Long-term cortisol stress response in depression and comorbid anxiety is linked with reduced N-acetylaspartate in the anterior cingulate cortex.

OBJECTIVES: Major Depression (MDD) and anxiety disorders are stress-related disorders that share pathophysiological mechanisms. There is evidence for alterations of glutamate-glutamine, N-acetylaspartate (NAA) and GABA in the anterior cingulate cortex (ACC), a stress-sensitive region affected by hypothalamic-pituitary-adrenal axis (HPA). The aim was to investigate metabolic alterations in the ACC and whether hair cortisol, current stress or early life adversity predict them. METHODS: We investigated 22 patients with MDD and comorbid anxiety disorder and 23 healthy controls. Proton magnetic resonance spectroscopy was performed with voxels placed in pregenual (pg) and dorsal (d) ACC in 3 T. Analysis of hair cortisol was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The N-acetylaspartate/Creatin ratio (NAA/Cr) was reduced in patients in both pgACC (p = .040) and dACC (p = .016). A significant interactive effect of diagnosis and cortisol on both pg-NAA/Cr (F = 5.00, p = .033) and d-NAA/Cr (F = 7.86, p = .009) was detected, whereby in controls cortisol was positively correlated with d-NAA/Cr (r = 0.61, p = .004). CONCLUSIONS: Our results suggest a relationship between NAA metabolism in ACC and HPA axis activity as represented by long-term cortisol output.

Decreased functional connectivity in patients with major depressive disorder and a history of childhood traumatization through experiences of abuse.

BACKGROUND: Childhood trauma (CT) increases vulnerability for the development of major depressive disorder (MDD). Alterations in resting-state functional connectivity (RSFC) have frequently been reported for MDD. These alterations may be much more prominent in depressive patients with a history of CT. The present study aims to compare RSFC in different brain networks of patients with MDD and CT (MDD+CT) vs. MDD and no CT compared to healthy controls. METHODS: 45 patients (22 with CT) were compared to 23 age-and-gender-matched healthy control subjects. Demographic parameters, severity of MDD, severity of CT and comorbid anxiety disorders were assessed. For assessment of RSFC alterations, a seed-based approach within five well-established RSFC networks was used. RESULTS: CT in MDD patients predicts severity of comorbid anxiety. A significant decrease in in-between network RSFC-values of MDD patients compared to controls was found in the network pairs of default mode network (DMN) - dorsal attention network (DAN), ventral attention network (VAN) - DMN and DAN - affective network (AN). MDD+CT patients presented more aberrant RSFC than MDD-CT patients. MDD scores predicted the decrease in RSFC for MDD patients. Higher Childhood Trauma Questionnaire (CTQ) scores are linked to reduced functional connectivity (FC) between DMN - DAN. CONCLUSIONS: Our study shows reduced RSFC in MDD patients for DMN - DAN, VAN - DMN, DAN - AN and MDD+CT patients presented more aberrant RSFC so that we suspect CT to be a considerable factor in the etiology of MDD. Through dysregulated neural circuits, CT is likely to contribute to a distinct MDD pathophysiology.

Mapping Visual Field Defects With fMRI - Impact of Approach and Experimental Conditions.

