Cerebellar Lobules Research Articles

P-22 Smaller cerebellar lobules are associated with tremor severity in Parkinson’s disease

P-22 Smaller cerebellar lobules are associated with tremor severity in Parkinson’s disease

Regional brain glucose metabolism is differentially affected by ketogenic diet: a human semiquantitative positron emission tomography.

Ketogenic diet (KD) is recommended to avoid intense [18F]FDG myocardial physiologic uptake in PET imaging. Neuroprotective and anti-seizure effects of KD have been suggested, but their mechanisms remain to be elucidated. This [18F]FDG PET study aims to evaluate the effect of KD on glucose brain metabolism. Subjects who underwent KD prior to whole-body and brain [18F]FDG PET between January 2019 and December 2020 in our department for suspected endocarditis were retrospectively included. Myocardial glucose suppression (MGS) on whole-body PET was analyzed. Patients with brain abnormalities were excluded. Thirty-four subjects with MGS (mean age: 61.8 ± 17.2years) were included in the KD population, and 14 subjects without MGS were considered for a partial KD group (mean age: 62.3 ± 15.1years). Brain SUVmax was first compared between these two KD groups to determine possible global uptake difference. Semiquantitative voxel-based intergroup analyses were secondarily performed to determine possible inter-regional differences by comparing KD groups with and without MGS, separately, to 27 healthy subjects fasting for at least 6h (mean age of 62.4 ± 10.9years), and KD groups between them (p-voxel < 0.001, and p-cluster < 0.05, FWE-corrected). A 20% lower brain SUVmax was found in subjects under KD with MGS in comparison to those without MGS (Student's t-test, p = 0.02). Whole-brain voxel-based intergroup analysis revealed that patients under KD with and without MGS had relative hypermetabolism of limbic regions including medial temporal cortices and cerebellum lobes and relative hypometabolism of bilateral posterior regions (occipital), without significant difference between them. KD globally reduces brain glucose metabolism but with regional differences, requiring special attention to clinical interpretation. On a pathophysiological perspective, these findings could help understand underlying neurological effects of KD through possible decrease of oxidative stress in posterior regions and functional compensation in the limbic regions.

New insights into cerebellar dysfunction in patients with delusional disorder: A systematic review

IntroductionThe cerebellum has been implicated in cognitive, affective and motor functions, including emotion regulation, executive control and sensorimotor processing. In schizophrenia, cerebellar dysfunction has been associated with treatment resistance and clinical features. However, few studies have been focused on delusional disorder (DD).ObjectivesOur main purpose was to review the evidence available on cerebellum abnormalities and dysfunctions in patients with DD.MethodsA systematic review was conducted through PubMed, Scopus and ClinicalTrials.gov (inception-June 2022) according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) directives. The following search terms were used: cerebellum OR cerebellar AND (“delusional disorder” AND paranoia). Reference lists from included studies were hand-checked to find other potential relevant papers.ResultsSix studies were included from a total of 119 retrieved records (PubMed: 52, Scopus: 66, ClinicalTrials.gov: 1). Study 1:Patients with DD somatic type (n=14) presented a decreased gray matter volume in cerebellar lobules compared to healthy controls (HC) (n=32, left lobule VIIIa) and non-somatic DD (n=18, lobule V). Cerebellar volumes did not seem to differ between HC and non-somatic DD. Study 2:Abnormalities of voluntary saccadic eye movements, linking frontal and cerebellar functions, were found in DD patients (n=34) compared to HC (n=40). Study 3: Abnormal smooth pursuit eye movements in DD (n=15) compared with HC (n=40) and similar to schizophrenia (n=40). Case reports (n=3): DD associated with Dandy-Walker variant (partial vermian hypoplasia), unruptured intracerebral aneurysm of basilar artery, and megacisterna magna.ConclusionsCerebellar deficits in patients with DD has been reported, particularly in those presenting somatic delusional contents.Disclosure of InterestNone Declared

Morphometric evaluation of cerebellar lobules in individuals with unilateral vertebral artery hypoplasia.

