Lesions Causing Alice in Wonderland Syndrome Map to a Common Brain Network Linking Body and Size Perception.

OBJECTIVE: Alice in Wonderland syndrome (AIWS) profoundly affects human perception of size and scale, particularly regarding one's own body and the environment. Its neuroanatomical basis has remained elusive, partly because brain lesions causing AIWS can occur in different brain regions. Here, we aimed to determine if brain lesions causing AIWS map to a distributed brain network. METHODS: A retrospective case-control study analyzing 37 cases of lesion-induced AIWS identified through systematic literature review was conducted. Using resting-state functional connectome data from 1,000 healthy individuals, the whole-brain connections of each lesion were estimated and contrasted with those from a control dataset comprising 1,073 lesions associated with 25 other neuropsychiatric syndromes. Additionally, connectivity findings from lesion-induced AIWS cases were compared with functional neuroimaging results from 5 non-lesional AIWS cases. RESULTS: AIWS-associated lesions were located in various brain regions with minimal overlap (≤33%). However, the majority of lesions (≥85%) demonstrated shared connectivity to the right extrastriate body area, known to be selectively activated by viewing body part images, and the inferior parietal cortex, involved in size and scale judgements. This pattern was uniquely characteristic of AIWS when compared with other neuropsychiatric disorders (family-wise error-corrected p < 0.05) and consistent with functional neuroimaging observations in AIWS due to nonlesional causes (median correlation r = 0.56, interquartile range 0.24). INTERPRETATION: AIWS-related perceptual distortions map to one common brain network, encompassing regions critical for body representation and size-scale processing. These findings lend insight into the neuroanatomical localization of higher-order perceptual functions, and may inform future therapeutic strategies for perceptual disorders. ANN NEUROL 2024.

Mapping Motor Cortical Network Excitability and Connectivity Changes in De Novo Parkinson's Disease.

BACKGROUND: Transcranial magnetic stimulation-electroencephalography (TMS-EEG) has demonstrated decreased excitability in the primary motor cortex (M1) and increased excitability in the pre-supplementary motor area (pre-SMA) in moderate-advanced Parkinson's disease (PD). OBJECTIVES: The aim was to investigate whether these abnormalities are evident from the early stages of the disease, their behavioral correlates, and relationship to cortico-subcortical connections. METHODS: Twenty-eight early, drug-naive (de novo) PD patients and 28 healthy controls (HCs) underwent TMS-EEG to record TMS-evoked potentials (TEPs) from the primary motor cortex (M1) and the pre-SMA, kinematic recording of finger-tapping movements, and a 3T-MRI (magnetic resonance imaging) scan to obtain diffusion tensor imaging (DTI) reconstruction of white matter (WM) tracts connecting M1 to the ventral lateral anterior thalamic nucleus and pre-SMA to the anterior putamen. RESULTS: We found reduced M1 TEP P30 amplitude in de novo PD patients compared to HCs and similar pre-SMA TEP N40 amplitude between groups. PD patients exhibited smaller amplitude and slower velocity in finger-tapping movements and altered structural integrity in WM tracts of interest, although these changes did not correlate with TEPs. CONCLUSIONS: M1 hypoexcitability is a characteristic of PD from early phases and may be a marker of the parkinsonian state. Pre-SMA hyperexcitability is not evident in early PD and possibly emerges at later stages of the disease. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Role of Cerebellum and Basal Ganglia Functional Connectivity in Altered Voluntary Movement Execution in Essential Tremor.

