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Excessive iron levels are believed to contribute to the development of neurodegenerative disorders by promoting oxidative stress and harmful protein clustering. Novel chelation treatments that can effectively remove excess iron while minimizing negative effects on the nervous system are being explored. This study focuses on the creation and evaluation of innovative nanobubble (NB) formulations, shelled with various polymers such as glycol-chitosan (GC) and glycol-chitosan conjugated with deferoxamine (DFO), to enhance their ability to bind iron. Various methods were used to evaluate their physical and chemical properties, chelation capacity in diverse iron solutions and impact on reactive oxygen species (ROS). Notably, the GC-DFO NBs demonstrated the ability to decrease amyloid-β protein misfolding caused by iron. To assess potential toxicity, in vitro cytotoxicity testing was conducted using organotypic brain cultures from the substantia nigra, revealing no adverse effects at appropriate concentrations. Additionally, the impact of NBs on spontaneous electrical signaling in hippocampal neurons was examined. Our findings suggest a novel nanochelation approach utilizing DFO-conjugated NBs for the removal of excess iron in cerebral regions, potentially preventing neurotoxic effects.

Previous studies demonstrated sex-related differences in several areas of the human brain, including patterns of brain activation in males and females when observing their own bodies and faces (versus other bodies/faces or morphed versions of themselves), but a complex paradigm touching multiple aspects of embodied self-identity is still lacking. We enrolled 24 healthy individuals (12 M, 12 F) in 3 different fMRI experiments: the vision of prototypical body silhouettes, the vision of static images of the face of the participants morphed with prototypical male and female faces, the vision of short videos showing the dynamic transformation of the morphing. We found differential sexual activations in areas linked to self-identity and to the ability to attribute mental states: In Experiment 1, the male group activated more the bilateral thalamus when looking at sex congruent body images, while the female group activated more the middle and inferior temporal gyrus. In Experiment 2, the male group activated more the supplementary motor area when looking at their faces; the female group activated more the dorsomedial prefrontal cortex (dmPFC). In Experiment 3, the female group activated more the dmPFC when observing either the feminization or the masculinization of their face. The defeminization produced more activations in females in the left superior parietal lobule and middle occipital gyrus. The performance of all classifiers built using single ROIs exceeded chance level, reaching an area under the ROC curves > 0.85 in some cases (notably, for Experiment 2 using the V1 ROI). The results of the fMRI tasks showed good agreement with previously published studies, even if our sample size was small. Therefore, our functional MRI protocol showed significantly different patterns of activation in males and females, but further research is needed both to investigate the gender-related differences in activation when observing a morphing of their face/body, and to validate our paradigm using a larger sample.

ObjectiveIn this study, we investigate whether a Convolutional Neural Network (CNN) can generate informative parametric maps from the pre-processed CT perfusion data in patients with acute ischemic stroke in a clinical setting.MethodsThe CNN training was performed on a subset of 100 pre-processed perfusion CT dataset, while 15 samples were kept for testing. All the data used for the training/testing of the network and for generating ground truth (GT) maps, using a state-of-the-art deconvolution algorithm, were previously pre-processed using a pipeline for motion correction and filtering. Threefold cross validation had been used to estimate the performance of the model on unseen data, reporting Mean Squared Error (MSE). Maps accuracy had been checked through manual segmentation of infarct core and total hypo-perfused regions on both CNN-derived and GT maps. Concordance among segmented lesions was assessed using the Dice Similarity Coefficient (DSC). Correlation and agreement among different perfusion analysis methods were evaluated using mean absolute volume differences, Pearson correlation coefficients, Bland-Altman analysis, and coefficient of repeatability across lesion volumes.ResultsThe MSE was very low for two out of three maps, and low in the remaining map, showing good generalizability. Mean Dice scores from two different raters and the GT maps ranged from 0.80 to 0.87. Inter-rater concordance was high, and a strong correlation was found between lesion volumes of CNN maps and GT maps (0.99, 0.98, respectively).ConclusionThe agreement between our CNN-based perfusion maps and the state-of-the-art deconvolution-algorithm perfusion analysis maps, highlights the potential of machine learning methods applied to perfusion analysis. CNN approaches can reduce the volume of data required by deconvolution algorithms to estimate the ischemic core, and thus might allow the development of novel perfusion protocols with lower radiation dose deployed to the patient.

