Cerebellar Regions Of Interest Research Articles

Understanding the role of cerebellum in early Parkinson’s disease: a structural and functional MRI study

Increasing evidence suggests that the cerebellum may have a role in the pathophysiology of Parkinson’s disease (PD). Hence, the scope of this study was to investigate whether there are structural and functional alterations of the cerebellum and whether they correlate with motor and non-motor symptoms in early PD patients. Seventy-six patients with early PD and thirty-one age and sex-matched healthy subjects (HS) were enrolled and underwent a 3 T magnetic resonance imaging (MRI) protocol. The following MRI analyses were performed: (1) volumes of 5 cerebellar regions of interest (sensorimotor and cognitive cerebellum, dentate, interposed, and fastigial nuclei); (2) microstructural integrity of the cerebellar white matter connections (inferior, middle, and superior cerebellar peduncles); (3) functional connectivity at rest of the 5 regions of interest already described in point 1 with the rest of brain. Compared to controls, early PD patients showed a significant decrease in gray matter volume of the dentate, interposed and fastigial nuclei, bilaterally. They also showed abnormal, bilateral white matter microstructural integrity in all 3 cerebellar peduncles. Functional connectivity of the 5 cerebellar regions of interest with several areas in the midbrain, basal ganglia and cerebral cortex was altered. Finally, there was a positive correlation between abnormal functional connectivity of the fastigial nucleus with the volume of the nucleus itself and a negative correlation with axial symptoms severity. Our results showed that structural and functional alterations of the cerebellum are present in PD patients and these changes contribute to the pathophysiology of PD in the early phase.

Daily artificial gravity partially mitigates vestibular processing changes associated with head-down tilt bedrest

Microgravity alters vestibular signaling and reduces body loading, driving sensory reweighting. The unloading effects can be modelled using head-down tilt bedrest (HDT). Artificial gravity (AG) has been hypothesized to serve as an integrated countermeasure for the declines associated with HDT and spaceflight. Here, we examined the efficacy of 30 min of daily AG to counteract brain and behavior changes from 60 days of HDT. Two groups received 30 min of AG delivered via short-arm centrifuge daily (n = 8 per condition), either in one continuous bout, or in 6 bouts of 5 min. To improve statistical power, we combined these groups (AG; n = 16). Another group served as controls in HDT with no AG (CTRL; n = 8). We examined how HDT and AG affect vestibular processing by collecting fMRI scans during vestibular stimulation. We collected these data prior to, during, and post-HDT. We assessed brain activation initially in 12 regions of interest (ROIs) and then conducted an exploratory whole brain analysis. The AG group showed no changes in activation during vestibular stimulation in a cerebellar ROI, whereas the CTRL group showed decreased activation specific to HDT. Those that received AG and showed little pre- to post-HDT changes in left vestibular cortex activation had better post-HDT balance performance. Whole brain analyses identified increased pre- to during-HDT activation in CTRLs in the right precentral gyrus and right inferior frontal gyrus, whereas AG maintained pre-HDT activation levels. These results indicate that AG could mitigate activation changes in vestibular processing that is associated with better balance performance.

NCOG-37. MICROSTRUCTURAL CEREBELLAR INJURY IS ASSOCIATED WITH PROCESSING SPEED DECLINE IN ADULTS WITH PRIMARY BRAIN TUMORS: IMPLICATIONS FOR COGNITIVE PRESERVATION

