Zazen meditation and no-task resting EEG compared with LORETA intracortical source localization

Meditation is a self-induced and willfully initiated practice that alters the state of consciousness. The meditation practice of Zazen, like many other meditation practices, aims at disregarding intrusive thoughts while controlling body posture. It is an open monitoring meditation characterized by detached moment-to-moment awareness and reduced conceptual thinking and self-reference. Which brain areas differ in electric activity during Zazen compared to task-free resting? Since scalp electroencephalography (EEG) waveforms are reference-dependent, conclusions about the localization of active brain areas are ambiguous. Computing intracerebral source models from the scalp EEG data solves this problem. In the present study, we applied source modeling using low resolution brain electromagnetic tomography (LORETA) to 58-channel scalp EEG data recorded from 15 experienced Zen meditators during Zazen and no-task resting. Zazen compared to no-task resting showed increased alpha-1 and alpha-2 frequency activity in an exclusively right-lateralized cluster extending from prefrontal areas including the insula to parts of the somatosensory and motor cortices and temporal areas. Zazen also showed decreased alpha and beta-2 activity in the left angular gyrus and decreased beta-1 and beta-2 activity in a large bilateral posterior cluster comprising the visual cortex, the posterior cingulate cortex and the parietal cortex. The results include parts of the default mode network and suggest enhanced automatic memory and emotion processing, reduced conceptual thinking and self-reference on a less judgmental, i.e., more detached moment-to-moment basis during Zazen compared to no-task resting.

Rivastigmine effects on EEG spectra and three-dimensional LORETA functional imaging in Alzheimer's disease

OBJECTIVE The objective of the study is to investigate the electrocortical and the global cognitive effects of 3 months rivastigmine medication in a group of mild to moderate Alzheimer's disease patients. MATERIALS AND METHODS Multichannel EEG and cognitive performances measured with the Mini Mental State Examination in a group of 16 patients with mild to moderate Alzheimer's Disease were collected before and 3 months after the onset of rivastigmine medication. RESULTS Spectral analysis of the EEG data showed a significant power decrease in the delta and theta frequency bands during rivastigmine medication, i.e., a shift of the power spectrum towards 'normalization'. Three-dimensional low resolution electromagnetic tomography (LORETA) functional imaging localized rivastigmine effects in a network that includes left fronto-parietal regions, posterior cingulate cortex, bilateral parahippocampal regions, and the hippocampus. Moreover, a correlation analysis between differences in the cognitive performances during the two recordings and LORETA-computed intracortical activity showed, in the alpha1 frequency band, better cognitive performance with increased cortical activity in the left insula. CONCLUSION The results point to a 'normalization' of the EEG power spectrum due to medication, and the intracortical localization of these effects showed an increase of cortical activity in frontal, parietal, and temporal regions that are well-known to be affected in Alzheimer's disease. The topographic convergence of the present results with the memory network proposed by Vincent et al. (J. Neurophysiol. 96:3517-3531, 2006) leads to the speculation that in our group of patients, rivastigmine specifically activates brain regions that are involved in memory functions, notably a key symptom in this degenerative disease.

I feel good whether my friends win or my foes lose: brain mechanisms underlying feeling similarity.

People say they enjoy both seeing a preferred social group succeed and seeing an adversary social group fail. At the same time, they state they dislike seeing a preferred social group fail and seeing an adversary social group succeed. The current magnetic resonance imaging study investigated whether-and if so, how-such similarities in reported feeling states are reflected in neural activities. American football fans anticipated success and failure situations for their favorite or their adversary teams. The data support the idea that feeling similarities and divergences expressed in verbal reports carry with them significant neural similarities and differences, respectively. Desired (favorite team likely to win and adversary team likely to lose) rather than undesired (favorite team likely to lose and adversary team likely to win) outcomes were associated with heightened activity in the supramarginal gyrus, posterior cingulate cortex, insula, and cerebellum. Precuneus activity additionally distinguished anticipated desirable outcomes for favorite versus adversary teams.

Serotonin versus catecholamine deficiency: behavioral and neural effects of experimental depletion in remitted depression

Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catecholaminergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or catecholamine neurotransmission hold the potential to optimize the prescriber's selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Using identical neuroimaging procedures with [(18)F] fluorodeoxyglucose positron emission tomography after tryptophan depletion (TD) and catecholamine depletion (CD), subjects with remitted depression were compared with healthy controls in a double-blind, randomized, crossover design. Although TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex. Although we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. In conclusion, this study showed that serotonin and catecholamines have common and differential roles in the pathophysiology of depression.

Altered directed functional connectivity in temporal lobe epilepsy in the absence of interictal spikes: A high density EEG study.

