Hearing loss in beta-thalassaemia: An Italian multicentre case-control study.

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.

Association between childhood maltreatment and cortical folding in women with eating disorders.

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.

Magnetic Resonance T1w/T2w Ratio in the Putamen and Cerebellum as a Marker of Cognitive Impairment in MSA: a Longitudinal Study.

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 (T0) and 1-year follow-up (T1). Patients were then divided according to cognitive status into MSA with normal cognition (MSA-NC) and MSA with mild cognitive impairment (MCI). At T1, we divided the sample according to worsening/non worsening of cognitive status compared to baseline evaluation. Logistic regression analysis showed that age (ß = - 9.45, p = .02) and T1w/T2w value in the left putamen (ß = 230.64, p = .01) were significant predictors of global cognitive status at T0, explaining 65% of the variance. Logistic regression analysis showed that ∆-values of WM density in the cerebellum/brainstem (ß = 2188.70, p = .02) significantly predicted cognitive worsening at T1, 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.

Frequency and imaging correlates of neuropsychiatric symptoms in Progressive Supranuclear Palsy.

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.

Childhood maltreatment is associated with cortical thinning in people with eating disorders.

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.

Sex differences in the taste-evoked functional connectivity network.

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.

Uncovering clinical and radiological asymmetry in progressive supranuclear palsy-Richardson's syndrome.

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.

Semantics-weighted lexical surprisal modeling of naturalistic functional MRI time-series during spoken narrative listening.

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.

Intensity-related distribution of sweet and bitter taste fMRI responses in the insular cortex.

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.

Cortical pattern of reduced perfusion in hearing loss revealed by ASL-MRI.

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.

Automated search of control points in surface-based morphometry.

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.

Spectral signatures of mirror movements in the sensori-motor connectivity in kallmann syndrome.

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.

Interhemispheric functional connectivity in anorexia and bulimia nervosa.

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.

Intraparenchymal ventricular diverticula in chronic obstructive hydrocephalus: prevalence, imaging features and evolution.

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.

Effect of carbonation on brain processing of sweet stimuli in humans.

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.

Intracranial internal carotid artery changes in acromegaly: a quantitative magnetic resonance angiography study.

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.

Brain perfusion changes in beta-thalassemia.

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.

Brainstem activation in cluster headache: an adaptive behavioural response?

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.

Catechol-O-methyltransferase genotype modifies executive functioning and prefrontal functional connectivity in women with anorexia nervosa.

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.