Current initiatives to restore vision emphasize the need for objective assessments of visual field (VF) defects as pursued with functional magnetic resonance imaging (fMRI) approaches. Here, we compared population receptive field (pRF) mapping-based VF reconstructions to an fMRI method that uses more robust visual stimulation (on-off block design) in combination with individualized anatomy-driven retinotopic atlas-information (atlas-based VF). We investigated participants with sizable peripheral VF-deficits due to advanced glaucoma (n = 4) or retinitis pigmentosa (RP; n = 2) and controls (n = 6) with simulated scotoma. We obtained (1) standard automated perimetry (SAP) data as reference VFs and 3T fMRI data for (2) pRF-mapping [8-direction bar stimulus, fixation color change task] and (3) block-design full-field stimulation [8-direction drifting contrast patterns during (a) passive viewing (PV) and (b) one-back-task (OBT; reporting successions of identical motion directions) to probe the impact of previously reported task-related unspecific visual cortex activations]. Correspondence measures between the SAP and fMRI-based VFs were accuracy, assisted by sensitivity and specificity. We found an accuracy of pRF-based VF from V1 in patients [median: 0.62] that was similar to previous reports and increased by adding V2 and V3 to the analysis [0.74]. In comparison to the pRF-based VF, equivalent accuracies were obtained for the atlas-based VF for both PV [0.67] and, unexpectedly, the OBT [0.59], where, however, unspecific cortical activations were reflected by a reduction in sensitivity [0.71 (PV) and 0.35 (OBT)]. In conclusion, in patients with peripheral VF-defects, we demonstrate that previous fMRI procedures to obtain VF-estimates might be enhanced by: (1) pooling V1-V3 to enhance accuracy; (2) reporting sensitivity and specificity measures to increase transparency of the VF-reconstruction metric; (3) applying atlas-based procedures, if pRF-based VFs are not available or difficult to obtain; and (4) giving, counter-intuitively, preference to PV. These findings are expected to provide guidance to overcome current limitations of translating fMRI-based methods to a clinical work-up.

Functional Dynamics of Deafferented Early Visual Cortex in Glaucoma.

In advanced retinitis pigmentosa with retinal lesions, the lesion projection zone (LPZ) in the early visual cortex can be driven during visual tasks, while it remains unresponsive during passive viewing. We tested whether this finding translates to advanced glaucoma, a major cause of acquired blindness. During visual stimulation, 3T fMRI scans were acquired for participants with advanced glaucoma (n = 4; age range: 51-72) and compared to two reference groups, i.e., advanced retinitis pigmentosa (n = 3; age range: 46-78) and age-matched healthy controls with simulated defects (n = 7). The participants viewed grating patterns drifting in 8 directions (12 s) alternating with uniform gray (12 s), either during passive viewing (PV), i.e., central fixation, or during a one-back task (OBT), i.e., reports of succeeding identical motion directions. As another reference, a fixation-dot task condition was included. Only in glaucoma and retinitis pigmentosa but not in controls, fMRI-responses in the lesion projection zone (LPZ) of V1 shifted from negative for PV to positive for OBT (p = 0.024 and p = 0.012, respectively). In glaucoma, these effects also reached significance in V3 (p = 0.006), while in V2 there was a non-significant trend (p = 0.069). The general absence of positive responses in the LPZ during PV underscores the lack of early visual cortex bottom-up plasticity for acquired visual field defects in humans. Trends in our exploratory analysis suggesting the task-dependent LPZ responses to be inversely related to visual field loss, indicate the benefit of patient stratification strategies in future studies with greater sample sizes. We conclude that top-down mechanisms associated with task-elicited demands rather than visual cortex remapping appear to shape LPZ responses not only in retinitis pigmentosa, but also in glaucoma. These insights are of critical importance for the development of schemes for treatment and rehabilitation in glaucoma and beyond.

Reinstatement of Cortical Outcome Representations during Higher-Order Learning.

Naturalistic learning scenarios are characterized by infrequent experience of external feedback to guide behavior. Higher-order learning mechanisms like second-order conditioning (SOC) may allow stimuli that were never experienced together with reinforcement to acquire motivational value. Despite its explanatory potential for real-world learning, surprisingly little is known about the neural mechanism underlying such associative transfer of value in SOC. Here, we used multivariate cross-session, cross-modality searchlight classification on functional magnetic resonance imaging data obtained from humans during SOC. We show that visual first-order conditioned stimuli (CS) reinstate cortical patterns representing previously paired gustatory outcomes in the lateral orbitofrontal cortex (OFC). During SOC, this OFC region showed increased functional covariation with amygdala, where neural pattern similarity between second-order CS and outcomes increased from early to late stages of SOC. Our data suggest a mechanism by which motivational value is conferred to stimuli that were never paired with reinforcement.

