Outcome after acute ischemic stroke is linked to sex-specific lesion patterns.

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.

Activation response and functional connectivity change in rat cortex after bilateral transcranial direct current stimulation-An exploratory study.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique implicated as a promising adjunct therapy to improve motor function through the neuromodulation of brain networks. Particularly bilateral tDCS, which affects both hemispheres, may yield stronger effects on motor learning than unilateral stimulation. Therefore, the aim of this exploratory study was to develop an experimental model for simultaneous magnetic resonance imaging (MRI) and bilateral tDCS in rats, to measure instant and resultant effects of tDCS on network activity and connectivity. Naïve, male Sprague-Dawley rats were divided into a tDCS (n = 7) and sham stimulation group (n = 6). Functional MRI data were collected during concurrent bilateral tDCS over the sensorimotor cortex, while resting-state functional MRI and perfusion MRI were acquired directly before and after stimulation. Bilateral tDCS induced a hemodynamic activation response, reflected by a bilateral increase in blood oxygenation level-dependent signal in different cortical areas, including the sensorimotor regions. Resting-state functional connectivity within the cortical sensorimotor network decreased after a first stimulation session but increased after a second session, suggesting an interaction between multiple tDCS sessions. Perfusion MRI revealed no significant changes in cerebral blood flow after tDCS. Our exploratory study demonstrates successful application of an MRI-compatible bilateral tDCS setup in an animal model. Our results indicate that bilateral tDCS can locally modulate neuronal activity and connectivity, which may underlie its therapeutic potential.

Intracranial-Intracranial Bypass Using a Y-Shaped Artery Graft for Growing Unruptured Gemella morbillorum Infectious Aneurysm on Artery Supplying Sensory Cortex.

BACKGROUND: Vascular reconstruction is required to treat infectious intracranial aneurysms (IIAs) on arteries supplying the eloquent area. However, extracranial-intracranial bypass is sometimes impossible because IIAs are frequently located distally on arteries and the length of a donor artery is limited. We report a rare case of an unruptured Gemella morbillorum IIA, which was successfully treated by intracranial-intracranial (IC-IC) bypass using a Y-shaped superficial temporal artery (STA) interposition graft. CASE DESCRIPTION: A 52-year-old man presented with heart failure and an unruptured IIA in the right anterior parietal artery because of acute G. morbillorum endocarditis. The patient was treated with urgent replacement of cardiac valves and antibiotic therapy. However, the IIA increased in size during the following 1 month, and therefore was treated surgically to prevent the rupture. End-to-side IC-IC bypass using a Y-shaped STA graft followed by aneurysmal trapping was performed to overcome the limited length of the STA as a donor artery to prevent cerebral ischemia in the artery territory and to avoid direct injury to the sensory cortex adhering tightly to the IIA. Postoperative courses were uneventful, and he recovered from the infectious diseases. CONCLUSIONS: This case suggests that end-to-side IC-IC bypass using a Y-shaped STA graft can be a good option for surgical treatment of IIAs, which are located in eloquent areas.

Olanzapine exposure diminishes perfusion and decreases volume of sensorimotor cortex in rats.

BACKGROUND: Olanzapine is a frequently used atypical antipsychotic drug known to exert structural brain alterations in animals. This study investigated whether chronic olanzapine exposure alters regional blood brain perfusion assessed by Arterial Spin Labelling (ASL) magnetic resonance imaging (MRI) in a validated model of olanzapine-induced metabolic disturbances. An effect of acute olanzapine exposure on brain perfusion was also assessed for comparison. METHODS: Adult Sprague-Dawley female rats were treated by intramuscular depot olanzapine injections (100 mg/kg every 14 days) or vehicle for 8 weeks. ASL scanning was performed on a 9.4 T Bruker BioSpec 94/30USR scanner under isoflurane anesthesia. Serum samples were used to assay leptin and TNF-α level while brains were sliced for histology. Another group received only one non-depot intraperitoneal dose of olanzapine (7 mg/kg) during MRI scanning, thus exposing its acute effect on brain perfusion. RESULTS: Both acute and chronic dosing of olanzapine resulted in decreased perfusion in the sensorimotor cortex, while no effect was observed in the piriform cortex or hippocampus. Furthermore, in the chronically treated group decreased cortex volume was observed. Chronic olanzapine dosing led to increased body weight, adipose tissue mass and leptin level, confirming its expected metabolic effects. CONCLUSION: This study demonstrates region-specific decreases in blood perfusion associated with olanzapine exposure present already after the first dose. These findings extend our understanding of olanzapine-induced functional and structural brain changes.

