Search

Background: Brain injury in hereditary hemoglobinopathies is commonly attributed to anemia-related relative hypoperfusion in terms of impaired oxygen blood supply. Supratentorial and infratentorial vascular watershed regions seem to be especially vulnerable, but data are very scarce., Aims: We investigated a large beta-thalassemia sample with arterial spin labeling in order to characterize regional perfusion changes and their correlation with phenotype and anemia severity., Methods: We performed a multicenter single-scanner cross-sectional 3T-MRI study analyzing non-invasively the brain perfusion in 54 transfusion-dependent thalassemia (TDT), 23 non-transfusion-dependent thalassemia (NTDT) patients and 56 Healthy Controls (HC). Age, hemoglobin levels, and cognitive functioning were recorded., Results: Both TDT and NTDT patients showed globally increased brain perfusion values compared to healthy controls, while no difference was found between patient subgroups. Using age and sex as covariates and scaling the perfusion maps for the global cerebral blood flow, beta-thalassemia patients showed relative hyperperfusion in supratentorial/infratentorial watershed regions. Perfusion changes correlated with hemoglobin levels (p = 0.013) and were not observed in the less severely anemic patients (hemoglobin level > 9.5 g/dL). In the hyperperfused regions, white matter density was significantly decreased (p = 0.0003) in both patient subgroups vs. HC. In NTDT, white matter density changes correlated inversely with full-scale Intelligence Quotient (p = 0.007) while in TDT no correlation was found., Conclusion: Relative hyperperfusion of watershed territories represents a hemodynamic hallmark of beta-thalassemia anemia challenging previous hypotheses of brain injury in hereditary anemias. A careful management of anemia severity might be crucial for preventing structural white matter changes and subsequent long-term cognitive impairment., (© 2024. The Author(s).)

Background: Despite numerous studies, the true scenario of hearing loss in beta-thalassaemia remains rather nebulous., Materials and Methods: Pure tone audiometry, chelation therapy, demographics and laboratory data of 376 patients (mean age 38.5 ± 16.6 years, 204 females, 66 non-transfusion-dependent) and 139 healthy controls (mean age 37.6 ± 17.7 years, 81 females) were collected., Results: Patient and control groups did not differ for age (p = 0.59) or sex (p = 0.44). Hypoacusis rate was higher in patients (26.6% vs. 7.2%; p < 0.00001), correlated with male sex (32.6% in males vs. 21.8% in females; p = 0.01) and it was sensorineural in 79/100. Hypoacusis rate correlated with increasing age (p = 0.0006) but not with phenotype (13/66 non-transfusion-dependent vs. 87/310 transfusion-dependent patients; p = 0.16). Sensorineural-notch prevalence rate did not differ between patients (11.4%) and controls (12.2%); it correlated with age (p = 0.01) but not with patients' sex or phenotype. Among adult patients without chelation therapy, the sensorineural hypoacusis rate was non-significantly lower compared to chelation-treated patients while it was significantly higher compared to controls (p = 0.003)., Conclusions: Sensorineural hypoacusis rate is high in beta-thalassaemia (about 21%) and it increases with age and in males while disease severity or chelation treatment seems to be less relevant. The meaning of sensorineural-notch in beta-thalassaemia appears questionable., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Using ultra-high field (7 Tesla) functional MRI (fMRI), we conducted the first in-vivo functional neuroimaging study of the normal human brainstem specifically designed to examine neural signals in the Nucleus Tractus Solitarius (NTS) in response to all basic taste stimuli. NTS represents the first relay station along the mammalian taste processing pathway which originates at the taste buds in the oral cavity and passes through the thalamus before reaching the primary taste cortex in the brain. In our proof-of-concept study, we acquired data from one adult volunteer using fMRI at 1.2 mm isotropic resolution and performed a univariate general linear model analysis. During fMRI acquisition, three shuffled injections of sweet, bitter, salty, sour, and umami solutions were administered following an event-related design. We observed a statistically significant blood oxygen level-dependent (BOLD) response in the anatomically predicted location of the NTS for all five basic tastes. The results of this study appear statistically robust, even though they were obtained from a single volunteer. The information derived from a similar experimental strategy may inspire novel research aimed at clarifying important details of central nervous system involvement in eating disorders, at designing and monitoring tailored therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Canna, Cantone, Roefs, Franssen, Prinster, Formisano, Di Salle and Esposito.)

The exact pathophysiology of cognitive impairment in multiple system atrophy (MSA) is unclear. In our longitudinal study, we aimed to analyze (I) the relationships between cognitive functions and some subcortical structures, such as putamen and cerebellum assessed by voxel-based morphometry (VBM) and T1-weighted/T2-weighted (T1w/T2w) ratio, and (II) the neuroimaging predictors of the progression of cognitive deficits. Twenty-six patients with MSA underwent a comprehensive neuropsychological battery, motor examination, and brain MRI at baseline (T 0 ) and 1-year follow-up (T 1 ). Patients were then divided according to cognitive status into MSA with normal cognition (MSA-NC) and MSA with mild cognitive impairment (MCI). At T 1 , we divided the sample according to worsening/non worsening of cognitive status compared to baseline evaluation. Logistic regression analysis showed that age (β =  - 9.45, p = .02) and T1w/T2w value in the left putamen (β = 230.64, p = .01) were significant predictors of global cognitive status at T 0 , explaining 65% of the variance. Logistic regression analysis showed that ∆-values of WM density in the cerebellum/brainstem (β = 2188.70, p = .02) significantly predicted cognitive worsening at T 1 , explaining 64% of the variance. Our results suggest a role for the putamen and cerebellum in the cognitive changes of MSA, probably due to their connections with the cortex. The putaminal T1w/T2w ratio may deserve further studies as a marker of cognitive impairment in MSA., (© 2022. The Author(s).)

Neuropsychiatric symptoms are intrinsic to Progressive Supranuclear Palsy (PSP) and a spoonful of studies investigated their imaging correlates. Describe (I) the frequency and severity of neuropsychiatric symptoms in PSP and (II) their structural imaging correlates. Twenty-six PSP patients underwent Neuropsychiatric Inventory (NPI) and brain 3D T1-weighted MRI. Spearman's rho with Bonferroni correction was used to investigate correlations between NPI scores and volumes of gray matter regions. More than 80% of patients presented at least one behavioral symptom of any severity. The most frequent and severe were depression/dysphoria, apathy, and irritability/lability. Significant relationships were found between the severity of irritability and right pars opercularis volume (p < 0.001) as well as between the frequency of agitation/aggression and left lateral occipital volume (p < 0.001). Depression, apathy, and irritability are the most common neuropsychiatric symptoms in PSP. Moreover, we found a relationship between specific positive symptoms as irritability and agitation/aggression and greater volume of the right pars opercularis cortex and lower volume of the left occipital cortex, respectively, which deserve further investigations., (© 2023. The Author(s).)