Increased Hippocampal Excitability and Altered Learning Dynamics Mediate Cognitive Mapping Deficits in Human Aging.

Learning the spatial layout of a novel environment is associated with dynamic activity changes in the hippocampus and in medial parietal areas. With advancing age, the ability to learn spatial environments deteriorates substantially but the underlying neural mechanisms are not well understood. Here, we report findings from a behavioral and a fMRI experiment where healthy human older and younger adults of either sex performed a spatial learning task in a photorealistic virtual environment (VE). We modeled individual learning states using a Bayesian state-space model and found that activity in retrosplenial cortex (RSC)/parieto-occipital sulcus (POS) and anterior hippocampus did not change systematically as a function learning in older compared with younger adults across repeated episodes in the environment. Moreover, effective connectivity analyses revealed that the age-related learning deficits were linked to an increase in hippocampal excitability. Together, these results provide novel insights into how human aging affects computations in the brain's navigation system, highlighting the critical role of the hippocampus.SIGNIFICANCE STATEMENT Key structures of the brain's navigation circuit are particularly vulnerable to the deleterious consequences of aging, and declines in spatial navigation are among the earliest indicators for a progression from healthy aging to neurodegenerative diseases. Our study is among the first to provide a mechanistic account about how physiological changes in the aging brain affect the formation of spatial knowledge. We show that neural activity in the aging hippocampus and medial parietal areas is decoupled from individual learning states across repeated episodes in a novel spatial environment. Importantly, we find that increased excitability of the anterior hippocampus might constitute a potential neural mechanism for cognitive mapping deficits in old age.

Peripheral Nerve Imaging Aids in the Diagnosis of Immune-Mediated Neuropathies-A Case Series.

BACKGROUND: Diagnosis of immune-mediated neuropathies and their differentiation from amyotrophic lateral sclerosis (ALS) can be challenging, especially at early disease stages. Accurate diagnosis is, however, important due to the different prognosis and available treatment options. We present one patient with a left-sided dorsal flexor paresis and initial suspicion of ALS and another with multifocal sensory deficits. In both, peripheral nerve imaging was the key for diagnosis. METHODS: We performed high-resolution nerve ultrasound (HRUS) and 7T or 3T magnetic resonance neurography (MRN). RESULTS: In both patients, HRUS revealed mild to severe, segmental or inhomogeneous, nerve enlargement at multiple sites, as well as an area increase of isolated fascicles. MRN depicted T2 hyperintense nerves with additional contrast-enhancement. DISCUSSION: Peripheral nerve imaging was compatible with the respective diagnosis of an immune-mediated neuropathy, i.e., multifocal motor neuropathy (MMN) in patient 1 and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) in patient 2. Peripheral nerve imaging, especially HRUS, should play an important role in the diagnostic work-up for immune-mediated neuropathies and their differentiation from ALS.

Decisions bias future choices by modifying hippocampal associative memories.

Decision-making is guided by memories of option values. However, retrieving items from memory renders them malleable. Here, we show that merely retrieving values from memory and making a choice between options is sufficient both to induce changes to stimulus-reward associations in the hippocampus and to bias future decision-making. After allowing participants to make repeated choices between reward-conditioned stimuli, in the absence of any outcome, we observe that participants prefer stimuli they have previously chosen, and neglect previously unchosen stimuli, over otherwise identical-valued options. Using functional brain imaging, we show that decisions induce changes to hippocampal representations of stimulus-outcome associations. These changes are correlated with future decision biases. Our results indicate that choice-induced preference changes are partially driven by choice-induced modification of memory representations and suggest that merely making a choice - even without experiencing any outcomes - induces associative plasticity.

