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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.

Mental imagery, the generation and manipulation of mental representations in the absence of sensory stimulation, is a core element of numerous cognitive processes. We investigate the cortical mechanisms underlying imagery and spatial analysis in the visual domain using event-related functional magnetic resonance imaging during the mental clock task. The time-resolved analysis of cortical activation from auditory perception to motor response reveals a sequential activation of the left and right posterior parietal cortex, suggesting that these regions perform distinct functions in this imagery task. This is confirmed by a trial-by-trial analysis of correlations between reaction time and onset, width, and amplitude of the hemodynamic response. These findings pose neurophysiological constraints on cognitive models of mental imagery.

Introduction. Magnetic Resonance angiography (MRA) is an accurate and non-invasive diagnostic method to evaluate vascular disease. On the basis of its technological advancements, this technique has gained an important role in the diagnostic protocol of cerebral and cervical vascular diseases. Nonetheless, MRA efficacy changes in different anatomic districts as a consequence of the specific anatomy and flow features. Cardiac and respiratory artifact and different coil sensitivity also affect MRA results. For these reasons, intrathoracic epiaortic vessels are a difficult applications for MRA. Material and methods. We examined 20 patients affected with epiaortic atherosclerosis with MRA, carried out with an 0.5 T MR unit (Vectra, GE). Examinations consisted of Phase Contrast (PC) 3D sequences (TR/TE/FA/Venc=30/13/45/30-50), with 3 axes of flow encode, matrix 128x256, 2 mm partition thickness, and axial and/or coronal acquisition volume. The MRA was repeated after Gd-DTPA intravenous perfusion and a qualitative and quantitative evaluation of pre- and post-contrast results was performed. Specific parameters of evaluation were: angiographic contrast, contrast to noise ratio, saturation effect of longitudinal magnetization, contrast between arteries and veins. All patients were examined with Doppler US and angiography. MRA data were compared to angiography in order to establish MRA sensitivity and specificity. Results and conclusions. PC sequences showed high accuracy in the examination of the proximal tract of epiaortic vessels; Gd-DTPA administration substantially improved MRA results. The perspectives of technological improvement will probably candidate PC MRA to be a valid alternative to US-Doppler and, perhaps, to angiographic study.

Cerebral toxoplasmosis is a rare late complication in allogeneic bone marrow transplanted patients. Neuroradiological findings may suggest the correct diagnosis. We report a patient in whom cerebral magnetic resonance imaging (MRI) showed a lesion characteristic of toxoplasmosis. Anti- toxoplasma treatment led to clinical and radiological improvement. MRI seems to be a valid tool for detection and follow-up of cerebral toxoplasmosis.

The "default-mode" network is an ensemble of cortical regions that are typically deactivated during demanding cognitive tasks in functional magnetic resonance imaging (fMRI) studies. Using functional connectivity analysis, this network can be studied as a "stand-alone" brain system whose functional role is supposed to consist in the dynamic control of intrinsic processing activities like attention focusing and task-unrelated thought generation and suppression. Independent component analysis (ICA) is the method of choice for generating a statistical image of the "default-mode" network (DMN) using a task- and seed-independent distributed model of fMRI functional connectivity without prior specification of node region extent and timing of neural activation. We used a standard graded working-memory task (n-back) to induce fMRI changes in the default-mode regions and ICA to evaluate to DMN functional connectivity in nineteen healthy volunteers. Based on the known spatial variability of the ICA-DMN maps with the task difficulty levels, we hypothesized the ICA-DMN may also correlate with the subject performances. We confirmed that the relative extent of the anterior and posterior midline spots within the DMN were oppositely (resp. positively in the anterior and negatively in the posterior cingulate cortex) correlated with the level of task difficulty and found out that the spatial distribution of DMN also correlates with the individual task performances. We conclude that the working-memory function is related to a spatial re-configuration of the DMN functional connectivity, and that the relative involvement of the cingulate regions within the DMN might function as a novel predictor of the working-memory efficiency.

We report 2 cases of 'de novo' aneurysm formation in a vessel which appeared to be normal at a previous angiography. The first patient developed an anterior communicating artery aneurysm nine years after occlusion of the right internal carotid artery by Gianturco coils for the treatment of a giant intracavernous carotid aneurysm. In the second case a 'de novo' aneurysm of the internal angle A1-A2 segment of the left anterior cerebral artery developed 6 years after successful clipping of another aneurysm of the same location. De novo formation of an aneurysm in a vessel which was found to be normal in a previous angiographic study, may occur as result of hemodynamic changes, such as after internal carotid occlusion or in presence of an arteriovenous malformation or variations of the circle of Willis. However, definite hemodynamic changes may also be absent. We conclude that patients operated on for aneurysm clipping must be periodically explored by magnetic resonance angiography to evaluate the possibility of de novo appearance of another aneurysm.

Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) represent brain activity in terms of a reliable anatomical localization and a detailed temporal evolution of neural signals. Simultaneous EEG-fMRI recordings offer the possibility to greatly enrich the significance and the interpretation of the single modality results because the same neural processes are observed from the same brain at the same time. Nonetheless, the different physical nature of the measured signals by the two techniques renders the coupling not always straightforward, especially in cognitive experiments where spatially localized and distributed effects coexist and evolve temporally at different temporal scales. The purpose of this article is to illustrate the combination of simultaneously recorded EEG and fMRI signals exploiting the principles of EEG distributed source modeling. We define a common source space for fMRI and EEG signal projection and gather a conceptually unique framework for the spatial and temporal comparative analysis. We illustrate this framework in a graded-load working-memory simultaneous EEG-fMRI experiment based on the n-back task where sustained load-dependent changes in the blood-oxygenation-level-dependent (BOLD) signals during continuous item memorization co-occur with parametric changes in the EEG theta power induced at each single item. In line with previous studies, we demonstrate on two single-subject cases how the presented approach is capable of colocalizing in midline frontal regions two phenomena simultaneously observed at different temporal scales, such as the sustained negative changes in BOLD activity and the parametric EEG theta synchronization. We discuss the presented approach in relation to modeling and interpretation issues typically arising in simultaneous EEG-fMRI studies.

We reviewed the brain MRI of 66 patients with the adult form of myotonic dystrophy type 1 (DM1) to evaluate the extent and significance of white matter involvement and to look for a pattern of MRI abnormalities suggestive of DM1. White matter lesions (WMLs) and large Virchow Robin spaces (VRSs) were rated by semiquantitative methods and the signal intensity of white matter superior and posterior to the trigones (WMPST) by reference to standard images. Disease duration was correlated positively with WML and negatively with VRS scores. Patients were divided into four groups according to increasing severity of WMPST involvement: group A with mild WMPST hyperintensity, group B with large VRSs and mild or moderate WMPST hyperintensity, group C with moderate WMPST hyperintensity or mild WMPST hyperintensity with small WMLs, group D with severe WMPST hyperintensity or moderate WMPST hyperintensity with small WMLs. Disease duration, muscular impairment, lobar WMLs and brain atrophy significantly increased from groups A and B (not significantly different) to C and from C to D, while convexity VRSs significantly decreased from group B to C and from C to D. Lobar white matter involvement in DM1 seems progressive during the disease and may be characterized initially by large VRSs or mild WMPST hyperintensity, then by small WMLs or moderate WMPST hyperintensity, and finally by more extensive and confluent WMLs or diffuse white matter hyperintensity and by brain atrophy.

To compare and characterize the magnetic resonance imaging (MRI) of brain in the congenital and adult form of myotonic dystrophy type 1, we evaluated five patients with congenital dystrophy type 1, 10 age- and 10 disease duration-matched patients with adult-form dystrophy type 1 and 20 age-matched healthy volunteers. The ventricular enlargement was evaluated by the ventricular:brain ratio, the signal intensity of white matter posterosuperior to trigones by reference to standard images and the white matter lesions by a semiquantitative method. In the congenital dystrophy type 1, MRI was characterized by ventriculomegaly and moderate/severe hyperintensity of white matter posterosuperior to trigones, which showed no correlation with the age. MRI in the adult-form dystrophy type 1 was strictly related to disease duration and varied between normal findings, except for temporo-polar white matter lesions, in age-matched patients and ventriculomegaly with white matter hyperintensities in disease duration-matched patients. These results suggest that the origin of MRI abnormalities in myotonic dystrophy type 1 is mainly developmental for the congenital form and mainly degenerative for the adult form.

To study the frequency, extent and significance of dilated Virchow-Robin spaces (VRSs) in dystrophia myotonica (DM), we evaluated the cranial magnetic resonance imaging (MRI) of 41 patients with the adult form of DM and 41 healthy controls. Dilated VRSs and white matter lesions (WMLs) were rated according to semiquantitative methods. Convexity VRSs were more frequent (68 vs. 34%; p < 0.01) and severer (median scores: 4 vs. 0; p < 0.01) in DM patients than in controls, while lenticulostriate VRSs did not show significant differences in frequency (83 vs. 70%; p > 0.05) and severity (median scores: 4 vs. 3; p > 0.05). WMLs were more frequent (66 vs. 22%; p < 0.01) and severer (median scores: 5 vs. 0; p < 0.01) in patients. Disease duration was negatively correlated with convexity VRSs and positively with lobar (centrum semiovale) WML scores. Dilated convexity VRSs might be one of the initial findings in cranial MRI of DM, preceding the appearance of lobar WMLs.