Different effects of prenatal MAM vs. perinatal THC exposure on regional cerebral blood perfusion detected by Arterial Spin Labelling MRI in rats.

Clinical studies consistently report structural impairments (i.e.: ventricular enlargement, decreased volume of anterior cingulate cortex or hippocampus) and functional abnormalities including changes in regional cerebral blood flow in individuals suffering from schizophrenia, which can be evaluated by magnetic resonance imaging (MRI) techniques. The aim of this study was to assess cerebral blood perfusion in several schizophrenia-related brain regions using Arterial Spin Labelling MRI (ASL MRI, 9.4 T Bruker BioSpec 94/30USR scanner) in rats. In this study, prenatal exposure to methylazoxymethanol acetate (MAM, 22 mg/kg) at gestational day (GD) 17 and the perinatal treatment with Δ-9-tetrahydrocannabinol (THC, 5 mg/kg) from GD15 to postnatal day 9 elicited behavioral deficits consistent with schizophrenia-like phenotype, which is in agreement with the neurodevelopmental hypothesis of schizophrenia. In MAM exposed rats a significant enlargement of lateral ventricles and perfusion changes (i.e.: increased blood perfusion in the circle of Willis and sensorimotor cortex and decreased perfusion in hippocampus) were detected. On the other hand, the THC perinatally exposed rats did not show differences in the cerebral blood perfusion in any region of interest. These results suggest that although both pre/perinatal insults showed some of the schizophrenia-like deficits, these are not strictly related to distinct hemodynamic features.

Abstinence to chronic methamphetamine switches connectivity between striatal, hippocampal and sensorimotor regions and increases cerebral blood volume response.

Methamphetamine (meth), and other psychostimulants such as cocaine, present a persistent problem for society with chronic users being highly prone to relapse. We show, in a chronic methamphetamine administration model, that discontinuation of drug for more than a week produces much larger changes in overall meth-induced brain connectivity and cerebral blood volume (CBV) response than changes that occur immediately following meth administration. Areas showing the largest changes were hippocampal, limbic striatum and sensorimotor cortical regions as well as brain stem areas including the pedunculopontine tegmentum (PPTg) and pontine nuclei - regions known to be important in mediating reinstatement of drug-taking after abstinence. These changes occur concomitantly with behavioral sensitization and appear to be mediated through increases in dopamine D1 and D3 and decreases in D2 receptor protein and mRNA expression. We further identify a novel region of dorsal caudate/putamen, with a low density of calbindin neurons, that has an opposite hemodynamic response to meth than the rest of the caudate/putamen and accumbens and shows very strong correlation with dorsal CA1 and CA3 hippocampus. This correlation switches following meth abstinence from CA1/CA3 to strong connections with ventral hippocampus (ventral subiculum) and nucleus accumbens. These data provide novel evidence for temporal alterations in brain connectivity where chronic meth can subvert hippocampal - striatal interactions from cognitive control regions to regions that mediate drug reinstatement. Our results also demonstrate that the signs and magnitudes of the induced CBV changes following challenge with meth or a D3-preferring agonist are a complementary read out of the relative changes that occur in D1, D2 and D3 receptors using protein or mRNA levels.

Response of Cerebral Blood Flow and Blood Pressure to Dynamic Exercise: A Study Using PET.