Abstract PURPOSE We investigated associations between imaging biomarkers of cerebellar injury and neurocognitive function among primary brain tumor patients receiving partial brain radiotherapy (RT). METHODS On a prospective trial, 65 patients underwent volumetric brain MRI, diffusion tensor imaging, and memory, executive function, language, attention, and processing speed (PS) assessment pre-, 3, 6, and 12 months post-RT. Delis-Kaplan Executive Function System Trail Making [DKEFS-TM] Visual Scanning and Number and Letter Sequencing and Wechsler-Adult Intelligence Scale-IV [WAIS] Coding subtests evaluated PS. Cerebellar regions of interest (ROIs) were autosegmented, including cortex and white matter (WM). Supratentorial cortical and WM structures subserving the above cognitive domains were also autosegmented. Supratentorial PS-associated ROIs included the posterior, mid-posterior, central, mid-anterior, and anterior corpus callosum along with the bilateral intrahemispheric WM. Volume (cm3) was measured in all ROIs at each timepoint. Diffusion biomarkers (fractional anisotropy [FA] and mean diffusivity [MD]) were measured in all WM structures at each timepoint. Linear mixed-effects models assessed cerebellar biomarkers as predictors of neurocognitive scores. If found to be associated, cerebellar biomarkers were subsequently evaluated as predictors of cognitive scores controlling for domain-specific supratentorial ROI biomarkers. RESULTS Left (p=0.04) and right (p< 0.001) cerebellar WM volume declined over time. Cerebellar biomarkers were not associated with memory, executive function, or language. Left cerebellar cortex atrophy correlated with worse DKEFS-TM Number (p=0.01) and Letter (p=0.01) Sequencing scores. Right cerebellar cortex atrophy correlated with worse DKEFS-TM Visual Scanning (p=0.02) and Number (p=0.03) and Letter (p=0.02) Sequencing scores. Greater right cerebellar WM MD correlated with worse DKFS-TM Visual Scanning performance (p=0.03). These associations remained significant after controlling for corpus callosum and intrahemispheric WM injury biomarkers. CONCLUSION Biomarkers of cerebellar injury correlated with worse post-RT PS, independent of corpus callosum and intrahemispheric WM damage. Cerebellar dose avoidance may preserve PS.

Cerebellar Volumes and Sensorimotor Behavior in Autism Spectrum Disorder.

BackgroundSensorimotor issues are common in autism spectrum disorder (ASD), though their neural bases are not well understood. The cerebellum is vital to sensorimotor control and reduced cerebellar volumes in ASD have been documented. Our study examined the extent to which cerebellar volumes are associated with multiple sensorimotor behaviors in ASD.Materials and MethodsFifty-eight participants with ASD and 34 typically developing (TD) controls (8–30 years) completed a structural MRI scan and precision grip testing, oculomotor testing, or both. Force variability during precision gripping as well as absolute error and trial-to-trial error variability of visually guided saccades were examined. Volumes of cerebellar lobules, vermis, and white matter were quantified. The relationships between each cerebellar region of interest (ROI) and force variability, saccade error, and saccade error variability were examined.ResultsRelative to TD controls, individuals with ASD showed increased force variability. Individuals with ASD showed a reduced volume of cerebellar vermis VI-VII relative to TD controls. Relative to TD females, females with ASD showed a reduced volume of bilateral cerebellar Crus II/lobule VIIB. Increased volume of Crus I was associated with increased force variability. Increased volume of vermal lobules VI-VII was associated with reduced saccade error for TD controls but not individuals with ASD. Increased right lobule VIII and cerebellar white matter volumes as well as reduced right lobule VI and right lobule X volumes were associated with greater ASD symptom severity. Reduced volumes of right Crus II/lobule VIIB were associated with greater ASD symptom severity in only males, while reduced volumes of right Crus I were associated with more severe restricted and repetitive behaviors only in females.ConclusionOur finding that increased force variability in ASD is associated with greater cerebellar Crus I volumes indicates that disruption of sensory feedback processing supported by Crus I may contribute to skeletomotor differences in ASD. Results showing that volumes of vermal lobules VI-VII are associated with saccade precision in TD but not ASD implicates atypical organization of the brain systems supporting oculomotor control in ASD. Associations between volumes of cerebellar subregions and ASD symptom severity suggest cerebellar pathological processes may contribute to multiple developmental challenges in ASD.

316 Frontal-cerebellar EEG source localization and functional connectivity as predictors of Alzheimer’s disease-related cognitive decline