To investigate whether previous treatment with bromocriptine (BRC) or quinagolide (CV) impairs a subsequent response to long-term cabergoline (CAB) treatment, we prospectively studied 110 patients with macroprolactinoma. Four groups of patients were considered: 1) naive: 26 untreated patients with a mean serum PRL levels of 1013.4 +/- 277.7 microg/L (+/- SEM; range, 185.5-5611 microg/L); 2) intolerant: 19 patients previously shown to be intolerant of BRC treatment with a mean serum PRL level of 539.4 +/- 172.2 microg/L (range, 174-3564 microg/L); 3) resistant: 37 patients shown to be resistant/hyporesponsive to BRC, CV, or both, with a mean serum PRL level of 602.6 +/- 136.8 microg/L (range, 148-3511 microg/L); and 4) responsive: 28 patients previously treated with BRC or CV for 1-5 yr, achieving normoprolactinemia and restoration of gonadal function, but no longer treated with BRC or CV because of poor compliance or because the drug was not available. After a 15- to 30-day washout period, the serum PRL level was 397 +/- 43.1 microg/L (140-978 microg/L). CAB treatment was given at doses ranging 0.25-3.5 mg weekly for 1 yr to 110 patients, for 2 yr to 104 patients, and for 3 yr to 81 patients. Magnetic resonance imaging was performed before and after 12, 24, and 36 months of CAB treatment to evaluate significant tumor shrinkage (>80% reduction of pretreatment tumor volume). Among the 26 naive patients, normoprolactinemia was achieved in 21 (80.8%) after 1-6 months at 0.25-2 mg/week and in 5 patients after 24 months at 0.5-3 mg/week. Tumor volume was reduced from 1431.5 +/- 310.3 to 47.2 +/- 21.5 mm3 (P < 0.0001); average tumor shrinkage was 92.1 +/- 2.9%; significant tumor shrinkage was observed in 92.3% of patients, and tumor mass completely disappeared in 16 patients (61.5%). Among the 19 intolerant patients, normoprolactinemia was achieved in 18 (94.7%) after 1-6 months of CAB treatment at 0.25-1 mg/week. One patient remained mildly hyperprolactinemic. Tumor volume was reduced from 1925 +/- 423.1 to 842.0 +/- 330.7 mm3 (P < 0.001); average tumor shrinkage was 66.2 +/- 6.4%; significant tumor shrinkage was obtained in 42.1% of patients, and tumor mass completely disappeared in 4 patients (21%). Among the 37 resistant patients, normoprolactinemia was achieved in 19 (51.3%) after 6-12 months at 1-2 mg/week and in the remaining 18 patients after 18-24 months at 3-3.5 mg/week. Tumor volume was reduced from 1208.0 +/- 173.7 to 471.2 +/- 87.3 mm3 (P < 0.005); average tumor shrinkage was 58.4 +/- 4.9%; significant tumor shrinkage was obtained in 10 of 33 patients (30.3%), and in no patient did tumor mass completely disappear. Among the 28 responsive patients, normoprolactinemia was achieved in 23 (82.1%) after 1-6 months at 1-2 mg/week and in 5 patients after 12 months at 3 mg/week. Tumor volume was reduced from 1351.3 +/- 181.5 to 757.1 +/- 193.6 mm3 (P < 0.01); average tumor shrinkage was 59.2 +/- 6.2%; significant tumor shrinkage was obtained in 10 of 26 patients (38.4%), and tumor mass completely disappeared in 4 patients (15.4%). Nadir PRL levels and percent tumor shrinkage during CAB treatment in naive patients were significantly lower (P < 0.001) and higher (P < 0.001), respectively, than those in the remaining three groups, and the average weekly dose of CAB in resistant patients was significantly higher (P < 0.001) than that in the remaining three groups. A significant association was found between tumor shrinkage and previous treatments (chi2 = 27.1; P < 0.0001). At the multistep correlation analysis, nadir PRL levels were the strongest predictors of tumor shrinkage (r2 = 0.556; P < 0.0001), followed by CAB dose (r2 = 0.577; P < 0.0001). The tolerability was excellent in 105 patients (95.4%). In conclusion, the prevalence of macroprolactinoma shrinkage after CAB treatment at standard doses for 1-3 yr was higher in naive patients (92.3%) than in intolerant (42.1%), resistant (30.3%), and responsive patients (38.4%). Thus, C

The authors have examined the relationship between magnetic resonance imaging (MRI) and histopathological features in 35 surgically verified intracranial meningiomas. Tumor signals on T1-weighted images were rather similar regardless of the histologic subtype of the tumors. On T2-weighted images, hypointense meningiomas were mainly fibroblastic and hyperintense tumors were mainly syncytial and angioblastic, and partly transitional. Isointense tumors were mainly transitional and partly fibroblastic and syncytial. The authors conclude that the signal intensity of the MRI may be useful in the preoperative characterization of intracranial meningiomas. T1-weighted images may predict the presence of cysts and intratumoral blood vessels; whereas T2-weighted images can give information about histological subtype, vascularity and consistency. Meningiomas hyperintense to the cortex on T2 are usually soft, more vascular and more frequently of syncytial or angioblastic subtype; tumors hypointense or hypo-isointense on T2 tend to have a more hard consistency and are more often of fibroblastic or transitional subtype.

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.

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.

Highlights • Iron overload is a life-threatening condition in beta-thalassemia. • Data on brain involvement in systemic iron overload are conflicting. • MRI quantification of brain tissue iron content is feasible in a voxel-based approach. • No iron tissue excess is evident in beta-thalassemia but in the choroid plexuses., 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

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.

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.

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.

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

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.

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. Afterthese sessions, each subject underwent 2 fMRI scan acquisitions while listening to a Syntonic (SP) andan A-Syntonic (AP) Production from the AMT sessions. A 3T 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 ofthe 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.