Substantial evidence highlights the role of the cerebellum in the pathophysiology of tremor in essential tremor (ET), although its potential involvement in altered movement execution in this condition remains unclear. This study aims to explore potential correlations between the cerebellum and basal ganglia functional connectivity and voluntary movement execution abnormalities in ET, objectively assessed with kinematic techniques. A total of 20 patients diagnosed with ET and 18 healthy subjects were enrolled in this study. Tremor and repetitive finger tapping were recorded using an optoelectronic kinematic system. All participants underwent comprehensive 3T-MRI examinations, including 3D-T1 and blood-oxygen-level dependent (BOLD) sequences during resting state. Morphometric analysis was conducted on the 3D-T1 images, while a seed-based analysis was performed to investigate the resting-state functional connectivity (rsFC) of dorsal and ventral portions of the dentate nucleus and the external and internal segments of the globus pallidus. Finally, potential correlations between rsFC alterations in patients and clinical as well as kinematic scores were assessed. Finger tapping movements were slower in ET than in healthy subjects. Compared to healthy subjects, patients with ET exhibited altered FC of both dentate and globus pallidus with cerebellar, basal ganglia, and cortical areas. Interestingly, both dentate and pallidal FC exhibited positive correlations with movement velocity in patients, differently from that we observed in healthy subjects, indicating the higher the FC, the faster the finger tapping. The findings of this study indicate the possible role of both cerebellum and basal ganglia in the pathophysiology of altered voluntary movement execution in patients with ET.

Relationship between default mode network and resting-state electroencephalographic alpha rhythms in cognitively unimpaired seniors and patients with dementia due to Alzheimer's disease.

Here we tested the hypothesis of a relationship between the cortical default mode network (DMN) structural integrity and the resting-state electroencephalographic (rsEEG) rhythms in patients with Alzheimer's disease with dementia (ADD). Clinical and instrumental datasets in 45 ADD patients and 40 normal elderly (Nold) persons originated from the PDWAVES Consortium (www.pdwaves.eu). Individual rsEEG delta, theta, alpha, and fixed beta and gamma bands were considered. Freeware platforms served to derive (1) the (gray matter) volume of the DMN, dorsal attention (DAN), and sensorimotor (SMN) cortical networks and (2) the rsEEG cortical eLORETA source activities. We found a significant positive association between the DMN gray matter volume, the rsEEG alpha source activity estimated in the posterior DMN nodes (parietal and posterior cingulate cortex), and the global cognitive status in the Nold and ADD participants. Compared with the Nold, the ADD group showed lower DMN gray matter, lower rsEEG alpha source activity in those nodes, and lower global cognitive status. This effect was not observed in the DAN and SMN. These results suggest that the DMN structural integrity and the rsEEG alpha source activities in the DMN posterior hubs may be related and predict the global cognitive status in ADD and Nold persons.

Methods for Brain Atrophy MR Quantification in Multiple Sclerosis: Application to the Multicenter INNI Dataset.

BACKGROUND: Current therapeutic strategies in multiple sclerosis (MS) target neurodegeneration. However, the integration of atrophy measures into the clinical scenario is still an unmet need. PURPOSE: To compare methods for whole-brain and gray matter (GM) atrophy measurements using the Italian Neuroimaging Network Initiative (INNI) dataset. STUDY TYPE: Retrospective (data available from INNI). POPULATION: A total of 466 patients with relapsing-remitting MS (mean age = 37.3 ± 10 years, 323 women) and 279 healthy controls (HC; mean age = 38.2 ± 13 years, 164 women). FIELD STRENGTH/SEQUENCE: A 3.0-T, T1-weighted (spin echo and gradient echo without gadolinium injection) and T2-weighted spin echo scans at baseline and after 1 year (170 MS, 48 HC). ASSESSMENT: Structural Image Evaluation using Normalization of Atrophy (SIENA-X/XL; version 5.0.9), Statistical Parametric Mapping (SPM-v12); and Jim-v8 (Xinapse Systems, Colchester, UK) software were applied to all subjects. STATISTICAL TESTS: In MS and HC, we evaluated the intraclass correlation coefficient (ICC) among FSL-SIENA(XL), SPM-v12, and Jim-v8 for cross-sectional whole-brain and GM tissue volumes and their longitudinal changes, the effect size according to the Cohen's d at baseline and the sample size requirement for whole-brain and GM atrophy progression at different power levels (lowest = 0.7, 0.05 alpha level). False discovery rate (Benjamini-Hochberg procedure) correction was applied. A P value <0.05 was considered statistically significant. RESULTS: SPM-v12 and Jim-v8 showed significant agreement for cross-sectional whole-brain (ICC = 0.93 for HC and ICC = 0.84 for MS) and GM volumes (ICC = 0.66 for HC and ICC = 0.90) and longitudinal assessment of GM atrophy (ICC = 0.35 for HC and ICC = 0.59 for MS), while no significant agreement was found in the comparisons between whole-brain and GM volumes for SIENA-X/XL and both SPM-v12 (P = 0.19 and P = 0.29, respectively) and Jim-v8 (P = 0.21 and P = 0.32, respectively). SPM-v12 and Jim-v8 showed the highest effect size for cross-sectional GM atrophy (Cohen's d = -0.63 and -0.61). Jim-v8 and SIENA(XL) showed the smallest sample size requirements for whole-brain (58) and GM atrophy (152), at 0.7 power level. DATA CONCLUSION: The findings obtained in this study should be considered when selecting the appropriate brain atrophy pipeline for MS studies. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 1.

