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Purpose: Electrical epidural spinal cord stimulation (SCS) is used as a treatment for chronic pain as well as to partially restore motor function after a spinal cord injury. Monitoring the spinal cord activity during SCS with fMRI could provide important and objective measures of integrative responses to treatment. Unfortunately, spinal cord fMRI is severely challenged by motion and susceptibility artifacts induced by the implanted electrode and bones. This pilot study introduces multi-band sweep imaging with Fourier transformation (MB-SWIFT) technique for spinal cord fMRI during SCS in rats. Given the close to zero acquisition delay and high bandwidth in 3 dimensions, MB-SWIFT is demonstrated to be highly tolerant to motion and susceptibility-induced artifacts and thus holds promise for fMRI during SCS. Methods: MB-SWIFT with 0.78 × 0.78 × 1.50 mm3 spatial resolution and 3-s temporal resolution was used at 9.4 Tesla in rats undergoing epidural SCS at different frequencies. Its performance was compared with spin echo EPI. The origin of the functional contrast was also explored using suppression bands. Results: MB-SWIFT was tolerant to electrode-induced artifacts and respiratory motion, leading to substantially higher fMRI sensitivity than spin echo fMRI. Clear stimulation frequency-dependent responses to SCS were detected in the rat spinal cord close to the stimulation site. The origin of MB-SWIFT fMRI signals was consistent with dominant inflow effects. Conclusion: fMRI of the rat spinal cord during SCS can be consistently achieved with MB-SWIFT, thus providing a valuable experimental framework for assessing the effects of SCS on the central nervous system. publishedVersion

Even though well known in type 2 diabetes, the existence of brain changes in type 1 diabetes (T1D) and both their neuroanatomical and clinical features are less well characterized. To fill the void in the current understanding of this disease, we sought to determine the possible neural correlate in long-duration T1D at several levels, including macrostructural, microstructural cerebral damage, and blood flow alterations. In this cross-sectional study, we compared a cohort of 61 patients with T1D with an average disease duration of 21 years with 54 well-matched control subjects without diabetes in a multimodal MRI protocol providing macrostructural metrics (cortical thickness and structural volumes), microstructural measures (T1-weighted/T2-weighted [T1w/T2w] ratio as a marker of myelin content, inflammation, and edema), and cerebral blood flow. Patients with T1D had higher T1w/T2w ratios in the right parahippocampal gyrus, the executive part of both putamina, both thalami, and the cerebellum. These alterations were reflected in lower putaminal and thalamic volume bilaterally. No cerebral blood flow differences between groups were found in any of these structures, suggesting nonvascular etiologies of these changes. Our findings implicate a marked nonvascular disruption in T1D of several essential neural nodes engaged in both cognitive and motor processing.

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.

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.

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 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.

Traumatic events can produce emotional, cognitive and autonomous physical responses. This may ultimately lead to post-traumatic stress disorder (PTSD), a psychiatric syndrome which requires comprehensive treatment. Trauma exposure alters functional connectivity; however, onset and nature of these changes are unknown. Here, we explore functional connectivity changes at rest directly after experimental trauma exposure. Seventy-three healthy subjects watched either a trauma or a control film. Resting state functional magnetic resonance imaging measurements were conducted before and directly after the film. Seed-based analyses revealed trauma-related changes in functional connectivity, specifically including decreases of connectivity between amygdala and middle temporal gyrus and increases between hippocampus and precuneus. These central effects were accompanied by trauma-related increases in heart rate. Moreover, connectivity between the amygdala and middle temporal gyrus predicted subsequent trauma-related valence. Our results demonstrate rapid functional connectivity changes in memory-related brain regions at rest after experimental trauma, selectively relating to changes in emotions evoked by the trauma manipulation. Results could represent an early predictive biomarker for the development of trauma-related PTSD and thus provide an indication for the need of early targeted preventive interventions. Electronic supplementary material The online version of this article (10.1007/s11682-020-00396-2) contains supplementary material, which is available to authorized users.

