreted body of two distinct objects with 'onion-like' stratification, which formed before they merged. We conclude that gentle, low-velocity collisions occurred between two fully formed kilometre-sized cometesimals in the early stages of the Solar System. The notable structural similarities between the two lobes of comet 67P/Churyumov-Gerasimenko indicate that the early-forming cometesimals experienced similar primordial stratified accretion, even though they formed independently.

Large heterogeneities in comet 67P as revealed by active pits from sinkhole collapse.

Pits have been observed on many cometary nuclei mapped by spacecraft. It has been argued that cometary pits are a signature of endogenic activity, rather than impact craters such as those on planetary and asteroid surfaces. Impact experiments and models cannot reproduce the shapes of most of the observed cometary pits, and the predicted collision rates imply that few of the pits are related to impacts. Alternative mechanisms like explosive activity have been suggested, but the driving process remains unknown. Here we report that pits on comet 67P/Churyumov-Gerasimenko are active, and probably created by a sinkhole process, possibly accompanied by outbursts. We argue that after formation, pits expand slowly in diameter, owing to sublimation-driven retreat of the walls. Therefore, pits characterize how eroded the surface is: a fresh cometary surface will have a ragged structure with many pits, while an evolved surface will look smoother. The size and spatial distribution of pits imply that large heterogeneities exist in the physical, structural or compositional properties of the first few hundred metres below the current nucleus surface.

The temporal sensitivity to the tactile-induced double flash illusion mediates the impact of beta oscillations on schizotypal personality traits.

The coherent experience of the self and the world depends on the ability to integrate vs. segregate sensory information. Optimal temporal integration between the senses is mediated by oscillatory properties of neural activity. Previous research showed reduced temporal sensitivity to multisensory events in schizotypy, a personality trait linked to schizophrenia. Here we used the tactile-induced Double-Flash-Illusion (tDFI) to investigate the tactile-to-visual temporal sensitivity in schizotypy, as indexed by the temporal window of illusion (TWI) and its neural underpinnings. We measured EEG oscillations within the beta band, recently shown to correlate with the tDFI. We found individuals with higher schizotypal traits to have wider TWI and slower beta waves accounting for the temporal window within which they perceive the illusion. Our results indicate reduced tactile-to-visual temporal sensitivity to mediate the effect of slowed oscillatory beta activity on schizotypal personality traits. We conclude that slowed oscillatory patterns might constitute an early marker for psychosis proneness.

Altered temporal variance and functional connectivity of BOLD signal is associated with state anxiety during acute systemic inflammation.

Systemic inflammation is accompanied by complex behavioral changes and disturbed emotion regulation that have been related to the pathophysiology of mood disorders including depression and anxiety. However, the causal role of systemic inflammation on mood disorders is still unclear. We herein investigated neural resting state patterns of temporal variance of the amygdala and functional connectivity within the salience network underlying changes in state anxiety during experimentally-induced systemic inflammation. In this randomized, double-blind study, N = 43 healthy men received an intravenous injection of either low-dose lipopolysaccharide (LPS, 0.4 ng/kg body weight) or saline. Resting state functional magnetic resonance imaging was assessed before and 3.5 h after injection. State anxiety, assessed with a standardized questionnaire, and plasma cytokine concentrations were repeatedly measured. LPS administration induced a transient systemic inflammatory response reflected in increases in plasma Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-α concentration. Compared to placebo, state anxiety and temporal variance in the amygdala significantly increased while functional connectivity in the salience network decreased during LPS-induced systemic inflammation. Together, these data indicate that acute systemic inflammation alters temporal variance of the BOLD signal as well as functional connectivity in brain regions and networks implicated in emotion processing and regulation. These results are of translational importance to encourage further research on the role of inflammatory pathways in the pathophysiology of neuropsychiatric conditions including anxiety disorders.

Functional connections between activated and deactivated brain regions mediate emotional interference during externally directed cognition.

