Radiological and Not Clinical Variables Guide the Surgical Plan in Patients with Glioblastoma.

Background and Purpose: The extent of resection is the most important prognostic factor in patients with glioblastoma. However, the factors influencing the decision to perform a biopsy instead of maximal resection have not been clearly established. The aim of this study was to analyze the factors associated with the intention to achieve maximal resection in glioblastoma patients. Methods: A retrospective single-center case-series analysis of patients with a new diagnosis of glioblastoma was performed. Patients were distributed into two groups: the biopsy (B) and complete resection (CR) groups. To identify factors associated with the decision to perform a B or CR, uni- and multivariate binary logistic regression analyses were performed. Cox regression analysis was also performed in the B and CR groups. Results: Ninety-nine patients with a new diagnosis of glioblastoma were included. Sixty-eight patients (68.7%) were treated with CR. Ring-enhancement and edema volume on presurgical magnetic resonance imaging were both associated with CR. Corpus callosum involvement and proximity to the internal capsule were identified as factors associated with the decision to perform a biopsy. In the multivariate analysis, edema volume (OR = 1.031; p = 0.002) and proximity to the internal capsule (OR = 0.104; p = 0.001) maintained significance and were considered independent factors. In the survival analysis, only corpus callosum involvement (HR = 2.055; p = 0.035) and MGMT status (HR = 0.484; p = 0.027) presented statistical significance in the CR group. Conclusions: The volume of edema and proximity to the internal capsule were identified as independent factors associated with the surgical decision. The radiological evaluation and not the clinical situation of the patient influences the decision to perform a biopsy or CR.

Optimizing the Endoscopic Transorbital Approach: MacCarty Keyhole for Enhanced Surgical Exposure in the Opticocarotid Region.

BACKGROUND: In recent years, the endoscopic transorbital (TO) approach has gained increasing interest for the treatment of middle cranial fossa lesions. We propose a technical refinement to the conventional superior eyelid TO approach, which improves the surgical exposure and augments the working angles when targeting the opticocarotid region. METHODS: Four embalmed adult cadaveric specimens (8 sides) were dissected at the Laboratory of Surgical Neuroanatomy of our institution. A TO approach was performed, with removal of the anterior clinoid process and the lateral orbital rim. Subsequently, the MacCarty keyhole was drilled in the superolateral orbital wall. Given that the lesser sphenoid wing was already drilled in the conventional TO craniectomy, the opening of the keyhole was essentially a lateral extension of the craniectomy. RESULTS: The procedure was successfully conducted in all 4 orbits. Clinoidectomy was performed either before or after extending the craniectomy to the MacCarty point. Extending the craniectomy made anterior clinoidectomy easier, by increasing the surgical exposure, and allowing a more lateral entrance for the endoscope. The extension also facilitated frontal lobe retraction, and it facilitated the optic nerve and carotid artery manipulation. Postoperative computed tomography scans showed a minimal 10-mm craniectomy extension, which remained covered by the temporal muscle after reconstruction. CONCLUSIONS: The modified endoscopic TO approach with the extension of the craniectomy to MacCarty point improves surgical access and visualization of the opticocarotid region. This facilitates anterior clinoidectomy and optic nerve decompression. Although it implies judicious instrument manipulation and a larger incision size, further studies can define its potential benefits.

Evaluation of Zonulin Expression and Its Potential Clinical Significance in Glioblastoma.