Brain functional connectivity differences between responders and non-responders to sleeve gastrectomy.

PURPOSE: To compare resting-state functional connectivity (RSFC) of obese patients responders or non-responders to sleeve gastrectomy (SG) with a group of obese patients with no past medical history of metabolic or bariatric surgery. METHODS: MR images were acquired at 1.5 Tesla. Resting-state fMRI data were analyzed with statistical significance threshold set at p < 0.05, family-wise error (FWE) corrected. RESULTS: Sixty-two subjects were enrolled: 20 controls (age range 25-64; 14 females), 24 responders (excess weight loss > 50%; age range 23-68; 17 females), and 18 non-responders to sleeve gastrectomy (SG) (excess weight loss < 50%; age range 23-67; 13 females). About within-network RSFC, responders showed significantly lower RSFC with respect to both controls and non-responders in the default mode and frontoparietal networks, positively correlating with psychological scores. Non-responders showed significantly higher (p < 0.05, family-wise error (few) corrected) RSFC in regions of the lateral visual network as compared to controls. Regarding between-network RSFC, responders showed significantly higher anti-correlation between executive control and salience networks (p < 0.05, FWE corrected) with respect to both controls and non-responders. Significant positive correlation (Spearman rho = 0.48, p = 0.0012) was found between % of excess weight loss and executive control-salience network RSFC. CONCLUSION: There are differences in brain functional connectivity in either responders or non-responders patients to SG. The present results offer new insights into the neural correlates of outcome in patients who undergo SG and expand knowledge about neural mechanisms which may be related to surgical response.

Functional connectivity alterations in migraineurs with Alice in Wonderland syndrome.

BACKGROUND AND PURPOSE: Alice in Wonderland syndrome (AIWS) is a neurological disorder characterized by erroneous perception of the body schema or surrounding space. Migraine is the primary cause of AIWS in adults. The pathophysiology of AIWS is largely unknown, especially regarding functional abnormalities. In this study, we compared resting-state functional connectivity (FC) of migraine patients experiencing AIWS, migraine patients with typical aura (MA) and healthy controls (HCs). METHODS: Twelve AIWS, 12 MA, and 24 HCs were enrolled and underwent 3 T MRI scanning. Independent component analysis was used to identify RSNs thought to be relevant for AIWS: visual, salience, basal ganglia, default mode, and executive control networks. Dual regression technique was used to detect between-group differences in RSNs. Finally, AIWS-specific FC alterations were correlated with clinical measures. RESULTS: With respect to HCs, AIWS and MA patients both showed significantly lower (p < 0.05, FDR corrected) FC in lateral and medial visual networks and higher FC in salience and default mode networks. AIWS patients alone showed higher FC in basal ganglia and executive control networks than HCs. When directly compared, AIWS patients showed lower FC in visual networks and higher FC in all other investigated RSNs than MA patients. Lastly, AIWS-specific FC alterations in the executive control network positively correlated with migraine frequency. CONCLUSIONS: AIWS and MA patients showed similar FC alterations in several RSNs, although to a different extent, suggesting common pathophysiological underpinnings. However, AIWS patients showed additional FC alterations, likely due to the complexity of AIWS symptoms involving high-order associative cortical areas.