OBJECTIVES/GOALS: Novel EEG source localization and functional connectivity will assess frontal and cerebellar activity as predictors of subsequent memory and executive functioning (EF) decline in healthy, asymptomatic older adults who carry the Apolipoprotein-E ε4 allele (ε4+), which conveys up to 12x increased risk for Alzheimers disease (AD). METHODS/STUDY POPULATION: Healthy, cognitively intact ε4+ older adults (n = 23; ages 65-89) completed neuropsychological testing (focus on memory and EF) and EEG at Time 1, returning an average of one year later for neuropsychological retesting. EEG data during successful stop-signal inhibitory control trials will be used for advanced source localization and functional connectivity, with a focus on frontal and cerebellar regions of interest (ROIs). Source analyses will focus on the N200 time window (~200-350ms) to assess conflict processing and P300 (~300-550ms) for performance evaluation. Connectivity analyses are frequency-based, and will focus on theta band connectivity to assess conflict processing and delta to assess performance evaluation. RESULTS/ANTICIPATED RESULTS: Using hierarchical linear regression models, the magnitude of source activation within ROIs and connectivity metrics between ROIs will be used to predict residualized change in memory and executive function metrics between Time 1 and Time 2. We anticipate that 1) greater, compensatory activation in frontal ROIs during the N200 window, and 2) less cerebellar activation during P300, will predict memory and executive decline over the retest interval. Decline will also be predicted by 3) greater inter-hemispheric frontal connectivity in the theta band (conflict processing) and 4) less frontal-cerebellar delta connectivity (performance evaluation). DISCUSSION/SIGNIFICANCE: At most, ~50% of ε4 carriers will develop AD. Thus, identifying which carriers will decline is crucial to enabling successful, early intervention. Cerebellar dysfunction and impaired connectivity may be among the earliest indicators of incipient AD. Cutting-edge cerebellar EEG may enable an accessible option for early discernment of AD risk.

Cerebello-cerebral Functional Connectivity Networks in Major Depressive Disorder: a CAN-BIND-1 Study Report.

Neuroimaging studies have demonstrated aberrant structure and function of the "cognitive-affective cerebellum" in major depressive disorder (MDD), although the specific role of the cerebello-cerebral circuitry in this population remains largely uninvestigated. The objective of this study was to delineate the role of cerebellar functional networks in depression. A total of 308 unmedicated participants completed resting-state functional magnetic resonance imaging scans, of which 247 (148 MDD; 99 healthy controls, HC) were suitable for this study. Seed-based resting-state functional connectivity (RsFc) analysis was performed using three cerebellar regions of interest (ROIs): ROI1 corresponded to default mode network (DMN)/inattentive processing; ROI2 corresponded to attentional networks, including frontoparietal, dorsal attention, and ventral attention; ROI3 corresponded to motor processing. These ROIs were delineated based on prior functional gradient analyses of the cerebellum. A general linear model was used to perform within-group and between-group comparisons. In comparison to HC, participants with MDD displayed increased RsFc within the cerebello-cerebral DMN (ROI1) and significantly elevated RsFc between the cerebellar ROI1 and bilateral angular gyrus at a voxel threshold (p < 0.001, two-tailed) and at a cluster level (p < 0.05, FDR-corrected). Group differences were non-significant for ROI2 and ROI3. These results contribute to the development of a systems neuroscience approach to the diagnosis and treatment of MDD. Specifically, our findings confirm previously reported associations between MDD, DMN, and cerebellum, and highlight the promising role of these functional and anatomical locations for the development of novel imaging-based biomarkers and targets for neuromodulation therapies. ClinicalTrials.gov TRN: NCT01655706; Date of Registration: August 2nd, 2012.

Automatic classification of idiopathic Parkinson’s disease and atypical Parkinsonian syndromes combining [11C]raclopride PET uptake and MRI grey matter morphometry