Childhood maltreatment (CM) is associated with distinct clinical and biological characteristics in people with eating disorders (EDs). The measurement of local gyrification index (lGI) may help to better characterize the impact of CM on cortical structure. Thus, the present study investigated the association of CM with lGI in women with EDs. Twenty-six women with anorexia nervosa (AN) and 24 with bulimia nervosa (BN) underwent a 3T MRI scan. All participants filled in the Childhood Trauma Questionnaire. All neuroimaging data were processed by FreeSurfer. LGI maps underwent a general linear model to evaluate differences between groups with or without CM. People with AN and BN were merged together. Based on the Childhood Trauma Questionnaire cutoff scores, 24 participants were identified as maltreated and 26 as non-maltreated. Maltreated people with EDs showed a significantly lower lGI in the left middle temporal gyrus compared with non-maltreated people, whereas no differences emerged in the right hemisphere between groups. The present study showed that in people with EDs, CM is associated with reduced cortical folding in the left middle temporal gyrus, an area that could be involved in ED psychopathology. This finding corroborates the hypothesis of a 'maltreated ecophenotype', which argues that CM may allow to biologically, other than clinically, distinguish individuals with the same psychiatric disorder., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Emergent carotid artery stenting (eCAS) is performed during mechanical thrombectomy for acute ischemic stroke due to tandem occlusion. However, the optimal management strategy in this setting is still unclear., Objective: To carry out a systematic review and meta-analysis to investigate the safety and efficacy of eCAS in patients with tandem occlusion., Methods: Systematic review followed the PRISMA guidelines. Medline, EMBASE, and Scopus were searched from January 1, 2004 to March 7, 2022 for studies evaluating eCAS and no-stenting approach in patients with stroke with tandem occlusion. Primary endpoint was the 90-day modified Rankin Scale score 0-2; secondary outcomes were (1) symptomatic intracerebral hemorrhage (sICH), (2) recurrent stroke, (3) successful recanalization (Thrombolysis in Cerebral Infarction score 2b-3), (4) embolization in new territories, and (5) restenosis rate. Meta-analysis was performed using the Mantel-Haenszel method and random-effects modeling., Results: Forty-six studies reached synthesis. eCAS was associated with higher good functional outcome compared with the no-stenting approach (OR=1.52, 95% CI 1.19 to 1.95), despite a significantly increased risk of sICH (OR=1.97, 95% CI 1.23 to 3.15), and higher successful recanalization rate (OR=1.91, 95% CI 1.29 to 2.85). Restenosis rate was lower in the eCAS group than in the no-stenting group (2% vs 9%, p=0.001). Recanalization rate was higher in retrograde than antegrade eCAS (OR=0.51, 95% CI 0.28 to 0.93). Intraprocedural antiplatelets during eCAS were associated with higher rate of good functional outcome (60% vs 46%, p=0.016) and lower rate of sICH (7% vs 11%; p=0.08) compared with glycoprotein IIb/IIIa inhibitors., Conclusions: In observational studies, eCAS seems to be associated with higher good functional outcome than no-stenting in patients with acute ischemic stroke due to tandem occlusion, despite the higher risk of sICH. Dedicated trials are needed to confirm these results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Childhood maltreatment (CM) is a non-specific risk factor for eating disorders (ED) and is associated with a greater severity in their clinical presentation and poorer treatment outcome. These data suggest that maltreated people with ED may be biologically other than clinically different from non-maltreated people. The aim of the present study was to investigate cortical thickness (CT), a possible biomarker of neurodevelopment, in people with ED with or without history of CM and in healthy women. Twenty-four healthy women, 26 with anorexia nervosa and 24 with bulimia nervosa underwent a 3T MRI scan. All participants filled in the childhood trauma questionnaire. All neuroimaging data were processed by FreeSurfer. Twenty-four participants with ED were identified as maltreated and 26 participants with ED as non-maltreated. All healthy women were non-maltreated. Compared to healthy women, maltreated people with ED showed lower CT in the left rostral anterior cingulate gyrus, while compared to people with ED without history of CM showed lower CT values in the left superior frontal and in right caudal middle frontal and superior parietal gyri. No significant differences emerged in CT measures between healthy women and people with ED without history of CM. The present findings show for the first time that in adult people with ED childhood maltreatment is associated with cortical thinning in areas implicated in the modulation of brain processes that are acknowledged to play a role in the psychopathology of ED., (© 2022. The Author(s).)

Deep learning (DL) approaches may also inform the analysis of human brain activity. Here, a state-of-art DL tool for natural language processing, the Generative Pre-trained Transformer version 2 (GPT-2), is shown to generate meaningful neural encodings in functional MRI during narrative listening. Linguistic features of word unpredictability (surprisal) and contextual importance (saliency) were derived from the GPT-2 applied to the text of a 12-min narrative. Segments of variable duration (from 15 to 90 s) defined the context for the next word, resulting in different sets of neural predictors for functional MRI signals recorded in 27 healthy listeners of the narrative. GPT-2 surprisal, estimating word prediction errors from the artificial network, significantly explained the neural data in superior and middle temporal gyri (bilaterally), in anterior and posterior cingulate cortices, and in the left prefrontal cortex. GPT-2 saliency, weighing the importance of context words, significantly explained the neural data for longer segments in left superior and middle temporal gyri. These results add novel support to the use of DL tools in the search for neural encodings in functional MRI. A DL language model like the GPT-2 may feature useful data about neural processes subserving language comprehension in humans, including next-word context-related prediction., (© 2022. The Author(s).)

Several MRI techniques have become available to support the early diagnosis of multiple system atrophy (MSA), but few longitudinal studies on both MSA variants have been performed, and there are no established MRI markers of disease progression. We aimed to characterize longitudinal brain changes in 26 patients with MSA (14 MSA-P and 12 MSA-C) over a 1-year follow-up period in terms of local tissue density and T1w/T2w ratio in a-priori regions, namely, bilateral putamen, cerebellar gray matter (GM), white matter (WM), and substantia nigra (SN). A significant GM density decrease was found in cerebellum and left putamen in the entire group (10.7 and 33.1% variation, respectively) and both MSA subtypes (MSA-C: 15.4 and 33.0% variation; MSA-P: 7.7 and 33.2%) and in right putamen in the entire group (19.8% variation) and patients with MSA-C (20.9% variation). A WM density decrease was found in the entire group (9.3% variation) and both subtypes in cerebellum-brainstem (MSA-C: 18.0% variation; MSA-P: 5% variation). The T1w/T2w ratio increase was found in the cerebellar and left putamen GM (6.6 and 24.9% variation), while a significant T1w/T2w ratio decrease was detected in SN in the entire MSA group (31% variation). We found a more progressive atrophy of the cerebellum in MSA-C with a similar progression of putaminal atrophy in the two variants. T1w/T2w ratio can be further studied as a potential marker of disease progression, possibly reflecting decreased neuronal density or iron accumulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ponticorvo, Manara, Russillo, Andreozzi, Forino, Erro, Picillo, Amboni, Cuoco, Di Salle, Di Salle, Barone, Esposito and Pellecchia.)

Word-predictability measures, such as surprisal, have been used to show that linguistic prediction is an essential neural mechanism for successful comprehension. However, the neural dynamic of this mechanism may differ across individuals listening to the same narrative, revealing possible idiosyncrasies. Therefore, in this study, we investigated the ability of the surprisal measure to address the linguistic prediction in terms of the intersubject phase synchronization (ISPS) among healthy volunteers listening to a narrative during continuous functional Magnetic Resonance Imaging (fMRI) scanning. The data of twenty-seven participants, acquired in a previous study, were re-analyzed to estimate the ISPS associated with an audiobook listening, played forward and backward. Mean ISPS differences between playing conditions were first analyzed across the whole brain. ISPS time-series during the forward condition was explained with both a lexical-only and a semantics-weighted lexical surprisal model of the narrative word series to detect correlations between ISPS and word surprisal values. Compared to the backward condition, mean ISPS was significantly higher during forward condition in a broad network encompassing frontal, temporal, and parietal areas. The lexical-only model disclosed significant negative ISPS-surprisal correlations in the angular gyrus bilaterally, precuneus, left inferior parietal lobule, left middle frontal gyrus, left cerebellum, and left inferior frontal gyrus. The semantics-weighted surprisal model disclosed significant negative ISPS-surprisal correlations in the right angular gyrus, right precuneus, and left inferior frontal gyrus. Besides engaging language-related areas, narrative processing induces significant ISPS levels beyond the language network. The negative ISPS-surprisal correlations observed would signal divergent neural dynamics among individuals, leading to lower group synchronization, when the words to be integrated are characterized by higher surprisal levels. These results provide further support to the use of language models, such as the surprisal, to explain the neural processes of narrative comprehension and additional information into how the human brain exploits predictions during language comprehension., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Richardson's syndrome (RS) is considered the most symmetric phenotype of progressive supranuclear palsy (PSP) as opposed to PSP with predominant corticobasal syndrome (PSP-CBS) or parkinsonism (PSP-P)., Objectives: Evaluate asymmetrical motor and higher cortical features in probable PSP-RS and compare the degree of asymmetry of cortical lobes and hemispheres between PSP-RS, PSP-CBS, PSP-P, and age-matched healthy controls (HC)., Methods: Asymmetry of motor and higher cortical features evaluated with an extensive videotaped neurologic examination was investigated in 28 PSP-RS, 8 PSP-CBS, and 14 PSP-P. Brain MRI to compute the laterality index (LI) was performed in 36 patients as well as in 56 HC., Results: In PSP-RS, parkinsonism was the most common asymmetric motor feature (53.6%), followed by dystonia and myoclonus (21.4% and 17.9%, respectively). Among higher cortical features, limb apraxia was found asymmetric in about one-third of patients. PSP-RS disclosed higher LI for hemispheres compared to HC, indicating a greater degree of asymmetry (p = 0.003). The degree of asymmetry of clinical features was not different between PSP-RS and those qualifying for PSP-CBS or PSP-P. As for imaging, LI was not different between PSP-RS, PSP-CBS, and PSP-P in any cortical region., Conclusions: Motor and higher cortical features are asymmetric in up to 50% of PSP-RS who also present a greater degree of asymmetry in hemispheres compared to age-matched HC. Lateralization of clinical features should be annotated in PSP., (© 2022. The Author(s).)