Alice in Wonderland syndrome: a lesion mapping study.

BACKGROUND AND PURPOSE: Alice in Wonderland syndrome (AIWS) is a rare neurological disorder, characterized by an erroneous perception of the body schema or surrounding space. It may be caused by a variety of neurological disorders, but to date, there is no agreement on which brain areas are affected. The aim of this study was to identify brain areas involved in AIWS. METHODS: We conducted a literature search for AIWS cases following brain lesions. Patients were classified according to their symptoms as type A (somesthetic), type B (visual), or type C (somesthetic and visual). Using a lesion mapping approach, lesions were mapped onto a standard brain template and sites of overlap were identified. RESULTS: Of 30 lesions, maximum spatial overlap was present in six cases. Local maxima were identified in the right occipital lobe, specifically in the extrastriate visual cortices and white matter tracts, including the ventral occipital fasciculus, optic tract, and inferior fronto-occipital fasciculus. Overlap was primarily due to type B patients (the most prevalent type, n = 22), who shared an occipital site of brain damage. Type A (n = 5) and C patients (n = 3) were rarer, with lesions disparately located in the right hemisphere (thalamus, insula, frontal lobe, hippocampal/parahippocampal cortex). CONCLUSIONS: Lesion-associated AIWS in type B patients could be related to brain damage in visual pathways located preferentially, but not exclusively, in the right hemisphere. Conversely, the lesion location disparity in cases with somesthetic symptoms suggests underlying structural/functional disconnections requiring further evaluation.

Resting-state functional connectivity of anterior and posterior cerebellar lobes is altered in multiple sclerosis.

BACKGROUND: Damage to the cerebellar sensorimotor and cognitive domains may underlie physical and cognitive disability. OBJECTIVE: To investigate resting-state functional connectivity (FC) of sensorimotor and cognitive cerebellum, and clinical correlates in multiple sclerosis (MS). METHODS: A total of 119 patients with MS and 42 healthy subjects underwent multimodal 3T-magnetic resonance imaging (MRI). Patients were evaluated using the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite Scale. After parcellation of sensorimotor (lobules I-V + VIII) and cognitive cerebellum (lobules VI, VII, IX, X), we calculated cerebellar resting-state FC using a seed-based approach. RESULTS: In patients with MS, the sensorimotor cerebellum showed increased FC mainly with cerebellar, thalamic, and cortical (frontal, parietal, temporal) areas and decreased FC with insular areas; the cognitive cerebellum showed increased FC mainly with thalamic and cortical (temporal-occipital) areas, and decreased FC with frontal-insular areas. Both sensorimotor and cognitive cerebellar FC negatively correlated with disability, and positively with cognitive scores. Cerebellar structural damage only partially influenced results. CONCLUSION: The two neocerebellar circuits showed altered FC with subcortical and cortical areas. The association between increased sensorimotor and cognitive cerebellar FC and low levels of physical and cognitive disability suggests that altered FC might modulate the effects of cerebellar structural damage on clinical condition.

Within-network brain connectivity in Crohn's disease patients with gadolinium deposition in the cerebellum.

PURPOSE: Patients with Crohn's disease (CD) undergo multiple gadolinium-based contrast agent injections across their lifespan to enhance signal intensity of the intestinal wall and differentiate active from quiescent inflammatory disease. Thus, CD patients are prone to gadolinium accumulation in the brain and represent a non-neurological population to explore gadolinium-related brain toxicity. Possible effects are expected to be greater on the cerebellar network due to the high propensity of the dentate nucleus to accumulate gadolinium. Herein, we provide a whole-brain network analysis of resting-state fMRI dynamics in long-term quiescent CD patients with normal renal function and MRI evidence of gadolinium deposition in the brain. METHODS: Fifteen patients with CD and 16 healthy age- and gender-matched controls were enrolled in this study. Relevant resting-state networks (RSNs) were identified using independent component analysis (ICA) from functional magnetic resonance imaging data. An unpaired two-sample t test (with age and sex as nuisance variables) was used to investigate between different RSNs. Clusters were determined by using threshold-free cluster enhancement and a family-wise error corrected cluster significance threshold of p < 0.05. RESULTS: Patients showed significantly decreased resting-state functional connectivity (p < 0.05, FWE corrected) of several regions of the right frontoparietal (FPR) and the dorsal attention (DAN) RSNs. No differences between the two groups were found in the functional connectivity maps of all the other RSNs, including the cerebellar network. CONCLUSION: Our findings suggest a non-significant impact of gadolinium deposition on within-network cerebellar functional connectivity of long-term quiescent CD patients.