INTRODUCTION:\ud \ud 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.\ud METHODS:\ud \ud 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.\ud RESULTS:\ud \ud 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.\ud CONCLUSIONS:\ud \ud 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.

Spatial independent component analysis (sICA) of functional magnetic resonance imaging (fMRI) time series can generate meaningful activation maps and associated descriptive signals, which are useful to evaluate datasets of the entire brain or selected portions of it. Besides computational implications, variations in the input dataset combined with the multivariate nature of ICA may lead to different spatial or temporal readouts of brain activation phenomena. By reducing and increasing a volume of interest (VOI), we applied sICA to different datasets from real activation experiments with multislice acquisition and single or multiple sensory‐motor task‐induced blood oxygenation level‐dependent (BOLD) signal sources with different spatial and temporal structure. Using receiver operating characteristics (ROC) methodology for accuracy evaluation and multiple regression analysis as benchmark, we compared sICA decompositions of reduced and increased VOI fMRI time‐series containing auditory, motor and hemifield visual activation occurring separately or simultaneously in time. Both approaches yielded valid results; however, the results of the increased VOI approach were spatially more accurate compared to the results of the decreased VOI approach. This is consistent with the capability of sICA to take advantage of extended samples of statistical observations and suggests that sICA is more powerful with extended rather than reduced VOI datasets to delineate brain activity. Hum Brain Mapp, 2005. © 2006 Wiley‐Liss, Inc.

In the present work, an arteriovenous malformation was taken as a pathological model for studying task-related flow decreases during a motor task. Combined Blood Oxygen Level Dependent (BOLD)-perfusion experiments were applied in order to evaluate the relative sensitivity of these techniques to task-related reductions in cerebral blood flow (CBF). Results shows that, by matching the sensitivity of the methods (which exhibit a different contrast-to-noise ratio) in the primary motor cortex, the spatial extent of the regions of decreased perfusion signal is larger than those of the BOLD signal reduction. The above finding suggests that perfusion imaging, that already represents a gold standard method in the detection of vascular phenomena, may estimate task-related flow decreases in a functional time-series better than BOLD.

Diagnosis of autoimmune central diabetes insipidus (CDI) is based on the presence of autoantibodies to AVP-secreting cells (AVPcAb) or the coexistence of other autoimmune polyendocrine syndromes; moreover, it can be also suggested by the presence of lymphocytic infundibulo-neurohypophysitis, evidenced by biopsy of pituitary stalk and/or by pituitary stalk thickening on magnetic resonance imaging (MRI). However, so far, in clinical CDI patients with lymphocytic infundibulo-neurohypophysitis, AVPcAb have not been investigated and in those with or without autoimmune polyendocrine syndromes (APS), longitudinal studies on the behavior of AVPcAb alone, or of both AVPcAb and hypothalamic pituitary imaging on MRI are lacking. Aim of this work was to investigate in these patients the occurrence of AVPcAb (by indirect immunofluorescence) and of pituitary stalk thickening (by MRI) and their longitudinal changes during a follow-up period. We studied 22 patients, aged 29-53, with APS and complete CDI, grouped as follows: 10 with recent onset (< or =1.5 yr) of CDI (group 1a) and 12 with CDI of long-term duration (> or = 7 yr) (group 1b); moreover, a group of 13 patients with apparent idiopathic CDI of recent onset (

We aimed at verifying whether the hemispheric specialisation for categorical/coordinate spatial judgements also applies to the spatial imagery domain by the use of whole-brain fMRI. In a block-design experiment we used the “coordinate” mental clock test, contrasting it with a “categorical” task applied to the same clock stimuli; as a control task we used a syllable counting task requiring a verbal-phonological judgement on the same material of the two imagery tasks. Our results showed that categorical and coordinate spatial judgements on imagined stimuli rely on the activation of a set of cortical areas, centred upon the superior parietal lobule (SPL) bilaterally. These regions, together with other parietal and prefrontal areas, showed a pattern of relative lateralization, with the left hemisphere being mainly activated during the categorical task and the right in the coordinate task. These data confirm the strong involvement of the SPL in spatial processing. Moreover, our findings suggest that different interconnected neural networks are activated to comply with specific test requirements, giving rise to functional imaging patterns compatible with psychological theories on hemispheric specialization.

Independent component analysis (ICA) has been successfully employed to decompose functional MRI (fMRI) time‐series into sets of activation maps and associated time‐courses. Several ICA algorithms have been proposed in the neural network literature. Applied to fMRI, these algorithms might lead to different spatial or temporal readouts of brain activation. We compared the two ICA algorithms that have been used so far for spatial ICA (sICA) of fMRI time‐series: the Infomax (Bell and Sejnowski [1995]: Neural Comput 7:1004–1034) and the Fixed‐Point (Hyvärinen [1999]: Adv Neural Inf Proc Syst 10:273–279) algorithms. We evaluated the Infomax‐ and Fixed Point‐based sICA decompositions of simulated motor, and real motor and visual activation fMRI time‐series using an ensemble of measures. Log‐likelihood (McKeown et al. [1998]: Hum Brain Mapp 6:160–188) was used as a measure of how significantly the estimated independent sources fit the statistical structure of the data; receiver operating characteristics (ROC) and linear correlation analyses were used to evaluate the algorithms' accuracy of estimating the spatial layout and the temporal dynamics of simulated and real activations; cluster sizing calculations and an estimation of a residual gaussian noise term within the components were used to examine the anatomic structure of ICA components and for the assessment of noise reduction capabilities. Whereas both algorithms produced highly accurate results, the Fixed‐Point outperformed the Infomax in terms of spatial and temporal accuracy as long as inferential statistics were employed as benchmarks. Conversely, the Infomax sICA was superior in terms of global estimation of the ICA model and noise reduction capabilities. Because of its adaptive nature, the Infomax approach appears to be better suited to investigate activation phenomena that are not predictable or adequately modelled by inferential techniques. Hum. Brain Mapping 16:146–157, 2002. © 2002 Wiley‐Liss, Inc.