Objective. Real-time functional magnetic resonance imaging neurofeedback (rt-fMRI-NF) is a non-invasive procedure allowing the self-regulation of brain functions via enhanced self-control of fMRI based neural activation. In semantic rt-fMRI-NF, an estimated relation between multivariate fMRI activation patterns and abstract mental states is exploited for a multi-dimensional feedback stimulus via real-time representational similarity analysis (rt-RSA). Here, we assessed the performances of this framework in a multi-subject multi-session study on a 3 T MRI clinical scanner. Approach. Eighteen healthy volunteers underwent two semantic rt-fMRI-NF sessions on two different days. In each session, participants were first requested to engage in specific mental states while local fMRI patterns of brain activity were recorded during stimulated mental imagery of concrete objects (pattern generation). The obtained neural representations were to be replicated and modulated by the participants in subsequent runs of the same session under the guidance of a rt-RSA generated visual feedback (pattern modulation). Performance indicators were derived from the rt-RSA output to assess individual abilities in replicating (and maintaining over time) a target pattern. Simulations were carried out to assess the impact of the geometric distortions implied by the low-dimensional representation of patterns' dissimilarities in the visual feedback. Main results. Sixteen subjects successfully completed both semantic rt-fMRI-NF sessions. Considering some performance indicators, a significant improvement between the first and the second runs, and within run increasing modulation performances were observed, whereas no improvements were found between sessions. Simulations confirmed that in a small percentage of cases visual feedback could be affected by metric distortions due to dimensionality reduction implicit to the rt-RSA approach. Significance. Our results proved the feasibility of the semantic rt-fMRI-NF at 3 T, showing that subjects can successfully modulate and maintain a target mental state when guided by rt-RSA derived feedback. Further development is needed to encourage future clinical applications., (© 2022 IOP Publishing Ltd.)

The central gustatory pathway encompasses multiple subcortical and cortical regions whose neural functional connectivity can be modulated by taste stimulation. While gustatory perception has been previously linked to sex, whether and how the gustatory network differently responds to basic tastes between men and women is unclear. Here, we defined the regions of the central gustatory network by a meta-analysis of 35 fMRI taste activation studies and then analyzed the taste-evoked functional connectivity between these regions in 44 subjects (19 women) in a separate 3 Tesla activation study where sweet and bitter solutions, at five concentrations each, were administered during scanning. From the meta-analysis, a network model was set up, including bilateral anterior, middle and inferior insula, thalamus, precentral gyrus, left amygdala, caudate and dorsolateral prefrontal cortex. Higher functional connectivity than in women was observed in men between the right middle insula and bilateral thalami for bitter taste. Men exhibited higher connectivity than women at low bitter concentrations and middle-high sweet concentrations between bilateral thalamus and insula. A graph-based analysis expressed similar results in terms of nodal characteristics of strength and centrality. Our findings add new insights into the mechanisms of taste processing by highlighting sex differences in the functional connectivity of the gustatory network as modulated by the perception of sweet and bitter tastes. These results shed more light on the neural origin of sex-related differences in gustatory perception and may guide future research on the pathophysiology of taste perception in humans., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Diagnosis of multiple system atrophy (MSA) may be improved by using multimodal imaging approaches. We investigated the use of T1-weighted/T2-weighted (T1w/T2w) images ratio combined with voxel-based morphometry to evaluate brain tissue integrity in MSA compared to Parkinson's disease (PD) and healthy controls (HC). Twenty-six patients with MSA, 43 patients with PD and 56 HC were enrolled. Whole brain voxel-based and local regional analyses were performed to evaluate gray and white matter (GM and WM) tissue integrity and mean regional values were used for patients classification using logistic regression. Increased mean regional values of T1w/T2w in bilateral putamen were detected in MSA-P compared to PD and HC. The combined use of regional GM and T1w/T2w values in the right and left putamen showed the highest accuracy in discriminating MSA-P from PD and good accuracy in discriminating MSA from PD and HC. A good accuracy was also found in discriminating MSA from PD and HC by either combining regional GM and T1w/T2w values in the cerebellum or regional WM and T1w/T2w in the cerebellum and brainstem. The T1w/T2w image ratio alone or combined with validated MRI parameters can be further considered as a potential candidate biomarker for differential diagnosis of MSA., (© 2021. The Author(s).)

Background: Sensorineural hearing loss in beta-thalassemia is common and it is generally associated with iron chelation therapy. However, data are scarce, especially on adult populations, and a possible involvement of the central auditory areas has not been investigated yet. We performed a multicenter cross-sectional audiological and single-center 3Tesla brain perfusion MRI study enrolling 77 transfusion-dependent/non transfusion-dependent adult patients and 56 healthy controls. Pure tone audiometry, demographics, clinical/laboratory and cognitive functioning data were recorded., Results: Half of patients (52%) presented with high-frequency hearing deficit, with overt hypoacusia (Pure Tone Average (PTA) > 25 dB) in 35%, irrespective of iron chelation or clinical phenotype. Bilateral voxel clusters of significant relative hypoperfusion were found in the auditory cortex of beta-thalassemia patients, regardless of clinical phenotype. In controls and transfusion-dependent (but not in non-transfusion-dependent) patients, the relative auditory cortex perfusion values increased linearly with age (p < 0.04). Relative auditory cortex perfusion values showed a significant U-shaped correlation with PTA values among hearing loss patients, and a linear correlation with the full scale intelligence quotient (right side p = 0.01, left side p = 0.02) with its domain related to communication skills (right side p = 0.04, left side p = 0.07) in controls but not in beta-thalassemia patients. Audiometric test results did not correlate to cognitive test scores in any subgroup., Conclusions: In conclusion, primary auditory cortex perfusion changes are a metabolic hallmark of adult beta-thalassemia, thus suggesting complex remodeling of the hearing function, that occurs regardless of chelation therapy and before clinically manifest hearing loss. The cognitive impact of perfusion changes is intriguing but requires further investigations., (© 2021. The Author(s).)

Background: Patients with age-related sensorineural hearing loss (HL) may benefit from auditory input amplification by using hearing aids (HAs). However, the impact of both HL- and HA-based rehabilitation on central auditory functional connectivity (FC) is not clear. Methodology: Sixty-two HL (22 females, aged 64.4 ± 7.6 years, pure-tone average 50.9 ± 14.7 dB right ear, 50.7 ± 12.9 dB left ear) and 32 normal hearing (NH) subjects (22 females, aged 59.3 ± 7.3 years) were examined in a 3T magnetic resonance imaging (MRI) study. HL patients were analyzed cross-sectionally at baseline (vs. NH subjects) and longitudinally at 6-month follow-up. Between the 2 scans, 31/62 patients used the HA 9.5 ± 3.8 h a day. Arterial spin labeling and blood oxygen level-dependent resting-state functional MRI were performed to measure regional perfusion in the primary auditory cortex and, from here to the whole brain, seed-based FC was performed. Before each scan, HL patients underwent audiological and neurological assessments. Results: At baseline, the HL condition was associated with regional hypoperfusion in right Heschl's gyrus (seed) and negative seed-based FC (anticorrelation) in posterior brain regions. Long-range FC in the precuneus correlated negatively with pure-tone and speech reception average thresholds. At 6-month follow-up, HA usage was associated with seed-based FC increase in the right superior frontal gyrus (SFG) and seed-based FC reduction in the right middle temporal gyrus. Long-range FC changes in the SFG correlated positively with executive function improvements. Conclusions: These findings suggest that HA-based rehabilitation may not reverse HL-related neural effects and yet carry neurological benefits by retuning long-range FC of the auditory system. Impact statement Age-related sensorineural hearing loss (HL) affects 40% to 60% of the worldwide population and a common, viable rehabilitation strategy is to provide auditory input amplification through hearing aids (HAs). By targeting metabolically depressed, auditory cortical centers, our work reveals a possible neural link between peripheral and central vulnerability in HL patients in the form of aberrant, long-range, functional connectivity effects. Similarly, we unveil how wearing HAs for 6 months may induce neuroplastic changes that positively correlate with improved neuropsychological performances.