Absence of dentate nucleus resting-state functional connectivity changes in nonneurological patients with gadolinium-related hyperintensity on T1 -weighted images.

BACKGROUND: The dentate nuclei of the cerebellum are the areas where gadolinium predominantly accumulates. It is not yet known whether gadolinium deposition affects brain functions. PURPOSE/HYPOTHESIS: To assess whether gadolinium-dependent high signal intensity of the cerebellum on T1 -weighted images of nonneurological adult patients with Crohn's disease is associated with modifications of resting-state functional connectivity (RSFC) of the cerebellum and dentate nucleus. STUDY TYPE: Observational, cross-sectional. POPULATION: Fifteen patients affected by Crohn's disease were compared with 16 healthy age- and gender-matched control subjects. All participants underwent neurological, neurocognitive-psychological assessment, and blood sampling. FIELD STRENGTH/SEQUENCE: 1.5-T magnet blood oxygenation level-dependent (BOLD) functional MRI. ASSESSMENT: High signal intensity on T1 -weighted images, cerebellum functional connectivity, neurocognitive performance, and blood circulating gadolinium levels. STATISTICAL TESTS: An unpaired two-sample t-test (age and sex were nuisance variables) was used to investigate between-group differences in cerebellar and dentate nucleus functional connectivity. Z-statistical images were set using clusters determined by Z > 2.3 and a familywise error (FWE)-corrected cluster significance threshold of P = 0.05. RESULTS: Dentate nuclei RSFC was not different (P = n.s.) between patients with gadolinium-dependent high signal intensity on T1 -weighted images and controls. Pre- and postcentral gyrus bilaterally and the right supplementary motor cortex showed a decrease of RSFC with the cerebellum hemispheres (P < 0.05 FWE-corrected) and was related to disease duration but not to gadodiamide cumulative doses (P = n.s.). DATA CONCLUSION: Crohn's disease patients with gadolinium-dependent hyperintense dentate nuclei on unenhanced T1 -weighted images do not show dentate nucleus RSFC changes. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:445-455.

Altered thalamo­cortical and occipital­parietal­ temporal­frontal white matter connections in patients with anorexia and bulimia nervosa: a systematic review of diffusion tensor imaging studies

Background: Anorexia nervosa and bulimia nervosa are complex mental disorders, and their etiology is still not fully understood. This paper reviews the literature on diffusion tensor imaging studies in patients with anorexia nervosa and bulimia nervosa to explore the usefulness of white matter microstructural analysis in understanding the pathophysiology of eating disorders. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify diffusion tensor imaging studies that compared patients with an eating disorder to control groups. We searched relevant databases for studies published from database inception to August 2018, using combinations of select keywords. We categorized white matter tracts according to their 3 main classes: projection (i.e., thalamo­cortical), association (i.e., occipital­parietal­temporal­frontal) and commissural (e.g., corpus callosum). Results: We included 19 papers that investigated a total of 427 participants with current or previous eating disorders and 444 controls. Overall, the studies used different diffusion tensor imaging approaches and showed widespread white matter abnormalities in patients with eating disorders. Despite differences among the studies, patients with anorexia nervosa showed mainly white matter microstructural abnormalities of thalamo­cortical tracts (i.e., corona radiata, thalamic radiations) and occipital­parietal­temporal­frontal tracts (i.e., left superior longitudinal and inferior fronto-occipital fasciculi). It was less clear whether white matter alterations persist after recovery from anorexia nervosa. Available data on bulimia nervosa were partially similar to those for anorexia nervosa. Limitations: Study sample composition and diffusion tensor imaging analysis techniques were heterogeneous. The number of studies on bulimia nervosa was too limited to be conclusive. Conclusion: White matter microstructure appears to be affected in anorexia nervosa, and these alterations may play a role in the pathophysiology of this eating disorder. Although we found white matter alterations in bulimia nervosa that were similar to those in anorexia nervosa, white matter changes in bulimia nervosa remain poorly investigated, and these findings were less conclusive. Further studies with longitudinal designs and multi-approach analyses are needed to better understand the role of white matter changes in eating disorders.