Glioblastoma, the deadliest adult brain tumor, poses a significant therapeutic challenge with a dismal prognosis despite current treatments. Zonulin, a protein influencing tight junctions and barrier functions, has gained attention for its diverse roles in various diseases. This study aimed to preliminarily analyze the circulating and tumor zonulin levels, evaluating their impact on disease prognosis and clinical-radiological factors. Additionally, we investigated in vitro zonulin expression in different glioblastoma cell lines under two different conditions. The study comprised 34 newly diagnosed glioblastoma patients, with blood samples collected before treatment for zonulin and haptoglobin analysis. Tumor tissue samples from 21 patients were obtained for zonulin expression. Clinical, molecular, and radiological data were collected, and zonulin protein levels were assessed using ELISA and Western blot techniques. Furthermore, zonulin expression was analyzed in vitro in three glioblastoma cell lines cultured under standard and glioma-stem-cell (GSC)-specific conditions. High zonulin expression in glioblastoma tumors correlated with larger preoperative contrast enhancement and edema volumes. Patients with high zonulin levels showed a poorer prognosis (progression-free survival [PFS]). Similarly, elevated serum levels of zonulin were associated with a trend of shorter PFS. Higher haptoglobin levels correlated with MGMT methylation and longer PFS. In vitro, glioblastoma cell lines expressed zonulin under standard cell culture conditions, with increased expression in tumorsphere-specific conditions. Elevated zonulin levels in both the tumor and serum of glioblastoma patients were linked to a poorer prognosis and radiological signs of increased disruption of the blood-brain barrier. In vitro, zonulin expression exhibited a significant increase in tumorspheres.

Androgen deficiency is associated with a better prognosis in glioblastoma.

BACKGROUND: The androgen receptor (AR) has been demonstrated to play a role in the pathogenesis of glioblastoma; however, the implications of circulating testosterone levels in the biology of glioblastoma remain unknown. AIM: This study aimed to analyze the association between circulating testosterone levels and the prognosis of patients with glioblastoma. METHODS: Forty patients with primary glioblastoma were included in the study. The main prognostic endpoint was progression-free survival (PFS). Circulating testosterone levels were used to determine the state of androgen deficiency (AD). AR expression was analyzed by reverse-transcriptase polymerase chain reaction, Western blot, and immunofluorescence. Survival analysis was performed using the log-rank test and univariate and multivariate Cox regression analysis. RESULTS: Most of the patients showed AR expression, and it was mainly located in the cytoplasm, as well as in the nucleus of tumor cells. Patients with AD presented a better PFS than those patients with normal levels (252.0 vs. 135.0 days; p = 0.041). Furthermore, normal androgenic status was an independent risk factor for progression in a multivariate regression model (hazard ratio = 6.346; p = 0.004). CONCLUSION: Circulating testosterone levels are associated with the prognosis of glioblastoma because patients with AD show a better prognosis than those with normal androgenic status.

Can NIRS be a surrogate indicator of elective shunt in carotid endarterectomy? A single-center observational retrospective study says no.

BACKGROUND: Neuromonitoring during carotid endarterectomy (CEA) under general anesthesia is desirable and may be useful for preventing brain ischemia, but the selection of the most appropriate method remains controversial. PURPOSE: To determine the effectiveness of near infrared spectroscopy (NIRS) compared to multimodality intraoperative neuromonitoring (IONM) in indicating elective shunts and predicting postoperative neurological status. METHODS: This is a retrospective observational study including 86 consecutive patients with CEA under general anesthesia. NIRS and multimodality IONM were performed during the procedure. IONM included electroencephalography (EEG), somatosensory evoked potentials (SSEPs) and transcranial motor-evoked potentials (TcMEPs). Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated for each neuromonitoring modality. RESULTS: NIRS presented a sensitivity and a specificity for detecting brain ischemia of 77.7% and 89.6%, respectively (PPV = 46.6% and NPV = 97.2%). In contrast, a 100% sensitivity and specificity for multimodality IONM was determined (PPV and NPV = 100%). No significant difference (in demographical or clinical data) between "true positive" and "false-positive" patients was identified. Among the methods included in multimodality IONM, EEG showed the best results for predicting postoperative outcome after CEA (PPV and NPV=100%). CONCLUSION: NIRS is inferior to multimodality IONM in detecting brain ischemia and predicting postoperative neurological status during CEA under general anesthesia.