Objective. To explore the viability of developing a computer-aided diagnostic system for Parkinsonian syndromes using dynamic [11C]raclopride positron emission tomography (PET) and T1-weighted magnetic resonance imaging (MRI) data. Approach. The biological heterogeneity of Parkinsonian syndromes renders their statistical classification a challenge. The unique combination of structural and molecular imaging data allowed different classifier designs to be tested. Datasets from dynamic [11C]raclopride PET and T1-weighted MRI scans were acquired from six groups of participants. There were healthy controls (CTRL n = 15), patients with Parkinson’s disease (PD n = 27), multiple system atrophy (MSA n = 8), corticobasal degeneration (CBD n = 6), and dementia with Lewy bodies (DLB n = 5). MSA, CBD, and DLB patients were classified into one category designated as atypical Parkinsonism (AP). The distribution volume ratio (DVR) kinetic parameters obtained from the PET data were used to quantify the reversible tracer binding to D2/D3 receptors in the subcortical regions of interest (ROI). The grey matter (GM) volumes obtained from the MRI data were used to quantify GM atrophy across cortical, subcortical, and cerebellar ROI. Results. The classifiers CTRL vs PD and CTRL vs AP achieved the highest balanced accuracy combining DVR and GM (DVR-GM) features (96.7%, 92.1%, respectively), followed by the classifiers designed with DVR features (93.3%, 88.8%, respectively), and GM features (69.6%, 86.1%, respectively). In contrast, the classifier PD vs AP showed the highest balanced accuracy (78.9%) using DVR features only. The integration of DVR-GM (77.9%) and GM features (72.7%) produced inferior performances. The classifier CTRL vs PD vs AP showed high weighted balanced accuracy when DVR (80.5%) or DVR-GM features (79.9%) were integrated. GM features revealed poorer performance (59.5%). Significance. This work was unique in its combination of structural and molecular imaging features in binary and triple category classifications. We were able to demonstrate improved binary classification of healthy/diseased status (concerning both PD and AP) and equate performance to DVR features in multiclass classifications.

Abnormal effective connectivity in the sensory network in writer’s cramp

BackgroundWriter’s cramp (WC), a task specific form of dystonia, is considered to be a motor network disorder, but abnormal sensory tactile processing has also been acknowledged. The sensory spatial discrimination threshold (SDT) can be determined with a spatial acuity test (JVP domes). In addition to increased SDT, patients with WC exhibited dysfunctional sensory processing in the sensory cortex, insula, basal ganglia and cerebellum in a functional magnetic resonance imaging (fMRI) study while performing the spatial acuity test. ObjectivesTo assess whether effective connectivity (EC) in the sensory network including cortical, basal ganglia, thalamic and cerebellar regions of interest in WC patients is abnormal. MethodsWe used fMRI and applied a block design, while 19 WC patients and 13 age-matched healthy controls performed a spatial discrimination task. Before we assessed EC using dynamic causal modelling, we compared three model structures based on the current literature. We enclosed regions of interest that are established for sensory processing during right hand stimulation: Left thalamus, somatosensory, parietal and insular cortex, posterior putamen, and right cerebellum. ResultsThe EC analysis revealed task-dependent decreased unidirectional connectivity between the insula and the posterior putamen. The connectivity involving the primary sensory cortex, parietal cortex and cerebellum were not abnormal in WC. The two groups showed no differences in their behavioural data. ConclusionsPerception and integration of sensory information requires the exchange of information between the insula cortex and the putamen, a sensory process that was disturbed in WC patients.

Alterations in Cerebellar Functional Connectivity Are Correlated With Decreased Psychomotor Vigilance Following Total Sleep Deprivation.

Previous studies have reported significant changes in functional connectivity among various brain networks following sleep restriction. The cerebellum plays an important role in information processing for motor control and provides this information to higher-order networks. However, little is known regarding how sleep deprivation influences functional connectivity between the cerebellum and the cerebral cortex in humans. The present study aimed to investigate the changes in cerebellar functional connectivity induced by sleep deprivation, and their relationship with psychomotor vigilance. A total of 52 healthy men underwent resting-state functional magnetic resonance imaging before and after 36 h of total sleep deprivation. Functional connectivity was evaluated using region of interest (ROI)-to-ROI analyses, using 26 cerebellar ROIs as seed regions. Psychomotor vigilance was assessed using the psychomotor vigilance test (PVT). Decreased functional connectivity was observed between cerebellar seed regions and the bilateral postcentral, left inferior frontal, left superior medial frontal, and right middle temporal gyri. In contrast, increased functional connectivity was observed between the cerebellum and the bilateral caudate. Furthermore, decrease in functional connectivity between the cerebellum and the postcentral gyrus was negatively correlated with increase in PVT reaction times, while increase in functional connectivity between the cerebellum and the bilateral caudate was positively correlated with increase in PVT reaction times. These results imply that altered cerebellar functional connectivity is associated with impairment in psychomotor vigilance induced by sleep deprivation.

Accuracy of brain perfusion single-photon emission computed tomography for detecting misery perfusion in adult patients with symptomatic ischemic moyamoya disease.