Background: Two statistical models have been established to evaluate characteristics associated with postoperative motor outcome in patients with glioma associated to the motor cortex (M1) or the corticospinal tract (CST). One model is based on a clinicoradiological prognostic sum score (PrS) while the other one relies on navigated transcranial magnetic stimulation (nTMS) and diffusion-tensor-imaging (DTI) tractography. The objective was to compare the models regarding their prognostic value for postoperative motor outcome and extent of resection (EOR) with the aim of developing a combined, improved model. Methods: We retrospectively analyzed a consecutive prospective cohort of patients who underwent resection for motor associated glioma between 2008 and 2020, and received a preoperative nTMS motor mapping with nTMS-based diffusion tensor imaging tractography. The primary outcomes were the EOR and the motor outcome (on the day of discharge and 3 months postoperatively according to the British Medical Research Council (BMRC) grading). For the nTMS model, the infiltration of M1, tumor-tract distance (TTD), resting motor threshold (RMT) and fractional anisotropy (FA) were assesed. For the PrS score (ranging from 1 to 8, lower scores indicating a higher risk), we assessed tumor margins, volume, presence of cysts, contrast agent enhancement, MRI index (grading white matter infiltration), preoperative seizures or sensorimotor deficits. Results: Two hundred and three patients with a median age of 50 years (range: 20–81 years) were analyzed of whom 145 patients (71.4%) received a GTR. The rate of transient new motor deficits was 24.1% and of permanent new motor deficits 18.8%. The nTMS model demonstrated a good discrimination ability for the short-term motor outcome at day 7 of discharge (AUC = 0.79, 95 %CI: 0.72–0.86) and the long-term motor outcome after 3 months (AUC = 0.79, 95 %CI: 0.71–0.87). The PrS score was not capable to predict the postoperative motor outcome in this cohort but was moderately associated with the EOR (AUC = 0.64; CI 0.55–0.72). An improved, combined model was calculated to predict the EOR more accurately (AUC = 0.74, 95 %CI: 0.65–0.83). Conclusion: The nTMS model was superior to the clinicoradiological PrS model for potentially predicting the motor outcome. A combined, improved model was calculated to estimate the EOR. Thus, patient counseling and surgical planning in patients with motor-associated tumors should be performed using functional nTMS data combined with tractography.

Frailty is a dynamic clinical condition characterized by the reduction of interconnections among different psychobiological domains, which leads to a homeostatic vulnerability. The association between physical frailty and cognitive dysfunctions is a possible predictor of poor prognosis in patients with neurodegenerative disorders. However, this construct has not been fully analyzed by a multidimensional neuropsychogeriatric assessment matched with multimodal neuroimaging methods in patients with behavioral variant frontotemporal dementia (bvFTD). We have investigated cognitive dysfunctions and frailty status, assessed by both a neuropsychological evaluation and the Multidimensional Prognostic Index (MPI), in a sample of 18 bvFTD patients and compared to matched healthy controls. Gray matter (GM) volume (as assessed by voxel-based morphometry) and metabolism (on 18fluorodeoxyglucose positron emission tomography) were first separately compared between groups, then voxelwise compared and correlated to each other within patients. Linear regression of the MPI was performed on those voxels presenting a significant correlation between altered GM volume and metabolism. The neuropsychological assessment reflected the diagnoses and the functional–anatomical alterations documented by neuroimaging analyses. In particular, the majority of patients presented significant executive dysfunction and mood changes in terms of apathy, depression, and anxiety. In the overall MPI score, the patients fell in the lower range (indicating an early frailty status). On imaging, they exhibited a bilateral decrease of GM density and hypometabolism involving the frontal pole, the anterior opercular region, and the anterior cingulate cortex. Greater atrophy than hypometabolism was observed in the bilateral orbitofrontal cortex, the triangular part of the inferior frontal gyrus, and the ventral striatum, whereas the contrary was detected in the bilateral dorsal anterior cingulate cortex and pre-supplementary motor area. MPI scores significantly correlated only with the co-occurrence of a decrease of GM density and hypometabolism in the right anterior insular cortex, but not with the separate pathological phenomena. Our results show a correlation between a specific pattern of co-occurring GM atrophy and hypometabolism with early frailty in bvFTD patients. These aspects, combined with executive dysfunction and mood changes, may lead to an increased risk of poor prognosis, highlighting a potentially critical and precocious role of the insula in the pathogenesis of frailty.