OBJECTIVE In patients with epilepsy, seizure relapse and behavioral impairments can be observed despite the absence of interictal epileptiform discharges (IEDs). Therefore, the characterization of pathologic networks when IEDs are not present could have an important clinical value. Using Granger-causal modeling, we investigated whether directed functional connectivity was altered in electroencephalography (EEG) epochs free of IED in left and right temporal lobe epilepsy (LTLE and RTLE) compared to healthy controls. METHODS Twenty LTLE, 20 RTLE, and 20 healthy controls underwent a resting-state high-density EEG recording. Source activity was obtained for 82 regions of interest (ROIs) using an individual head model and a distributed linear inverse solution. Granger-causal modeling was applied to the source signals of all ROIs. The directed functional connectivity results were compared between groups and correlated with clinical parameters (duration of the disease, age of onset, age, and learning and mood impairments). RESULTS We found that: (1) patients had significantly reduced connectivity from regions concordant with the default-mode network; (2) there was a different network pattern in patients versus controls: the strongest connections arose from the ipsilateral hippocampus in patients and from the posterior cingulate cortex in controls; (3) longer disease duration was associated with lower driving from contralateral and ipsilateral mediolimbic regions in RTLE; (4) aging was associated with a lower driving from regions in or close to the piriform cortex only in patients; and (5) outflow from the anterior cingulate cortex was lower in patients with learning deficits or depression compared to patients without impairments and to controls. SIGNIFICANCE Resting-state network reorganization in the absence of IEDs strengthens the view of chronic and progressive network changes in TLE. These resting-state connectivity alterations could constitute an important biomarker of TLE, and hold promise for using EEG recordings without IEDs for diagnosis or prognosis of this disorder.

Le rôle de la méthylation de l’ADN dans les fonctions cérébrales fronto-limbiques et la réactivité au stress quotidien

La sérotonine (5-HT) joue un rôle crucial dans l'étiologie des troubles mentaux comme la dépression majeure, les troubles de comportement et les troubles anxieux. Des études ont montré que des altérations précoces du système 5-HT peuvent potentiellement influencer le développement du cerveau et le fonctionnement du système fronto-limbique, engendrant des conséquences pour la régulation émotionnelle. Il existe aussi des évidences que le stress précoce peut affecter la méthylation de l'ADN résultant d'une altération de l'expression génique. Toutefois, le lien entre la méthylation de l'ADN et la réactivité comportementale à des facteurs de stress de la vie quotidienne est inconnu. La méthylation du gène transporteur 5-HT (SLC6A4) est d'un intérêt particulier, étant donné le rôle de SLC6A4 dans le développement du cerveau, les troubles mentaux et la régulation du stress. L'objectif de cette thèse est d'étudier l'association entre (1) les niveaux périphériques de méthylation de l'ADN dans le gène SLC6A4 et les réponses neurales aux stimuli émotionnels dans les circuits fronto-limbiques du cerveau, ainsi qu’entre (2) la méthylation périphérique de SLC6A4 et la réactivité comportementale au stress de la vie quotidienne. Nous explorons également l'association entre les réponses neuronales fronto-limbique à des stimuli émotionnels et la réactivité comportementale au stress de la vie quotidienne (3). À cette fin, vingt-deux personnes (11 femmes) d’âge moyen de 34,0 ans (SD : 1,5) avec différents niveaux de méthylation au gène SLC6A4 ont été recrutés à partir de deux études longitudinales. Les participants ont subi une analyse IRMf qui comprenait une tâche de traitement émotionnel. Un questionnaire en ligne sur la réactivité au stress quotidien de la vie a été réalisé pendant 5 jours consécutifs. Des analyses corrélationnelles et de régression ont été effectuées pour examiner les associations entre les variables primaires. Les résultats préliminaires de cette étude ont montré que la méthylation de l'ADN est associée à la désactivation significative du gyrus précentral et gyrus fusiforme respectivement face à des stimuli de peur et de tristesse. Aucune association significative n'a été observée entre les niveaux de méthylation et l'activation de l'amygdale. En outre, les scores obtenus aux variables de stress de la vie quotidienne tels que la détresse chronique ont été associées à la désactivation du précuneus et du cortex cingulaire postérieur face à la tristesse. Ces résultats suggèrent l'implication potentielle des processus épigénétiques dans l'activation cérébrale spécifique et la sensibilité au stress de la vie courante.