We investigated the nature and extent of brain involvement in myotonic dystrophy (DM), examining possible T2 relaxation abnormalities in the brain of 20 patients with adult-onset DM and 20 sex- and age-matched normal controls. Brain MRI was performed at 0.5 T, and T2 values were calculated from signal intensity in two echoes. Regions of interest included: frontal, parietal, temporal, occipital and callosal (rostral and splenial) normal-appearing white matter; frontal, occipital, insular and hippocampal cortex; caudate nucleus, putamen, globus pallidus and thalamus. All white-matter and occipital and right frontal cortex regions showed a significantly longer T2 in the patients. Multiple regression analysis, including grey- and white-matter T2 as dependent variables, plus age at onset and at imaging, disease duration, muscular disability, brain atrophy and CTG trinucleotide repeats as independent variables, revealed that only white-matter T2 elongation and disease duration correlated positively. White-matter involvement in DM is more extensive than previously reported by MRI and neuropathological studies and seems to be progressive in the course of disease.

The gradient switching during fast echoplanar functional magnetic resonance imaging (EPI-fMRI) produces loud noises that may interact with the functional activation of the central auditory system induced by experimental acoustic stimuli. This interaction is unpredictable and is likely to confound the interpretation of functional maps of the auditory cortex. In the present study we used an experimental design which does not require the presentation of stimuli during EPI acquisitions and allows for mapping of the auditory cortex without the interference of scanner noise. The design relies on the physiological delays between the onset, or the end, of stimulation and the corresponding hemodynamic response. Owing to these delays and through a time-resolved acquisition protocol it is possible to analyze the decay of the stimulus-specific signal changes after the cessation of the stimulus itself and before the onset of the EPI-acoustic noise related activation (decay-sampling technique). This experimental design, which might permit a more detailed insight in the auditory cortex, has been applied to the study of the cortical responses to pulsed 1000 Hz sine tones. Distinct activation clusters were detected in the Heschl's gyri and the planum temporale, with an increased extension compared to a conventional block-design paradigm. Furthermore, the comparison of the hemodynamic response of the most anterior and the posterior clusters of activation highlighted differential response patterns to the sound stimulation and to the EPI-noise. These differences, attributable to reciprocal saturation effects unevenly distributed over the superior temporal cortex, provided evidence for functionally distinct auditory fields. © 2001 Academic Press.

Empathy and affective appraisals for conspecifics are among the hallmarks of social interaction. Using functional MRI, we hypothesized that vegetarians and vegans, who made their feeding choice for ethical reasons, might show brain responses to conditions of suffering involving humans or animals different from omnivores. We recruited 20 omnivore subjects, 19 vegetarians, and 21 vegans. The groups were matched for sex and age. Brain activation was investigated using fMRI and an event-related design during observation of negative affective pictures of human beings and animals (showing mutilations, murdered people, human/animal threat, tortures, wounds, etc.). Participants saw negative-valence scenes related to humans and animals, alternating with natural landscapes. During human negative valence scenes, compared with omnivores, vegetarians and vegans had an increased recruitment of the anterior cingulate cortex (ACC) and inferior frontal gyrus (IFG). More critically, during animal negative valence scenes, they had decreased amygdala activation and increased activation of the lingual gyri, the left cuneus, the posterior cingulate cortex and several areas mainly located in the frontal lobes, including the ACC, the IFG and the middle frontal gyrus. Nonetheless, also substantial differences between vegetarians and vegans have been found responding to negative scenes. Vegetarians showed a selective recruitment of the right inferior parietal lobule during human negative scenes, and a prevailing activation of the ACC during animal negative scenes. Conversely, during animal negative scenes an increased activation of the inferior prefrontal cortex was observed in vegans. These results suggest that empathy toward non conspecifics has different neural representation among individuals with different feeding habits, perhaps reflecting different motivational factors and beliefs.