Empathy Modulates the Activity of the Sensorimotor Mirror Neuron System during Pain Observation.

AIM: The aim of this study is to analyze the brain activity patterns during the observation of painful expressions and to establish the relationship between this activity and the scores obtained on the Interpersonal Reactivity Index (IRI). METHODS: The study included twenty healthy, right-handed subjects (10 women). We conducted a task-based and resting-state functional magnetic resonance imaging (fMRI) study. The task involved observing pictures displaying painful expressions. We performed a region of interest (ROI) analysis focusing on the core regions of the sensorimotor mirror neuron system (MNS). Resting-state fMRI was utilized to assess the functional connectivity of the sensorimotor MNS regions with the rest of the cortex using a seed-to-voxel approach. Additionally, we conducted a regression analysis to examine the relationship between brain activity and scores from the IRI subtests. RESULTS: Observing painful expressions led to increased activity in specific regions of the frontal, temporal, and parietal lobes. The largest cluster of activation was observed in the left inferior parietal lobule (IPL). However, the ROI analysis did not reveal any significant activity in the remaining core regions of the sensorimotor MNS. The regression analysis demonstrated a positive correlation between brain activity during the observation of pain and the "empathic concern" subtest scores of the IRI in both the cingulate gyri and bilateral IPL. Finally, we identified a positive relationship between the "empathic concern" subtest of the IRI and the functional connectivity (FC) of bilateral IPLs with the bilateral prefrontal cortex and the right IFG. CONCLUSION: Observing expressions of pain triggers activation in the sensorimotor MNS, and this activation is influenced by the individual's level of empathy.

Androgen Receptor Activity Is Associated with Worse Survival in Glioblastoma.

BACKGROUND: Some evidence about the role of the androgen receptor (AR) in pathogenesis of glioblastoma have been reported, but no study has focused on measuring the activity of the AR in GB. Therefore, the aim of this work is to study the role of AR and its activity as prognostic biomarkers in glioblastoma (GB). METHODS: Molecular and clinical data from The Cancer Genome Atlas database were used. The AR-expression at protein-level was obtained from reversed phase protein array (RPPA) assays. The AR-activity was determined by calculating the AR-score, an index calculated by using the expression (at RNA-level) of 13 androgen-responsive-genes. Univariate and multivariate Cox-regression analyses were performed. Finally, a correlation analysis was conducted between protein expression data and the AR-score. RESULTS: Two-hundred and thirty-three patients were included. RPPA data showed a mean AR abundance of 0.027(Statistical Deviation = 0.38) in GB. The univariate Cox-regression analysis showed that the AR-Score was associated with a worse prognosis (Hazard Ratio (HR) = 1.070) while the AR-expression did not show any relationship with survival (HR = 0.869). The association of the AR-score with worse overall survival (OS) was still significant in the multivariate analysis (HR = 1.054). The highest correlation coefficients between the AR-score and RPPA were identified in a group of proteins involved in apoptotic process regulation. CONCLUSIONS: GB patients with a high AR-activity present a worse prognosis in terms of OS. Thus, the activity of the AR may have a pathogenic role in GB. In this regard, the activation of the AR in GB may be associated with a dysregulation of apoptosis.

Biomarkers for characterization and therapeutic orientation in castration-resistant prostate cancer. / Biomarcadores para la caracterización y orientación terapéutica en Cáncer de Próstata Resistente a la Castración (CPRC).