Corrélats neuronaux du circuit des récompenses chez les jeunes à risque parental de troubles de l'humeur

Cette thèse a pour objectif l’investigation du circuit des récompenses, sur les plans comportementaux et neuronaux, chez des adolescents à risque parental élevé de dépression majeure et de trouble bipolaire, en comparaison à des jeunes à risque parental peu élevé. Plus précisément, le but est d’identifier des marqueurs comportementaux et neuronaux du risque de développer une dépression majeure ou un trouble bipolaire, afin d’être en mesure de détecter et de prévenir ces troubles le plus tôt possible pour éviter, ou du moins retarder, leur émergence. Pour ce faire, nous avons réalisé deux études, présentées ici dans deux articles empiriques. Dans le premier article, le fonctionnement comportemental et neuronal du circuit des récompenses a été investigué au moyen d’une tâche d’anticipation et d’obtention de gains et de pertes monétaires, chez des adolescents à risque parental de dépression majeure (i.e., jeunes asymptomatiques dont un des parents souffre de dépression majeure), des adolescents à risque parental de trouble bipolaire (i.e., jeunes asymptomatiques dont un des parents souffre de trouble bipolaire) et des adolescents contrôles (i.e., jeunes asymptomatiques dont les deux parents sont en bonne santé mentale). Au niveau comportemental, les résultats ont révélé une meilleure performance chez les jeunes à risque de dépression majeure lorsqu’ils devaient éviter d’obtenir des pertes monétaires de magnitude variée (0,20$, 1$ ou 5$), ainsi qu’une meilleure performance chez les jeunes à risque de trouble bipolaire sur les essais impliquant d’éviter des pertes monétaires de magnitude nulle (0$). Au niveau neuronal, les jeunes à risque de dépression majeure démontraient une diminution de l’activation du cortex préfrontal dorsolatéral lors de l’anticipation de potentielles pertes monétaires de magnitude variée, tandis que les jeunes à risque de trouble bipolaire démontraient une diminution de l’activation du cortex préfrontal dorsolatéral lors de l’anticipation de potentielles pertes monétaires de magnitude nulle. De plus, les jeunes à risque de dépression majeure tendaient à démontrer une augmentation de l’activité du cortex orbitofrontal durant l’évitement réussi de pertes monétaires, tandis que les jeunes à risque de trouble bipolaire tendaient à démontrer une augmentation de l’activité du cortex orbitofrontal lors de l’obtention de pertes monétaires. Dans le deuxième article, l’intégrité structurelle des régions fronto-limbiques a été investiguée, au moyen de mesures du volume, de l’épaisseur corticale et de la superficie corticale. Les résultats ont mis en évidence, chez les jeunes à risque de trouble bipolaire, un volume plus élevé du cortex préfrontal dorsolatéral, par rapport aux jeunes à risque de dépression majeure et contrôles. De plus, les jeunes à risque de trouble bipolaire présentaient un volume plus élevé du cortex cingulaire postérieur, en comparaison aux jeunes à risque de dépression majeure. Enfin, une diminution de l’épaisseur corticale du cortex orbitofrontal et du gyrus frontal moyen a été observée chez les adolescents à risque de trouble bipolaire, en comparaison au groupe contrôle. L’ensemble de ces résultats démontre ainsi l’existence de particularités comportementales et d’altérations neuronales sur les plans fonctionnel et structurel, chez des jeunes à risque élevé de troubles de l’humeur, et ce, avant même l’émergence des premiers symptômes thymiques. Plus particulièrement, ces caractéristiques pourraient constituer des marqueurs du risque de développer un trouble de l’humeur. Par conséquent, ces marqueurs pourraient aider à mieux identifier les jeunes qui sont le plus à risque de développer un trouble de l’humeur, et ainsi permettre la mise en place précoce de stratégies préventives adaptées, afin d’éviter des trajectoires développementales psychopathologiques.

Corrélats neuronaux du circuit des récompenses chez les jeunes à risque parental de troubles de l'humeur