Vertebral arteries (VAs) provide blood circulation to the posterior fossa in general and are the main blood supply of the posterior fossa structures of the brain. Our aim in this study is to analyze the segmental volumetric values of cerebellar structures with the voxel-based volumetric analysis system in individuals with unilateral vertebral artery hypoplasia. In this retrospective study, segmental volumetric values/percentile ratios of cerebellar lobules were calculated using 3D fast spoiled gradient recall acquisition in steady-state (3D T1 FSPGR) MRI sequence images of the brain in individuals with unilateral vertebral artery hypoplasia (VAH) and in those without bilateral VAH and any symptoms of vertebrobasilar insufficiency as the control group was evaluated in volBrain ( http://volbrain.upv.es/ ). The VAH group consisted of 50 (19 males/31 females) and the control group had 50 (21 males/29 females) individuals. The cerebellar lobule III, IV, VIIIA and X total volumes and the cerebellar lobule I-II, III, IV, VIIIA and X gray matter volumes were lower in the hypoplastic side than the non-hypoplastic cases and also than the contralateral side of the hypoplastic cases in the VAH group. In addition, it was found that that lobules IV and V had lower cortical thickness and lobules I-II had a higher coverage rate in the intracranial cavity in the hypoplastic side than the non-hypoplastic cases and also than the contralateral side of the hypoplastic cases (p < 0.05). In this study, it was found that cerebellar lobule III, IV, VIIIA, X total volumes and cerebellar lobule I-II, III, IV, VIIIA, X gray matter volumes in addition to lobule IV, V cortical thicknesses were low in individuals with unilateral VAH. Being aware of these variations and taking them into account during future volumetric studies on the cerebellum are very important.

Smaller Cerebellar Lobule VIIb is Associated with Tremor Severity in Parkinson's Disease.

Alterations in the cerebellum's morphology in Parkinson's disease (PD) point to its pathophysiological involvement in this movement disorder. Such abnormalities have previously been attributed to different PD motor subtypes. The aim of the study was to relate volumes of specific cerebellar lobules to motor symptom severity, in particular tremor (TR), bradykinesia/rigidity (BR), and postural instability and gait disorders (PIGD) in PD. We performed a volumetric analysis based on T1-weighted MRI images of 55 participants with PD (22 females, median age 65years, Hoehn and Yahr stage 2). Multiple regression models were fitted to investigate associations between volumes of cerebellar lobules with clinical symptom severity based on MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score and sub-scores for TR, BR, and PIGD; adjusted for age, sex, disease duration, and intercranial volume as cofactors. Smaller volume of lobule VIIb was associated with higher tremor severity (P = 0.004). No structure-function relationships were detected for other lobules or other motor symptoms. This distinct structural association denotes the involvement of the cerebellum in PD tremor. Characterizing morphological features of the cerebellum leads to a better understanding of its role in the spectrum of motor symptoms in PD and contributes further to identifying potential biological markers.

Cognitive function and neuroimaging characteristics in patients with childhood-onset type 1 diabetes mellitus.

In this study, we used neuropsychological tests and neuroimaging to examine the cognitive functions and neuroimaging characteristics to explore the brain mechanism of cognitive deficits in patients with childhood-onset type 1 diabetes mellitus (T1DM). A total of 30 patients with childhood-onset T1DM and 28 healthy controls (HC) participated in the study. Neuropsychological tests were used to assess intelligence quotient, memory, and executive function. Voxel-based morphometry-diffeomorphic anatomical registration through exponential lie algebra analysis and amplitude of low-frequent fluctuation (ALFF) were performed to evaluate the brain grey matter volume and neural spontaneous activity for each participant. Compared with HC, patients with childhood-onset T1DM showed a significant decline in verbal memory (p=0.001) and visual memory (p=0.002). Patients with T1DM had smaller grey matter volumes at the midbrain, thalamus, and cerebellar culmen. They demonstrated an increased ALFF value in the left precentral gyrus, left postcentral gyrus, left insula, and left supramarginal gyrus and a decreased ALFF value in the basal ganglia (putamen nucleus), right insula, right superior temporal gyrus, and cerebellar posterior lobe than the healthy control group. In the T1DM group, the ALFF value in the right insula was positively related to the verbal memory scores (r=0.423, p=0.025). Childhood-onset T1DM was associated with cognitive deficits and changes in brain structure and function. These findings suggest that the brain structural and functional alterations in these regions may be the neuropathology of cognitive deficits in patients with T1DM.