Dynamic exercise elicits fluctuations in blood pressure (BP) and cerebral blood flow (CBF). This study investigated responses in BP and CBF during cycling exercise and post-exercise hypotension (PEH) using positron emission tomography (PET). CBF was measured using oxygen-15-labeled water (H215O) and PET in 11 human subjects at rest (Rest), at the onset of exercise (Ex1), later in the exercise (Ex2), and during PEH. Global CBF significantly increased by 13% at Ex1 compared with Rest, but was unchanged at Ex2 and during PEH. Compared with at Rest, regional CBF (rCBF) increased at Ex1 (20~42%) in the cerebellar vermis, sensorimotor cortex for the bilateral legs (M1Leg and S1Leg), insular cortex and brain stem, but increased at Ex2 (28~31%) only in the vermis and M1Leg and S1Leg. During PEH, rCBF decreased compared with Rest (8~13%) in the cerebellum, temporal gyrus, piriform lobe, thalamus and pons. The areas showing correlations between rCBF and mean BP during exercise and PEH were consistent with the central autonomic network, including the brain stem, cerebellum, and hypothalamus (R2=0.25-0.64). The present study suggests that higher brain regions are coordinated through reflex centers in the brain stem in order to regulate the cardiovascular response to exercise.

Functional near-infrared spectroscopy to probe sensorimotor region activation during electrical stimulation-evoked movement.

This study used non-invasive functional near-infrared spectroscopy (fNIRS) neuroimaging to monitor bilateral sensorimotor region activation during unilateral voluntary (VOL) and neuromuscular electrical stimulation (NMES)-evoked movements. METHODS: In eight healthy male volunteers, fNIRS was used to measure relative changes in oxyhaemoglobin (O2 Hb) and deoxyhaemoglobin (HHb) concentrations from a cortical sensorimotor region of interest in the left (LH) and right (RH) hemispheres during NMES-evoked and VOL wrist extension movements of the right arm. RESULTS: NMES-evoked movements induced significantly greater activation (increase in O2 Hb and concomitant decrease in HHb) in the contralateral LH than in the ipsilateral RH (O2 Hb: 0·44 ± 0·16 µM and 0·25 ± 0·22 µM, P = 0·017; HHb: -0·19 ± 0·10 µM and -0·12 ± 0·09 µM, P = 0·036, respectively) as did VOL movements (0·51 ± 0·24 µΜ and 0·34 ± 0·21 µM, P = 0·031; HHb: -0·18 ± 0·07 µΜ and -0·12 ± 0·04 µΜ, P = 0·05, respectively). There was no significant difference between conditions for O2 Hb (P = 0·144) and HHb (P = 0·958). CONCLUSION: fNIRS neuroimaging enables quantification of bilateral sensorimotor regional activation profiles during voluntary and NMES-evoked wrist extension movements.

Unilateral forelimb sensorimotor cortex devascularization disrupts the topographic and kinematic characteristics of hand movements while string-pulling for food in the rat.

String-pulling by the rat is a bimanual act, in which an upright animal retrieves a piece of food attached to the end of the string by downward hand-over-hand movements. The present study compared the movements of string-pulling, using topographic and kinematic measures of hand movement, in control rats and rats with unilateral sensorimotor motor cortex lesion produced by removal of the pia matter. In the first week following devascularization, the rhythmicity and accuracy of string-pulling movements decomposed; however, thereafter the rhythm of bilateral alternation was restored. Over 70days of testing, distance traveled decreased for both hands in the control and lesion groups, suggesting that both groups displayed an increase in string-pulling efficiency. Nevertheless, the lesion group exhibited more missed string contacts with the (contralateral-to-lesion) hand and more grasps in which the string was hooked between the digits with both hands. In addition, an increase in mouth grasps was observed in the lesion group. Motion capture analyses revealed that the lesion group exhibited longer reach and withdraw movements and these movements were longer for the ipsilateral-to-lesion vs contralateral-to-lesion hand. Thus, although rhythmicity of string-pulling behavior recovers after sensorimotor cortex devascularization, the contralateral-to-lesion hand contributed less to string pulling and requires mouth grasps to stabilize the string for grasping. The results are discussed in relation to contemporary theories of the contributions of the forelimb motor cortex to skilled movement and the potential use of string-pulling as a therapy for brain injury.

EFFICACY OF MESENCHYMAL STEM CELLS USED FOR THE IMPROVEMENT CEREBRAL MICROCIRCULATION IN SPONTANEOUSLY HYPERTENSIVE RATS.