Objective . Real-time functional magnetic resonance imaging neurofeedback (rt-fMRI-NF) is a non-invasive MRI procedure allowing examined participants to learn to self-regulate brain activity by performing mental tasks. A novel two-step rt-fMRI-NF procedure is proposed whereby the feedback display is updated in real-time based on high-level representations of experimental stimuli (e.g. objects to imagine) via real-time representational similarity analysis of multi-voxel patterns of brain activity. Approach . In a localizer session, the stimuli become associated with anchored points on a two-dimensional representational space where distances approximate between-pattern (dis)similarities. In the NF session, participants modulate their brain response, displayed as a movable point, to engage in a specific neural representation. The developed method pipeline is verified in a proof-of-concept rt-fMRI-NF study at 7 T involving a single healthy participant imagining concrete objects. Based on this data and artificial data sets with similar (simulated) spatio-temporal structure and variable (injected) signal and noise, the dependence on noise is systematically assessed. Main results . The participant in the proof-of-concept study exhibited robust activation patterns in the localizer session and managed to control the neural representation of a stimulus towards the selected target in the NF session. The offline analyses validated the rt-fMRI-NF results, showing that the rapid convergence to the target representation is noise-dependent. Significance . Our proof-of-concept study introduces a new NF method allowing the participant to navigate among different mental states. Compared to traditional NF designs (e.g. using a thermometer display to set the level of the neural signal), the proposed approach provides content-specific feedback to the participant and extra degrees of freedom to the experimenter enabling real-time control of the neural activity towards a target brain state without suggesting a specific mental strategy to the subject., (© 2021 IOP Publishing Ltd.)

Prolonged mastication may induce an asymmetric modification of the local perfusion of the trigeminal principal nucleus. The aim of the present study was to evaluate the possible influence of vitamin C (vit. C) on such effect. Four groups of healthy volunteers underwent arterial spin labeling magnetic resonance imaging (ASL-MRI) to evaluate the local perfusion of the trigeminal nuclei after a vit. C-enriched lunch or a control lunch. Two ASL-MRI scans were acquired, respectively, before and after a 1 h-long masticating exercise or a 1 h long resting period. The results showed (i) an increased global perfusion of the brain in the vit. C-enriched lunch groups, (ii) an increased local perfusion of the right principal trigeminal nucleus (Vp) due to mastication, and (iii) a reduction of the rightward asymmetry of the Vp perfusion, due to mastication, after the vit C-enriched meal compared to the control meal. These results confirmed a long-lasting effect of prolonged mastication on Vp perfusion and also suggest a possible effect of vit. C on cerebral vascular tone regulation. Moreover, the data strongly draw attention on the side-to-side relation in Vp perfusion as a possible physiological parameter to be considered to understand the origin of pathological conditions like migraine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Viggiano, Ponticorvo, Canna, Secondulfo, Sbordone, Russo, Monda, Di Salle and Esposito.)

The present research investigated the neural correlates of nominal inflection and aimed at disclosing their possible link with the frequency distribution of noun inflectional features: grammatical gender, inflectional suffixes and inflectional classes. The properties of the Italian nominal system were exploited since it allows to explore exhaustively fine-grained phenomena in the inflectional processing. An event-related functional magnetic resonance imaging (fMRI) experiment was carried out where Italian masculine and feminine nouns were visually presented to 50 healthy participants in an overt inflectional task: the generation of the plural from the singular and vice versa. The grammatical gender and the citation form suffix of nouns were manipulated in a factorial design. Functional data showed that inflectional operations for nouns activate an extensive cortical network involving the left inferior and right superior frontal gyri, the left and right middle temporal gyri, the posterior cingulate cortex and the cerebellum. Activations were variably modulated by the distributional features of gender-dependent properties of nouns. Particularly, cortical activity increased during inflectional operations for small and/or scarcely consistent inflectional classes. These findings demonstrate the relevance of specific morphological (inflectional suffixes) and distributional features (size and consistency) shared by groups of words (inflectional classes) in a language, particularly when implementing cognitive operations required for language processing., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The Therapeutic Alliance (TA) between patient and health provider (therapist or clinician) is one of the most relevant factors for the success of a therapy. In the case of people suffering from Autism Spectrum Disorder (ASD), the alliance is extended to all the people involved in their care (i.e., teachers, therapists, clinicians, relatives). In this paper, we propose a multimedia application named Thea for empowering the TA of children with ASD by improving the communication among the TA members, sharing guidelines, multimedia contents, and strategies to comply with challenging behaviors and progress with particular attention towards end-users who are occasional smart-users. A detailed process for empowering the TA members by enhancing the informed interaction among all of them is proposed and implemented. A vocal assistant also supports patients/caregivers and therapists in documenting their activity with the person with ASD by recording videos in a free-hand modality. After a contextual analysis based on Thematic Analysis Template, Thea has been implemented using a user-centered development approach. We performed three iterations involving the end-users. A user study is performed at the third iteration. Results of the user study revealed a positive attitude towards the application. In particular, the perception of empowerment of participants increased after the tool had been used. We also highlighted the guidelines and tools that may be adopted for empowering different kinds of patients. The first results seem to suggest that the use of Thea may increase the belief of the caregivers of a person with ASD to be able to better take care of her, in a more controlled and informed way., (© The Author(s) 2021.)

Probabilistic language models are increasingly used to provide neural representations of linguistic features under naturalistic settings. Word surprisal models can be applied to continuous fMRI recordings during task-free listening of narratives, to detect regions linked to language prediction and comprehension. Here, to this purpose, a novel semantics-weighted lexical surprisal is applied to naturalistic fMRI data. FMRI was performed at 3 Tesla in 31 subjects during task-free listening to a 12-minute audiobook played in both original and word-reversed (control) version. Lexical-only and semantics-weighted lexical surprisal models were estimated for the original and control word series. The two series were alternatively chosen to build the predictor of interest in the first-level general linear model and were compared in the second-level (group) analysis. The addition of the surprisal predictor to the stimulus-related predictors significantly improved the fitting of the neural signal. In average, the semantics-weighted model yielded lower surprisal values and, in some areas, better fitting of the fMRI data compared to the lexical-only model. The two models produced both overlapping and distinct activations: while lexical-only surprisal activated secondary auditory areas in the superior temporal gyri and the cerebellum, semantics-weighted surprisal additionally activated the left inferior frontal gyrus. These results confirm the usefulness of surprisal models in the naturalistic fMRI analysis of linguistic processes and suggest that the use of semantic information may increase the sensitivity of a probabilistic language model in higher-order language-related areas, with possible implications for future naturalistic fMRI studies of language under normal and (clinically or pharmacologically) modified conditions., Competing Interests: Declaration of Competing Interest The authors report no disclosures., (Copyright © 2020. Published by Elsevier Inc.)

The human gustatory cortex analyzes the chemosensory properties of tastants, particularly the quality, intensity, and affective valence, to determine whether a perceived substance should be ingested or rejected. Among previous studies, the spatial distribution of taste intensity-related activations within the human insula has been scarcely addressed. To spatially characterize a specialized or distributed nature of the cortical responses to taste intensities, a functional magnetic resonance imaging study was performed at 3 T in 44 healthy subjects where sweet and bitter tastants were administered at five increasing concentrations and cortex-based factorial and parametric analyses were performed. Two clusters in the right middle-posterior and left middle insula were found specialized for taste intensity processing, exhibiting a highly nonlinear profile across concentrations. Multiple clusters were found activated by sweet and bitter taste stimuli at most concentrations, in the anterior, middle-posterior, and inferior portion of the bilateral insula. Across these clusters, respectively, for the right and left insula, a superior-to-inferior and an anterior-to-posterior spatial gradient for high-to-low concentrations were observed for the most responsive intensity of both tastes. These findings may gather new insights regarding how the gustatory cortex is spatially organized during the perceptual processing of taste intensity for two basic tastants., (© 2019 Wiley Periodicals, Inc.)