The role of the cerebellum in sequencing and predicting social and non-social events in patients with bipolar disorder.

Advances in the operational mode of the cerebellum indicate a role in sequencing and predicting non-social and social events, crucial for individuals to optimize high-order functions, such as Theory of Mind (ToM). ToM deficits have been described in patients with remitted bipolar disorders (BD). The literature on BD patients' pathophysiology reports cerebellar alterations; however, sequential abilities have never been investigated and no study has previously focused on prediction abilities, which are needed to properly interpret events and to adapt to changes. To address this gap, we compared the performance of BD patients in the euthymic phase with healthy controls using two tests that require predictive processing: a ToM test that require implicit sequential processing and a test that explicitly assesses sequential abilities in non-ToM functions. Additionally, patterns of cerebellar gray matter (GM) alterations were compared between BD patients and controls using voxel-based morphometry. Impaired ToM and sequential skills were detected in BD patients, specifically when tasks required a greater predictive load. Behavioral performances might be consistent with patterns of GM reduction in cerebellar lobules Crus I-II, which are involved in advanced human functions. These results highlight the importance of deepening the cerebellar role in sequential and prediction abilities in patients with BD.

To Do or Not to Do: The cerebellum and neocortex contribute to predicting sequences of social intentions

Humans read the minds of others to predict their actions and efficiently navigate social environments, a capacity called mentalizing. Accumulating evidence suggests that the cerebellum, especially Crus 1 and 2, and lobule IX are involved in identifying the sequence of others’ actions. In the current study, we investigated the neural correlates that underly predicting others’ intentions and how this plays out in the sequence of their actions. We developed a novel intention prediction task, which required participants to put protagonists’ behaviors in the correct chronological order based on the protagonists’ honest or deceitful intentions (i.e., inducing true or false beliefs in others). We found robust activation of cerebellar lobule IX and key mentalizing areas in the neocortex when participants ordered protagonists’ intentional behaviors compared with not ordering behaviors or to ordering object scenarios. Unlike a previous task that involved prediction based on personality traits that recruited cerebellar Crus 1 and 2, and lobule IX (Haihambo et al., 2021), the present task recruited only the cerebellar lobule IX. These results suggest that cerebellar lobule IX may be generally involved in social action sequence prediction, and that different areas of the cerebellum are specialized for distinct mentalizing functions.

Changes in brain gray matter volume in nasopharyngeal carcinoma patients after radiotherapy in long-term follow-up

ObjectivesThe aim of this study was to examine the changes in gray matter in nasopharyngeal carcinoma patients with normal hearing (Group 1) and nasopharyngeal carcinoma patients with hearing loss (Group 2) after radiotherapy using voxel-based morphological analysis and to analyze the relationship with the radiation doses of the temporal lobe. Methods21 patients in Group 1, 14 patients in Group 2, and 21 healthy volunteers were selected. All participants underwent an otologic examination and three-dimensional magnetization preparatory rapid acquisition gradient echo sequence scan. The correlation between the variation of whole brain gray matter volume and the doses of the temporal lobe was analyzed by Data Processing & Analysis for Brain Imaging software. ResultsCompared with the normal control group, the brain areas with reduced gray matter volume in nasopharyngeal carcinoma patients after radiotherapy were mainly in the left posterior cerebellar lobe (T = −8.797), left insular lobe (T = −7.96), and the right insular lobe (T = −6.632). Compared to Group 1, the brain areas of Group 2 patients with reduced gray matter volume were mainly in the left superior temporal gyrus (T = −2.366), left olfactory bulb (T = −2.52), left Rolandic operculum (T = −2.431), and right olfactory bulb (T = −3.100). Compared with Group 1, the brain areas of Group 2 patients with increased gray matter volume were mainly in the left calcarine sulcus (T=3.425) and right calcarine sulcus (T=3.169). There were no correlations between the changes of brain gray matter volume and the radiation doses of the temporal lobe in both Group 1 and Group 2. ConclusionsThe radiotherapy may cause the changes of brain areas associated with cognitive function in nasopharyngeal carcinoma in a long-term follow-up. At the same time, nasopharyngeal carcinoma patients with the radiation-induced hearing loss had abnormal gray matter volumes in the auditory center and other sensory centers. Our findings might provide new understanding into the pathogenesis of radiation-induced brain damage in normal-appearing brain tissue. Yet this exploratory study should be taken with caution.