Objective To assess the performance of a combination of three quantitative MRI markers (iron deposition, basal neuronal metabolism, and regional atrophy) for differential diagnosis between amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Methods In total, 33 ALS, 12 PLS, and 28 healthy control (HC) subjects underwent a 3T MRI study including single‐ and multi‐echo sequences for gray matter (GM) volumetry and quantitative susceptibility mapping (QSM) and a pseudo‐continuous arterial spin labeling (ASL) sequence for cerebral blood flow (CBF) measurement. Mean values of QSM, CBF, and GM volumes were extracted in the motor cortex, basal ganglia, thalamus, amygdala, and hippocampus. A generalized linear model was applied to the three measures to binary discriminate between groups. The diagnostic performances were evaluated via receiver operating characteristic analyses. Results A significant discrimination was obtained: between ALS and HCs in the left and right motor cortex, where QSM increases were respectively associated with disability scores and disease duration; between PLS and ALS in the left motor cortex, where PLS patients resulted significantly more atrophic; between ALS and HC in the right motor cortex, where GM volumes were associated with upper motor neuron scores. Significant discrimination between ALS and HC was achieved in subcortical structures only combining all three parameters. Interpretation While increased QSM values in the motor cortex of ALS patients is a consolidated finding, combining QSM, CBF, and GM volumetry shows higher diagnostic potential for differentiating ALS patients from HC subjects and, in the motor cortex, between ALS and PLS.

Age-related sensorineural hearing loss (HL) leads to localized brain changes in the primary auditory cortex, long-range functional alterations, and is considered a risk factor for dementia. Non-human studies have repeatedly highlighted cross-modal brain plasticity in sensorial brain networks other than those primarily involved in the peripheral damage, thus in this study, the possible cortical alterations associated with HL have been analyzed using a whole-brain multimodal connectomic approach. Fifty-two HL and 30 normal hearing participants were examined in a 3T MRI study along with audiological and neurological assessments. Between-regions functional connectivity and whole-brain probabilistic tractography were calculated in a connectome-based manner and graph theory was used to obtain low-dimensional features for the analysis of brain connectivity at global and local levels. The HL condition was associated with a different functional organization of the visual subnetwork as revealed by a significant increase in global efficiency, density, and clustering coefficient. These functional effects were mirrored by similar (but more subtle) structural effects suggesting that a functional repurposing of visual cortical centers occurs to compensate for age-related loss of hearing abilities.

Epidural spinal cord stimulation (ESCS) is widely used for chronic pain treatment, and is also a promising tool for restoring motor function after spinal cord injury. Despite significant positive impact of ESCS, currently available protocols provide limited specificity and efficiency partially due to the limited number of contacts of the leads and to the limited flexibility to vary the spatial distribution of the stimulation field in respect to the spinal cord. Recently, we introduced Orientation Selective (OS) stimulation strategies for deep brain stimulation, and demonstrated their selectivity in rats using functional MRI (fMRI). The method achieves orientation selectivity by controlling the main direction of the electric field gradients using individually driven channels. Here, we introduced a similar OS approach for ESCS, and demonstrated orientation dependent brain activations as detected by brain fMRI. The fMRI activation patterns during spinal cord stimulation demonstrated the complexity of brain networks stimulated by OS-ESCS paradigms, involving brain areas responsible for the transmission of the motor and sensory information. The OS approach may allow targeting ESCS to spinal fibers of different orientations, ultimately making stimulation less dependent on the precision of the electrode implantation.

Even though well known in type 2 diabetes, the existence of brain changes in type 1 diabetes (T1D) and both their neuroanatomical and clinical features are less well characterized. To fill the void in the current understanding of this disease, we sought to determine the possible neural correlate in long-duration T1D at several levels including macrostructural, microstructural cerebral damage and blood flow alterations. In this cross-sectional study, we compared a cohort of 61 patients with T1D with an average disease duration of 21 years with 54 well-matched non-diabetic controls in a multimodal magnetic resonance imaging (MRI) protocol providing macrostructural metrics (cortical thickness and structural volumes), microstructural measures (T1w/T2w ratio as a marker myelin content, inflammation and oedema), and cerebral blood flow. T1D patients had higher T1w/T2w ratios in the right parahippocampal gyrus, the executive part of both putamina, both thalami and in the cerebellum. These alterations were reflected in lower putaminal and thalamic volume bilaterally. No cerebral blood flow differences between groups were found in any of these structures, suggesting non-vascular aetiologies of these changes. Our findings implicate a marked non-vascular disruption in T1D of several essential neural nodes engaged in both cognitive and motor processing.