Elaboration of new methods of correction of microcirculatory disorder in the brain caused by persistent high blood pressure is a topical task both for medicine and for biology. We studied influence of intracerebral transplantation of human mesenchymal stem cells (MSCh) to cerebral microcirculation in young (4 months) and aged (12 months) spontaneously hypertensive rats (SHR). It was shown that transplantation MSCh promoted the rise of the density of microvascular network of young SHR ca. 1.6-fold; density of the arteriolar area of microvascular network of the pia mater increased ca. 1.9-fold. The density of microvascular network of aged SHR increased ca. 1.4­1.5-fold after transplantation MSCh. The perfusion and tissue saturation of sensorimotor cortex of young SHR increased to the level of young normotensive rats, and in aged SHR the perfusion and tissue saturation of sensorimotor cortex was not increased. Conclusion: the intracerebral transplantation MSCh almost completely leveled the pathological changes of the microcirculation in the sensorimotor cortex of the brain of young SHR and improved unimportantly microcirculation in aged SHR.

Effects of Vascular Peptide Bioregulator on the Density of Microvascular Network in the Brain Cortex of Aged Rats.

Using a TV unit for microcirculation studies, we studied the density of the entire microvascular network and its arterial compartment in the pia mater of the sensorimotor cortex in intact young and aged rats (2-3 and 22-24 months) and aged rats after a course of vascular peptide bioregulator Slavinorm. The experiments showed that the density of microvascular network in intact animals decreased by 1.6 times with aging. Treatment with the peptide bioregulator 2.5-fold increased the density of the microvascular network in aged rats in comparison with intact animals of the same age, the density of the arterial compartment of the microvascular network in the pia mater increased by 2.8 times.

Quantitative imaging of microvascular blood flow networks in deep cortical layers by 1310 nm µODT.

There is growing interest in new neuroimage techniques that permit not only high-resolution quantification of cerebral blood flow velocity (CBFv) in capillaries, but also a large field of view to map the CBFv network dynamics. Such image capabilities are of great importance for decoding the functional difference across multiple cortical layers under stimuli. To tackle the limitation of optical penetration depth, we present a new ultrahigh-resolution optical coherence Doppler tomography (µODT) system at 1310 nm and compare it with a prior 800 nm µODT system for mouse brain 3D CBFv imaging. We show that the new 1310 nm µODT allows for dramatically increased depth (∼4 times) of quantitative CBFv imaging to 1.4 mm, thus covering the full thickness of the mouse cortex (i.e., layers I-VI). Interestingly, we show that such a unique 3D CBFv imaging capability allows identification of microcirculatory redistribution across different cortical layers resulting from repeated cocaine exposures.

Functional brain connectome and sensorimotor networks in rolandic epilepsy.

PURPOSE: Rolandic epilepsy (RE) is a form of well-characterized childhood epilepsy whose focal electroencephalographic abnormalities affect the same well-delineated local brain regions. Little is known about how the focal electroencephalographic discharges interfere with the topological organization of whole-brain networks in RE patients. METHODS: Seventy-three patients RE patients and 73 healthy children underwent rsfMRI. The whole-brain functional networks were constructed by thresholding the partial correlation matrices of 90 brain regions, and their topological properties were analyzed using graph theory-based approaches. We used network-based statistics to evaluate functional connectivity. The correlations between the network properties and the clinical and cognitive characteristics were calculated. RESULTS: The global topologic organization of the functional brain network was disrupted in RE patients, as manifested by reduced clustering coefficient and local and global efficiency and increased characteristic path length. The RE patients exhibited less connectivity among the sensorimotor areas; this reduction in the mean functional connectivity in this network correlated to altered global small-world properties. The RE patients exhibited decreased nodal centralities, predominantly in the bilateral postcentral gyrus, in the frontal, parietal and temporal lobes around the rolandic fissure and in areas related to linguistics and attention control (p<0.05, FDR-corrected). The altered nodal centralities in the bilateral postcentral gyrus and the left posterior cingulate cortex were correlated with subscales in Child Behavior Checklist. CONCLUSIONS: These results support the hypothesis that RE is associated with systemic brain disorganization and that the functional defect in rolandic areas contribute to symptomatology and electrophysiology in RE. Nodal abnormalities appear to imply the disturbances in linguistics and attention observed in RE patients.