Whole exome sequencing studies haverevealed the molecular landscape of metastatic CastrateResistant Prostate Cancer (mCRPC) providingnew information about prognostic and predictive factorsof response to therapies. These studies highlightedpotentially actionable targets leading to the beginingof the biomarker-driven era in prostate cancer.Alterations in androgen receptor (AR), DNA repair genes,PI3K-AKT-MTOR pathway or in genes involved incell cycle are frequently observed in mCRPC patientsand may be relevant in the resistance induced mechanismto approve therapy in this setting. Poly(ADP-ribose)polymerase (PARP) inhibitor in BRCA mutatedpatients, pembrolizumab (inmune checkpoint inhibitors)in mCRPC patients with mismatch repair genedefects and microsatellite instability and ipatasertib(AKT inhibitor) in patients with loss of function inPTEN are examples on how molecular information canbe useful to improve treatment selection. Nonethelessthe heterogeneity of advanced PC, the lack of consensusregarding the optimal biological source of analysisand the optimal time and technique for the analisysare still challenges that need to be defined in the nextfuture. The aim is to review the current literature concerningprognostic and predictive marker of responseto therapies in the mCRPC setting.

Estudios de secuenciación completa delexoma han revelado el perfil molecular del pacientecon Cáncer de Próstata Resistente a la Castración metastásico(CPRCm) proporcionando nueva informaciónsobre factores pronósticos y predictivos de respuestaa las distintas alternativas terapéuticas. Muchos deestos estudios han resaltado numerosas dianas molecularesaccionables desde un punto de vista farmacológico,conduciéndonos al comienzo de la medicina deprecisión en el Cáncer de Próstata (CP). Alteracionesen el Receptor de Andrógenos (RA), en genes reparadoresde DNA, en la vía de PI3K-AKT-MTOR o en genesimplicados en el ciclo celular son frecuentementeobservadas en CPRCm y pueden ser relevantes en la selección terapéutica y en la comprensión de los mecanismosde resistencia.Los inhibidores de la poli (ADP-ribosa) polimerasaen pacientes con mutaciones en BRCA, pembrolizumab(inhibidor de los puntos de control inmunológico)en pacientes CPRCm con alteraciones en genesimplicados en el "mismatch repair" o inestabilidad demicrosatélites e ipatasertib (inhibidor de AKT) en pacientescon pérdida de función de PTEN son ejemplosde cómo la información molecular puede ser útil paraoptimizar la selección terapéutica en este escenario.No obstante, la heterogeneidad del CP avanzado, lafalta de consenso sobre la fuente biológica óptima parael análisis, el momento y la técnica de análisis continúansiendo desafíos a definir en un fututo próximo.El objetivo es revisar la literatura actual sobre marcadorespronósticos y predictivos de respuesta a tratamientoen el entorno del CPRCm.

Biomarcadores para la caracterización y orientación terapéutica en cáncer de próstata resistente a la castración (cprc) / Biomarkers for characterization and therapeutic orientation in castration-resistant prostate cáncer

- Estudios de secuenciación completa delexoma han revelado el perfil molecular del pacientecon Cáncer de Próstata Resistente a la Castración metastásico (CPRCm) proporcionando nueva informaciónsobre factores pronósticos y predictivos de respuestaa las distintas alternativas terapéuticas. Muchos deestos estudios han resaltado numerosas dianas moleculares accionables desde un punto de vista farmacológico, conduciéndonos al comienzo de la medicina deprecisión en el Cáncer de Próstata (CP). Alteracionesen el Receptor de Andrógenos (RA), en genes reparadores de DNA, en la vía de PI3K-AKT-MTOR o en genes implicados en el ciclo celular son frecuentementeobservadas en CPRCm y pueden ser relevantes en la selección terapéutica y en la comprensión de los mecanismos de resistencia.Los inhibidores de la poli (ADP-ribosa) polimerasaen pacientes con mutaciones en BRCA, pembrolizumab (inhibidor de los puntos de control inmunológico) en pacientes CPRCm con alteraciones en genesimplicados en el “mismatch repair” o inestabilidad demicrosatélites e ipatasertib (inhibidor de AKT) en pacientes con pérdida de función de PTEN son ejemplosde cómo la información molecular puede ser útil paraoptimizar la selección terapéutica en este escenario.No obstante, la heterogeneidad del CP avanzado, lafalta de consenso sobre la fuente biológica óptima parael análisis, el momento y la técnica de análisis continúan siendo desafíos a definir en un fututo próximo.El objetivo es revisar la literatura actual sobre marcadores pronósticos y predictivos de respuesta a tratamiento en el entorno del CPRCm. (AU)