Alzheimer's disease (AD) is the most common form of dementia, characterized by a complex etiology that makes therapeutic strategies still not effective. A true understanding of key pathological mechanisms and new biomarkers are needed, to identify alternative disease-modifying therapies counteracting the disease progression. Iron is an essential element for brain metabolism and its imbalance is implicated in neurodegeneration, due to its potential neurotoxic effect. However, the role of iron in different stages of dementia is not clearly established. This study aimed to investigate the potential impact of iron both in cerebrospinal fluid (CSF) and in serum to improve early diagnosis and the related therapeutic possibility. In addition to standard clinical method to detect iron in serum, a precise quantification of total iron in CSF was performed using graphite-furnace atomic absorption spectrometry in patients affected by AD, mild cognitive impairment, frontotemporal dementia, and non-demented neurological controls. The application of machine learning techniques, such as clustering analysis and multiclassification algorithms, showed a new potential stratification of patients exploiting iron-related data. The results support the involvement of iron dysregulation and its potential interaction with biomarkers (Tau protein and Amyloid-beta) in the pathophysiology and progression of dementia.

AimThe present study aims to extend the knowledge of the neural correlates of emotion processing in first episode subjects affected by anorexia nervosa (AN) or bulimia nervosa (BN). We applied an emotional distress paradigm targeting negative emotions thought to be relevant for interpersonal difficulties and therapeutic resistance mechanisms.MethodsThe current study applied to 44 female participants with newly diagnosed AN or BN and 20 matched controls a neuroimaging paradigm eliciting affective responses. The measurements also included an extensive assessment comprising clinical scales, neuropsychological tests, measures of emotion processing and empathy.ResultsAN and BN did not differ from controls in terms of emotional response, emotion matching, self-reported empathy and cognitive performance. However, eating disorder and psychopathological clinical scores, as well as alexithymia levels, were increased in AN and BN. On a neural level, no significant group differences emerged, even when focusing on a region of interest selected a priori: the amygdala. Some interesting findings put in relation the hippocampal activity with the level of Body Dissatisfaction of the participants, the relative importance of the key nodes for the common network in the decoding of different emotions (BN = right amygdala, AN = anterior cingulate area), and the qualitative profile of the deactivations.ConclusionsOur data do not support the hypothesis that participants with AN or BN display reduced emotional responsiveness. However, peculiar characteristics in emotion processing could be associated to the three different groups. Therefore, relational difficulties in eating disorders, as well as therapeutic resistance, could be not secondary to a simple difficulty in feeling and identifying basic negative emotions in AN and BN participants.