Increased cerebellar volume and BDNF level following quadrato motor training.

Using whole-brain structural measures coupled to analysis of salivary brain-derived neurotrophic factor (BDNF), we demonstrate sensory motor training-induced plasticity, including cerebellar gray matter volume increment and increased BDNF level. The increase of cerebellar volume was positively correlated with the increase of BDNF level.

Diameter, length, speed, and conduction delay of callosal axons in macaque monkeys and humans: comparing data from histology and magnetic resonance imaging diffusion tractography.

Three macaque monkeys and 13 healthy human volunteers underwent diffusion tensor MRI with a 3 Tesla scanner for diffusion tract tracing (DTT) reconstruction of callosal bundles from different areas. In six macaque monkeys and three human subjects, the length of fiber tracts was obtained from histological data and combined with information on the distribution of axon diameter, so as to estimate callosal conduction delays from different areas. The results showed that in monkeys, the spectrum of tract lengths obtained with DTT closely matches that estimated from histological reconstruction of axons labeled with an anterogradely transported tracer. For each sector of the callosum, we obtained very similar conduction delays regardless of whether conduction distance was obtained from tractography or from histological analysis of labeled axons. This direct validation of DTT measurements by histological methods in monkeys was a prerequisite for the computation of the callosal conduction distances and delays in humans, which we had previously obtained by extrapolating the length of callosal axons from that of the monkey, proportionally to the brain volumes in the two species. For this analysis, we used the distribution of axon diameters from four different sectors of the corpus callosum. As in monkeys, in humans the shortest callosal conduction delays were those of motor, somatosensory, and premotor areas; the longer ones were those of temporal, parietal, and visual areas. These results provide the first histological validation of anatomical data about connection length in the primate brain based on DTT imaging.

The brief repeatable battery of neuropsychological tests (BRB-N) version a: update of Italian normative data from the Italian Neuroimaging Network Initiative (INNI).

BACKGROUND: Cognitive impairment is a common clinical manifestation in people with multiple sclerosis (PwMS) and significantly impacts patients' quality life. Cognitive assessment is crucial for treatment decisions and understanding disease progression. Several neuropsychological batteries are used in MS, including the Brief Repeatable Battery of Neuropsychological Tests (BRB-N), Minimal Assessment of Cognitive Function in MS (MACFIMS), and Brief International Cognitive Assessment for MS (BICAMS). However, normative data for BRB-N version A in Italy are outdated. OBJECTIVES: To revise and update normative data for the BRB-N version A in the Italian population. METHODS: From the Italian Neuroimaging Network Initiative (INNI) database, we retrospectively selected 342 healthy subjects (172 males and 170 females) evaluated at four Italian INNI-affiliated sites (Milan, Siena, Rome, Naples). The subjects underwent neuropsychological assessment using the BRB-N version A. Regression-based method relying on scaled scores was used to calculate demographic correction procedures. RESULTS: No significant differences were found in age, education, and sex distribution among the four sites (p ≥ 0.055). Regression analysis provided normative data to calculate demographically adjusted z-scores for each BRB-N version A test. DISCUSSION: This study provides updated normative data for the BRB-N version A in the Italian population. The use of a regression-based method and scaled scores ensures consistency with other neuropsychological batteries commonly used in Italy, namely MACFIMS and BICAMS. The availability of updated normative data increases reliability of neuropsychological assessment of cognitive function in Italian PwMS and other clinical populations using BRB-N version A, providing valuable insights for both clinical and research applications.