Recent evidence shows that task-deactivations are functionally relevant for cognitive performance. Indeed, higher cognitive engagement has been associated with higher suppression of activity in task-deactivated brain regions - usually ascribed to the Default Mode Network (DMN). Moreover, a negative correlation between these regions and areas actively engaged by the task is associated with better performance. DMN regions show positive modulation during autobiographical, social, and emotional tasks. However, it is not clear how processing of emotional stimuli affects the interplay between the DMN and executive brain regions. We studied this interplay in an fMRI experiment using emotional negative stimuli as distractors. Activity modulations induced by the emotional interference of negative stimuli were found in frontal, parietal, and visual areas, and were associated with modulations of functional connectivity between these task-activated areas and DMN regions. A worse performance was predicted both by lower activity in the superior parietal cortex and higher connectivity between visual areas and frontal DMN regions. Connectivity between right inferior frontal gyrus and several DMN regions in the left hemisphere was related to the behavioral performance. This relation was weaker in the negative than in the neutral condition, likely suggesting less functional inhibitions of DMN regions during emotional processing. These results show that both executive and DMN regions are crucial for the emotional interference process and suggest that DMN connections are related to the interplay between externally-directed and internally-focused processes. Among DMN regions, superior frontal gyrus may be a key node in regulating the interference triggered by emotional stimuli.

Is There a Nonadditive Interaction Between Spontaneous and Evoked Activity? Phase-Dependence and Its Relation to the Temporal Structure of Scale-Free Brain Activity.

The aim of our study was to use functional magnetic resonance imaging to investigate how spontaneous activity interacts with evoked activity, as well as how the temporal structure of spontaneous activity, that is, long-range temporal correlations, relate to this interaction. Using an extremely sparse event-related design (intertrial intervals: 52-60 s), a novel blood oxygen level-dependent signal correction approach (accounting for spontaneous fluctuations using pseudotrials) and phase analysis, we provided direct evidence for a nonadditive interaction between spontaneous and evoked activity. We demonstrated the discrepancy between the present and previous observations on why a linear superposition between spontaneous and evoked activity can be seen by using co-occurring signals from homologous brain regions. Importantly, we further demonstrated that the nonadditive interaction can be characterized by phase-dependent effects of spontaneous activity, which is closely related to the degree of long-range temporal correlations in spontaneous activity as indexed by both power-law exponent and phase-amplitude coupling. Our findings not only contribute to the understanding of spontaneous brain activity and its scale-free properties, but also bear important implications for our understanding of neural activity in general.

Higher proneness to multisensory illusions is driven by reduced temporal sensitivity in people with high schizotypal traits.

A coherent sense of self, typically altered in schizophrenia, is accompanied by a coherent ability to integrate sensory information. According to the idea of a psychosis continuum, high schizotypal traits in the general population may be associated to higher proneness to multisensory illusions, akin to schizophrenia. We directly tested this hypothesis by means of the double-flash illusion in participants with low and high schizotypal scores. We confirmed the higher proneness to illusions in the high-schizotypal group. Crucially, such higher proneness was fully explained by a significantly reduced temporal sensitivity to integrate sensory information. We conclude that reduced temporal sensitivity accounts for enhanced proneness to illusions in people at higher risk and represents an early marker of psychosis.

The role of expectation in multisensory body representation - neural evidence.

Sensory events contribute to body ownership, the feeling that the body belongs to me. However, the encoding of sensory events is not only reactive, but also proactive in that our brain generates prediction about forthcoming stimuli. In previous studies, we have shown that prediction of sensory events is a sufficient condition to induce the sense of body ownership. In this study, we investigated the underlying neural mechanisms. Participants were seated with their right arm resting upon a table just below another smaller table. Hence, the real hand was hidden from the participant's view and a life-sized rubber model of a right hand was placed on the small table in front of them. Participants observed a wooden plank while approaching - without touching - the rubber hand. We measured the phenomenology of the illusion by means of questionnaire. Neural activity was recorded by means of near-infrared spectroscopy (fNIRS). Results showed higher activation of multisensory parietal cortices in the rubber hand illusion induced by touch expectation. Furthermore, such activity was correlated with the subjective feeling of owning the rubber hand. Our results enrich current models of body ownership suggesting that our multisensory brain regions generate prediction on what could be my body and what could not. This finding might have interesting implications in all those cases in which body representation is altered, anorexia, bulimia nervosa and obesity, among others.