While investigating the possible synergistic effect of the conventional anticancer therapies, which, taken individually, are often ineffective against critical tumors, such as central nervous system (CNS) ones, the design of a theranostic nanovector able to carry and deliver chemotherapy drugs and magnetic hyperthermic agents to the target radiosensitizers (oxygen) was pursued. Alongside the original formulation of polymeric biodegradable oxygen-loaded nanostructures, their properties were fine-tuned to optimize their ability to conjugate therapeutic doses of drugs (doxorubicin) or antitumoral natural substances (curcumin). Oxygen-loaded nanostructures (diameter = 251 ± 13 nm, ζ potential = −29 ± 5 mV) were finally decorated with superparamagnetic iron oxide nanoparticles (SPIONs, diameter = 18 ± 3 nm, ζ potential = 14 ± 4 mV), producing stable, effective and non-agglomerating magnetic nanovectors (diameter = 279 ± 17 nm, ζ potential = −18 ± 7 mV), which could potentially target the tumoral tissues under magnetic driving and are monitorable either by US or MRI imaging.

In brain/head-and-neck radiotherapy (RT), thermoplastic immobilization masks guarantee reproducible patient positioning in treatment position between MRI, CT, and irradiation. Since immobilization masks do not fit in the diagnostic MR head/head-and-neck coils, flexible surface coils are used for MRI imaging in clinical practice. These coils are placed around the head/neck, in contact with the immobilization masks. However, the positioning of these flexible coils is technician dependent, thus leading to poor image reproducibility. Additionally, flexible surface coils have an inferior signal-to-noise-ratio (SNR) compared to diagnostic coils. The aim of this work was to create a new immobilization setup which fits into the diagnostic MR coils in order to enhance MR image quality and reproducibility. For this purpose, a practical immobilization setup was constructed. The performances of the standard clinical and the proposed setups were compared with four tests: SNR, image quality, motion restriction, and reproducibility of inter-fraction subject positioning. The new immobilization setup resulted in 3.4 times higher SNR values on average than the standard setup, except directly below the flexible surface coils where similar SNR was observed. Overall, the image quality was superior for brain/head-and-neck images acquired with the proposed RT setup. Comparable motion restriction in feet-head/left-right directions (maximum motion ≈1 mm) and comparable inter-fraction repositioning accuracy (mean inter-fraction movement 1 ± 0.5 mm) were observed for the standard and the new setup.

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

Obiettivo dello studio: La ventilazione a pressione positiva continua (Continuous Positive Airways Pressure - CPAP) è il trattamento migliore per la Sindrome delle Apnee Ostruttive del Sonno (OSAS), ma l'aderenza limita la sua efficacia. Strategie educative e multidimensionali sembrano essere gli interventi più efficaci per migliorare l'aderenza. In questo studio sono stati analizzati i dati di una popolazione di pazienti affetti da OSAS di grado severo al fine di valutare l'effetto di un intervento educativo e di altri principali fattori sull'aderenza alla CPAP. Metodi: Un programma educativo strutturato è stato somministrato ai pazienti OSAS che avevano indicazione all'utilizzo della CPAP. I dati sono stati raccolti dal colloquio clinico, dall'analisi dei report dei ventilatori CPAP e dalla registrazione poligrafica notturna. Sono stati presi in considerazione i seguenti fattori: età, indice di massa corporea, fumo, severità del disturbo, tipo di maschera, tipo di ventilazione, comorbilità cardiologica, comorbilità psichiatrica o neurologica, scolarità, stato maritale, numero di giorni e numero di accessi al Centro del Sonno (CS) necessari per raggiungere un adeguato trattamento e misure di efficacia terapeutica. Sono state considerate come misure di outcome l'aderenza e la media delle ore di utilizzo CPAP. Risutati: E' stato osservato che l'aderenza a lungo termine non è direttamente correlata al tempo dedicato all'intervento educativo, ma la percentuale cumulativa di pazienti che presentano una buona aderenza è correlata al numero di accessi al CS per colloqui di rinforzo con una relazione quadratica. Una buona aderenza è fortemente correlata alla scomparsa della sonnolenza diurna e al miglioramento della sintomatologia soggettiva ed è stata osservata anche in pazienti con maschera oronasale o comorbilità cognitiva o psichiatrica. Conclusioni: Le strategie educative sono tecniche efficaci per migliorare l'adrenza alla CPAP anche in popolazioni che abitualmente presentano bassa compliance come i pazienti senza beneficio soggettivo dalla terapia con CPAP o pazienti con comorbilità psichiatrica o cognitiva. Tuttavia sono raccomandati interventi educativi brevi.