Macroscopic information-based taste representations in insular cortex are shaped by stimulus concentration.

Taste processing is an essential ability in all animals signaling potential harm or benefit of ingestive behavior. However, current evidence for cortical taste representations remains contradictory. To address this issue, high-resolution functional MRI (fMRI) and multivariate pattern analysis were used to characterize taste-related informational content in human insular cortex, which contains primary gustatory cortex. Human participants judged pleasantness and intensity of low- and high-concentration tastes (salty, sweet, sour, and bitter) in two fMRI experiments on two different days to test for task- and concentration-invariant taste representations. We observed patterns of fMRI activity within insular cortex narrowly tuned to specific tastants consistently across tasks in all participants. Fewer patterns responded to more than one taste category. Importantly, changes in taste concentration altered the spatial layout of putative taste-specific patterns with distinct, almost nonoverlapping patterns for each taste category at different concentration levels. Together, our results point at macroscopic representations in human insular cortex as a complex function of taste category and concentration rather than representations based solely on taste identity.

7T MR neurography-ultrasound fusion for peripheral nerve imaging.

BACKGROUND: We present one patient with an initial diagnosis of Guillain-Barré syndrome (GBS) and one with Charcot-Marie-Tooth disease (CMT) type 1A. METHODS: Both patients underwent ankle tibial nerve fusion-imaging of high-resolution ultrasound (HRUS) with 7T MR neurography (MRN). RESULTS: In GBS, the nerve was enlarged, T2-hyperintense, and showed increased vascularization 21 months after symptom onset. In CMT1A, the enlarged nerve was T2-isointense with normal endoneurial blood flow. CONCLUSIONS: We demonstrate the utility of 7T-MRN-HRUS-fusion-imaging. In GBS, there was evidence of ongoing inflammation resulting in a changed diagnosis to acute-onset chronic demyelinating polyradiculoneuropathy and maintenance of immunotherapy. By MRN-HRUS-fusion, patients with presumed peripheral axonal degeneration could be shown to display imaging markers associated with peripheral nervous system inflammation. Thus, more accurate identification of a treatable inflammatory component may become possible.

The anterior insula channels prefrontal expectancy signals during affective processing.

Expectancy shapes our perception of impending events. Although such an interplay between cognitive and affective processes is often impaired in mental disorders, it is not well understood how top-down expectancy signals modulate future affect. We therefore track the information flow in the brain during cognitive and affective processing segregated in time using task-specific cross-correlations. Participants in two independent fMRI studies (N1 = 37 & N2 = 55) were instructed to imagine a situation with affective content as indicated by a cue, which was then followed by an emotional picture congruent with expectancy. To correct for intrinsic covariance of brain function, we calculate resting-state cross-correlations analogous to the task. First, using factorial modeling of delta cross-correlations (task-rest) of the first study, we find that the magnitude of expectancy signals in the anterior insula cortex (AIC) modulates the BOLD response to emotional pictures in the anterior cingulate and dorsomedial prefrontal cortex in opposite directions. Second, using hierarchical linear modeling of lagged connectivity, we demonstrate that expectancy signals in the AIC indeed foreshadow this opposing pattern in the prefrontal cortex. Third, we replicate the results in the second study using a higher temporal resolution, showing that our task-specific cross-correlation approach robustly uncovers the dynamics of information flow. We conclude that the AIC arbitrates the recruitment of distinct prefrontal networks during cued picture processing according to triggered expectations. Taken together, our study provides new insights into neuronal pathways channeling cognition and affect within well-defined brain networks. Better understanding of such dynamics could lead to new applications tracking aberrant information processing in mental disorders.

Compromised Grid-Cell-like Representations in Old Age as a Key Mechanism to Explain Age-Related Navigational Deficits.