Regional hippocampal atrophy reflects memory impairment in patients with early relapsing remitting multiple sclerosis.

BACKGROUND: Research work has shown that hippocampal subfields are atrophic to varying extents in multiple sclerosis (MS) patients. However, studies examining the functional implications of subfield-specific hippocampal damage in early MS are limited. We aim to gain insights into the relationship between hippocampal atrophy and memory function by investigating the correlation between global and regional hippocampal atrophy and memory performance in early MS patients. METHODS: From the Italian Neuroimaging Network Initiative (INNI) dataset, we selected 3D-T1-weighted brain MRIs of 219 early relapsing remitting (RR)MS and 246 healthy controls (HC) to identify hippocampal atrophic areas. At the time of MRI, patients underwent Selective-Reminding-Test (SRT) and Spatial-Recall-Test (SPART) and were classified as mildly (MMI-MS: n.110) or severely (SMI-MS: n:109) memory impaired, according to recently proposed cognitive phenotypes. RESULTS: Early RRMS showed lower hippocampal volumes compared to HC (p < 0.001), while these did not differ between MMI-MS and SMI-MS. In MMI-MS, lower hippocampal volumes correlated with worse memory tests (r = 0.23-0.37, p ≤ 0.01). Atrophic voxels were diffuse in the hippocampus but more prevalent in cornu ammonis (CA, 79%) than in tail (21%). In MMI-MS, decreased subfield volumes correlated with decreases in memory, particularly in the right CA1 (SRT-recall: r = 0.38; SPART: r = 0.34, p < 0.01). No correlations were found in the SMI-MS group. CONCLUSION: Hippocampal atrophy spreads from CA to tail from early disease stages. Subfield hippocampal atrophy is associated with memory impairment in MMI-MS, while this correlation is lost in SMI-MS. This plays in favor of a limited capacity for an adaptive functional reorganization of the hippocampi in MS patients.

Parkinsonism Is Associated with Altered SMA-Basal Ganglia Structural and Functional Connectivity in Frontotemporal Degeneration.

BACKGROUND: Patients with frontotemporal degeneration (FTD) often manifest parkinsonism, which likely results from cortical and subcortical degeneration of brain structures involved in motor control. We used a multimodal magnetic resonance imaging (MRI) approach to investigate possible structural and/or functional alterations in FTD patients with and without parkinsonism (Park+ and Park-). METHODS: Thirty FTD patients (12 Park+, 18 Park-) and 30 healthy controls were enrolled and underwent 3T MRI scanning. MRI analyses included: (1) surface-based morphometry; (2) basal ganglia and thalamic volumetry; (3) diffusion-based probabilistic tractography of fiber tracts connecting the supplementary motor area (SMA) and primary motor cortex (M1) to the putamen, globus pallidus, and thalamus; and (4) resting-state functional connectivity (RSFC) between the aforementioned regions. RESULTS: Patients in Park+ and Park- groups showed comparable patterns of cortical thinning in frontotemporal regions and reduced thalamic volume with respect to controls. Only Park+ patients showed reduced putaminal volume and reduced fractional anisotropy of the fibers connecting the SMA to the globus pallidus, putamen, and thalamus, with respect to controls. Park+ patients also showed decreased RSFC between the SMA and putamen with respect to both Park- patients and controls. CONCLUSIONS: The present findings support the hypothesis that FTD patients with parkinsonism are characterized by neurodegenerative processes in specific corticobasal ganglia-thalamocortical motor loops.

Neuroimaging markers of Alice in Wonderland syndrome in patients with migraine with aura.