Background No information is currently available regarding the natural history of asymptomatic intracranial aneurysms in beta-thalassemia, raising several concerns about their proper management. Methods We performed a prospective longitudinal three-year-long MR-angiography study on nine beta-thalassemia patients (mean-age 40.3 ± 7.5, six females, 8 transfusion dependent) harboring ten asymptomatic intracranial aneurysms. In addition, we analyzed the clinical files of all adult beta-thalassemia patients (160 patients including those followed with MR-angiography, 121 transfusion dependent) referring to our Centers between 2014 and 2019 searching for history of subarachnoid hemorrhage or history of symptomatic intracranial aneurysms. Results At the end of the three-year-long follow-up, no patient showed any change in the size and shape of the aneurysms, none presented new intracranial aneurysms or artery stenoses, none showed new brain vascular-like parenchymal lesions or enlargement of the preexisting ones. Besides, in our database of all adult beta-thalassemia patients, no one had history of subarachnoid hemorrhage or history of symptomatic intracranial aneurysms. Conclusions Incidental asymptomatic intracranial aneurysms do not seem to be associated, in beta-thalassemia, with an increased risk of complications (enlargement or rupture) at least in the short term period, helping to optimize human and economic resources and patient compliance during their complex long-lasting management.

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.

Objectives A strikingly increased headache prevalence was recently noted in Sri Lankan beta-thalassemia patients, raising several concerns regarding long-term neurological involvement in this condition. Methods We interviewed on headache occurrence and characteristics 102 Italian beta-thalassemia patients and 129 healthy controls. 3T-MRI, MR-angiography, MR-venography, cognitive and psychiatric findings were considered. Results Headache was diagnosed in 39/102 (38.2%) beta-thalassemia patients without significant phenotype-related differences and in 51/129 (39.5%) controls. Patients and controls did not differ significantly regarding episode number (5.9 ± 6.2 vs 5.4 ± 4.4 days/month), subjective severity-score (6.8 ± 1.4 vs 7.1 ± 1.3), age-at-onset (24.3 ± 13.0 vs 19.5 ± 9.6 years) and headache-subtype rate. No main demographic, clinical or laboratory data was associated with headache but female gender. Headache was not associated with white matter lesions (number or maximal diameter), intracranial aneurysms, intracranial artery stenoses or venous sinus thrombosis. Cognitive and psychiatric evaluations were worse in beta-thalassemia, however, headache did not correlate with full-scale Intelligence Quotient (75.4 ± 18.0 vs 76.7 ± 15.3, with and without headache, respectively) or Brief Psychiatric Rating Scale scores (29.1 ± 2.7 vs 28.5 ± 3.4). Conclusions Among Italian beta-thalassemia patients, headache does not seem to be more common or severe than in the general population. In addition, patients with headache do not seem to present increased conventional MRI, MR-angiography and cognitive/psychiatric changes.

Eating disorders (EDs) have a possible neurodevelopmental pathogenesis. Our study aim was to assess regional cortical thickness (CT), local gyrification index (lGI) and fractal dimensionality (FD), as specific markers of cortical neurodevelopment in ED females. Twenty-two women with acute anorexia nervosa (acuAN), 10 with recovered anorexia nervosa (recAN), 24 with bulimia nervosa (BN) and 35 female healthy controls (HC) underwent a 3T MRI scan. All data were processed by FreeSurfer. Compared to recAN group women with acuAN showed a lower CT in multiple areas, while compared to HC they showed lower CT in temporal regions. BN group showed higher CT values in temporal and paracentral areas compared to HC. In multiple cortical areas, AcuAN group showed greater values of lGI compared to recAN group and lower values of lGI compared to HC. The BN group showed lower lGI in left medial orbitofrontal cortex compared to HC. No significant differences were found in FD among the groups. Present results provide evidence of CT and lGI alterations in patients with AN and, for the first time, in those with BN. Although these alterations could be state-dependent phenomena, they may underlie psychopathological aspects of EDs.