Changes in brain structure and related functional connectivity during menstruation in women with primary dysmenorrhea.

Neuroimaging studies have identified altered brain structures and functions in women with primary dysmenorrhea (PDM). However, previous studies focused on either structural or functional changes in specific brain regions rather than combining structural and functional analysis. Therefore, this prospective cross-sectional study aimed to investigate the changes in whole brain structure, and functional variation along with structural abnormalities in women with PDM during menstruation. In all, 31 patients with PDM (PTs) and 31 healthy controls (HCs) were recruited. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses were applied to investigate structural changes based on high-resolution T1-weighted magnetic resonance images. Functional connectivity (FC) analysis was performed to evaluate functional variations related to the brain regions that showed structural group differences. Pearson correlation analysis was performed to assess the relationship between neuroimaging changes and clinical measures. Compared to HCs, PTs had reduced gray matter volume (GMV) in the right superior temporal gyrus (STG) and reduced thickness in the bilateral orbitofrontal cortex (OFC), left postcentral gyrus (PoCG), and left superior occipital gyrus (SOG). Among these areas, the STG and PoCG are responsible for altered resting-state FC patterns in PTs. Results showed decreased FC between the STG and the left cerebellar posterior lobe (poCb), the right dorsolateral prefrontal cortex (DLPFC), and the left precentral gyrus (PrCG). Results also showed decreased FC between the PoCG and the right precuneus and the right DLPFC. We also found greater FCs between the PoCG and the bilateral poCb, the left middle temporal gyrus (MTG), and the left angular gyrus. In addition, the FCs between the STG and poCb, and DLPFC in PTs were positively correlated with history and Cox menstrual symptom scale (CMSS) scores, respectively, while the FCs between STG and PrCG were negatively correlated with the onset age of PDM. Our research found structural abnormalities and related FC changes in several brain regions that were mainly involved in the emotional and sensory aspects of menstrual pain in PDM. These findings could help us understand the occurrence of PDM from a neuroimaging perspective.

Frequency-Dependent Alterations in the Amplitude of Low-Frequency Fluctuations in Patients with Acute Pericoronitis: A Resting-State fMRI Study.

Acute pericoronitis (AP) is a common cause of odontogenic toothache. Pain significantly affects the structure and function of the brain, but alterations in spontaneous brain activity in patients with AP are unclear. To apply the amplitude of low-frequency fluctuations (ALFF) method in resting-state functional magnetic resonance imaging to investigate altered spontaneous brain activity characteristics in patients with AP in different frequency bands (typical, slow-4, and slow-5 bands) and assess their correlation with clinical scores. Thirty-four right-handed patients with AP and 31 healthy controls (HC), matched for age, sex, education, and right-handedness, were enrolled. All subjects underwent resting-state functional magnetic resonance imaging. DPABI software was used for data preprocessing and extracting the ALFF values in different frequency bands. Subsequently, differences in ALFF values in the three bands were compared between the two groups. Correlation between ALFF values in the differential brain regions and clinical scores was assessed. In the typical band, ALFF values were higher in the left insula, left superior occipital gyrus, left inferior parietal lobule, left posterior cerebellar lobule, and right postcentral gyrus in the AP than in the HC group. In the slow-4 band, ALFF values in the left superior occipital gyrus, right superior occipital gyrus, and right middle occipital gyrus were higher, and those in the right cingulate gyrus and right superior temporal gyrus were lower in the AP than in the HC group. In the slow-5 band, the ALFF values in the left insula and left superior occipital gyrus were higher in the AP than in the HC group. The ALFF values of the typical bands in the left insula, left inferior parietal lobule, and right postcentral gyrus correlated negatively, those of the slow-4 band in the right middle occipital gyrus correlated positively, and those of the slow-5 band in the left insula correlated negatively with the visual analogue scale score in the AP group. Our results suggested that the intrinsic brain activity of AP patients was abnormal and frequency-dependent. This provides new insights to explore the neurophysiological mechanisms of AP.