Background: The Alice in Wonderland syndrome (AIWS) is a transient neurological disturbance characterized by sensory distortions most frequently associated with migraine in adults. Some lines of evidence suggest that AIWS and migraine might share common pathophysiological mechanisms, therefore we set out to investigate the common and distinct neurophysiological alterations associated with these conditions in migraineurs. Methods: We conducted a case-control study acquiring resting-state fMRI data from 12 migraine patients with AIWS, 12 patients with migraine with typical aura (MA) and 24 age-matched healthy controls (HC). We then compared the interictal thalamic seed-to-voxel and ROI-to-ROI cortico-cortical resting-state functional connectivity between the 3 groups. Results: We found a common pattern of altered thalamic connectivity in MA and AIWS, compared to HC, with more profound and diffuse alterations observed in AIWS. The ROI-to-ROI functional connectivity analysis highlighted an increased connectivity between a lateral occipital region corresponding to area V3 and the posterior part of the superior temporal sulcus (STS) in AIWS, compared to both MA and HC. Conclusion: The posterior STS is a multisensory integration area, while area V3 is considered the starting point of the cortical spreading depression (CSD), the neural correlate of migraine aura. This interictal hyperconnectivity might increase the probability of the CSD to directly diffuse to the posterior STS or deactivating it, causing the AIWS symptoms during the ictal phase. Taken together, these results suggest that AIWS in migraineurs might be a form of complex migraine aura, characterized by the involvement of associative and multisensory integration areas.

White and gray matter alterations in de novo PD patients: which matter most?

OBJECTIVES: This paper aimed to identify white matter (WM) and gray matter (GM) abnormalities in a sample of early PD patients, and their correlations with motor and non-motor symptom severity. METHODS: We enrolled 62 de novo PD patients and 31 healthy subjects. Disease severity and non-motor symptom burden were assessed by the Unified Parkinson's Disease Rating Scale part III and the Non-Motor Symptoms Scale, respectively. Cognitive performance was assessed using Montreal Cognitive Assessment and Frontal Assessment Battery. All subjects underwent a 3-Tesla MRI protocol. MRI analyses included tract-based spatial statistics, cortical thickness, and subcortical and cerebellar volumetry. RESULTS: In comparison to control subjects, PD patients exhibited lower fractional anisotropy and higher mean, axial, and radial diffusivity in most WM bundles, including corticospinal tracts, the internal and external capsule, the anterior and posterior thalamic radiations, the genu and body of the corpus callosum, cerebellar peduncles, and superior and inferior longitudinal and fronto-occipital fasciculi. Correlations between Montreal Cognitive Assessment scores and fractional anisotropy values in the right posterior thalamic radiation, left superior corona radiata, right inferior-fronto-occipital fasciculus, left inferior longitudinal fasciculus, bilateral anterior thalamic radiations, and bilateral superior longitudinal fasciculi were found. Smaller cerebellar volumes in early PD patients in the left and right crus I were also found. No GM changes were present in subcortical or cortical regions. CONCLUSION: The combined evaluation of WM and GM in the same patient sample demonstrates that WM microstructural abnormalities precede GM structural changes in early PD patients.

Cortico-Subcortical White Matter Bundle Changes in Cervical Dystonia and Blepharospasm.

Dystonia is thought to be a network disorder due to abnormalities in the basal ganglia-thalamo-cortical circuit. We aimed to investigate the white matter (WM) microstructural damage of bundles connecting pre-defined subcortical and cortical regions in cervical dystonia (CD) and blepharospasm (BSP). Thirty-five patients (17 with CD and 18 with BSP) and 17 healthy subjects underwent MRI, including diffusion tensor imaging (DTI). Probabilistic tractography (BedpostX) was performed to reconstruct WM tracts connecting the globus pallidus, putamen and thalamus with the primary motor, primary sensory and supplementary motor cortices. WM tract integrity was evaluated by deriving their DTI metrics. Significant differences in mean, radial and axial diffusivity between CD and HS and between BSP and HS were found in the majority of the reconstructed WM tracts, while no differences were found between the two groups of patients. The observation of abnormalities in DTI metrics of specific WM tracts suggests a diffuse and extensive loss of WM integrity as a common feature of CD and BSP, aligning with the increasing evidence of microstructural damage of several brain regions belonging to specific circuits, such as the basal ganglia-thalamo-cortical circuit, which likely reflects a common pathophysiological mechanism of focal dystonia.