Whole exome sequencing studies haverevealed the molecular landscape of metastatic Castrate Resistant Prostate Cancer (mCRPC) providingnew information about prognostic and predictive factors of response to therapies. These studies highlighted potentially actionable targets leading to the begining of the biomarker-driven era in prostate cancer.Alterations in androgen receptor (AR), DNA repair genes, PI3K-AKT-MTOR pathway or in genes involved incell cycle are frequently observed in mCRPC patientsand may be relevant in the resistance induced mechanism to approve therapy in this setting. Poly(ADP-ribose) polymerase (PARP) inhibitor in BRCA mutatedpatients, pembrolizumab (inmune checkpoint inhibitors) in mCRPC patients with mismatch repair genedefects and microsatellite instability and ipatasertib (AKT inhibitor) in patients with loss of function inPTEN are examples on how molecular information canbe useful to improve treatment selection. Nonethelessthe heterogeneity of advanced PC, the lack of consensus regarding the optimal biological source of analysisand the optimal time and technique for the analisysare still challenges that need to be defined in the nextfuture. The aim is to review the current literature concerning prognostic and predictive marker of responseto therapies in the mCRPC setting. (AU)

Changes in resting-state measures of prostate cancer patients exposed to androgen deprivation therapy.

The aim of the present work is to describe the differences in rs-fMRI measures (Amplitude of low frequency fluctuations [ALFF], Regional Homogeneity [ReHo] and Functional Connectivity [FC]) between patients exposed to Androgen deprivation therapy (ADT) and a control group. Forty-nine ADT patients and fifteen PC-non-ADT patients (Controls) were included in the study. A neuropsychological evaluation and a resting-state fMRI was performed to evaluate differences in ALFF and ReHo. Region of interest (ROI) analysis was also performed. ROIs were selected among those whose androgen receptor expression (at RNA-level) was the highest. FC analysis was performed using the same ROIs. Higher ALFF in frontal regions and temporal regions was identified in Controls than in ADT patients. In the ROI analysis, higher activity for Controls than ADT patients was shown in the left inferior frontal gyrus and in the left precentral gyrus. Lower ALFF in the right hippocampus and the lateral geniculate nucleus of the right thalamus was identified for Controls than ADT patients. Higher ReHo was observed in Controls in the left parietal-occipital area. Finally, ADT patients presented an increase of FC in more regions than Controls. These differences may reflect an impairment in brain functioning in ADT users.

High Expression of FOXP2 Is Associated with Worse Prognosis in Glioblastoma.

OBJECTIVE: FOXP2 expression has been associated with the prognosis of some tumors, but the role of FOXP2 in glioblastoma remains unclear. The aim of the present work is to study the role of FOXP2 as a prognostic biomarker in glioblastoma. METHODS: This is a retrospective observational case series study in which the expression of FOXP2 has been analyzed both at protein level (immunohistochemistry, n = 62) and at mRNA level (RNAseq, in a cohort of glioblastoma patients from The Cancer Genome Atlas [TCGA] database, n = 148). Other molecular and clinical data have also been included in the study, with special focus on miRNA expression data. Survival analysis using log-rank test and COX-regression have been used. Non-parametric statistical tests were also used to study differences between low and high FOXP2 expression groups. RESULTS: Patients with a high expression of FOXP2 protein showed a worse prognosis than those patients with low expression in progression-free survival (hazard ratio 1.711; P = 0.034) and overall survival (hazard ratio 1.809; P = 0.014). These associations were still statistically significant in multivariate analysis. No prognostic association was found with FOXP2 RNA expression. Interestingly, 2 miRNAs that target FOXP2 (hsa-miR-181a-2-3p and hsa-miR-20a-3p) showed an interaction effect on overall survival with FOXP2 expression. A low level of these miRNA expression was associated with a significantly worse prognosis in patients with high FOXP2 RNA expression (log-rank test; P < 0.05). CONCLUSIONS: Greater expression of FOXP2 at the protein level is associated with a worse prognosis. This protein expression may be regulated by the expression of specific miRNAs that target FOXP2 mRNA: hsa-miR-181a-2-3p and hsa-miR-20a-3p.