Cerebellar network changes in depressed patients with and without autism spectrum disorder: A case-control study

Pathophysiological difference of depression in patients with and without autistic spectrum disorder (ASD) has not been investigated previously. Therefore, we sought to determine whether there were differences between non-ASD and ASD groups on resting-state functional magnetic resonance imaging (rs-fMRI) in patients with depression. We performed 3T MRI under resting state in 8 patients with depression and ASD and 12 patients with depression but without ASD. The ASD group showed increased functional connectivity in the cerebellar network of the left posterior inferior temporal gyrus and anterior cerebellar lobes compared to the non-ASD group in an analysis of covariance. Adding antipsychotics, antidepressants, benzodiazepines, nonbenzodiazepines, anxiolytics, hypnotics, or age as covariates showed a similar increase in functional connectivity. Thus, this study found that depressive patients with ASD had increased functional connectivity in the cerebellar network. Our findings suggest that fMRI may be able to evaluate differences in depressed patients with and without ASD.

Morphological characteristics and expression of the S-100 protein in Purkinje cells of the cerebellum of a young and senile human

The problem of aging of the human body and the prevention of age-associated diseases in modern scientific literature is devoted to many studies. Researchers are showing increased interest in the aging of the cerebellum. Purkinje cells, which form the ganglionic layer of the cerebellar cortex, are considered to be very sensitive to various influences.The aim is to reveal the morphofunctional features of the Purkinje cells of the human cerebellum in the senile age in comparison with the young age.Material and methods. Morphological study of the cerebellum of 59 men and 52 women, right-handed, with anamnestic data that excluded diseases and injuries of the organs of the central and peripheral nervous system, as well as alcohol or drug addiction, was carried out during autopsy. The material for the study was taken from the region of the inferior semilunar lobule of the cerebellum. The studied material was divided into two groups: group I (n=59) included samples obtained from 31 men and 28 young women (from 25 to 32 years old inclusive), group II (n=52) – from 28 men and 24 women of senile age (from 79 to 88 years inclusive). We used general and neurohistological, immunohistochemical and morphometric research methods. Morphological assessment of Purkinje cells was carried out and the distance between their bodies was determined. An immunohistochemical study used a panel of antibodies to the S-100 protein.Results. A comparative analysis of the data obtained showed a statistically significant predominance of the distance between the bodies of Purkinje cells in the elderly compared to the young. Immunohistochemical study revealed an increase in the number of S-100-immunopositive Purkinje cells in old age.Conclusion. New data have been obtained on the age-related structural transformation of the cytoarchitectonics of the human cerebellar nervous tissue, which must be taken into account when studying age-associated diseases and movement coordination disorders.

Decreased frontal and orbital volumes and increased cerebellar volumes in patients with anosmia Of Unknown origin: A subtle connection?

PurposeNeuroimaging studies have shown that anosmia is accompanied by a decreased olfactory bulb volume, yet little is known about alterations in cerebral and cerebellar lobule volumes. The purpose of this study was to investigate structural brain alterations in anosmic patients. MethodsSixteen anosmic patients (mean age 42.62 ± 16.57 years; 6 women and 10 men) and 16 healthy controls (mean age 43.37 ± 18.98 years; 9 women and 7 men) were included in this retrospective study. All subjects who underwent magnetic resonance imaging scans were analyzed using VolBrain and voxel-based morphometry after olfactory testing. ResultsDespite being statistically insignificant, analysis using VBM revealed greater gray matter (GM) and white matter in the anosmia group compared to the healthy subjects. However, decreased GM (p < 0.001) and increased cerebellar (p = 0.046) volumes were observed in the anosmic patients. ConclusionsThe study revealed structural brain alterations in specific areas beyond the olfactory bulb. Our results indicate that the cerebellum may play an exceptional role in the olfactory process and that this will be worth evaluating with further dynamic neuroimaging studies.

The relationship between drop vertical jump action-observation brain activity and kinesiophobia after anterior cruciate ligament reconstruction: A cross-sectional fMRI study.