Age-related hearing loss (HL) can be related to brain dysfunction or structural damage and may result in cerebral metabolic/perfusion abnormalities. Arterial spin labeling (ASL) magnetic resonance imaging (MRI) allows investigating noninvasively brain perfusion changes. Pseudocontinuous ASL and T1-weighted MRI (at 3 T) and neuropsychological testing (Montreal Cognitive Assessment) were performed in 31 HL (age range = 47-77 years, mean age ± SD = 63.4 ± 8.4 years, pure-tone average [PTA] HL > 50 dB) and 28 normal hearing (NH; age range = 48-78 years, mean age ± SD = 59.7 ± 7.4 years) subjects. Cerebral blood flow (CBF) and gray matter volume (GMV) were analyzed in the cortical volume to assess perfusion and structural group differences. Two HL subjects showing cognitive impairment were excluded from group comparisons. No significant differences in either global or local atrophy were detected between groups but the HL group exhibited significant regional effects of reduced perfusion within the bilateral primary auditory cortex, with maximal CBF difference (-17.2%) in the right lateral Heschl's gyrus. For the whole sample of HL and NH subjects (n = 59 = 31 HL + 28 NH), the regional CBF was correlated positively to the regional GMV (p = 0.020). In HL subjects (n = 31), the regional CBF was correlated negatively to the audiogram steepness (frequency range: 2-4 kHz, right ear: p = 0.022, left ear: p = 0.015). The observed cortical pattern of perfusion reduction suggests that neuronal metabolism can be related to HL before the recognition of brain structural damage. This also illustrates the potential of ASL-MRI to contribute early functional markers of reduced central processing associated with HL., (© 2019 Wiley Periodicals, Inc.)

Objectives: Childhood maltreatment is a non-specific risk factor for eating disorders (EDs). However, so far, no study has assessed the impact of childhood maltreatment on brain structure of adults with EDs. Therefore, we investigated brain area volumes and fibre tract integrity of childhood maltreated (Mal) and non-maltreated (noMal) patients with EDs. Methods: Thirty-six ED women and 16 healthy women underwent an MRI scan, including acquisition of a diffusion tensor imaging (DTI) sequence and a high-resolution T1-weighted scan. ED participants were classified as Mal (18 patients) or noMal (18 patients) according to their childhood exposure to traumatic events assessed by the Childhood Trauma Questionnaire (CTQ). Results: Significantly reduced grey matter volume was detected in the right paracentral lobule and in the left inferior temporal gyrus of Mal patients. DTI analyses revealed reduced white matter integrity in the corpus callosum, internal capsule, posterior thalamic radiation, longitudinal fasciculus and corona radiata of Mal patients. Negative correlations emerged between white/grey matter changes and CTQ emotional and physical neglect scores. Conclusions: These results show that childhood trauma affects the integrity of brain structures modulating brain processes, such as reward, taste and body image perception, which play a fundamental role in the psychopathology of EDs.

Objective: Multisystem iron poisoning is a major concern for long-term beta-thalassemia management. Quantitative MRI-based techniques routinely show iron overload in heart, liver, endocrine glands and kidneys. However, data on the brain are conflicting and monitoring of brain iron content is still matter of debate., Methods: This 3T-MRI study applied a well validated high-resolution whole-brain quantitative MRI assessment of iron content on 47 transfusion-dependent (mean-age: 36.9 ± 10.3 years, 63% females), 23 non-transfusion dependent (mean-age: 29.2 ± 11.7 years, 56% females) and 57 healthy controls (mean-age: 33.9 ± 10.8 years, 65% females). Clinical data, Wechsler Adult Intelligence Scale scores and treatment regimens were recorded. Beside whole-brain R2* analyses, regional R2*-values were extracted in putamen, globus pallidum, caudate nucleus, thalamus and red nucleus; hippocampal volumes were also determined., Results: Regional analyses yielded no significant differences between patients and controls, except in those treated with deferiprone that showed lower R2*-values (p<0.05). Whole-brain analyses of R2*-maps revealed strong age-R2* correlations (r 2 =0.51) in both groups and clusters of significantly increased R2*-values in beta-thalassemia patients in the hippocampal formations and around the Luschka foramina; transfusion treatment was associated with additional R2* increase in dorsal thalami. Hippocampal formation R2*-values did not correlate with hippocampal volume; hippocampal volume did not differ between patients and controls. All regions with increased R2*-values shared a strict anatomical contiguity with choroid plexuses suggesting a blooming effect as the likely cause of R2* increase, in agreement with the available histopathologic literature evidence., Conclusion: According to our MRI findings and the available histopathologic literature evidence, concerns about neural tissue iron overload in beta-thalassemia appear to be unjustified., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Tasting is a complex process involving chemosensory perception and cognitive evaluation. Different experimental designs and solution delivery approaches may in part explain the variability reported in literature. These technical aspects certainly limit the development of taste-related brain computer interface devices., New Method: We propose a novel modular, scalable and low-cost device for rapid injection of small volumes of taste solutions during fMRI experiments that gathers the possibility to flexibly increase the number of channels, allowing complex multi-dimensional taste experiments. We provide the full description of the hardware and software architecture and illustrate the application of the working prototype in single-subject event-related fMRI experiments by showing the BOLD responses to basic taste qualities and to five intensities of tastes during the course of perception., Results: The device is shown to be effective in activating multiple clusters within the gustatory pathway and a precise time-resolved event-related analysis is shown to be possible by the impulsive nature of the induced perception., Comparison With Existing Method(s): This gustometer represents the first implementation of a low-cost, easily replicable and portable device that is suitable for all kinds of fMRI taste experiments. Its scalability will boost the experimental design of more complex multi-dimensional fMRI studies of the human taste pathway., Conclusions: The gustometer represents a valid open-architecture alternative to other available devices and its spread and development may contribute to an increased standardization of experimental designs in human fMRI studies of taste perception and pave the way to the development of novel taste-related BCIs., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Quantitative MRI (qMRI) provides surrogate brain maps of myelin and iron content. After spatial normalization to a common standard brain space, these may be used to detect altered myelination and iron accumulation in clinical populations. Here, volumetric and combined volumetric and surface-based (CVS) normalization were compared to identify which procedure would afford the greatest sensitivity to inter-regional differences (contrast), and the lowest inter-subject variability (under normal conditions), of myelin- and iron-related qMRI parameters, in whole-brain group-level studies. Ten healthy volunteers were scanned twice at 3 Tesla. Three-dimensional T1-weighted, T2-weighted and multi-parametric mapping sequences for brain qMRI were used to map myelin and iron content over the whole brain. Parameter maps were spatially normalized using volumetric (DARTEL) and CVS procedures. Tissue probability weighting and isotropic Gaussian smoothing were integrated in DARTEL for voxel-based quantification (VBQ). Contrasts, coefficients of variations and sensitivity to detecting differences in the parameters were estimated in standard space for each approach on region of interest (ROI) and voxel-by-voxel bases. The contrast between cortical and subcortical ROIs with respectively different myelin and iron content was higher following CVS, compared to DARTEL-VBQ, normalization. Across cortical voxels, the inter-individual variability of myelin and iron qMRI maps were comparable between CVS (with no smoothing) and DARTEL-VBQ (with smoothing). CVS normalization of qMRI maps preserves higher myelin and iron contrast than DARTEL-VBQ over the entire brain, while exhibiting comparable variability in the cerebral cortex without extra smoothing. Thus, CVS may prove useful for detecting small microstructural differences in whole-brain group-level qMRI studies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cortical surface-based morphometry is based on a semi-automated analysis of structural MRI images. In FreeSurfer, a widespread tool for surface-based analyses, a visual check of gray-white matter borders is followed by the manual placement of control points to drive the topological correction (editing) of segmented data. A novel algorithm combining radial sampling and machine learning is presented for the automated control point search (ACPS). Four data sets with 3 T MRI structural images were used for ACPS validation, including raw data acquired twice in 36 healthy subjects and both raw and FreeSurfer preprocessed data of 125 healthy subjects from public databases. The unedited data from a subgroup of subjects were submitted to manual control point search and editing. The ACPS algorithm was trained on manual control points and tested on new (unseen) unedited data. Cortical thickness (CT) and fractal dimensionality (FD) were estimated in three data sets by reconstructing surfaces from both unedited and edited data, and the effects of editing were compared between manual and automated editing and versus no editing. The ACPS-based editing improved the surface reconstructions similarly to manual editing. Compared to no editing, ACPS-based and manual editing significantly reduced CT and FD in consistent regions across different data sets. Despite the extra processing of control point driven reconstructions, CT and FD estimates were highly reproducible in almost all cortical regions, albeit some problematic regions (e.g. entorhinal cortex) may benefit from different editing. The use of control points improves the surface reconstruction and the ACPS algorithm can automate their search reducing the burden of manual editing., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Mirror movements (MM) might be observed in congenital and acquired neurodegenerative conditions but their anatomic-functional underpinnings are still largely elusive. This study investigated the spectral changes of resting-state functional connectivity in Kallmann Syndrome (hypogonadotropic hypogonadism with hypo/anosmia with or without congenital MM) searching for insights into the phenomenon of MM. Forty-four Kallmann syndrome patients (21 with MM) and 24 healthy control subjects underwent task (finger tapping) and resting-state functional MRI. The spatial pattern of task-related activations was used to mask regions and select putative motor networks in a spatially independent component analysis of resting-state signals. For each resting-state independent component time-course power spectrum, we extracted the relative contribution of four separate bands: slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), slow-3 (0.073-0.198 Hz), slow-2 (0.198-0.25 Hz), and analyzed the variance between groups. For the sensorimotor network, the analysis revealed a significant group by frequency interaction (P = 0.002) pointing to a frequency shift in the spectral content among subgroups with lower slow-5 band and higher slow-3 band contribution in Kallmann patients with MM versus controls (P = 0.028) and with lower slow-5 band contribution between patients with and without MM (P = 0.057). In specific regions, as obtained from hand motor activation task analysis, spectral analyses demonstrated a lower slow-5 band contribution in Kallmann patients with MM versus both controls and patients without MM (P < 0.05). In Kallmann syndrome, the peculiar phenomenon of bimanual synkinesis is associated at rest with regionally and spectrally selective functional connectivity changes pointing to a distinctive cortical and subcortical functional reorganization. Hum Brain Mapp 39:42-53, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: Right insular cortex is involved in taste discrimination, but its functional organization is still poorly known. In general, sensory cortices represent the spatial prevalence of relevant features for each sensory modality (visual, auditory, somatosensory) in an ordered way across the cortical space. Following this analogy, we hypothesized that primary taste cortex is organized in similar ordered way in response to six tastes with known receptorial mechanisms (sweet, bitter, sour, salt, umami, CO2)., Design: Ten normal subjects were enrolled in a pilot study. We used functional magnetic resonance imaging (fMRI), a high resolution cortical registration method, and specialized procedures of feature prevalence localization, to map fMRI responses within the right insular cortex, to water solutions of quinine hydrochloride (bitter), Acesulfamate K (sweet), sodium chloride (salt), mono potassium glutamate + inosine 5' mono phosphate (Umami), citric acid (sour) and carbonated water (CO2). During an fMRI scan delivery of the solutions was applied in pseudo-random order interleaved with cleaning water., Results: Two subjects were discarded due to excessive head movements. In the remaining subjects, statistically significant activations were detected in the fMRI responses to all tastes in the right insular cortex (p<0.05, family-wise corrected for multiple comparisons). Cortical representation of taste prevalence highlighted two spatially segregated clusters, processing two and three tastes coupled together (sweet-bitter and salt-umami-sour), with CO2 in between., Conclusions: Cortical representation of taste prevalence within the right primary taste cortex appears to follow the ecological purpose of enhancing the discrimination between safe nutrients and harmful substances.