Anaesthesia and multimodality intraoperative neuromonitoring in carotid endarterectomy. Chronological evolution and effects on intraoperative neurophysiology.

Contingency data was retrospectively collected to evaluate the historical and current ability to provide multimodality intraoperative neurophysiological monitoring during carotid endarterectomy under two conditions: total intravenous anaesthesia (TIVA) and low dose halogenated anaesthesia (SEVO). 229 patients were monitored during carotid endarterectomy procedures under general anaesthesia between 2012 and 2020. 121 Patients were monitored with SEVO at a minimum alveolar concentration less than 0.7 and 108 were monitored using TIVA, according to common anaesthetic practice standards in our hospital across the years. Multimodality IONM was established with electroencephalography, somatosensory evoked potentials and motor evoked potentials. As compared to TIVA, patients monitored with SEVO showed significantly higher motor evoked potential thresholds (313.52 ± 77.74 SEVO and 218.93 V ± 103.2 V TIVA p < 0.05) and lower reproducibility. Electroencephalography and somatosensory evoked potentials showed no significant differences among the groups. When using SEVO, multimodality intraoperative neurophysiological monitoring during carotid endarterectomy could mask or miss a motor isolated change in patients in spite of low dose minimum alveolar concentration and of apparently adequate electroencephalography and somatosensory evoked potentials for monitoring. Given these difficulties, we believe the chronological transfer to TIVA could have improved our ability to establish multimodality intraoperative neurophysiological monitoring during carotid endarterectomy in recent times.

Music Style Not Only Modulates the Auditory Cortex, but Also Motor Related Areas.

The neuroscience of music has recently attracted significant attention, but the effect of music style on the activation of auditory-motor regions has not been explored. The aim of the present study is to analyze the differences in brain activity during passive listening to non-vocal excerpts of four different music genres (classical, reggaeton, electronic and folk). A functional magnetic resonance imaging (fMRI) experiment was performed. Twenty-eight participants with no musical training were included in the study. They had to passively listen to music excerpts of the above genres during fMRI acquisition. Imaging analysis was performed at the whole-brain-level and in auditory-motor regions of interest (ROIs). Furthermore, the musical competence of each participant was measured and its relationship with brain activity in the studied ROIs was analyzed. The whole brain analysis showed higher brain activity during reggaeton listening than the other music genres in auditory-related areas. The ROI-analysis showed that reggaeton led to higher activity not only in auditory related areas, but also in some motor related areas, mainly when it was compared with classical music. A positive relationship between the melodic-Music Ear Test (MET) score and brain activity during reggaeton listening was identified in some auditory and motor related areas. The findings revealed that listening to different music styles in musically inexperienced subjects elicits different brain activity in auditory and motor related areas. Reggaeton was, among the studied music genres, the one that evoked the highest activity in the auditory-motor network. These findings are discussed in connection with acoustic analyses of the musical stimuli.

Neurofunctional correlates of eye to hand motor transfer.