Resting-state functional magnetic resonance imaging (RS-fMRI) is a technique used to investigate the spontaneous correlations of blood-oxygen-level-dependent signals across different regions of the brain. Using functional connectivity tools, it is possible to investigate a specific RS-fMRI network, referred to as "default-mode" (DM) network, that involves cortical regions deactivated in fMRI experiments with cognitive tasks. Previous works have reported a significant effect of aging on DM regions activity. Independent component analysis (ICA) is Often Used for generating spatially distributed DM Functional connectivity patterns front RS-fMRI data without the need for a reference region. This aspect and the relatively easy setup of an RS-fMRI experiment even in clinical trials have boosted the combined use of RS-fMRI and ICA-based DM analysis for noninvasive research of brain disorders, In this work, we considered different strategies for combining ICA results from individual-level and population-level analyses and used them to evaluate and predict the effect of aging on the DM component. Using RS-fMRI data from 20 normal subjects and a previously developed group-level ICA methodology, we generated group DM maps and showed that the overall ICA-DM connectivity is negatively correlated with age. A negative correlation of the ICA voxel weights with age existed in all DM regions at it variable degree. As an alternative approach, we generated a distributed DIM spatial template and evaluated the correlation of each individual DM component fit to this template with age. Using a "leave-one-out" procedure, we discuss the importance of removing the bias from the DM template-generation process.

This study aimed to determine whether white matter lesions, previously described as a frequent feature in myotonic dystrophy type 1 (DM1), aggregate within DM1 families or are sporadic findings, and to explore the relationship between these lesions and clinical or genetic features. Brain MRI of 60 DM1 patients belonging to 22 families were evaluated and white matter lesions were rated according to a semiquantitative method. Presence and extent of lobar, temporal or periventricular lesions showed a significant association with the family history of lesions and the disease duration, and no association with the CTG repeat size. Furthermore, parent-offspring and sibling pairs showed a significant positive concordance for lesion severity. White matter lesions demonstrate familial aggregation in DM1 and no relationship with CTG repeat length. These findings suggest that other genetic causes and/or unknown environmental factors influence the occurrence and severity of lesions in patients carrying the DM1 genetic defect.

Processing of vestibular information at the cortical and subcortical level is essential for head and body orientation in space and self-motion perception, but little is known about the neural dynamics of the brain regions of the vestibular system involved in this task. Neuroimaging studies using both galvanic and caloric stimulation have shown that several distinct cortical and subcortical structures can be activated during vestibular information processing. The insular cortex has been often targeted and presented as the central hub of the vestibular cortical system. Since very short pulses of cold water ear irrigation can generate a strong and prolonged vestibular response and a nystagmus, we explored the effects of this type of caloric stimulation for assessing the blood-oxygen-level-dependent (BOLD) dynamics of neural vestibular processing in a whole-brain event-related functional magnetic resonance imaging (fMRI) experiment. We evaluated the spatial layout and the temporal dynamics of the activated cortical and subcortical regions in time-locking with the instant of injection and were able to extract a robust pattern of neural activity involving the contra-lateral insular cortex, the thalamus, the brainstem and the cerebellum. No significant correlation with the temporal envelope of the nystagmus was found. The temporal analysis of the activation profiles highlighted a significantly longer duration of the evoked BOLD activity in the brainstem compared to the insular cortex suggesting a functional de-coupling between cortical and subcortical activity during the vestibular response.

Objective: To address the potential contribution of subcortical brain regions in the functional reorganization of the motor system in patients with sporadic ALS (sALS) and to investigate whether functional changes in brain activity are different in sALS patients with predominant upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction. Methods: We studied 16 patients with sALS and 13 healthy controls, using BOLD-fMRI, while they performed a simple visually paced motor task. Seven patients had definite clinical UMN signs while nine patients had prevalent clinical and electrophysiological LMN involvement. fMRI data were analyzed with Brain Voyager QX. Results: Task-related functional changes were identified in motor cortical regions in both patients and healthy controls. Direct group comparisons revealed relatively decreased BOLD fMRI responses in left sensorimotor cortex, lateral premotor area, supplementary motor area and right posterior parietal cortex (p < 0.05 corrected) and relatively increased responses in the left anterior putamen (p < 0.001 uncorrected) in sALS patients. Additional analyses between the two patients subgroups demonstrated significant BOLD fMRI response differences in the anterior cingulate cortex and right caudate nucleus (p < 0.001 uncorrected) with more robust activation of these areas in patients with greater UMN burden. Importantly, there were no significant differences in performance of the motor task between sALS patients and controls as well as between sALS patient subgroups. Conclusions: Our data demonstrate a different BOLD fMRI pattern between our sALS patients and healthy controls even during simple motor behavior. Furthermore, patients with sALS and greater UMN involvement show a different reorganization of the motor system compared to sALS patients with greater LMN dysfunction. (c) 2006 Elsevier Inc. All rights reserved.