Cette thèse a pour objectif l’investigation du circuit des récompenses, sur les plans comportementaux et neuronaux, chez des adolescents à risque parental élevé de dépression majeure et de trouble bipolaire, en comparaison à des jeunes à risque parental peu élevé. Plus précisément, le but est d’identifier des marqueurs comportementaux et neuronaux du risque de développer une dépression majeure ou un trouble bipolaire, afin d’être en mesure de détecter et de prévenir ces troubles le plus tôt possible pour éviter, ou du moins retarder, leur émergence. Pour ce faire, nous avons réalisé deux études, présentées ici dans deux articles empiriques. Dans le premier article, le fonctionnement comportemental et neuronal du circuit des récompenses a été investigué au moyen d’une tâche d’anticipation et d’obtention de gains et de pertes monétaires, chez des adolescents à risque parental de dépression majeure (i.e., jeunes asymptomatiques dont un des parents souffre de dépression majeure), des adolescents à risque parental de trouble bipolaire (i.e., jeunes asymptomatiques dont un des parents souffre de trouble bipolaire) et des adolescents contrôles (i.e., jeunes asymptomatiques dont les deux parents sont en bonne santé mentale). Au niveau comportemental, les résultats ont révélé une meilleure performance chez les jeunes à risque de dépression majeure lorsqu’ils devaient éviter d’obtenir des pertes monétaires de magnitude variée (0,20$, 1$ ou 5$), ainsi qu’une meilleure performance chez les jeunes à risque de trouble bipolaire sur les essais impliquant d’éviter des pertes monétaires de magnitude nulle (0$). Au niveau neuronal, les jeunes à risque de dépression majeure démontraient une diminution de l’activation du cortex préfrontal dorsolatéral lors de l’anticipation de potentielles pertes monétaires de magnitude variée, tandis que les jeunes à risque de trouble bipolaire démontraient une diminution de l’activation du cortex préfrontal dorsolatéral lors de l’anticipation de potentielles pertes monétaires de magnitude nulle. De plus, les jeunes à risque de dépression majeure tendaient à démontrer une augmentation de l’activité du cortex orbitofrontal durant l’évitement réussi de pertes monétaires, tandis que les jeunes à risque de trouble bipolaire tendaient à démontrer une augmentation de l’activité du cortex orbitofrontal lors de l’obtention de pertes monétaires. Dans le deuxième article, l’intégrité structurelle des régions fronto-limbiques a été investiguée, au moyen de mesures du volume, de l’épaisseur corticale et de la superficie corticale. Les résultats ont mis en évidence, chez les jeunes à risque de trouble bipolaire, un volume plus élevé du cortex préfrontal dorsolatéral, par rapport aux jeunes à risque de dépression majeure et contrôles. De plus, les jeunes à risque de trouble bipolaire présentaient un volume plus élevé du cortex cingulaire postérieur, en comparaison aux jeunes à risque de dépression majeure. Enfin, une diminution de l’épaisseur corticale du cortex orbitofrontal et du gyrus frontal moyen a été observée chez les adolescents à risque de trouble bipolaire, en comparaison au groupe contrôle. L’ensemble de ces résultats démontre ainsi l’existence de particularités comportementales et d’altérations neuronales sur les plans fonctionnel et structurel, chez des jeunes à risque élevé de troubles de l’humeur, et ce, avant même l’émergence des premiers symptômes thymiques. Plus particulièrement, ces caractéristiques pourraient constituer des marqueurs du risque de développer un trouble de l’humeur. Par conséquent, ces marqueurs pourraient aider à mieux identifier les jeunes qui sont le plus à risque de développer un trouble de l’humeur, et ainsi permettre la mise en place précoce de stratégies préventives adaptées, afin d’éviter des trajectoires développementales psychopathologiques.

Disorders of arousal: a physiopathological window to explore the mechanisms regulating sleep arousal

Disorders of Arousal (DoA) belong to NREM parasomnias and are characterized by motor and emotional episodes arising from incomplete awakenings from NREM sleep. DoA episodes embody at the same time the double nature of the arousal process, that is preserving sleep as well as respond to sleep perturbations, thus being an ideal model to study sleep arousal. In the first part of this work, we performed a spectral whole scalp EEG analysis exploring the neurophysiologic correlates of the pre-motor onset of the episodes in a large sample of patients with DoA, disclosing the co-existence of both slow and fast EEG frequencies over overlapping areas before DoA episodes, suggesting an alteration of local sleep mechanisms. Episodes of different complexity were preceded by a similar EEG activation, implying that they possibly share a similar pathophysiology. In the second part of this work, we performed a spectral whole scalp EEG analysis comparing the pre-motor onset of the episodes and normal arousals from healthy sleepers, disclosing the persistence of slow frequencies as well as sigma band (expression of sleep spindles) in DoA episodes. Overall, these results might subtend a higher tendence to preserve sleep and a more defective mechanism toward developing a complete arousal in patients with DoA. In the last part of our work, we evaluated 15 patients with DoA with 15 controls in a functional MRI study during wakefulness in addition to a proton magnetic resonance spectroscopy (1H-MRS) focused on cingulate cortex. We disclosed subtle alterations on posterior cingulate cortex as well as an increased connectivity in sensory-motor network, possibly representing a trait-functional feature responsible for the dysfunctional arousal process in DoA patients

Stereologic investigation of the posterior part of the hippocampus in schizophrenia

Structural magnetic resonance imaging and postmortem studies showed volume loss in the hippocampus in schizophrenia. The noted tissue reduction in the posterior section suggests that some cellular subfractions within this structure might be reduced in schizophrenia. To address this, we investigated numbers and densities of neurons, oligodendrocytes and astrocytes in the posterior hippocampal subregions in postmortem brains from ten patients with schizophrenia and ten matched controls using design-based stereology performed on Nissl-stained sections. Compared to the controls, the patients with schizophrenia showed a significant decrease in the mean number of oligodendrocytes in the left and right CA4. This is the first finding of reduced numbers of oligodendrocytes in CA4 of the posterior part of the hippocampus in schizophrenia. Our results are in line with earlier findings in the literature concerning decreased numbers of oligodendrocytes in the prefrontal cortex in schizophrenia. Our results may indicate disturbed connectivity of the CA4 of the posterior part of the hippocampus in schizophrenia and, thus, contribute to the growing number of studies showing the involvement of posterior hippocampal pathology in the pathophysiology of schizophrenia.