This work investigates the transfer of motor learning from the eye to the hand and its neural correlates by using functional magnetic resonance imaging (fMRI) and a sensorimotor task consisting of the continuous tracking of a virtual target. In pretraining evaluation, all the participants (experimental and control group) performed the tracking task inside an MRI scanner using their right hand and a joystick. After which, the experimental group practiced an eye-controlled version of the task for 5 days using an eye tracking system outside the MRI environment. Post-training evaluation was done 1 week after the first scanning session, where all the participants were scanned again while repeating the manual pretraining task. Behavioral results show that the training in the eye-controlled task produced a better performance not only in the eye-controlled modality (motor learning) but also in the hand-controlled modality (motor transfer). Neural results indicate that eye to hand motor transfer is supported by the motor cortex, the basal ganglia and the cerebellum, which is consistent with previous research focused on other effectors. These results may be of interest in neurorehabilitation to activate the motor systems and help in the recovery of motor functions in stroke or movement disorder patients.

Direct cortical stimulation with cylindrical depth electrodes in the interhemispheric fissure for leg motor evoked potential monitoring.

OBJECTIVE: To evaluate cylindrical depth electrodes in the interhemispheric fissure as an alternative to subdural strip electrodes for direct cortical stimulation (DCS) leg motor evoked potential (MEP) monitoring. METHODS: A cylindrical depth electrode was positioned in the interhemispheric fissure of 37 patients who underwent supratentorial brain surgery. Leg sensory and motor cortices were localized by highest tibial nerve somatosensory evoked potential amplitude and lowest DCS leg MEP threshold; the lowest-threshold electrode was then used for DCS leg MEP monitoring. RESULTS: Intraoperative leg MEPs were obtained from all the patients in the series. The mean intensity applied for leg MEP monitoring with the cylindrical depth electrode was 15.2 ± 4.0 mA. No complications secondary to neurophysiological monitoring were detected. CONCLUSIONS: Lower extremity MEPs were consistently recorded using a multi-contact cylindrical depth electrode in the interhemispheric fissure by DCS. SIGNIFICANCE: Cylindrical depth electrodes may be a safe and effective alternative for DCS in the interhemispheric fissure, where subdural strips are difficult to place.

Visual inputs decrease brain activity in frontal areas during silent lipreading.

AIM: The aim of the present work is to analyze the modulation of the brain activity within the areas involved in lipreading when an additional visual stimulus is included. METHODS: The experiment consisted of two fMRI runs (lipreading_only and lipreading+picture) where two conditions were considered in each one (oral speech sentences condition [OSS] and oral speech syllables condition [OSSY]). RESULTS: During lipreading-only, higher activity in the left middle temporal gyrus (MTG) was identified for OSS than OSSY; during lipreading+picture, apart from the left MTG, higher activity was also present in the supplementary motor area (SMA), the left precentral gyrus (PreCG) and the left inferior frontal gyrus (IFG). The comparison between these two runs revealed higher activity for lipreading-only in the SMA and the left IFG. CONCLUSION: The presence of a visual reference during a lipreading task leads to a decrease in activity in frontal areas.

Androgen deprivation therapy increases brain ageing.

BACKGROUND: Prostate cancer (PC) is the most frequent neoplasia in the male population and androgen deprivation therapy (ADT) is frequently used in the management of the disease. AIM: To evaluate the effect of ADT exposure on cognitive status, grey matter volume (GMV) and white matter lesion (WML) load. METHODS: Fifty ADT patients and fifteen PC-non-ADT (control) patients were included in the study. A neuropsychological evaluation was performed and a magnetic resonance imaging (MRI), with anatomical T1 and FLAIR sequences, was performed to evaluate the GMV and the WML burden. RESULTS: Most of the patients included in the study presented a significant cognitive impairment (CI). No significant differences were identified in the cognitive assessment between the studied groups, but when considering the educational background intragroup differences were found.No significant difference of GMV and WML volume were identified between groups, but a negative relationship between the ADT period and the GMV was identified. Furthermore, a significant positive association between the age and the lesion volume was found in the ADT group (ß=.406; p=.004). CONCLUSION: PC patients exposed to ADT present an acceleration of age-related brain changes, such as WML development and GMV loss.

Is it necessary to show virtual limbs in action observation neurorehabilitation systems?