Injury and reconstruction of anterior cruciate ligament (ACL) result in central nervous system alteration to control the muscles around the knee joint. Most individuals with ACL reconstruction (ACLR) experience kinesiophobia which can prevent them from returning to activity and is associated with negative outcomes after ACLR. However, it is unknown if kinesiophobia alters brain activity after ACL injury. To compare brain activity between an ACLR group and matched uninjured controls during an action-observation drop vertical jump (AO-DVJ) paradigm and to explore the association between kinesiophobia and brain activity in the ACLR group. This cross-sectional study enrolled 26 individuals, 13 with ACLR (5 males and 8 females, 20.62±1.93 years, 1.71±0.1m, 68.42±14.75kg) and 13 matched uninjured controls (5 males and 8 females, 22.92±3.17 years, 1.74±0.10m, 70.48±15.38kg). Individuals were matched on sex and activity level. Participants completed the Tampa Scale of Kinesiophobia-11 (TSK-11) to evaluate the level of movement-related fear. To assay the brain activity associated with a functional movement, the current study employed an action-observation/motor imagery paradigm during functional magnetic resonance imaging (fMRI). The ACLR group had lower brain activity in the right ventrolateral prefrontal cortex relative to the uninjured control group. Brain activity of the left cerebellum Crus I and Crus II, the right cerebellum lobule IX, amygdala, middle temporal gyrus, and temporal pole were positively correlated with TSK-11 scores in the ACLR group. Brain activity for the AO-DVJ paradigm was different between the ACLR group and uninjured controls. Secondly, in participants with ACLR, there was a positive relationship between TSK-11 scores and activity in brain areas engaged in fear and cognitive processes during the AO-DVJ paradigm.

Aberrant single-subject morphological cerebellar connectome in chronic insomnia

BackgroundTo systematically investigate the topological organisation of morphological networks of the cerebellum using structural MRI and examine their clinical relevance in chronic insomnia (CI). MethodsOne hundred and one patients with CI and 102 healthy controls (HCs) were recruited in this study. Individual morphological networks of the cerebellum were constructed based on regional grey matter volume, and topologically characterised using weighted graph theory-based network approaches. Between-group comparisons were performed using permutation tests, and Spearman’s correlation was used to examine the relationships between topological alterations and clinical variables. ResultsCompared with HCs, patients with CI exhibited a lower normalised clustering coefficient. Locally, CI patients exhibited lower nodal efficiency in the cerebellar lobule VIIb and vermis regions, but higher nodal efficiency in the right cerebellar lobule VIIIa regions. No correlations were observed between network alterations and clinical variables. ConclusionsIndividual morphological network analysis provides a new strategy for investigating cerebellar morphometric changes in CI, and our findings may have important implications in establishing diagnostic and categorical biomarkers.

Sleep deprivation aggravated amyloid β oligomers-induced damage to the cerebellum of rats: Evidence from magnetic resonance imaging

For quite a long time, researches on Alzheimer's disease (AD) primarily focused on the cortex and hippocampus, while the cerebellum has been ignored because of its abnormalities considered to appear in the late stage of AD. In recent years, increasing evidence suggest that the cerebellar pathological changes possibly occur in the preclinical phase of AD, which is also associated with sleep disorder. Sleep disturbance is a high risk factor of AD. However, the changes and roles of cerebellum has rarely been reported under conditions of AD accompanied with sleep disorders. In this study, using an amyloid-β oligomers (AβO)-induced rat model of AD subjected to sleep deprivation, combining with a 7.0 T animals structural magnetic resonance imaging (MRI), we assessed structural changes of cerebellum in MRI. Our results showed that sleep deprivation combined with AβO led to an increased FA value in the anterior lobe of cerebellum, decreased ADC value in the cerebellar lobes and cerebellar nuclei, and increased cerebellum volume. Besides that, sleep deprivation exacerbated the damage of AβO to the cerebellar structural network. This study demonstrated that sleep deprivation could aggravate the damage to cerebellum induced by AβO. The present findings provide supporting evidence for the involvement of cerebellum in the early pathology of AD and sleep loss. Our data would contribute to advancing the understanding of the mysterious role of cerebellum in AD and sleep disorders, as well as would be helpful for developing non-invasive MRI biomarkers for screening early AD patients with self-reported sleep disturbances.

The motor system is exceptionally vulnerable to absence of the ubiquitously expressed superoxide dismutase-1.