Central diabetes insipidus (CDI) is a rare hypothalamus-pituitary disease due to the deficiency of arginine vasopressin (AVP) synthesis from the hypothalamus and/or secretion from the neurohypophysis. The etiology of CDI is unknown in over one third of cases, classified as idiopathic CDI. The aim of this study was 2-fold: 1) to evaluate the occurrence of circulating autoantibodies to AVP-secreting cells (AVPcAb), and 2) to correlate it to clinical (sex, age of disease onset, disease duration, and degree), immunological (clinical history of autoimmune diseases and presence of related organ-specific autoantibodies), and radiological features (neurohypophyseal bright spot, pituitary stalk thickening, and empty sella) in a large cohort of patients with apparently idiopathic CDI or CDI of known etiology. To this purpose, 150 patients with CDI were studied: 64 idiopathic, 6 familial, 12 associated to granulomatous diseases, and 68 secondary to cranial trauma, tumor, or surgery. AVPcAb were measured by an indirect immunofluorescence method. AVPcAb were found in 23.3% of CDI patients: 21 idiopathic (32.8%) and 14 nonidiopathic (16.3%; chi(2) = 13.1; P < 0.001). AVPcAb were independently associated with age less than 30 yr at disease onset (P = 0.001) in patients with idiopathic CDI and with history of autoimmune diseases (P = 0.006 and P = 0.02, respectively) and radiological evidence of pituitary stalk thickening (P = 0.02 and P = 0.003, respectively) in both idiopathic and nonidiopathic CDI. The likelihood of autoimmunity in one patient with apparently idiopathic CDI with age of disease onset less than 30 yr was 53%, it increased to 91% when history of autoimmune diseases was associated and to 99% when pituitary stalk thickening was further associated. In conclusion, autoimmunity is associated with one third of patients with apparently idiopathic CDI, which should therefore be classified as autoimmune CDI. Autoimmune CDI is highly likely in young patients with a clinical history of autoimmune diseases and radiological evidence of pituitary stalk thickening. Conversely, autoimmunity probably represents an epiphenomenon in patients with nonidiopathic CDI.

The principles that the auditory cortex uses to decipher a stream of acoustic information have remained elusive. Neural responses in the animal auditory cortex can be broadly classified into transient and sustained activity. We examined the existence of similar principles in the human brain. Sound-evoked, blood oxygen level–dependent signal response was decomposed temporally into independent transient and sustained constituents, which predominated in different portions—core and belt—of the auditory cortex. Converging with unit recordings, our data suggest that this spatiotemporal pattern in the auditory cortex may represent a fundamental principle of analyzing sound information.

The therapeutic efficacy of lanreotide SR and octreotide LAR has been studied widely in patients treated previously with neurosurgery and/or radiotherapy. These therapies limit the evaluation of the long-term effects of somatostatin analogues on tumour shrinkage. Neurosurgical and radiotherapy treatments cause irreversible anatomical changes in pituitary morphology, which can make accurate evaluation of tumour shrinkage difficult. The aim of this study was to investigate the therapeutic efficacy of lanreotide SR and octreotide LAR in previously untreated patients with acromegaly. We aimed to investigate the long-term effects of these drugs on tumour shrinkage and growth hormone (GH) hypersecretion without the confounding influences of previous therapy.Twenty-three newly diagnosed patients with acromegaly (14 women, nine men) with active disease began the study; of these, three were lost for follow-up, leaving a total of 20 patients to complete the study. Patients were assigned randomly to lanreotide SR (12 patients) and octreotide LAR (eight patients), and the randomization stratified patients to assure a balance between the groups with respect to baseline tumour dimension, age and sex. Tumour volume was evaluated by magnetic resonance imaging of the sella, and calculated with the rotating ellipsoid formula. A morphological and biochemical evaluation was performed at baseline, 12 and 24 months after beginning lanreotide SR and octreotide LAR treatment. A reduction of tumour volume of at least 10% was considered significant.Biochemical control increased progressively throughout the study in patients with microadenomas more than in patients with macroadenomas (70% vs. 10%; P0.05) and without a difference between lanreotide SR and octreotide LAR (41.0% vs. 37.5%; P not significant). After 12 months of treatment, mean tumour shrinkage was 28.3 +/- 18.0%. A greater reduction was observed in macro- vs. microadenomas (40.5 +/- 17.0% vs. 16.1 +/- 8.0%, respectively; P0.05). No statistical difference in the tumour shrinking effects of lanreotide SR vs. octreotide LAR was observed (26.5 +/- 17.3% vs. 31.1 +/- 16.1%, respectively). At the 24th month of therapy, no further overall shrinkage was observed, compared to the 12-month evaluation (31.9 +/- 17.2% vs. 28.3 +/- 18.0%) at which there was no difference between lanreotide SR and octreotide LAR (30.0 +/- 17.2% vs. 34.8 +/- 16.5%, respectively).This study showed that the new long-acting somatostatin analogues, lanreotide SR and octreotide LAR, cause significant shrinkage of pituitary GH-secreting adenomas in previously untreated patients with acromegaly. This effect was more marked in macroadenomas than microadenomas, and did not correlate with control of GH hypersecretion.