Intertrial Variability in the Premotor Cortex Accounts for Individual Differences in Peripersonal Space.

We live in a dynamic environment, constantly confronted with approaching objects that we may either avoid or be forced to address. A multisensory and sensorimotor interface, the peripersonal space (PPS), mediates every physical interaction between our body and the environment. Behavioral investigations show high variability in the extension of PPS across individuals, but there is a lack of evidence on the neural underpinnings of these large individual differences. Here, we used approaching auditory stimuli and fMRI to capture the individual boundary of PPS and examine its neural underpinnings. Precisely, we tested the hypothesis that intertrial variability (ITV) in brain regions coding PPS predicts individual differences of its boundary at the behavioral level. Selectively in the premotor cortex, we found that ITV, rather than trial-averaged amplitude, of BOLD responses to far rather than near dynamic stimuli predicts the individual extension of PPS. Our results provide the first empirical support for the relevance of ITV of brain responses for individual differences in human behavior. SIGNIFICANCE STATEMENT: Peripersonal space (PPS) is a multisensory and sensorimotor interface mediating every physical interaction between the body and the environment. A major characteristic of the boundary of PPS in humans is the extremely high variability of its location across individuals. We show that interindividual differences in the extension of the PPS are predicted by variability of BOLD responses in the premotor cortex to far stimuli approaching our body. Our results provide the first empirical support to the relevance of variability of evoked responses for human behavior and its variance across individuals.

Functional connectivity and neuronal variability of resting state activity in bipolar disorder--reduction and decoupling in anterior cortical midline structures.

INTRODUCTION: The cortical midline structures seem to be involved in the modulation of different resting state networks, such as the default mode network (DMN) and salience network (SN). Alterations in these systems, in particular in the perigenual anterior cingulate cortex (PACC), seem to play a central role in bipolar disorder (BD). However, the exact role of the PACC, and its functional connections to other midline regions (within and outside DMN) still remains unclear in BD. METHODS: We investigated functional connectivity (FC), standard deviation (SD, as a measure of neuronal variability) and their correlation in bipolar patients (n = 40) versus healthy controls (n = 40), in the PACC and in its connections in different frequency bands (standard: 0.01-0.10 Hz; Slow-5: 0.01-0.027 Hz; Slow-4: 0.027-0.073 Hz). Finally, we studied the correlations between FC alterations and clinical-neuropsychological parameters and we explored whether subgroups of patients in different phases of the illness present different patterns of FC abnormalities. RESULTS: We found in BD decreased FC (especially in Slow-5) from the PACC to other regions located predominantly in the posterior DMN (such as the posterior cingulate cortex (PCC) and inferior temporal gyrus) and in the SN (such as the supragenual anterior cingulate cortex and ventrolateral prefrontal cortex). Second, we found in BD a decoupling between PACC-based FC and variability in the various target regions (without alteration in variability itself). Finally, in our subgroups explorative analysis, we found a decrease in FC between the PACC and supragenual ACC (in depressive phase) and between the PACC and PCC (in manic phase). CONCLUSIONS: These findings suggest that in BD the communication, that is, information transfer, between the different cortical midline regions within the cingulate gyrus does not seem to work properly. This may result in dysbalance between different resting state networks like the DMN and SN. A deficit in the anterior DMN-SN connectivity could lead to an abnormal shifting toward the DMN, while a deficit in the anterior DMN-posterior DMN connectivity could lead to an abnormal shifting toward the SN, resulting in excessive focusing on internal contents and reduced transition from idea to action or in excessive focusing on external contents and increased transition from idea to action, respectively, which could represent central dimensions of depression and mania. If confirmed, they could represent diagnostic markers in BD.

The neuropsychiatric profile of posterior cortical atrophy.