Magnetic Nanoparticles (MNPs) are of great interest in biomedicine, due to their wide range of applications. During recent years, one of the most challenging goals is the development of new strategies to finely tune the unique properties of MNPs, in order to improve their effectiveness in the biomedical field. This review provides an up-to-date overview of the methods of synthesis and functionalization of MNPs focusing on Iron Oxide Nanoparticles (IONPs). Firstly, synthesis strategies for fabricating IONPs of different composition, sizes, shapes, and structures are outlined. We describe the close link between physicochemical properties and magnetic characterization, essential to developing innovative and powerful magnetic-driven nanocarriers. In conclusion, we provide a complete background of IONPs functionalization, safety, and applications for the treatment of Central Nervous System disorders.

One of the most challenging goals in pharmacological research is overcoming the Blood Brain Barrier (BBB) to deliver drugs to the Central Nervous System (CNS). The use of physical means, such as steady and alternating magnetic fields to drive nanocarriers with proper magnetic characteristics may prove to be a useful strategy. The present review aims at providing an up-to-date picture of the applications of magnetic-driven nanotheranostics agents to the CNS. Although well consolidated on physical ground, some of the techniques described herein are still under investigation on in vitro or in silico models, while others have already entered in—or are close to—clinical validation. The review provides a concise overview of the physical principles underlying the behavior of magnetic nanoparticles (MNPs) interacting with an external magnetic field. Thereafter we describe the physiological pathways by which a substance can reach the brain from the bloodstream and then we focus on those MNP applications that aim at a nondestructive crossing of the BBB such as static magnetic fields to facilitate the passage of drugs and alternating magnetic fields to increment BBB permeability by magnetic heating. In conclusion, we briefly cite the most notable biomedical applications of MNPs and some relevant remarks about their safety and potential toxicity.

ObjectiveThe aim of this study was to investigate whether Transcranial Magnetic Stimulation (TMS) applied over the medial line of the scalp affects the subjective perception of continuous pain induced by means of electric stimulation. In addition, we wanted to identify the point of stimulation where this effect was maximum.MethodsSuperficial electrical stimulation was used to induce continuous pain on the dominant hand. At the beginning of the experiment we reached a pain rating of 5 on an 11-point numeric rating scale (NRS; 0 = no pain and 10 = maximum tolerable pain) for each subject by setting individually the current intensity. The TMS (five pulses at increasing intensities) was applied on 5 equidistant points (one per session) over the medial line of the scalp in 13 healthy volunteers using a double-cone coil to stimulate underlying parts of the brain cortex. In every experimental session the painful stimulation lasted 45 minutes, during which pain and distress intensities NRS were recorded continuously. We calculated the effect of adaptation and the immediate effect of the TMS stimulation for all locations. Additionally, an ALE (Activation Likelihood Estimation) meta-analysis was performed to compare our results with the neuroimaging literature on subjective pain rating.ResultsTMS stimulation temporarily decreased the pain ratings, and pain adaptation was suppressed when applying the TMS over the FCz site on the scalp. No effect was found for distress ratings.ConclusionsThe present data suggest that the medial cortex in proximity of the cingulated gyrus has a causal role in adaptation mechanisms and in processing ongoing pain and subjective sensation of pain intensity.