The purpose of the present study was to determine how accurately relative cerebral blood flow (RCBF) and relative cerebrovascular reactivity (RCVR) to acetazolamide assessed using brain perfusion single-photon emission computed tomography (SPECT) detected misery perfusion identified on positron emission tomography (PET) in adult patients with ischemic moyamoya disease (MMD). Oxygen extraction fraction (OEF), RCBF, and RCVR were assessed using 15O gas PET and N-isopropyl-p-[123I]-iodoamphetamine SPECT without and with acetazolamide challenge, respectively, in 45 patients. Regions of interest (ROIs) were automatically placed in the five middle cerebral artery (MCA) territories in the symptomatic cerebral hemisphere and in the ipsilateral cerebellar hemisphere using a three-dimensional stereotaxic ROI template. For RCBF and RCVR to acetazolamide, the ratio of the MCA ROI to cerebellar ROI was calculated. Of the five MCA ROIs in the symptomatic cerebral hemisphere in each patient, the ROI with the highest and lowest OEF value (two ROIs per patient) was selected for analyses. A significant square or linear correlation was observed between the OEF and RCBF (correlation coefficient, 0.780) or RCVR (correlation coefficient, - 0.345), respectively. The area under the receiver operating characteristic curve for detecting misery perfusion (OEF > 51.3%) was significantly greater for the RCBF than for the RCVR (difference between areas, 0.221; p < 0.0001). Sensitivity, specificity, and positive- and negative-predictive values for the RCBF for detecting misery perfusion were 100, 91, 67, and 100%, respectively. The specificity and positive-predictive value did not differ between the combination of the RCBF and RCVR and the CBF ratio alone. RCBF assessed using brain perfusion SPECT detects misery perfusion with high sensitivity, a high negative-predictive value, and a low positive-predictive value in adult patients with ischemic MMD. The accuracy of RCVR to acetazolamide assessed using brain perfusion SPECT is lower than that of RCBF.

The diminishing dominance of the dominant hemisphere: Language fMRI in focal epilepsy.

“Which is the dominant hemisphere?” is a question that arises frequently in patients considered for neurosurgery. The concept of the dominant hemisphere implies uniformity of language lateralisation throughout the brain. It is increasingly recognised that this is not the case in the healthy control brain, and it is especially not so in neurological diseases such as epilepsy.In the present work we adapt our published objective lateralisation method (based on the construction of laterality curves) for use with sub-lobar cortical, subcortical and cerebellar regions of interest (ROIs). We apply this method to investigate regional lateralisation of language activation in 12 healthy controls and 18 focal epilepsy patients, using three different block design language fMRI paradigms, each tapping different aspects of language processing. We compared lateralisation within each ROI across tasks, and investigated how the quantity of data collected affected the ability to robustly estimate laterality across ROIs.In controls, lateralisation was stronger, and the variance across individuals smaller, in cortical ROIs, particularly in the Inferior Frontal (Broca) region. Lateralisation within temporal ROIs was dependent on the nature of the language task employed. One of the healthy controls was left lateralised anteriorly and right lateralised posteriorly. Consistent with previous work, departures from normality occurred in ~ 15–50% of focal epilepsy patients across the different ROIs, with atypicality most common in the Lateral Temporal (Wernicke) region. Across tasks and ROIs the absolute magnitude of the laterality estimate increased and its across participant variance decreased as more cycles of task and rest were included, stabilising at ~ 4 cycles (~ 4 min of data collection).Our data highlight the importance of considering language as a complex task where lateralisation varies at the subhemispheric scale. This is especially important for presurgical planning for focal resections where the concept of ‘hemispheric dominance’ may be misleading. This is a precision medicine approach that enables objective evaluation of language dominance within specific brain regions and can reveal surprising and unexpected anomalies that may be clinically important for individual cases.