Individual differences in the effects of perceived controllability on pain perception: critical role of the prefrontal cortex

The degree to which perceived controllability alters the way a stressor is experienced varies greatly among individuals. We used functional magnetic resonance imaging to examine the neural activation associated with individual differences in the impact of perceived controllability on self-reported pain perception. Subjects with greater activation in response to uncontrollable (UC) rather than controllable (C) pain in the pregenual anterior cingulate cortex (pACC), periaqueductal gray (PAG), and posterior insula/SII reported higher levels of pain during the UC versus C conditions. Conversely, subjects with greater activation in the ventral lateral prefrontal cortex (VLPFC) in anticipation of pain in the UC versus C conditions reported less pain in response to UC versus C pain. Activation in the VLPFC was significantly correlated with the acceptance and denial subscales of the COPE inventory [Carver, C. S., Scheier, M. F., & Weintraub, J. K. Assessing coping strategies: A theoretically based approach. Journal of Personality and Social Psychology, 56, 267–283, 1989], supporting the interpretation that this anticipatory activation was associated with an attempt to cope with the emotional impact of uncontrollable pain. A regression model containing the two prefrontal clusters (VLPFC and pACC) predicted 64% of the variance in pain rating difference, with activation in the two additional regions (PAG and insula/SII) predicting almost no additional variance. In addition to supporting the conclusion that the impact of perceived controllability on pain perception varies highly between individuals, these findings suggest that these effects are primarily top-down, driven by processes in regions of the prefrontal cortex previously associated with cognitive modulation of pain and emotion regulation.

Transdural motor cortex stimulation reverses neuropathic pain in rats: A profile of neuronal activation

Motor cortex stimulation (MCS) has been used to treat patients with neuropathic pain resistant to other therapeutic approaches; however, the mechanisms of pain control by MCS are still not clearly understood. We have demonstrated that MCS increases the nociceptive threshold of naive conscious rats, with opioid participation. In the present study, the effect of transdural MCS on neuropathic pain in rats subjected to chronic constriction injury of the sciatic nerve was investigated. In addition, the pattern of neuronal activation, evaluated by Fos and Zif268 immunolabel, was performed in the spinal cord and brain sites associated with the modulation of persistent pain. MCS reversed the mechanical hyperalgesia and allodynia induced by peripheral neuropathy. After stimulation, Fos immunoreactivity (Fos-IR) decreased in the dorsal horn of the spinal cord and in the ventral posterior lateral and medial nuclei of the thalamus, when compared to animals with neuropathic pain. Furthermore, the MCS increased the Fos-IR in the periaqueductal gray, the anterior cingulate cortex and the central and basolateral amygdaloid nuclei. Zif268 results were similar to those obtained for Fos, although no changes were observed for Zif268 in the anterior cingulate cortex and the central amygdaloid nucleus after MCS. The present findings suggest that MCS reverts neuropathic pain phenomena in rats, mimicking the effect observed in humans, through activation of the limbic and descending pain inhibitory systems. Further investigation of the mechanisms involved in this effect may contribute to the improvement of the clinical treatment of persistent pain. (c) 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

The anatomical connections of the macaque monkey orbitofrontal cortex. A review

The orbitofrontal cortex (OfC) is a heterogeneous prefrontal sector selectively connected with a wide constellation of other prefrontal, limbic, sensory and premotor areas. Among the limbic cortical connections, the ones with the bippocampus and parabippocampal cortex are particularly salient. Sensory cortices connected with the OfC include areas involved in olfactory, gustatory, somatosensory, auditory and visual processing. Subcortical structures with prominent OfC connections include the amygdala, numerous thalamic nuclei, the striatum, hypothalamus, periaqueductal gray matter, and biochemically specific cell groups in the basal forebrain and brainstem. Architectonic and connectional evidence supports parcellation of the OfC. The rostrally placed isocortical sector is mainly connected with isocortical areas, including sensory areas of the auditory, somatic and visual modalities, whereas the caudal non-isocortical sector is principally connected with non-isocortical areas, and, in the sensory domain, with olfactory and gustatory areas. The connections of the isocortical and non- isocortical orbital sectors with the amygdala, thalamus, striatum, hypotbalamus and periaqueductal gray matter are also specific. The medial sector of the OfC is selectively connected with the bippocampus, posterior parabippocampal cortex, posterior cingulate and retrosplenial areas, and area prostriata, while the lateral orbitofrontal sector is the most heavily connected with sensory areas of the gustatory, somatic and visual modalities, with premotor regions, and with the amygdala.