A progressive loss of navigational abilities in old age has been observed in numerous studies, but we have only limited understanding of the neural mechanisms underlying this decline [1]. A central component of the brain's navigation circuit are grid cells in entorhinal cortex [2], largely thought to support intrinsic self-motion-related computations, such as path integration (i.e., keeping track of one's position by integrating self-motion cues) [3-6]. Given that entorhinal cortex is particularly vulnerable to neurodegenerative processes during aging and Alzheimer's disease [7-14], deficits in grid cell function could be a key mechanism to explain age-related navigational decline. To test this hypothesis, we conducted two experiments in healthy young and older adults. First, in an fMRI experiment, we found significantly reduced grid-cell-like representations in entorhinal cortex of older adults. Second, in a behavioral path integration experiment, older adults showed deficits in computations of self-position during path integration based on body-based or visual self-motion cues. Most strikingly, we found that these path integration deficits in older adults could be explained by their individual magnitudes of grid-cell-like representations, as reduced grid-cell-like representations were associated with larger path integration errors. Together, these results show that grid-cell-like representations in entorhinal cortex are compromised in healthy aging. Furthermore, the association between grid-cell-like representations and path integration performance in old age supports the notion that grid cells underlie path integration processes. We therefore conclude that impaired grid cell function may play a key role in age-related decline of specific higher-order cognitive functions, such as spatial navigation.

The role of auditory cortex in the spatial ventriloquism aftereffect.

Cross-modal recalibration allows the brain to maintain coherent sensory representations of the world. Using functional magnetic resonance imaging (fMRI), the present study aimed at identifying the neural mechanisms underlying recalibration in an audiovisual ventriloquism aftereffect paradigm. Participants performed a unimodal sound localization task, before and after they were exposed to adaptation blocks, in which sounds were paired with spatially disparate visual stimuli offset by 14° to the right. Behavioral results showed a significant rightward shift in sound localization following adaptation, indicating a ventriloquism aftereffect. Regarding fMRI results, left and right planum temporale (lPT/rPT) were found to respond more to contralateral sounds than to central sounds at pretest. Contrasting posttest with pretest blocks revealed significantly enhanced fMRI-signals in space-sensitive lPT after adaptation, matching the behavioral rightward shift in sound localization. Moreover, a region-of-interest analysis in lPT/rPT revealed that the lPT activity correlated positively with the localization shift for right-side sounds, whereas rPT activity correlated negatively with the localization shift for left-side and central sounds. Finally, using functional connectivity analysis, we observed enhanced coupling of the lPT with left and right inferior parietal areas as well as left motor regions following adaptation and a decoupling of lPT/rPT with contralateral auditory cortex, which scaled with participants' degree of adaptation. Together, the fMRI results suggest that cross-modal spatial recalibration is accomplished by an adjustment of unisensory representations in low-level auditory cortex. Such persistent adjustments of low-level sensory representations seem to be mediated by the interplay with higher-level spatial representations in parietal cortex.

How task demands shape brain responses to visual food cues.

Several previous imaging studies have aimed at identifying the neural basis of visual food cue processing in humans. However, there is little consistency of the functional magnetic resonance imaging (fMRI) results across studies. Here, we tested the hypothesis that this variability across studies might - at least in part - be caused by the different tasks employed. In particular, we assessed directly the influence of task set on brain responses to food stimuli with fMRI using two tasks (colour vs. edibility judgement, between-subjects design). When participants judged colour, the left insula, the left inferior parietal lobule, occipital areas, the left orbitofrontal cortex and other frontal areas expressed enhanced fMRI responses to food relative to non-food pictures. However, when judging edibility, enhanced fMRI responses to food pictures were observed in the superior and middle frontal gyrus and in medial frontal areas including the pregenual anterior cingulate cortex and ventromedial prefrontal cortex. This pattern of results indicates that task sets can significantly alter the neural underpinnings of food cue processing. We propose that judging low-level visual stimulus characteristics - such as colour - triggers stimulus-related representations in the visual and even in gustatory cortex (insula), whereas discriminating abstract stimulus categories activates higher order representations in both the anterior cingulate and prefrontal cortex. Hum Brain Mapp 38:2897-2912, 2017. © 2017 Wiley Periodicals, Inc.