Functional magnetic resonance imaging (fMRI) studies have displayed a dysregulation in the way in which the brain processes pleasant taste stimuli in patients with anorexia nervosa (AN) and bulimia nervosa (BN). However, exactly how the brain processes disgusting basic taste stimuli has never been investigated, even though disgust plays a role in food intake modulation and AN and BN patients exhibit high disgust sensitivity. Therefore, we investigated the activation of brain areas following the administration of pleasant and aversive basic taste stimuli in symptomatic AN and BN patients compared to healthy subjects. Twenty underweight AN women, 20 symptomatic BN women and 20 healthy women underwent fMRI while tasting 0.292 M sucrose solution (sweet taste), 0.5 mM quinine hydrochloride solution (bitter taste) and water as a reference taste. In symptomatic AN and BN patients the pleasant sweet stimulus induced a higher activation in several brain areas than that induced by the aversive bitter taste. The opposite occurred in healthy controls. Moreover, compared to healthy controls, AN patients showed a decreased response to the bitter stimulus in the right amygdala and left anterior cingulate cortex, while BN patients showed a decreased response to the bitter stimulus in the right amygdala and left insula. These results show an altered processing of rewarding and aversive taste stimuli in ED patients, which may be relevant for understanding the pathophysiology of AN and BN., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: The birth of a preterm infant and Neonatal Intensive Care Unit hospitalization constitute a potentially traumatic experience for mothers. Although behavioral studies investigated the parenting stress in preterm mothers, no study focused on the underlying neural mechanisms. We examined the effect of preterm births in mothers, by comparing brain activation in mothers of preterm and full-term infants., Study Design: We used functional magnetic resonance imaging to measure the cerebral response of 10 first-time mothers of preterm infants (gestational age <32 weeks and/or birth weight <1500) and 11 mothers of full-term infants, viewing happy-, neutral- and distress-face images of their own infant, along with a matched unknown infant., Results: While viewing own infant's face preterm mothers showed increased activation in emotional processing area (i.e., inferior frontal gyrus) and social cognition (i.e., supramarginal gyrus) and affiliative behavior (i.e., insula)., Conclusion: Differential brain activation patterns in mothers appears to be a function of the atypical parenthood transition related to prematurity.

The functional interplay between hemispheres is fundamental for behavioral, cognitive, and emotional control. Anorexia nervosa (AN) and bulimia nervosa (BN) have been largely studied with brain magnetic resonance imaging (MRI) in relation to the functional mechanisms of high-level processing, but not in terms of possible inter-hemispheric functional connectivity anomalies. Using resting-state functional MRI (fMRI), voxel-mirrored homotopic connectivity (VMHC) and regional inter-hemispheric spectral coherence (IHSC) were studied in 15 AN and 13 BN patients and 16 healthy controls (HC). Using T1-weighted and diffusion tensor imaging MRI scans, regional VMHC values were correlated with the left-right asymmetry of corresponding homotopic gray matter volumes and with the white matter callosal fractional anisotropy (FA). Compared to HC, AN patients exhibited reduced VMHC in cerebellum, insula, and precuneus, while BN patients showed reduced VMHC in dorso-lateral prefrontal and orbito-frontal cortices. The regional IHSC analysis highlighted that the inter-hemispheric functional connectivity was higher in the 'Slow-5' band in all regions except the insula. No group differences in left-right structural asymmetries and in VMHC vs. callosal FA correlations were significant in the comparisons between cohorts. These anomalies, not explained by structural changes, indicate that AN and BN, at least in their acute phase, are associated with a loss of inter-hemispheric connectivity in regions implicated in self-referential, cognitive control and reward processing. These findings may thus gather novel functional markers to explore aberrant features of these eating disorders., (© 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The aim of this study was to investigate the neurophysiological bases of Active Music Therapy (AMT) and its effects on the normal brain. Twelve right-handed, healthy, non-musician volunteers were recruited. The subjects underwent 2 AMT sessions based on the free sonorous-music improvisation using rhythmic and melodic instruments. After these sessions, each subject underwent 2 fMRI scan acquisitions while listening to a Syntonic (SP) and an A-Syntonic (AP) Production from the AMT sessions. A 3 T Discovery MR750 scanner with a 16-channel phased array head coil was used, and the image analysis was performed with Brain Voyager QX 2.8. The listening to SP vs AP excerpts mainly activated: (1) the right middle temporal gyrus and right superior temporal sulcus, (2) the right middle frontal gyrus and in particular the right precentral gyrus, (3) the bilateral precuneus, (4) the left superior temporal sulcus and (5) the left middle temporal gyrus. These results are consistent with the psychological bases of the AMT approach and with the activation of brain areas involved in memory and autobiographical processes, and also in personal or interpersonal significant experiences. Further studies are required to confirm these findings and to explain possible effects of AMT in clinical settings.

Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1 h at 1 bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans. The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume. These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Intraparenchymal cavities communicating with the ventricles may appear in patients with chronic obstructive hydrocephalus despite no identifiable surgerical, vascular or traumatic causes. The rate, features, pathogenesis, evolution and clinical impact of intraparenchymal diverticula have not been outlined, yet., Methods: Brain MRIs of 130 patients (mean age: 11.3 years; age range: 0-67; 60 females) with chronic obstructive hydrocephalus were analyzed. The pathogenesis, neurosurgical treatment, ventricle size, signs of transependymal reabsorption and septum pellucidum integrity of the hydrocephalus were recorded. Subarachnoid outpouching of the ventricles, post-hemorrhagic parenchymal cavities, paths of ventricular shunting and cavities not communicating with the ventricles were excluded. Of patients with intraparenchymal diverticula, all previous available CT and MRI scans were evaluated., Results: Eight patients (6.2 %, mean age: 18.7 years; age range: 2-42) harbored 11 intraparenchymal diverticula sprouting from the temporal (6), occipital (3) or frontal (2) horns of the lateral ventricles. Intraparenchymal diverticula were more frequent in males (p = 0.04) and older patients (18.7 ± 12.7 vs 11.3 ± 9.8 years, p = 0.04). Their presence or evolution (mean neuroradiological follow-up 3.6 years; range: 0-8) showed a trend of association with hydrocephalus severity (bifrontal index) and did not correlate with the surgical treatment. In three patients the diverticula progressed during follow-up. One patient presented with hemiparesis consistent with the intraparenchymal lesion and improved after ventricular shunting. A DTI study revealed that the cortico-spinal tract was partly included in the septum between the ventricle and the intraparenchymal diverticulum., Conclusions: Clinicians dealing with chronic severe obstructive hydrocephalus should be aware of ventricular intraparenchymal diverticulation. Studies aiming at clarifying their pathogenesis and proper management are warranted.

Background: The relationship between olfactory function, rhinencephalon and forebrain changes in Kallmann syndrome (KS) have not been adequately investigated. We evaluated a large cohort of male KS patients using Sniffin' Sticks and MRI in order to study olfactory bulb (OB) volume, olfactory sulcus (OS) depth, cortical thickness close to the OS, and olfactory phenotype., Methods: Olfaction was assessed administering Sniffin' Sticks®, in 38 KS patients and 17 controls (by means of Screening 12 test®). All subjects underwent magnetic resonance imaging (MRI) to study OB volume, sulcus depth, and cortical thickness., Results: Compared to controls, KS patients showed smaller OB volume (p<0.0001), reduced sulcus depth (p<0.0001), and thicker cortex in the region close to the OS (p<0.0001). Anosmic KS patients had smaller OB than controls and hyposmic KS patients; there was no difference between hyposmic KS patients and controls. OB volume correlated with Sniffin' Sticks score (r = 0.64; p < 0.001), OS depth (p<0.0001) and, inversely, with cortical thickness changes (p<0.0001). Sniffin' Sticks showed an inverse correlation with cortical thickness (r = -0.5; p<0.0001) and a trend toward a statistically significant correlation with OS depth., Conclusion: The present study provides further evidence of the strict relationship between olfaction and OB volume. The strong correlation between OB volume and the overlying cortical changes highlights the key role of rhinencephalon in forebrain embryogenesis., (© 2015 ARS-AAOA, LLC.)

Introduction: The default mode network and the working memory network are known to be anti-correlated during sustained cognitive processing, in a load-dependent manner. We hypothesized that functional connectivity among nodes of the two networks could be dynamically modulated by task phases across time., Methods: To address the dynamic links between default mode network and the working memory network, we used a delayed visuo-spatial working memory paradigm, which allowed us to separate three different phases of working memory (encoding, maintenance, and retrieval), and analyzed the functional connectivity during each phase within and between the default mode network and the working memory network networks., Results: We found that the two networks are anti-correlated only during the maintenance phase of working memory, i.e. when attention is focused on a memorized stimulus in the absence of external input. Conversely, during the encoding and retrieval phases, when the external stimulation is present, the default mode network is positively coupled with the working memory network, suggesting the existence of a dynamically switching of functional connectivity between "task-positive" and "task-negative" brain networks., Conclusions: Our results demonstrate that the well-established dichotomy of the human brain (anti-correlated networks during rest and balanced activation-deactivation during cognition) has a more nuanced organization than previously thought and engages in different patterns of correlation and anti-correlation during specific sub-phases of a cognitive task. This nuanced organization reinforces the hypothesis of a direct involvement of the default mode network in cognitive functions, as represented by a dynamic rather than static interaction with specific task-positive networks, such as the working memory network.

Background and Purpose: Alström syndrome is a rare inherited ciliopathy in which early progressive cone-rod dystrophy leads to childhood blindness. We investigated functional and structural changes of the optic pathway in Alström syndrome by using MR imaging to provide insight into the underlying pathogenic mechanisms., Materials and Methods: Eleven patients with genetically proved Alström syndrome (mean age, 23 years; range, 6-45 years; 5 females) and 19 age- and sex-matched controls underwent brain MR imaging. The study protocol included conventional sequences, resting-state functional MR imaging, and diffusion tensor imaging., Results: In patients with Alström syndrome, the evaluation of the occipital regions showed the following: 1) diffuse white matter volume decrease while gray matter volume decrease spared the occipital poles (voxel-based morphometry), 2) diffuse fractional anisotropy decrease and radial diffusivity increase while mean and axial diffusivities were normal (tract-based spatial statistics), and 3) reduced connectivity in the medial visual network strikingly sparing the occipital poles (independent component analysis). After we placed seeds in both occipital poles, the seed-based analysis revealed significantly increased connectivity in patients with Alström syndrome toward the left frontal operculum, inferior and middle frontal gyri, and the medial portion of both thalami (left seed) and toward the anterior portion of the left insula (right and left seeds)., Conclusions: The protean occipital brain changes in patients with Alström syndrome likely reflect the coexistence of diffuse primary myelin derangement, anterograde trans-synaptic degeneration, and complex cortical reorganization affecting the anterior and posterior visual cortex to different degrees., (© 2015 by American Journal of Neuroradiology.)

Among male patients affected by Kallmann syndrome, a genetically determined disease due to defective neural migration leading to hypogonadropic hypogonadism and hypo/anosmia, about 40% present the peculiar phenomenon of mirror movements, i.e. involuntary movements mirroring contralateral voluntary hand movements. Several pathogenic hypotheses have been proposed, but the ultimate neurological mechanisms are still elusive. The aim of the present study was to investigate brain anatomical substrates of mirror movements in Kallmann syndrome by means of a panel of quantitative MRI analyses. Forty-nine male Kallmann syndrome patients underwent brain MRI. The study protocol included 3D-T1-weighted gradient echo, fluid attenuated inversion recovery and diffusion tensor imaging. Voxel-based morphometry, sulcation, curvature and cortical thickness analyses and tract based spatial statistics were performed using SPM8, Freesurfer and FSL. All patients underwent a complete physical and neurological examination including the evaluation of mirror movements (according to the Woods and Teuber criteria). Kallmann syndrome patients presenting with mirror movements (16/49, 32%) displayed the following brain changes: 1) increased gray matter density in the depth of the left precentral sulcus behind the middle frontal gyrus; 2) decreased cortical thickness in the precentral gyrus bilaterally, in the depth of right precentral sulcus and in the posterior portion of the right superior frontal gyrus; and 3) decreased fractional anisotropy in the left hemisphere involving the temporal lobe and peritrigonal white matter. No differences were shown by cortical curvature and sulcation analyses. The composite array of brain changes observed in Kallmann syndrome patients with mirror movements likely represents the anatomical-structural underpinnings leading to the peculiar derangement of the complex circuitry committed to unilateral hand voluntary movements., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Although cerebrovascular mortality is increased up to eightfold in acromegaly, intracranial internal carotid artery (ICA) changes have not been well investigated. This is a magnetic resonance angiography (MRA) quantitative cross-sectional study of ICA tortuosity, ectasia and intercarotid distance in acromegalic patients with subsequent analysis of concomitant clinical, laboratory and neuroimaging findings., Methods: One hundred seventy six acromegalic patients (mean-age 55 ± 14 years, age range 21-88, 92 females) and 104 subjects with headache or transient neurological deficits underwent MRA with the same 1.5 T scanner. Clinical data, laboratory and pituitary adenoma imaging findings were recorded. Using a commercially available software, we measured the tortuosity index [(curved/linear ICA length from C3-midpoint to intracranial bifurcation) - 1], ICA ectasia index (intracavernous/petrous ICA diameter) and intercarotid distance at C3 and C4 levels., Results: Mean ICA tortuosity and ectasia indices were increased in acromegalic patients compared with controls (1.06 ± 0.29 vs 0.93 ± 0.26, p < 0.001; 1.02 ± 0.10 vs 0.92 ± 0.09, p < 0.001). Mean intercarotid distance was reduced at C3 and increased at C4 in acromegalic patients (16.7 ± 3.4 vs 17.9 ± 2.5 mm, p < 0.001; 16.7 ± 4.6 vs 15.4 ± 4.1 mm, p < 0.05; t test). ICA tortuosity and ectasia correlated neither with laboratory findings nor with previous or current treatment. On multivariate analysis, C3 intercarotid distance was reduced in patients on dopamine agonist treatment (p < 0.01) and increased in patients with GH-deficit (p = 0.01), while C4 intercarotid distance was increased with macroadenoma (p = 0.01) and reduced in patients under dopamine agonist (p < 0.01) or somatostatin analogue (p < 0.05) treatment., Conclusions: Intracranial ICA changes are common findings in acromegaly, and further studies focused on their possible clinical impact are needed.