The human vestibular cortex revealed by coordinate-based activation likelihood estimation meta-analysis.

The vestibular system contributes to the control of posture and eye movements and is also involved in various cognitive functions including spatial navigation and memory. These functions are subtended by projections to a vestibular cortex, whose exact location in the human brain is still a matter of debate (Lopez and Blanke, 2011). The vestibular cortex can be defined as the network of all cortical areas receiving inputs from the vestibular system, including areas where vestibular signals influence the processing of other sensory (e.g. somatosensory and visual) and motor signals. Previous neuroimaging studies used caloric vestibular stimulation (CVS), galvanic vestibular stimulation (GVS), and auditory stimulation (clicks and short-tone bursts) to activate the vestibular receptors and localize the vestibular cortex. However, these three methods differ regarding the receptors stimulated (otoliths, semicircular canals) and the concurrent activation of the tactile, thermal, nociceptive and auditory systems. To evaluate the convergence between these methods and provide a statistical analysis of the localization of the human vestibular cortex, we performed an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies using CVS, GVS, and auditory stimuli. We analyzed a total of 352 activation foci reported in 16 studies carried out in a total of 192 healthy participants. The results reveal that the main regions activated by CVS, GVS, or auditory stimuli were located in the Sylvian fissure, insula, retroinsular cortex, fronto-parietal operculum, superior temporal gyrus, and cingulate cortex. Conjunction analysis indicated that regions showing convergence between two stimulation methods were located in the median (short gyrus III) and posterior (long gyrus IV) insula, parietal operculum and retroinsular cortex (Ri). The only area of convergence between all three methods of stimulation was located in Ri. The data indicate that Ri, parietal operculum and posterior insula are vestibular regions where afferents converge from otoliths and semicircular canals, and may thus be involved in the processing of signals informing about body rotations, translations and tilts. Results from the meta-analysis are in agreement with electrophysiological recordings in monkeys showing main vestibular projections in the transitional zone between Ri, the insular granular field (Ig), and SII.

Pleasant sweeping grooming touch in rhesus monkey: effects on autonomic nervous system and its codification in posterior insular and secondary somatosensory cortex