In this study, we sought to determine by 3T MRI the cerebral blood flow (CBF) responses to hypoglycemia (HG) in nondiabetic controls exposed to either two euglycemic or two hypoglycemic clamps on the day before the MRI (EU- or HYPO-preconditioning, respectively). Under the belief that HYPO-preconditioning induces hypoglycemia-associated autonomic failure (HAAF) with blunting of the counter-regulatory hormone and symptom responses to HG (Arbelaez et al, 2008), we hypothesized that CBF responses after HYPO-preconditioning would resemble those reported in T1D subjects with impaired awareness of hypoglycemia (IAH) (Weigers et al, 2017). CBF was measured by arterial spin labeling during a 2-step hyperinsulinemic clamp [step 1 = 95 mg/dL normoglycemia (NG), step 2 = 50 mg/dL (HG)]. Symptom and counter-regulatory hormone were also measured. Full CBF datasets were obtained from 10 participants who underwent EU-preconditioning (7F/3M, age 37 ± 14 years, BMI 27.2 ± 3.7 kg/m2) and 9 who underwent HYPO-preconditioning (5F/4M, age 40 ± 14 years, BMI 26.2 ± 2.6 kg/m2). In contrast with our assumption, the HYPO-preconditioning did not induce blunting of symptom or counter-regulatory hormone responses to HG other than for glucagon (33 ± 19 and 14 ± 21 pg/mL for EU- and HYPO-preconditioning, respectively, p=0.04 uncorr). CBF responses did not differ between the two pre-conditionings, and resembled those reported in the literature in naïve nondiabetic controls (Weigers et al, 2017). In particular, the cortical grey matter CBF did not change during HG vs. NG for either the EU- or HYPO-preconditioning settings (1 ± 10% and 2 ± 10%, respectively), while thalamic CBF increased in both settings (21 ± 20%, p=0.012 corr, and 27 ± 30%, p=0.06 corr, respectively). We conclude that the preconditioning protocols should be used with caution in nondiabetic controls for investigating IAH, as the mechanisms of HAAF in T1D patients may be specific to their disease condition. Disclosure A. Canna: None. H. Grohn: None. D. Mascali: None. P. Filip: None. A. Moheet: None. A. Kumar: None. X. Li: None. E.A. Olawsky: None. L.E. Eberly: None. F. Esposito: None. E.R. Seaquist: Advisory Panel; Self; Eli Lilly and Company, Zucara Therapeutics Inc. Consultant; Self; 360 Consulting, MannKind Corporation. Research Support; Self; Eli Lilly and Company, JDRF, National Institutes of Health. Other Relationship; Self; American Diabetes Association, Sanofi, WebMD. S. Mangia: None. Funding National Institutes of Health

Beta-thalassemia-related anemia and chronic hypercoagulative state are supposed to cause cumulative cerebrovascular damage with consequent parenchymal/vascular changes and functional impairment. However, recent conventional MRI/MR-angiography investigations failed to show an increased cerebrovascular involvement in beta-thalassemia patients managed according to current treatment guidelines, in spite of significantly decreased full-scale IQ scores. We therefore investigated those patients and controls by means of advanced quantitative MRI analyses (based on magnetization transfer and diffusion tensor imaging) searching for signs of possible cerebrovascular injuries undetected by conventional MRI/MR-angiography. The 3 T-MRI study protocol included diffusion tensor imaging and 3D-multi-echo FLASH sequences for magnetization transfer analysis. Whole-brain voxel-based analyses showed that magnetization transfer, fractional anisotropy, and mean, radial and axial diffusivity do not differ between healthy controls and beta-thalassemia patients (considered as a whole group or as distinct transfusion dependent and non-transfusion dependent subgroups). No correlation emerged between all the considered MRI metrics and cognitive findings (full-scale IQ) or the main clinical and laboratory data. According to our findings, adult neurologically-asymptomatic beta-thalassemia patients (regardless of clinical severity) do not seem to present an increased disease-related cerebrovascular vulnerability compared to healthy controls downsizing the need of regular brain MRI monitoring, at least when the current treatment guidelines are followed.

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.

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.

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.