PTPS-18APPARENT DIFFUSION COEFFICIENT MEASUREMENT IN PATIENTS WITH DIFFUSE INTRINSIC PONTINE GLIIOMA (DIPG): WORK-IN-PROGRESS

BACKGROUND: Pediatric diffuse intrinsic pontine gliomas (DIPG) are pediatric brain tumors with an extremely poor prognosis. Diagnosis has historically been based on magnetic resonance (MR) imaging appearance of the lesion, which demonstrates an expansile pontine lesion; T1 hypo-/T2 hyperintense and without significant contrast enhancement. These imaging findings change during the course of treatment. Efforts have focused on identifying prognostically significant, quantifiable MR characteristics. PURPOSE: Measure the apparent diffusion coefficient (ADC) on serial MR examinations in patients with DIPG. SUBJECTS/METHODS: Medical records of 7 subjects, (2.11 -54.6 years), with the diagnosis of pontine glioma and diffusion imaging were reviewed. MR studies were retrieved from the online Agfa archives. After reviewing the MRIs, images with the most significant enhancing tumor/disease were identified from each patient's most recent/last imaging series. Regions of interest (ROIs) were drawn on the corresponding slices on the ADC maps. Similar ROIs were drawn on the same slices from prior examinations for each patient. Control ROI was obtained from measurements on normal appearing cerebellar white matter bilaterally. ADC values were recorded. Right and left values were combined for the pontine and cerebellar ROIs. Adjusted values were calculated for time points by dividing the pontine by the cerebellar value compensating for differences in the diffusion B-Value and scanner to scanner imaging parameter variability. Adjusted ADC values were plotted against the patient's age at the time of each MRI. A graph with ADC value vs. the number days remaining before patient's death (or last imaging study) was generated, reflecting patient's survival. RESULTS: We identified different patterns of change in the ADC over time for each patient. ADC values were higher than normal in all patients though interpatient variability was noted. Clinical significance of these differences is unclear at present. Correlation with clinical parameters, treatments and survival time is a work-in-progress.

Cerebro-cerebellar Resting-State Functional Connectivity in Children and Adolescents with Autism Spectrum Disorder

BackgroundThe cerebellum plays important roles in sensori-motor and supramodal cognitive functions. Cellular, volumetric, and functional abnormalities of the cerebellum have been found in autism spectrum disorders (ASD), but no comprehensive investigation of cerebro-cerebellar connectivity in ASD is available. MethodsWe used resting-state functional connectivity magnetic resonance imaging in 56 children and adolescents (28 subjects with ASD, 28 typically developing subjects) 8–17 years old. Partial and total correlation analyses were performed for unilateral regions of interest (ROIs), distinguished in two broad domains as sensori-motor (premotor/primary motor, somatosensory, superior temporal, and occipital) and supramodal (prefrontal, posterior parietal, and inferior and middle temporal). ResultsThere were three main findings: 1) Total correlation analyses showed predominant cerebro-cerebellar functional overconnectivity in the ASD group; 2) partial correlation analyses that emphasized domain specificity (sensori-motor vs. supramodal) indicated a pattern of robustly increased connectivity in the ASD group (compared with the typically developing group) for sensori-motor ROIs but predominantly reduced connectivity for supramodal ROIs; and 3) this atypical pattern of connectivity was supported by significantly increased noncanonical connections (between sensori-motor cerebral and supramodal cerebellar ROIs and vice versa) in the ASD group. ConclusionsOur findings indicate that sensori-motor intrinsic functional connectivity is atypically increased in ASD, at the expense of connectivity supporting cerebellar participation in supramodal cognition.

Perfusion-weighted magnetic resonance imaging detects recurrent isolated vertigo caused by cerebral hypoperfusion

Aim of the study: The etiology of isolated vertigo has been a substantial diagnostic challenge for both neurologists and otolaryngologists. This study was designed to detect recurrent isolated vertigo due to cerebral hypoperfusion using perfusion-weighted magnetic resonance imaging (PWI). Methods: We recruited isolated vertigo patients whose clinical condition was suspected to be caused by hypodynamics of the brain; these individuals formed the case group. We generated two additional groups: a negative group composed of vertigo patients whose symptoms were caused by problems associated with the ear and a healthy control group. Each subject underwent PWI, and seven regions of interest (ROIs) were chosen. The relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and mean transit time (MTT) were obtained from each ROI. We further calculated the absolute difference of relative parameter values between two mirrored ROIs. Results: The significant difference in the relative MTT from the mirrored cerebellar ROI (|rMTTleft-right|) of the case group was larger than those from the negative and healthy control groups (p = 0.026 and p = 0.038, respectively). Signal differences in |rrCBVleft-right| and |rrCBFleft-right| were not found among the three groups. Conclusions: In summary, disequilibrium in the rMTT of the bilateral cerebellum in the case group implied that hypoperfusion of the posterior circulation could trigger recurrent isolated vertigo and could be shown efficiently using PWI.