The dopamine agonists bromocriptine (BRC) and cabergoline (CAB) are very effective in normalizing serum prolactin (PRL) levels, restoring gonadal function in more than 90% of patients having a micro- or macroprolactinoma or "idiopathic" hyperprolactinemia. Between 10% and 20% of patients, however, fail to gain control of PRL secretion or tumor shrinkage despite high doses of various agonists. This retrospective study was planned to determine the frequency of resistance to CAB in 120 consecutive new patients: 56 with a macroadenoma, 60 with a microadenoma, and 4 with nontumoral hyperprolactinemia. They were compared with 87 similar patients who received BRC for 2 years. Resistance was said to be present when neither a normal serum PRL or tumor shrinkage was achieved. The CAB dose was adjusted at 2-month intervals and increased progressively when necessary, up to 7 mg weekly. BRC doses up to 20 mg daily were given as needed to gain a normal PRL. Standard replacement therapy was given to the 29 hypopituitary patients. Tumor mass was assessed semiquantitatively by MR imaging. CAB treatment led to normal serum PRL levels in more than 80% of patients with either macro- or microprolactinoma, and patients consistently recovered gonadal and sexual function. Galactorrhea resolved in four resistant women. At 2 years, however, none of 16 patients had persistently normal PRL levels. BRC therapy produced normal serum PRL in 46% to 57% of patients with prolactinomas. All but 2 patients recovered gonadal and sexual function. Galactorrhea disappeared in 40 responsive women. Both drugs led to tumor shrinkage in a large majority of patients. Visual field defects resolved after a year of treatment in 89.5% of patients given CAB and 73% of those treated with BRC. Both agents were well tolerated, and no patient had to withdraw because of side effects. Cabergoline appears to have controlled hyperprolactinemia and shrunk prolactinomas more consistently than bromocriptine in this trial. Even high doses of CAB, however, failed to produce normal PRL levels in some instances. Persistent visually compromised patients still require operative tumor removal.

Do spatial operations on mental images and those on visually presented material share the same neural substrate? We used the high spatial resolution of functional magnetic resonance imaging to determine whether areas in the parietal lobe that have been implicated in the spatial transformation of visual percepts are also activated during the generation and spatial analysis of imagined objects. Using a behaviourally controlled mental imagery paradigm, which did not involve any visual stimulation, we found robust activation in posterior parietal cortex in both hemispheres. We could thus identify the subset of spatial analysis-related activity that is involved in spatial operations on mental images in the absence of external visual input. This result clarifies the nature of top-down processes in the dorsal stream of the human cerebral cortex and provides evidence for a specific convergence of the pathways of imagery and visual perception within the parietal lobes.

Cytoplasmic autoantibodies to vasopressin-cells (AVPcAb) have been detected not only in patients with overt central diabetes insipidus (CDI), but also in patients with endocrine autoimmune diseases without CDI. This suggests that complete CDI can be preceded by a preclinical stage. Among 878 patients with endocrine autoimmune diseases without CDI, 9 patients found to be AVPcAb positive and 139 AVPcAb-negative controls were enrolled in this open prospective study. They were evaluated for AVPcAb and posterior pituitary function at least yearly for about 4 yr (range, 37‐ 48 months); during this span, magnetic resonance imaging (MRI) of posterior pituitary and stalk was performed only in the AVPcAb-positive patients. Five of the 9 AVPcAb-positive patients had normal posterior pituitary function at study entry. They were AVPcAb positive throughout the follow-up period. At later stages of the study, 3 of them developed partial CDI, and 1 developed complete CDI. The remaining 4 patients showed impaired response to the water deprivation test at study entry and were diagnosed as having partial CDI. Two of them agreed to receive desmopressin replacement for 1 yr. After this treatment, the patients became negative for AVPcAb and displayed normal posterior pituitary function until the end of the follow-up. Conversely, the 2 untreated patients with partial CDI remained AVPcAb positive. One of them developed overt CDI. None of the controls became AVPcAb positive or developed CDI. The normal hyperintense MRI signal of the posterior pituitary, present at study entry, persisted subsequently in all 9 AVPcAb-positive patients, including those developing overt CDI, only disappearing in the late phase of complete CDI. In asymptomatic subjects, the monitoring of AVPcAb, but not MRI, seems to be useful to predict a progression toward partial/overt CDI. Early desmopressin therapy in patients with partial CDI could interrupt or delay the autoimmune damage and the progression toward clinically overt CDI. (J Clin Endocrinol Metab 84: 3047‐3051, 1999)

We used single photon emission tomography to study regional cerebral perfusion in patients with different forms of spinocerebellar degeneration: 6 patients with Friedreich's ataxia (FA), 6 with early-onset cerebellar ataxia with retained tendon reflexes (EOCA), 5 with autosomal dominant cerebellar ataxia type 1 (ADCA I) and 11 with idiopathic late-onset cerebellar ataxia (ILOCA). The results were related to clinical and magnetic resonance imaging (MRI) findings. Cerebellar hypoperfusion was constant in ADCA I and frequent in patients with other spinocerebellar degenerations. Brain stem hypoperfusion was constant in ADCA I, frequent in ILOCA patients with pontocerebellar atrophy and absent in FA and EOCA. FA and EOCA often showed a reduction in the parietotemporal cortex blood flow, which was not related to cortical atrophy. ILOCA patients had an asymmetric pattern in the temporal areas with decreased blood flow in the right side only. Caudate hypoperfusion was found in ADCA I patients. Cerebral atrophy did not account for changes in regional blood flow, which probably indicate early involvement of cerebral structures.

The incidence of pineal cysts (PC) in "standard" MRI was reviewed. Seven cases of PC were found from 400 consecutive MRI examinations. PC did not produce clinically relevant symptoms in any of the patients. Our data, as well as those emerging from a critical review of the literature, suggest that PC are often asymptomatic and represent an incidental MRI finding.