Hyperfamiliarity for unknown faces is a rare selective disorder that consists of the disturbing and abnormal feeling of familiarity for unknown faces, while recognition of known faces is normal. In one such patient we investigated with a multimodal neuroimaging design the hitherto undescribed neural signature associated with hyperfamiliarity feelings. Behaviorally, signal detection methods revealed that the patient's discrimination sensitivity between familiar and unfamiliar faces was significantly lower than that of matched controls, and her response criterion for familiarity decisions was significantly more liberal. At the neural level, while morphometric analysis and single-photon emission CT (SPECT) showed the atrophy and hypofunctioning of the left temporal regions, functional magnetic resonance imaging (fMRI) revealed that hyperfamiliarity feelings were selectively associated to enhanced activity in the right medial and inferior temporal cortices. We therefore characterize the neurofunctional signature of hyperfamiliarity for unknown faces as related to the loss of coordinated activity between the complementary face processing functions of the left and right temporal lobes.

Gender differences in cooperative choices and their neural correlates were investigated in a situation where reputation represented a crucial issue. Males and females were involved in an economic exchange (trust game) where economic and reputational payoffs had to be balanced in order to increase personal welfare. At the behavioral level, females showed a stronger reaction to negative reputation judgments that led to higher cooperation than males, measured by back transfers in the game. The neuroanatomical counterpart of this gender difference was found within the reward network (engaged in producing expectations of positive results) and reputation-related brain networks, such as the self-control network (engaged in strategically resisting the temptation to defect) and the mentalizing network (engaged in thinking about how one is viewed by others), in which the dorsolateral prefrontal cortex (DLPFC) and the medial (M)PFC respectively play a crucial role. Furthermore, both DLPFC and MPFC activity correlated with the amount of back transfer, as well as with the personality dimensions assessed with the Big-Five Questionnaire (BFQ-2). Males, according to their greater DLPFC recruitment and their higher level of the BFQ-2 subscale of Dominance, were more focused on implementing a profit-maximizing strategy, pursuing this target irrespectively of others' judgments. On the contrary, females, according to their greater MPFC activity and their lower level of Dominance, were more focused on the reputation per se and not on the strategic component of reputation building. These findings shed light on the sexual dimorphism related to cooperative behavior and its neural correlates.

Two mechatronics prototypes, useful for robotic neurotreatments and new clinical trainings, are here presented. P.I.G.R.O. (pneumatic interactive gait rehabilitation orthosis) is an active exoskeleton with an electropneumatic control. It imposes movements on lower limbs in order to produce in the patient’s brain proper motor cortex activation. Bra.Di.P.O. (brain discovery pneumatic orthosis) is an MR-compatible device, designed to improve fMRI (functional magnetic resonance imaging) analysis. The two devices are presented together because both are involved in the study of new robotic treatments of patients affected by ictus or brain stroke or in some motor learning experimental investigations carried out on healthy subjects.

BackgroundTo date, few parameters have been found that can aid in patient selection and surgical strategy for eloquent area gliomas.AimsThe aim of the study was to analyze preoperative and intraoperative factors that can predict functional outcome and extent of resection in eloquent area tumors.Patients and methodsA retrospective analysis was conducted on 60 patients harboring supratentorial gliomas in eloquent areas undergoing awake surgery. The analysis considered clinical, neuroradiologic (morphologic), intraoperative, and postoperative factors. End-points were extent of resection (EOR) as well as functional short- and long-term outcome. Postoperatively, MRI objectively established the EOR. χ(2) analyses were used to evaluate parameters that could be predictive. Multivariate logistic regression analyses were used to evaluate the best combination to predict binary positive outcomes.ResultsIn 90% of the cases, subcortical stimulation was positive in the margins of the surgical cavity. Postoperatively, 51% of the patients deteriorated but 90% of the patients regained their preoperative neurological score. Factors negatively affecting EOR were volume, degree of subcortical infiltration, and presence of paresis (PConclusionsBiological and morphological factors such as type of margins, volume, preoperative neurological status, cystic components, histology and the type of infiltration into the white matter must be considered when planning intraoperative mapping.