Distinct regions of the cerebellum show gray matter decreases in autism, ADHD, and developmental dyslexia.

Differences in cerebellar structure have been identified in autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and developmental dyslexia. However, it is not clear if different cerebellar regions are involved in each disorder, and thus whether cerebellar anatomical differences reflect a generic developmental vulnerability or disorder-specific characteristics. To clarify this, we conducted an anatomic likelihood estimate (ALE) meta-analysis on voxel-based morphometry (VBM) studies which compared ASD (17 studies), ADHD (10 studies), and dyslexic (10 studies) participants with age-matched typically-developing (TD) controls. A second ALE analysis included studies in which the cerebellum was a region of interest (ROI). There were no regions of significantly increased gray matter (GM) in the cerebellum in ASD, ADHD, or dyslexia. Data from ASD studies revealed reduced GM in the inferior cerebellar vermis (lobule IX), left lobule VIIIB, and right Crus I. In ADHD, significantly decreased GM was found bilaterally in lobule IX, whereas participants with developmental dyslexia showed GM decreases in left lobule VI. There was no overlap between the cerebellar clusters identified in each disorder. We evaluated the functional significance of the regions revealed in both whole-brain and cerebellar ROI ALE analyses using Buckner and colleagues' 7-network functional connectivity map available in the SUIT cerebellar atlas. The cerebellar regions identified in ASD showed functional connectivity with frontoparietal, default mode, somatomotor, and limbic networks; in ADHD, the clusters were part of dorsal and ventral attention networks; and in dyslexia, the clusters involved ventral attention, frontoparietal, and default mode networks. The results suggest that different cerebellar regions are affected in ASD, ADHD, and dyslexia, and these cerebellar regions participate in functional networks that are consistent with the characteristic symptoms of each disorder.

Resting-state fMRI mapping of cerebellar functional dysconnections involving multiple large-scale networks in patients with schizophrenia

BackgroundRecent findings have indicated that patients with schizophrenia have altered cortico–cerebellar connectivity, but the nature of these network dysconnections remains unclear. AimsWe applied a network-based approach to investigate the functional connectivity (FC) of the cerebellum in patients with schizophrenia. MethodsThirty-six patients with schizophrenia and 36 healthy controls underwent resting functional magnetic resonance imaging. We derived the following 6 major networks by applying group independent component analysis: (1) the cingulo-opercular network (CON); (2) the dorsal default-mode networks (dDMN); (3) the ventral default-mode network (vDMN); (4) the left frontoparietal networks (lFPN); (5) the right frontoparietal network (rFPN); and (6) the motor network (MOT). We defined 12 regions of interest (ROIs) by selecting the first 2 peaks of each network in the cerebellum. The FC map of all ROIs was calculated for each participant and compared between groups. ResultsThe schizophrenic patients showed a decrease in FC between the cerebellar ROIs and the thalamus in all networks except the MOT. The FC decreased between cerebellar ROIs and the frontal cortex in the CON, rFPN, and MOT. However, the FC increased with the precentral gyrus and postcentral gyrus for the CON, lFPN, and dDMN. An increased FC with the occipital fusiform gyrus and the temporal occipital fusiform gyrus was also noted in the dDMN, vDMN, and MOT. ConclusionsThe dysconnection of the cerebellum in the examined patients with schizophrenia was network-specific. The cerebellar–thalamic dysconnections were the most prominent findings and were common to all cognitive-related networks, whereas the cortico–cerebellar connectivity involved both an increase and decrease in FC, and depended more on the nature of the specific network.