Intrinsic monitoring of learning success facilitates memory encoding via the activation of the SN/VTA-Hippocampal loop.

Humans constantly learn in the absence of explicit rewards. However, the neurobiological mechanisms supporting this type of internally-guided learning (without explicit feedback) are still unclear. Here, participants who completed a task in which no external reward/feedback was provided, exhibited enhanced fMRI-signals within the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop) when successfully grasping the meaning of new-words. Importantly, new-words that were better remembered showed increased activation and enhanced functional connectivity between the midbrain, hippocampus, and ventral striatum. Moreover, enhanced emotion-related physiological measures and subjective pleasantness ratings during encoding were associated with remembered new-words after 24 hr. Furthermore, increased subjective pleasantness ratings were also related to new-words remembered after seven days. These results suggest that intrinsic-potentially reward-related-signals, triggered by self-monitoring of correct performance, can promote the storage of new information into long-term memory through the activation of the SN/VTA-Hippocampal loop, possibly via dopaminergic modulation of the midbrain.

Interoception in insula subregions as a possible state marker for depression-an exploratory fMRI study investigating healthy, depressed and remitted participants.

BACKGROUND: Interoceptive awareness (iA), the awareness of stimuli originating inside the body, plays an important role in human emotions and psychopathology. The insula is particularly involved in neural processes underlying iA. However, iA-related neural activity in the insula during the acute state of major depressive disorder (MDD) and in remission from depression has not been explored. METHODS: A well-established fMRI paradigm for studying (iA; heartbeat counting) and exteroceptive awareness (eA; tone counting) was used. Study participants formed three independent groups: patients suffering from MDD, patients in remission from MDD or healthy controls. Task-induced neural activity in three functional subdivisions of the insula was compared between these groups. RESULTS: Depressed participants showed neural hypo-responses during iA in anterior insula regions, as compared to both healthy and remitted participants. The right dorsal anterior insula showed the strongest response to iA across all participant groups. In depressed participants there was no differentiation between different stimuli types in this region (i.e., between iA, eA and noTask). Healthy and remitted participants in contrast showed clear activity differences. CONCLUSIONS: This is the first study comparing iA and eA-related activity in the insula in depressed participants to that in healthy and remitted individuals. The preliminary results suggest that these groups differ in there being hypo-responses across insula regions in the depressed participants, whilst non-psychiatric participants and patients in remission from MDD show the same neural activity during iA in insula subregions implying a possible state marker for MDD. The lack of activity differences between different stimulus types in the depressed group may account for their symptoms of altered external and internal focus.

Changes in gray matter volume after microsurgical lumbar discectomy: a longitudinal analysis.

People around the world suffer chronic lower back pain. Because spine imaging often does not explain the degree of perceived pain reported by patients, the role of the processing of nociceptor signals in the brain as the basis of pain perception is gaining increased attention. Modern neuroimaging techniques (including functional and morphometric methods) have produced results that suggest which brain areas may play a crucial role in the perception of acute and chronic pain. In this study, we examined 12 patients with chronic low back pain and sciatica, both resulting from lumbar disc herniation. Structural magnetic resonance imaging (MRI) of the brain was performed 1 day prior to and about 4 weeks after microsurgical lumbar discectomy. The subsequent MRI revealed an increase in gray matter volume in the basal ganglia but a decrease in volume in the hippocampus, which suggests the complexity of the network that involves movement, pain processing, and aspects of memory. Interestingly, volume changes in the hippocampus were significantly correlated to preoperative pain intensity but not to the duration of chronic pain. Mapping structural changes of the brain that result from lumbar disc herniation has the potential to enhance our understanding of the neuropathology of chronic low back pain and sciatica and therefore may help to optimize the decisions we make about conservative and surgical treatments in the future. The possibility of illuminating more of the details of central pain processing in lumbar disc herniation, as well as the accompanying personal and economic impact of pain relief worldwide, calls for future large-scale clinical studies.