Background and Purpose: Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome-related brain changes with conventional and novel quantitative MR imaging analyses., Materials and Methods: Forty-five male patients with Kallmann syndrome (mean age, 30.7 years; range, 9-55 years) and 23 age-matched male controls underwent brain MR imaging. The MR imaging study protocol included 3D-T1, FLAIR, and diffusion tensor imaging (32 noncollinear gradient-encoding directions; b-value=800 s/mm2). Voxel-based morphometry, sulcation, curvature, and cortical thickness analyses and tract-based spatial statistics were performed by using Statistical Parametric Mapping 8, FreeSurfer, and the fMRI of the Brain Software Library., Results: Corpus callosum partial agenesis, multiple sclerosis-like white matter abnormalities, and acoustic schwannoma were found in 1 patient each. The total amount of gray and white matter volume and tract-based spatial statistics measures (fractional anisotropy and mean, radial, and axial diffusivity) did not differ between patients with Kallmann syndrome and controls. By specific analyses, patients with Kallmann syndrome presented with symmetric clusters of gray matter volume increase and decrease and white matter volume decrease close to the olfactory sulci; reduced sulcal depth of the olfactory sulci and deeper medial orbital-frontal sulci; lesser curvature of the olfactory sulcus and sharper curvature close to the medial orbital-frontal sulcus; and increased cortical thickness within the olfactory sulcus., Conclusions: This large MR imaging study on male patients with Kallmann syndrome featured significant morphologic and structural brain changes, likely driven by olfactory bulb hypo-/aplasia, selectively involving the basal forebrain cortex., (© 2014 by American Journal of Neuroradiology.)

Objective: To investigate functional connectivity between the default mode network (DMN) and other networks in disorders of consciousness., Methods: We analyzed MRI data from 11 patients in a vegetative state and 7 patients in a minimally conscious state along with age- and sex-matched healthy control subjects. MRI data analysis included nonlinear spatial normalization to compensate for disease-related anatomical distortions. We studied brain connectivity data from resting-state MRI temporal series, combining noninferential (independent component analysis) and inferential (seed-based general linear model) methods., Results: In DMN hypoconnectivity conditions, a patient's DMN functional connectivity shifts and paradoxically increases in limbic structures, including the orbitofrontal cortex, insula, hypothalamus, and the ventral tegmental area., Conclusions: Concurrently with DMN hypoconnectivity, we report limbic hyperconnectivity in patients in vegetative and minimally conscious states. This hyperconnectivity may reflect the persistent engagement of residual neural activity in self-reinforcing neural loops, which, in turn, could disrupt normal patterns of connectivity.

Little is known about how CO2 affects neural processing of taste. We used functional magnetic resonance imaging to investigate the effects of carbonation on brain processing of sweet stimuli, which has relevance to studies of food selection and satiety. The presence of carbonation produced an overall decrease in the neural processing of sweetness-related signals, especially from sucrose. CO2 reduced the neural processing of sucrose more than that of artificial sweeteners. These findings might be relevant to dietary interventions that include noncaloric beverages, whereas the combination of CO2 and sucrose might increase consumption of sucrose., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Anorexia nervosa is characterized by high levels of perseveration and inflexibility, which interfere with successful treatments. Dopamine (DA) signalling seems to play a key role in modulating the prefrontal cortex, since both DA deficiency and excess nega tively influence the efficiency of cognitive functions. The present study explores the effect of a functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene on the set-shifting abilities and prefrontal functional connectivity of patients with anorexia nervosa., Methods: All participants performed the Wisconsin Card Sorting Task, and a subsample underwent resting-state functional magnetic resonance imaging., Results: We included 166 patients with DSM-IV lifetime anorexia nervosa and 140 healthy women in our study. Both underweight and weight-recovered patients with anorexia nervosa showed high levels of perseveration, but only in the underweight group did the Val158Met polymorphism affect cognitive performance, showing the U-shaped curve characteristic of increased DA signalling in the prefrontal cortex. Underweight patients with anorexia nervosa who are Met homozygotes had significantly higher levels of perseveration and increased prefrontal functional connectivity than underweight patients in the other genotype groups, indicating abnormal regional cortical processing., Limitations: Although our data show that grey matter reduction in starving patients with anorexia nervosa did not explain our findings, the cross-sectional design of the present study did not allow us to distinguish between the effects of starvation and those of low estrogen levels., Conclusion: Starvation affects DA release in the prefrontal cortex of patients with anorexia nervosa with different effects on executive functioning and prefrontal functional connectivity according to the COMT genotype. This observation has several therapeutic implications that need to be addressed by future studies.

Introduction: The functional neuroimaging of headache patients has revolutionized our understanding of the pathophysiology of primary headaches, providing unique insights into these syndromes. Indeed, functional neuroimaging studies have shown the activation of specific brain structures, the brainstem in migraine and posterior hypothalamus in cluster headache (CH), as well as in other trigeminal autonomic cephalalgias. We describe the functional neuroimaging findings in a patient suffering from CH headache, investigated with functional magnetic resonance imaging (fMRI) during typical pain attacks., Material and Methods: Two typical, consecutive CH attacks were investigated by two fMRI imaging sessions on the same day. Both fMRI scans were performed at rest, during the CH attacks and the pain-free state induced by subcutaneous administration of sumatriptan., Results: Significant activation of the bilateral red nucleus, ventral pons and trigeminal root entry zone ipsilaterally to the pain side was detected during the pain state, in addition to the hypothalamic region ipsilaterally to the pain side., Conclusion: Being that such structures are mainly involved in motor function and reactive behaviour, their activation, in our hypothesis, may be linked to pain avoidance and may well represent a defence reaction in cluster headache, which is characterised by a "fight-or-flight" type behavioural pattern during pain attacks.

Background: Although body image disturbance is considered one of the core characteristics of anorexia nervosa (AN), the exact nature of this complex feature is poorly understood. Task-related functional magnetic resonance imaging studies can only partially explore the multimodal complexity of body consciousness, which is a complex cognition underpinned by aspects of visual perception, proprioception, and touch. The aim of the present study was to explore the functional connectivity of networks involved in visuospatial and somatosensory processing in AN., Methods: Twenty-nine subjects with AN, 16 women who had recovered from it, and 26 healthy women underwent a resting-state functional magnetic resonance imaging scan and neuropsychological assessment of their visuospatial abilities using the Rey-Osterrieth Complex Figure Test., Results: Both AN groups showed areas of decreased connectivity in the ventral visual network, a network involved in the "what?" pathway of visual perception. Even more interestingly, the AN group, but not the recovered AN group, displayed increased coactivation in the left parietal cortex, encompassing the somatosensory cortex, in an area implicated in long-term multimodal spatial memory and representation, even in the absence of visual information. A neuropsychological assessment of visuospatial abilities revealed that aspects of detail processing and global integration (central coherence) showed correlations with connectivity of this brain area in the AN group., Conclusions: Our findings show that AN is associated with double disruption of brain connectivity, which shows a specific association with visuospatial difficulties and may explain the failure of the integration process between visual and somatosensory perceptual information that might sustain body image disturbance., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)