An atlas-based image registration method for dopamine receptor imaging with PET in rats

For analysis of in vivo dopamine receptor binding in the rat brain by positron emission tomography (PET), a convenient method to obtain precise anatomical registration for striatum and cerebellum on the PET image was developed. On the PET measurements, a control, an anesthetized rat was positioned in a stereotaxic holder so that the horizontal plane of the PET image would be parallel to the horizontal plane of the brain atlas. After the positioning, [11C]raclopride was intravenously injected into the rats and scanned to obtain PET images of dopamine D2 receptor in the brain. The striatum was bilaterally identified in the obtained PET image. The atlas-based regions of interest (ROIs) of the whole brain were preliminarily created according to the atlas, and were superimposed on an early phase PET image. The early phase PET image was compatible to the whole brain ROI in the atlas, which enabled determination of striatal and cerebellar ROI difficult to determine by the PET image alone. Using the cerebellar radioactivity as a reference input function, rate constants between the free/nonspecific compartment and the receptor bound compartment (k3 and k4) were calculated by a two-parameter compartment model, and the binding potential (k3/k4) was estimated. The binding potential and its coefficients of variation were 1.56+/-0.30, 19.3% in Wistar rats, 1.05+/-0.14, 13.4% in Sprague-Dawley (SD) rats, and 1.29+/-0.07, 5.2% in Fischer F344 rats, in which binding potential in Wistar rats was significantly higher than that in SD rats. This method is objective and convenient in routine use for PET studies in rats, regardless of differences in the rat strains.

Influence of photon scattering and attenuation on ROI analysis in brain perfusion single-photon emission tomographic imaging of normal subjects

The aim of this study was to evaluate the effect of scatter and attenuation correction in region of interest (ROI) analysis in brain perfusion single-photon emission tomography (SPECT) and to assess the influence of selecting the reference area on semi-quantification. Ten normal subjects were enrolled and injected with 123I-iodoamphetamine to undergo simultaneous emission and transmission scanning for scatter and attenuation correction. We reconstructed three SPECT images from common projection data of each subject: with scatter correction and non-uniform attenuation correction, with scatter correction and uniform attenuation correction, and with uniform attenuation correction applied to data without scatter correction. A program for automated ROI drawing was used to set ROIs on various regions in brain images. Regional count ratios were compared in images with different correction procedures by using three different reference areas. The effect of the combination of scatter and attenuation correction was marked in the precentral, temporal, posterior, hippocampus and especially in the cerebellum. In contrast, it was not appreciable in the central and parietal areas. When using the cerebellar ROI as the reference, the count ratio varied widely depending on the correction procedures. On the other hand, the whole brain reference offered the least variation in the count ratio. The influence of photon scattering and attenuation was dependent on regions. Since the count in the cerebellar ROI is greatly affected by photon scattering and attenuation, nonuniform attenuation correction combined with scatter correction deserves consideration when using the cerebellar ROI as the reference.

Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis

Background: The cerebellum is of potential interest for understanding adaptive responses in motor control in patients with multiple sclerosis because of the high intrinsic synaptic plasticity of this brain region....

Age-specific cerebral perfusion in 4- to 15-year-old children: a high-resolution brain SPET study using 99mTc-ECD.

This study addresses the question of whether the normal range for distribution of local cerebral blood flow (lCBF) in adults can be transferred to the 4- to 15-year-old age group. Twenty-three children (age: 4-15 years; mean 11+/-3 years, group I) and 10 adults (age: 27-56 years; mean 45+/-10 years, group II) without evidence of cerebrovascular disease or other brain diseases underwent technetium-99m ethyl cysteinate dimer single-photon emission tomography. Counts in cortical and subcortical regions of interest (ROIs) were related to those in cerebellar ROIs (= 100%). Relative cortical activity in group I exceeded that in group II, particularly in left parietal (107.6%+/-9.8% vs 84.1%+/-12.4%), left frontal (97. 7%+/-6.7% vs 79.4%+/-8.9%) and left temporal areas (99.7%+/-7.4% vs 84.9%+/-10.1%) and in the cingulate cortex (112.1%+/-9.1% vs 95. 9%+/-10.1%, P<0.05). Cerebral activity uptake per injected dose was inversely correlated with age in 19 children of group I (r = -0.77, P<0.001). In group I, there was also an inverse correlation between age and the relative local count density in the parietal (r = -0.42 to -0.57), frontal (r = -0.48), temporal (r = -0.42 to -0.58) and occipital cortex (r = -0.44). In these cortical regions relative counts differed when subgroups of children aged 4-10 and 11-15 years were analysed. It is concluded that there are systematic differences between 4- to 15-year-old children and adults with regard to normal lCBF. Diagnostic use of perfusion agents has to consider age-adjusted normal flow maps; normal ranges should be determined separately for the age groups 4-10 and 11-15 years.