Multi-factorial causes jeopardize brain integrity in β-thalassaemia. Intracranial parenchymal and vascular changes have been reported among young β-thalassaemia patients but conventional magnetic resonance imaging (MRI) findings are contradictory making early MRI and magnetic resonance angiography (MRA)/venography monitoring a matter of debate. This study prospectively investigated 75 neurologically asymptomatic β-thalassaemia patients (mean-age 35·2±10·7years; 52/75 transfusion-dependent; 41/75 splenectomised) using a 3T magnetic resonance scanner; clinical, laboratory and treatment data were also collected. White matter ischaemic-like abnormalities, intracranial artery stenoses, aneurysms and sinus venous thrombosis were compared between patients and 56 healthy controls (mean-age 33·9±10·8years). No patient or control showed silent territorial or lacunar strokes, intracranial artery stenoses or signs of sinus thrombosis. White matter lesions were found both in patients (35/75, 46·7%) and controls (28/56, 50·0%), without differences in terms of number (4·0±10·6 vs. 4·6±9·1, P=0·63), size and Fazekas' Score. Intracranial aneurysms did not differ between patients and controls for incidence rate (7/75, 9·3% vs. 5/56, 8·9%), size and site. Vascular and parenchymal abnormality rate did not differ according to treatments or clinical phenotype. According to this study, asymptomatic β-thalassaemia patients treated according to current guidelines do not seem to carry an increased risk of brain and intracranial vascular changes, thus weakening recommendations for regular brain MRI monitoring.

Cognitive involvement in beta-thalassaemia is strikingly controversial and poorly studied in adulthood. This multicentre prospective study investigated 74 adult neurologically-asymptomatic beta-thalassaemia patients (mean-age 34 center dot 5 +/- 10 center dot 3 years; 53 transfusion-dependent [TDT], 21 non-transfusion dependent [NTDT]) and 45 healthy volunteers (mean-age 33 center dot 9 +/- 10 center dot 7 years). Participants underwent testing with Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), Brief Psychiatric Rating Scale (BPRS) and multiparametric brain 3T-magnetic resonance imaging (MRI) for parenchymal, vascular and iron content evaluation. Patients had lower Full-Scale Intelligence Quotient (FSIQ) than controls (75 center dot 5 +/- 17 center dot 9 vs. 97 center dot 4 +/- 18 center dot 1, P < 0 center dot 0001) even after correction for education level. Compared to TDT, NTDT showed a trend of higher FSIQ (P = 0 center dot 08) but a similar cognitive profile at WAIS-subtests. FSIQ correlated with total and indirect bilirubin (P P = 0 center dot 002, respectively); no correlation was found with splenectomy, intracranial MRI/magnetic resonance-angiography findings, brain tissue iron content or other disease-related clinical/laboratory/treatment data. FSIQ did not correlate with BPRS scores, although the latter were higher among patients (28 center dot 74 +/- 3 center dot 1 vs. 27 center dot 29 +/- 4 center dot 8, P = 0 center dot 01) mainly because of increased depression and anxiety levels. Occupation rate was higher among controls (84 center dot 4% vs. 64 center dot 9%, P = 0 center dot 004) and correlated with higher FSIQ (P = 0 center dot 001) and education level (P = 0 center dot 001). In conclusion, Italian adult beta-thalassaemia patients seem to present a characteristic cognitive profile impairment and an increased rate of psychological disorders with possible profound long-term socio-economic consequences.

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.

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.

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.

We aimed to evaluate the presence of venous stenosis and blood flow abnormalities in the neck vessels of patients with multiple sclerosis (MS), in respect to a group of age- and sex-matched healthy controls (HC), and their possible relations with clinical variables using a semi-automated quantitative MRI method.45 patients with relapsing remitting MS and 40 HC were enrolled in this study. Flow rates and cross-sectional areas of arterial and venous neck vessels were assessed by phase-contrast MRI at two different neck levels (C2-C3 and C6-C7), and differences between groups were evaluated with an unpaired t-test. Correlation between blood flow variables and clinical parameters was analyzed with Spearman's test.A significant internal jugular vein (IJV) stenosis was found in 23/45 (51.1%) patients with MS and 18/40 (45.0%) HC. No differences were observed between patients with MS and HC for any of the flow measures obtained. No correlations were found between MRI measures and any of the tested clinical variables.No differences in the IJV area emerged at quantitative MRI evaluation, suggesting that stenosis of the extracranial veins is unrelated to MS. Furthermore, no flow differences in the neck vessels were found between patients with MS and HC in any of the tested flow measures, with no correlation with clinical variables. Our results confirm that the hypothesis of the presence of extracranial venous abnormalities in MS, both in terms of stenosis or flow measures, is not suitable.Neck venous drainage abnormalities have been claimed to be associated with MS. Conversely, our quantitative MRI analysis seems to exclude that extracranial venous alterations are related to the disease.