Superoxide dismutase-1 is a ubiquitously expressed antioxidant enzyme. Mutations in SOD1 can cause amyotrophic lateral sclerosis, probably via a toxic gain-of-function involving protein aggregation and prion-like mechanisms. Recently, homozygosity for loss-of-function mutations in SOD1 has been reported in patients presenting with infantile-onset motor neuron disease. We explored the bodily effects of superoxide dismutase-1 enzymatic deficiency in eight children homozygous for the p.C112Wfs*11 truncating mutation. In addition to physical and imaging examinations, we collected blood, urine and skin fibroblast samples. We used a comprehensive panel of clinically established analyses to assess organ function and analysed oxidative stress markers, antioxidant compounds, and the characteristics of the mutant Superoxide dismutase-1. From around 8 months of age, all patients exhibited progressive signs of both upper and lower motor neuron dysfunction, cerebellar, brain stem, and frontal lobe atrophy and elevated plasma neurofilament concentration indicating ongoing axonal damage. The disease progression seemed to slow down over the following years. The p.C112Wfs*11 gene product is unstable, rapidly degraded and no aggregates were found in fibroblast. Most laboratory tests indicated normal organ integrity and only a few modest deviations were found. The patients displayed anaemia with shortened survival of erythrocytes containing decreased levels of reduced glutathione. A variety of other antioxidants and oxidant damage markers were within normal range. In conclusion, non-neuronal organs in humans show a remarkable tolerance to absence of Superoxide dismutase-1 enzymatic activity. The study highlights the enigmatic specific vulnerability of the motor system to both gain-of-function mutations in SOD1 and loss of the enzyme as in the here depicted infantile superoxide dismutase-1 deficiency syndrome.

Orbitofrontal cortex functional connectivity changes in patients with binge eating disorder and bulimia nervosa.

We aimed to define the shared and unshared functional neurobiological underpinnings of binge eating disorder (BED) and bulimia nervosa (BN). These disorders both involve loss of control over binge eating, but differ based on purging behavior and body image distortion. BED and BN have also been found to show differences in brain activation patterns in reward sensitivity. We enrolled 13 and 12 drug-naive and medication-free women with BED and BN, respectively, and 22 age- and sex-matched healthy controls. We performed an orbitofrontal cortex (OFC)-seeded resting-state whole brain functional connectivity (FC) analysis among the groups. In this study, BED patients exhibited significantly higher impulsivity than controls, whereas the difference in impulsivity between BN and controls was not significant. Participants with BED and BN showed weaker FC between the left lateral OFC and the right precuneus than controls. In the BED only group, the FC strength between these regions was negatively correlated with self-reported impulsivity. In both BED and BN, FC between the left lateral OFC and the right dorsolateral prefrontal cortex was weaker than that in controls. In BED, FC between the left medial OFC and the right cerebellar lobule IV was stronger than that of other groups. Our current results suggest similarities and differences between BED and BN in OFC-seeded FC with respect to reward processing. In particular, FC of the OFC in BED patients showed a significant correlation with their high impulsivity, which may reflect a decline in executive control over binge eating.

Cortical and cerebellar structural correlates of cognitive-motor integration performance in females with and without persistent concussion symptoms

ABSTRACT Introduction Fifteen percent of individuals who sustain a concussion develop persistent concussion symptoms (PCS). Recent literature has demonstrated atrophy of the frontal, parietal, and cerebellar regions following acute concussive injury. The frontoparietal-cerebellar network is essential for the performance of visuomotor transformation tasks requiring cognitive-motor integration (CMI), important for daily function. Purpose We investigated cortical and subcortical structural differences and how these differences are associated with CMI performance in those with PCS versus healthy controls. Methods Twenty-six age-matched female participants (13 PCS, 13 healthy) completed four visuomotor tasks. Additionally, MR-images were analyzed for cortical thickness and volume, and cerebellar lobule volume. Results No statistically significant group differences were found in CMI performance. However, those with PCS demonstrated a significantly thicker and larger precuneus, and significantly smaller cerebellar lobules (VIIIa, VIIIb, X) compared to controls. When groups were combined, volumes of both the cerebellar lobules and cortical regions were associated with CMI task performance. Conclusion The lack of behavioral differences combined with the structural differences may reflect a compensatory mechanism for those with PCS. In addition, this study highlights the effectiveness of CMI tasks in estimating the structural integrity of the frontoparietal-cerebellar network and is among the first to demonstrate structural correlates of PCS.