Brief anesthesia, but not voluntary locomotion, significantly alters cortical temperature.

Changes in brain temperature can alter electrical properties of neurons and cause changes in behavior. However, it is not well understood how behaviors, like locomotion, or experimental manipulations, like anesthesia, alter brain temperature. We implanted thermocouples in sensorimotor cortex of mice to understand how cortical temperature was affected by locomotion, as well as by brief and prolonged anesthesia. Voluntary locomotion induced small (∼ 0.1 °C) but reliable increases in cortical temperature that could be described using a linear convolution model. In contrast, brief (90-s) exposure to isoflurane anesthesia depressed cortical temperature by ∼ 2 °C, which lasted for up to 30 min after the cessation of anesthesia. Cortical temperature decreases were not accompanied by a concomitant decrease in the γ-band local field potential power, multiunit firing rate, or locomotion behavior, which all returned to baseline within a few minutes after the cessation of anesthesia. In anesthetized animals where core body temperature was kept constant, cortical temperature was still > 1 °C lower than in the awake animal. Thermocouples implanted in the subcortex showed similar temperature changes under anesthesia, suggesting these responses occur throughout the brain. Two-photon microscopy of individual blood vessel dynamics following brief isoflurane exposure revealed a large increase in vessel diameter that ceased before the brain temperature significantly decreased, indicating cerebral heat loss was not due to increased cerebral blood vessel dilation. These data should be considered in experimental designs recording in anesthetized preparations, computational models relating temperature and neural activity, and awake-behaving methods that require brief anesthesia before experimental procedures.

Intranasal delivery of bone marrow mesenchymal stem cells improved neurovascular regeneration and rescued neuropsychiatric deficits after neonatal stroke in rats.

Neonatal stroke is a major cause of mortality and long-term morbidity in infants and children. Currently, very limited therapeutic strategies are available to protect the developing brain against ischemic damage and promote brain repairs for pediatric patients. Moreover, children who experienced neonatal stroke often have developmental social behavior problems. Cellular therapy using bone marrow mesenchymal stem cells (BMSCs) has emerged as a regenerative therapy after stroke. In the present investigation, neonatal stroke of postnatal day 7 (P7) rat pups was treated with noninvasive and brain-specific intranasal delivery of BMSCs at 6 h and 3 days after stroke (1 × 10(6)cells/animal). Prior to transplantation, BMSCs were subjected to hypoxic preconditioning to enhance their tolerance and regenerative properties. The effects on regenerative activities and stroke-induced sensorimotor and social behavioral deficits were specifically examined at P24 of juvenile age. The BMSC treatment significantly reduced infarct size and blood-brain barrier disruption, promoted angiogenesis, neurogenesis, neurovascular repair, and improved local cerebral blood flow in the ischemic cortex. BMSC-treated rats showed better sensorimotor and olfactory functional recovery than saline-treated animals, measured by the adhesive removal test and buried food finding test. In social behavioral tests, we observed functional and social behavioral deficits in P24 rats subjected to stroke at P7, while the BMSC treatment significantly improved the performance of stroke animals. Overall, intranasal BMSC transplantation after neonatal stroke shows neuroprotection and great potential as a regenerative therapy to enhance neurovascular regeneration and improve functional recovery observed at the juvenile stage of development.

Resting-State Functional Connectivity of the Sensorimotor Network in Individuals with Nonspecific Low Back Pain and the Association with the Sit-to-Stand-to-Sit Task.