To evaluate changes in T1 and T2* relaxometry of dentate nuclei (DN) with respect to the number of previous administrations of Gadolinium-based contrast agents (GBCA). In 74 relapsing-remitting multiple sclerosis (RR-MS) patients with variable disease duration (9.8±6.8 years) and severity (Expanded Disability Status Scale scores:3.1±0.9), the DN R1 (1/T1) and R2* (1/T2*) relaxation rates were measured using two unenhanced 3D Dual-Echo spoiled Gradient-Echo sequences with different flip angles. Correlations of the number of previous GBCA administrations with DN R1 and R2* relaxation rates were tested, including gender and age effect, in a multivariate regression analysis. The DN R1 (normalized by brainstem) significantly correlated with the number of GBCA administrations (p

IntroductionTaste perception is a complex phenomenon modulated by different factors, such as taste receptors and memory brain circuits. The palatability of the food, that activates the central reward pathways, also plays an important role in taste perception. It means that taste is able to influence the choice of food and then eating behaviour.ObjectivesIt is well known that people with anorexia nervosa (AN) have a lower sensitivity to reward stimuli and recent studies suggested that altered function of taste neural circuitry may contribute to restricted eating in AN.AimsThe aim of this study was to evaluate, in patients suffering from AN, the activation of brain areas involved in taste perception and in central reward mechanisms to both pleasant and aversive taste stimuli and to correlate gustatory neurocircuitry activity with eating behaviours, temperament measures and/or sensitivity to reward and to punishment.MethodsFifteen underweight female AN patients and sixteen normal-weight healthy women underwent a functional MRI to measure brain areas activation to repeated stimuli of a pleasant taste (sucrose solution), alternated with an aversive taste (bitter solution), and water taste.ResultsCompared to healthy controls, patients with AN showed a significantly reduced activation of left insula and left dorsolateral prefrontal cortex to sweet stimulus and reduced activation of right parietal cortex to bitter stimulus.ConclusionsThese results, if confirmed in future studies, may improve our knowledge about the pathophysiological mechanisms of AN.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IntroductionThe functional interplay between brain hemispheres is fundamental for behavioral, cognitive and emotional control. Several pathophysiological aspects of eating disorders (EDs) have been investigated by the use of functional Magnetic Resonance Imaging (fMRI).ObjectivesThe objective of the study was to investigate functional brain asymmetry of resting-state fMRI correlations in symptomatic patients with anorexia nervosa (AN) and bulimia nervosa (BN).AimsWe aimed at revealing whether brain regions implicated in reward, cognitive control, starvation and emotion regulation show altered inter-hemispheric functional connectivity in patients with AN and BN.MethodsUsing resting-state fMRI, voxel-mirrored homotopic connectivity (VMHC) and regional inter-hemispheric spectral coherence (IHSC) analyses in two canonical slow frequency bands (“Slow-5”, “Slow-4”) were studied in 15AN and 13BN 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).ResultsCompared 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 found.ConclusionsThese anomalies 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.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Introduction Taste perception is a complex phenomenon modulated by different factors, such as taste receptors and memory brain circuitry. The palatability of the food, that activates central reward pathways, also plays an important role in taste perception. It means that taste is able to influence the choice of food and then the eating behavior. Objectives It's well known that people with anorexia nervosa (AN) have lower sensitivity to reward stimuli and recent studies have shown that altered function of taste neural circuitry may contribute to restricted eating in AN. Aims The aim of this study is to evaluate, in patients suffering from AN, the activation of the brain areas involved in taste perception and in central reward mechanisms to both pleasant and aversive taste stimuli and to correlate gustatory neural circuitry activity with eating behaviors, temperament measures and/or sensitivity to reward and to punishment. Methods 12 underweight AN patients and 12 normal-weight healthy subjects underwent a functional MRI to measure brain areas activation to repeated stimuli of a pleasant taste, a sucrose solution, alternated with an aversive taste, a bitter solution, and a water taste. Results Preliminary results showed, in patients with AN, a dysfunctional activation of brain areas involved in both taste perception and reward mechanisms following both the pleasant and aversive stimulus. Conclusions These results, if confirmed in future analyses, may improve our knowledge about the pathophysiological mechanism of AN.