Il tatto assume un'importanza fondamentale nella vita quotidiana, in quanto ci permette di discriminare le caratteristiche fisiche di un oggetto specifico, di identificarlo e di eventualmente integrare le suddette informazioni tattili con informazioni provenienti da altri canali sensoriali. Questa è la componente sensoriale-discriminativa del tatto. Tuttavia quotidianamente il tatto assume un ruolo fondamentale durante le diverse interazioni sociali, positive, come quando abbracciamo o accarezziamo una persona con cui abbiamo un rapporto affettivo e negative, per esempio quando allontaniamo una persona estranea dal nostro spazio peri-personale. Questa componente è la cosiddetta dimensione affettiva-motivazionale, la quale determina la codifica della valenza emotiva che l'interazione assume. Questa componente ci permette di creare, mantenere o distruggere i legami sociali in relazione al significato che il tocco assume durante l'interazione. Se per esempio riceviamo una carezza da un familiare, questa verrà percepita come piacevole e assumerà un significato affiliativo. Questo tipo di tocco è comunente definito come Tocco Sociale (Social Touch). Gli aspetti discriminativi del tatto sono stati ben caratterizzati, in quanto storicamente, il ruolo del tatto è stato considerato quello di discriminare le caratteristiche di ciò che viene toccato, mentre gli aspetti affettivi sono stati solo recentemente indagati considerando la loro importanza nelle interazioni sociali. Il tocco statico responsabile dell'aspetto discriminante attiva a livello della pelle le grandi fibre mieliniche (Aβ), modulando a livello del sistema nervoso centrale le cortecce sensoriali, sia primarie che secondarie. Questo permette la codifica a livello del sistema nervoso centrale delle caratteristiche fisiche oggettive degli oggetti toccati. Studi riguardanti le caratteristiche del tocco affiliativo sociale hanno messo in evidenza che suddetta stimolazione tattile 1) è un particolare tocco dinamico che avviene sul lato peloso delle pelle con una velocità di 1-10 cm/sec; 2) attiva le fibre amieliniche (fibre CT o C-LTMRs); 3) induce positivi effetti autonomici, ad esempio la diminuzione della frequenza cardiaca e l'aumento della variabilità della frequenza cardiaca; e 4) determina la modulazione di regioni cerebrali coinvolte nella codifica del significato affiliativo dello stimolo sensoriale periferico, in particolare la corteccia insulare. Il senso del tatto, con le sue due dimensioni discriminativa e affiliativa, è quotidianamente usato non solo negli esseri umani, ma anche tra i primati non umani. Infatti, tutti i primati non umani utilizzano la componente discriminativa del tatto per identificare gli oggetti e il cibo e l'aspetto emotivo durante le interazioni sociali, sia negative come durante un combattimento, che positive, come durante i comportamenti affiliativi tra cui il grooming. I meccanismi di codifica della componente discriminativa dei primati non umani sono simili a quelli umani. Tuttavia, si conosce ben poco dei meccanismi alla base della codifica del tocco piacevole affiliativo. Pur essendo ben noto che i meccanorecettori amilienici C-LTMRs sono presenti anche sul lato peloso della pelle dei primati non umani, attualmente non ci sono studi riguardanti la correlazione tra il tocco piacevole e la loro modulazione, come invece è stato ampiamente dimostrato nell'uomo. Recentemente è stato ipotizzato (Dunbar, 2010) il ruolo delle fibre C-LTMRs durante il grooming, in particolare durante il cosiddetto swepping. Il grooming è costituito da due azioni motorie, lo sweeping e il picking che vengono eseguite in modo ritmico. Durante lo sweeping la scimmia agente muove il pelo della scimmia ricevente con un movimento a mano aperta, per poter vedere il preciso punto della pelle dove eseguire il picking, ovvero dove prendere la pelle a livello della radice del pelo con le unghie dell'indice e del pollice e tirare per rimuovere parassiti o uova di parassiti e ciò che è rimasto incastrato nel pelo. Oltre il noto ruolo igenico, il grooming sembra avere anche una importante funzione sociale affiliativa. Come la carezza nella società umana, cosi il grooming tra i primati non umani è considerato un comportamento. Secondo l'ipotesi di Dunbar l'attivazione delle C-LTMRs avverrebbe durante lo sweeping e questo porta a supporre che lo sweeping, come la carezza umana, costituisca una componente affiliativa del grooming, determinando quindi a contribuire alla sua codifica come comportamento sociale. Fino ad ora non vi è però alcuna prova diretta a sostegno di questa ipotesi. In particolare, 1) la velocità cui viene eseguito lo sweeping è compatibile con la velocità di attivazione delle fibre CT nell'uomo e quindi con la velocità tipica della carezza piacevole di carattere sociale affiliativo (1-10 cm/sec)?; 2) lo sweeping induce la stessa modulazione del sistema nervoso autonomo in direzione della modulazione del sistema vagale, come il tocco piacevole nell'uomo, attraverso l'attivazione delle fibre CT?; 3) lo sweeping modula la corteccia insulare, cosi come il tocco piacevole viene codificato come affiliativo nell'uomo mediante le proiezioni delle fibre CT a livello dell'insula posteriore? Lo scopo del presente lavoro è quella di testare l'ipotesi di Dunbar sopra citata, cercando quindi di rispondere alle suddette domande. Le risposte potrebbero consentire di ipotizzare la somiglianza tra lo sweeping, caratteristico del comportamento affiliativo di grooming tra i primati non umani e la carezza. In particolare, abbiamo eseguito 4 studi pilota. Nello Studio 1 abbiamo valutato la velocità con cui viene eseguito lo sweeping tra scimmie Rhesus, mediante una analisi cinematica di video registrati tra un