A proof-of-principle study of multi-site real-time functional imaging at 3T and 7T: Implementation and validation.

Real-time functional Magnetic Resonance Imaging (rtfMRI) is used mainly for neurofeedback or for brain-computer interfaces (BCI). But multi-site rtfMRI could in fact help in the application of new interactive paradigms such as the monitoring of mutual information flow or the controlling of objects in shared virtual environments. For that reason, a previously developed framework that provided an integrated control and data analysis of rtfMRI experiments was extended to enable multi-site rtfMRI. Important new components included a data exchange platform for analyzing the data of both MR scanners independently and/or jointly. Information related to brain activation can be displayed separately or in a shared view. However, a signal calibration procedure had to be developed and integrated in order to permit the connecting of sites that had different hardware and to account for different inter-individual brain activation levels. The framework was successfully validated in a proof-of-principle study with twelve volunteers. Thus the overall concept, the calibration of grossly differing signals, and BCI functionality on each site proved to work as required. To model interactions between brains in real-time, more complex rules utilizing mutual activation patterns could easily be implemented to allow for new kinds of social fMRI experiments.

Increased functional connectivity between superior colliculus and brain regions implicated in bodily self-consciousness during the rubber hand illusion.

Bodily self-consciousness refers to bodily processes operating at personal, peripersonal, and extrapersonal spatial dimensions. Although the neural underpinnings of representations of personal and peripersonal space associated with bodily self-consciousness were thoroughly investigated, relatively few is known about the neural underpinnings of representations of extrapersonal space relevant for bodily self-consciousness. In the search to unravel brain structures generating a representation of the extrapersonal space relevant for bodily self-consciousness, we developed a functional magnetic resonance imaging (fMRI) study to investigate the implication of the superior colliculus (SC) in bodily illusions, and more specifically in the rubber hand illusion (RHi), which constitutes an established paradigm to study the neural underpinnings of bodily self-consciousness. We observed activation of the colliculus ipsilateral to the manipulated hand associated with eliciting of RHi. A generalized form of context-dependent psychophysiological interaction analysis unravelled increased illusion-dependent functional connectivity between the SC and some of the main brain areas previously involved in bodily self-consciousness: right temporoparietal junction (rTPJ), bilateral ventral premotor cortex (vPM), and bilateral postcentral gyrus. We hypothesize that the collicular map of the extrapersonal space interacts with maps of the peripersonal and personal space generated at rTPJ, vPM and the postcentral gyrus, producing a unified representation of space that is relevant for bodily self-consciousness. We suggest that processes of multisensory integration of bodily-related sensory inputs located in this unified representation of space constitute one main factor underpinning emergence of bodily self-consciousness.

The role of reward in word learning and its implications for language acquisition.

The exact neural processes behind humans' drive to acquire a new language--first as infants and later as second-language learners--are yet to be established. Recent theoretical models have proposed that during human evolution, emerging language-learning mechanisms might have been glued to phylogenetically older subcortical reward systems, reinforcing human motivation to learn a new language. Supporting this hypothesis, our results showed that adult participants exhibited robust fMRI activation in the ventral striatum (VS)--a core region of reward processing--when successfully learning the meaning of new words. This activation was similar to the VS recruitment elicited using an independent reward task. Moreover, the VS showed enhanced functional and structural connectivity with neocortical language areas during successful word learning. Together, our results provide evidence for the neural substrate of reward and motivation during word learning. We suggest that this strong functional and anatomical coupling between neocortical language regions and the subcortical reward system provided a crucial advantage in humans that eventually enabled our lineage to successfully acquire linguistic skills.