We analyzed scores obtained at the Neuropsychiatric Inventory (NPI) by 20 patients with posterior cortical atrophy (PCA) and contrasted it with 20 patients having Alzheimer disease (AD). Patients with hallucinations and delusions were not included due to the high probability of a diagnosis of Lewy body disease. Prevalence of behavioral and psychological symptoms (BPSD) was 95% in the PCA group, the most frequent being apathy and anxiety. Cluster analysis on NPI subscales highlighted a behavioral subsyndrome characterized by agitated temper and irritability. Depression, anxiety, and apathy did not cluster with any other BPSD nor with each other. The PCA group showed a significantly higher proportion of anxious patients and worse anxiety score than patients with AD. No correlation was found between NPI data and demographic, clinical, or neuropsychological features nor were there significant differences for the same variables between anxious and nonanxious cases with PCA. In agreement with anecdotal reports, anxiety seems particularly relevant in PCA.

Reach out and touch someone: anticipatory sensorimotor processes of active interpersonal touch.

Anticipating the sensorimotor consequences of an action for both self and other is fundamental for action coordination when individuals socially interact. Somatosensation constitutes an elementary component of social cognition and sensorimotor prediction, but its functions in active social behavior remain unclear. We hypothesized that the somatosensory system contributes to social haptic behavior as evidenced by specific anticipatory activation patterns when touching an animate target (human hand) compared with an inanimate target (fake hand). fMRI scanning was performed during a paradigm that allowed us to isolate the anticipatory representations of active interpersonal touch while controlling for nonsocial sensorimotor processes and possible confounds because of interpersonal relationships or socioemotional valence. Active interpersonal touch was studied both as skin-to-skin contact and as object-mediated touch. The results showed weaker deactivation in primary somatosensory cortex and medial pFC and stronger activation in cerebellum for the animate target, compared with the inanimate target, when intending to touch it with one's own hand. Differently, in anticipation of touching the human hand with an object, anterior inferior parietal lobule and lateral occipital-temporal cortex showed stronger activity. When actually touching a human hand with one's own hand, activation was stronger in medial pFC but weaker in primary somatosensory cortex. The findings provide new insight on the contribution of simulation and sensory prediction mechanisms to active social behavior. They also suggest that literally getting in touch with someone and touching someone by using an object might be approached by an agent as functionally distinct conditions.

The eye contact effect in request and emblematic hand gestures.

Request and emblematic gestures, despite being both communicative gestures, do differ in terms of social valence. Indeed, only the former are used to initiate/maintain/terminate an actual interaction. If such a difference is at stake, a relevant social cue, i.e. eye contact, should have different impacts on the neuronal underpinnings of the two types of gesture. We measured blood oxygen level-dependent signals, using functional magnetic resonance imaging, while participants watched videos of an actor, either blindfolded or not, performing emblems, request gestures, or meaningless control movements. A left-lateralized network was more activated by both types of communicative gestures than by meaningless movements, regardless of the accessibility of the actor's eyes. Strikingly, when eye contact was taken into account as a factor, a right-lateralized network was more strongly activated by emblematic gestures performed by the non-blindfolded actor than by those performed by the blindfolded actor. Such modulation possibly reflects the integration of information conveyed by the eyes with the representation of emblems. Conversely, a wider right-lateralized network was more strongly activated by request gestures performed by the blindfolded than by those performed by the non-blindfolded actor. This probably reflects the effect of the conflict between the observed action and its associated contextual information, in which relevant social cues are missing.

The spatial alignment effect in near and far space: a kinematic study.

The present experiment aimed at verifying whether the spatial alignment effect modifies kinematic parameters of pantomimed reaching-grasping of cups located at reachable and not reachable distance. The cup's handle could be oriented either to the right or to the left, thus inducing a grasp movement that could be either congruent or incongruent with the pantomime. The incongruence/congruence induced an increase/decrease in maximal finger aperture, which was observed when the cup was located near but not far from the body. This effect probably depended on influence of the size of the cup body on pantomime control when, in the incongruent condition, cup body was closer to the grasp hand as compared to the handle. Cup distance (near and far) influenced the pantomime even if it was actually executed in the same peripersonal space. Specifically, arm and hand temporal parameters were affected by actual cup distance as well as movement amplitudes. The results indicate that, when executing a reach-to-grasp pantomime, affordance related to the use of the object was instantiated (and in particular the spatial alignment effect became effective), but only when the object could be actually reached. Cup distance (extrinsic object property) influenced affordance, independently of the possibility to actually reach the target.