gruppo di scimmie Rhesus. Negli Studi 2 e 3 abbiamo valutato gli effetti sul sistema nervoso autonomo dello sweeping eseguito dallo sperimentatore su una scimmia Rhesus di sesso maschile in una tipica situazione sperimentale. La stimolazione tattile è stata eseguita a diverse velocità, in accordo con i risultati dello Studio 1 e degli studi umani che hanno dimostrato la velocità ottimale e non ottimale per l'attivazione delle C-LTMRs. In particolare, nello Studio 2 abbiamo misurato la frequenza cardiaca e la variabilità di questa, come indice della modulatione vagale, mentre nello Studio 3 abbiamo valutato gli effetti dello sweeping sul sistema nervoso autonomo in termini di variazioni di temperatura del corpo, nello specifico a livello del muso della scimmia. Infine, nello Studio 4 abbiamo studiato il ruolo della corteccia somatosensoriale secondaria e insulare nella codifica dello sweeping. A questo scopo abbiamo eseguito registrazioni di singoli neuroni mentre la medesima scimmia soggetto sperimentale dello Studio 2 e 3, riceveva lo sweeping a due velocità, una ottimale per l'attivazione delle C-LTMRs secondo gli studi umani e i risultati dei tre studi sopra citati, ed una non ottimale. I dati preliminari ottenuti, dimostrano che 1) (Studio 1) lo sweeping tra scimmie Rhesus viene eseguito con una velocità media di 9.31 cm/sec, all'interno dell'intervallo di attivazione delle fibre CT nell'uomo; 2) (Studio 2) lo sweeping eseguito dallo sperimentatore sulla schiena di una scimmia Rhesus di sesso maschile in una situazione sperimentale determina una diminuzione della frequenza cardiaca e l'aumento della variabilità della frequenza cardiaca se eseguito alla velocità di 5 e 10 cm/sec. Al contrario, lo sweeping eseguito ad una velocità minore di 1 cm/sec o maggiore di 10 cm/sec, determina l'aumento della frequenza cardiaca e la diminuzione della variabilità di questa, quindi il decremento dell'attivazione del sistema nervoso parasimpatico; 3) (Studio 3) lo sweeping eseguito dallo sperimentatore sulla schiena di una scimmia Rhesus di sesso maschile in una situazione sperimentale determina l'aumento della temperatura corporea a livello del muso della scimmia se eseguito alla velocità di 5-10 cm/sec. Al contrario, lo sweeping eseguito ad una velocità minore di 5 cm/sec o maggiore di 10 cm/sec, determina la diminuzione della temperatura del muso; 4) (Studio 4) la corteccia somatosensoriale secondaria e la corteccia insulare posteriore presentano neuroni selettivamente modulati durante lo sweeping eseguito ad una velocità di 5-13 cm/sec ma non neuroni selettivi per la codifica della velocità dello sweeping minore di 5 cm/sec. Questi risultati supportano l'ipotesi di Dunbar relativa al coinvolgimento delle fibre CT durante lo sweeping. Infatti i dati mettono in luce che lo sweeping viene eseguito con una velocità (9.31 cm/sec), simile a quella di attivazione delle fibre CT nell'uomo (1-10 cm/sec), determina gli stessi effetti fisiologici positivi in termini di frequenza cardiaca (diminuzione) e variabilità della frequenza cardiaca (incremento) e la modulazione delle medesime aree a livello del sistema nervoso centrale (in particolare la corteccia insulare). Inoltre, abbiamo dimostrato per la prima volta che suddetta stimolazione tattile determina l'aumento della temperatura del muso della scimmia. Il presente studio rappresenta la prima prova indiretta dell'ipotesi relativa alla modulazione del sistema delle fibre C-LTMRs durante lo sweeping e quindi della codifica della stimolazione tattile piacevole affiliativa a livello del sistema nervoso centrale ed autonomo, nei primati non umani. I dati preliminari qui presentati evidenziano la somiglianza tra il sistema delle fibre CT dell'uomo e del sistema C-LTMRs nei primati non umano, riguardanti il Social Touch. Nonostante ciò abbiamo riscontrato alcune discrepanze tra i risultati da noi ottenuti e quelli invece ottenuti dagli studi umani. La velocità media dello sweeping è di 9.31 cm / sec, rasente il limite superiore dell’intervallo di velocità che attiva le fibre CT nell'uomo. Inoltre, gli effetti autonomici positivi, in termini di battito cardiaco, variabilità della frequenza cardiaca e temperatura a livello del muso, sono stati evidenziati durante lo sweeping eseguito con una velocità di 5 e 10 cm/sec, quindi al limite superiore dell’intervallo ottimale che attiva le fibre CT nell’uomo. Al contrario, lo sweeping eseguito con una velocità inferiore a 5 cm/sec e superiore a 10 cm/sec determina effetti fisiologici negativo. Infine, la corteccia insula sembra essere selettivamente modulata dallo stimolazione eseguita alla velocità di 5-13 cm/sec, ma non 1-5 cm/sec. Quindi, gli studi sul sistema delle fibre CT nell’uomo hanno dimostrato che la velocità ottimale è 1-10 cm/sec, mentre dai nostri risultati la velocità ottimale sembra essere 5-13 cm / sec. Quindi, nonostante l'omologia tra il sistema delle fibre CT nell'umano deputato alla codifica del tocco piacevole affiliativo ed il sistema delle fibre C-LTMRs nei primati non umani, ulteriori studi saranno necessari per definire con maggiore precisione la velocità ottimale di attivazione delle fibre C-LTMR e per dimostrare direttamente la loro attivazione durante lo sweeping, mediante la misurazione diretta della loro modulazione. Studi in questa direzione potranno confermare l'omologia tra lo sweeping in qualità di tocco affiliativo piacevole tra i primati non umani e la carezza tra gli uomini. Infine, il presente studio potrebbe essere un importante punto di partenza per esplorare il meccanismo evolutivo dietro la trasformazione dello sweeping tra primati non umani, azione utilitaria eseguita durante il grooming, a carezza, gesto puramente affiliativo tra gli uomini.