Individuals with nonspecific low back pain (NSLBP) show a decreased sit-to-stand-to-sit (STSTS) performance. This dynamic sensorimotor task requires integration of sensory and motor information in the brain. Therefore, a better understanding of the underlying central mechanisms of impaired sensorimotor performance and the presence of NSLBP is needed. The aims of this study were to characterize differences in sensorimotor functional connectivity in individuals with NSLBP and to investigate whether the patterns of sensorimotor functional connectivity underlie the impaired STSTS performance. Seventeen individuals with NSLBP and 17 healthy controls were instructed to perform five consecutive STSTS movements as fast as possible. Based on the center of pressure displacement, the total duration of the STSTS task was determined. In addition, resting-state functional connectivity images were acquired and analyzed on a multivariate level using both functional connectivity density mapping and independent component analysis. Individuals with NSLBP needed significantly more time to perform the STSTS task compared to healthy controls. In addition, decreased resting-state functional connectivity of brain areas related to the integration of sensory and/or motor information was shown in the individuals with NSLBP. Moreover, the decreased functional connectivity at rest of the left precentral gyrus and lobule IV and V of the left cerebellum was associated with a longer duration of the STSTS task in both individuals with NSLBP and healthy controls. In summary, individuals with NSLBP showed a reorganization of the sensorimotor network at rest, and the functional connectivity of specific sensorimotor areas was associated with the performance of a dynamic sensorimotor task.

Microsurgical anatomy of the central lobe.

OBJECT: The central lobe consists of the pre- and postcentral gyri on the lateral surface and the paracentral lobule on the medial surface and corresponds to the sensorimotor cortex. The objective of the present study was to define the neural features, craniometric relationships, arterial supply, and venous drainage of the central lobe. METHODS: Cadaveric hemispheres dissected using microsurgical techniques provided the material for this study. RESULTS: The coronal suture is closer to the precentral gyrus and central sulcus at its lower rather than at its upper end, but they are closest at a point near where the superior temporal line crosses the coronal suture. The arterial supply of the lower two-thirds of the lateral surface of the central lobe was from the central, precentral, and anterior parietal branches that arose predominantly from the superior trunk of the middle cerebral artery. The medial surface and the superior third of the lateral surface were supplied by the posterior interior frontal, paracentral, and superior parietal branches of the pericallosal and callosomarginal arteries. The venous drainage of the superior two-thirds of the lateral surface and the central lobe on the medial surface was predominantly through the superior sagittal sinus, and the inferior third of the lateral surface was predominantly through the superficial sylvian veins to the sphenoparietal sinus or the vein of Labbé to the transverse sinus. CONCLUSIONS: The pre- and postcentral gyri and paracentral lobule have a morphological and functional anatomy that differentiates them from the remainder of their respective lobes and are considered by many as a single lobe. An understanding of the anatomical relationships of the central lobe can be useful in preoperative planning and in establishing reliable intraoperative landmarks.

Changes in corticostriatal connectivity during reinforcement learning in humans.

Many computational models assume that reinforcement learning relies on changes in synaptic efficacy between cortical regions representing stimuli and striatal regions involved in response selection, but this assumption has thus far lacked empirical support in humans. We recorded hemodynamic signals with fMRI while participants navigated a virtual maze to find hidden rewards. We fitted a reinforcement-learning algorithm to participants' choice behavior and evaluated the neural activity and the changes in functional connectivity related to trial-by-trial learning variables. Activity in the posterior putamen during choice periods increased progressively during learning. Furthermore, the functional connections between the sensorimotor cortex and the posterior putamen strengthened progressively as participants learned the task. These changes in corticostriatal connectivity differentiated participants who learned the task from those who did not. These findings provide a direct link between changes in corticostriatal connectivity and learning, thereby supporting a central assumption common to several computational models of reinforcement learning.

Development of the sensorimotor cortex in the human fetus: a morphological description.

Twenty-one human fetal brains from 13 to 28 gestational weeks were studied macroscopically to describe the morphological stages of sulcal and gyral development in the sensorimotor cortex. In particular, the morphological appearance of the pericentral lateral cortex (sensorimotor cortex) and opercula was noted, as well as the vascularization of these regions. The central cerebral sulci were the first macroscopical structures to be identified on the lateral surface of the human cerebral hemisphere. Four chronological stages of sensorimotor cortex development were defined: stage 1: appearance at 18-19 gestational weeks (GWs) of the inferior part of the central cerebral sulcus; stage 2: development of the pericentral lateral regions and the beginning of opercularization at 20-22 GWs; stage 3: development of parietal and temporal cortices and the covering of the postcentral insular region at 24-26 GWs; and finally stage 4: maturation of the central cerebral regions at 27-28 GWs. These observations indicate the concomitance in the initiation of maturation of the pericentral cerebral cortices.

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.