INTRODUCTION: Action observation neurorehabilitation systems are usually based on the observation of a virtual limb performing different kinds of actions. In this way, the activity in the frontoparietal Mirror Neuron System is enhanced, which can be helpful to rehabilitate stroke patients. However, the presence of limbs in such systems might not be necessary to produce mirror activity, for example, frontoparietal mirror activity can be produced just by the observation of virtual tool movements. The objective of this work was to explore to what point the presence of a virtual limb impacts the Mirror Neuron System activity in neurorehabilitation systems. METHODS: The study was conducted by using an action observation neurorehabilitation task during a functional magnetic resonance imaging (fMRI) experiment with healthy volunteers and comparing two action observation conditions that: 1 - included or 2 - did not include a virtual limb. RESULTS: It was found that activity in the Mirror Neuron System was similar during both conditions (i.e. virtual limb present or absent). CONCLUSIONS: These results open up the possibility of using new tasks that do not include virtual limbs in action observation neurorehabilitation environments, which can give more freedom to develop such systems.

The relationship between amplitude of low frequency fluctuations and gray matter volume of the mirror neuron system: Differences between low disability multiple sclerosis patients and healthy controls.

The study of the relationship between function and structure of the brain could be particularly interesting in neurodegenerative diseases like multiple sclerosis (MS). The aim of the present work is to identify differences of the amplitude of low frequency fluctuations (ALFF) in the mirror neuron system (MNS) between MS patients and healthy controls and to study the relationship between ALFF and the gray matter volume (GMV) of the regions that belong to the MNS. Relapsing-remitting MS patients with minor disability were compared to healthy controls (HC) using resting-state functional magnetic resonance imaging (fMRI), anatomic T1 weighted images and diffusion tensor imaging (DTI). Region of interest (ROI) analyses was performed in the MNS regions. A decrease of ALFF in MS patients was observed in the left inferior frontal gyrus (IFG). Furthermore, a correlation between ALFF in the IFG and the GMV of the left inferior parietal lobule (IPL) was identified. This relationship was different for MS patients than for HC, which may be associated with changes in diffusivity measures which were impaired in MS patients. MS patients with low disability may show ALFF differences in the MNS without clinical correspondence. This functional difference may be associated with cortical and subcortical changes related to the disease.

Can fibrinolytic system components explain cognitive impairment in multiple sclerosis?

BACKGROUND: The fibrinolytic system is capable of modulating inflammatory and degenerative events within the central nervous system. Specifically, the plasminogen activator inhibitor-1 (PAI-1) has been associated with different pathological conditions in multiple sclerosis (MS) and its role in cognitive functioning is also known. OBJECTIVES AND METHODS: To study the association between plasma levels and the polymorphic variants of the PAI-1 gene and cognitive performance in MS. 176 patients were studied. Neuropsychological evaluation was performed with the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). A Polymerase Chain Reaction (PCR) was used to determine PAI-1 4G/5G polymorphisms and quantification was performed using an Enzyme-Linked ImmunoSorbent Assay (ELISA). RESULTS: Participants were categorized as not cognitively impaired (NCI; n=114) and cognitively impaired (CI; n=62). The NCI group had a higher percentage of heterozygous subjects but no statistical differences were found between the CI and NCI group. Neuropsychological functioning did not correlate with plasma levels of PAI-1 or its genetic polymorphism. It is noteworthy that PAI-1 plasma levels were related to neurological impairment. DISCUSSION: Cognitive impairment in MS is due to strategic focal lesions affecting regions and tracts involved in cognitive processes and to diffuse damage in the white and gray matter. This complex etiology could explain the absence of a relationship between the cognitive functioning and PAI-1 in patients with MS that has been found in vascular dementia or Alzheimer's disease. Plasma curves of PAI-1 and its measures in cerebrospinal fluid could help elucidate the role of PAI-1 in MS.