The idea of a 'pain matrix' specifically devoted to the processing of nociceptive inputs has been challenged. Alternative views now propose that the activity of the primary and secondary somatosensory cortices (SI, SII), the insula and cingulate cortex may be related to a basic defensive system through which significant potentially dangerous events for the body's integrity are detected. By reviewing the role of the SI, SII, the cingulate and the insular cortices in the perception of nociceptive and tactile stimuli, in attentional, emotional and reward tasks, and in interoception and memory, we found that all these task-related networks overlap in the dorsal anterior cingulate cortex, the anterior insula and the dorsal medial thalamus. A thorough analysis revealed that the 'pain-related' network shares important functional similarities with both somatomotor-somatosensory networks and emotional-interoceptive ones. We suggest that these shared areas constitute the central part of an adaptive control system involved in the processing and integration of salient information coming both from external and internal sources. These areas are activated in almost all fMRI tasks and have been indicated to play a pivotal role in switching between externally directed and internally directed brain networks.

As different areas within the PMC have different connectivity patterns with various cortical and subcortical regions, we hypothesized that distinct functional modules may be present within the PMC. Because the PMC appears to be the most active region during resting state, it has been postulated to play a fundamental role in the control of baseline brain functioning within the default mode network (DMN). Therefore one goal of this study was to explore which components of the PMC are specifically involved in the DMN. In a sample of seventeen healthy volunteers, we performed an unsupervised voxelwise ROI-based clustering based on resting state functional connectivity. Our results showed four clusters with different network connectivity. Each cluster showed positive and negative correlations with cortical regions involved in the DMN. Progressive shifts in PMC functional connectivity emerged from anterior to posterior and from dorsal to ventral ROIs. Ventral posterior portions of PMC were found to be part of a network implicated in the visuo-spatial guidance of movements, whereas dorsal anterior portions of PMC were interlinked with areas involved in attentional control. Ventral retrosplenial PMC selectively correlated with a network showing considerable overlap with the DMN, indicating that it makes essential contributions in self-referential processing, including autobiographical memory processing. Finally, ventral posterior PMC was shown to be functionally connected with a visual network.The paper represents the first attempt to provide a systematic, unsupervised, voxelwise clustering of the human posteromedial cortex (PMC), using resting-state functional connectivity data. Moreover, a ROI-based parcellation was used to confirm the results.

BACKGROUND: The spontaneous component of neuropathic pain (NP) has not been explored sufficiently with neuroimaging techniques, given the difficulty to coax out the brain components that sustain background ongoing pain. Here, we address for the first time the correlates of this component in an fMRI study of a group of eight patients suffering from diabetic neuropathic pain and eight healthy control subjects. Specifically, we studied the functional connectivity that is associated with spontaneous neuropathic pain with spatial independent component analysis (sICA). PRINCIPAL FINDINGS: Functional connectivity analyses revealed a cortical network consisting of two anti-correlated patterns: one includes the left fusiform gyrus, the left lingual gyrus, the left inferior temporal gyrus, the right inferior occipital gyrus, the dorsal anterior cingulate cortex bilaterally, the pre and postcentral gyrus bilaterally, in which its activity is correlated negatively with pain and positively with the controls; the other includes the left precuneus, dorsolateral prefrontal, frontopolar cortex (both bilaterally), right superior frontal gyrus, left inferior frontal gyrus, thalami, both insulae, inferior parietal lobuli, right mammillary body, and a small area in the left brainstem, in which its activity is correlated positively with pain and negatively with the controls. Furthermore, a power spectra analyses revealed group differences in the frequency bands wherein the sICA signal was decomposed: patients' spectra are shifted towards higher frequencies. CONCLUSION: In conclusion, we have characterized here for the first time a functional network of brain areas that mark the spontaneous component of NP. Pain is the result of aberrant default mode functional connectivity.