Imaging Studies Research Articles

Doing a double take: when transthoracic echocardiography fails for mitral valve annuloplasty ring endocarditis with Streptococcus pyogenes: a case report

BackgroundThis case highlights several complications of a late and rare presentation of culture-negative Streptococcus pyogenes endocarditis of a previously repaired mitral valve with an annuloplasty ring including recurrent cardioembolic strokes, which was initially missed on transthoracic echocardiography.Case presentationA 66-year-old Caucasian female with prior mitral valve prolapse status post mitral valve annuloplasty and left atrial appendage occlusion, followed by two strokes, presented with supraventricular tachycardia that resolved spontaneously. During an inpatient admission, she developed symptoms of another stroke, and imaging studies were suggestive of recurrent cardioembolic phenomenon. Additional workup revealed two small intra-atrial masses adherent to the mitral annuloplasty ring missed on prior evaluation for recurrent stroke. She underwent surgical repair in the setting of a chronic culture-negative infectious endocarditis with Streptococcus pyogenes and recovered well with no further cardioembolic phenomenon.ConclusionThis case serves to highlight the importance of having a higher index of suspicion in any cardiac prosthesis patient for endocarditis when presenting with symptoms such as recurrent stroke, arrhythmias, and abnormal cardiac lab work. It also demonstrates the need for appropriate imaging with transthoracic echocardiography followed by transesophageal echocardiography and reviews surgical indications to diagnose and treat culture-negative endocarditis.

Feasibility study of nonlinear ultrasonic imaging using a contact pulse-echo method for fatigue damage evaluation

ABSTRACT A contact pulse-echo nonlinear imaging method is proposed for the detection and localisation of fatigue damage in solid materials. A dual element transducer is designed based on nonlinear wave simulations and manufactured to improve the signal-to-noise ratio of harmonic waves. The transducer is clamped on a fixture device for scanning. The proposed method is introduced for scanning and imaging stainless steel specimens with different fatigue damage states. Experimental results for the specimen in the initial state show that both the fundamental and second harmonic waves are well measured and the imaging of nonlinear parameters is very stable over the scanning area. The imaging results for the specimen with an initial fatigue crack show that the fundamental waves remain the same but the second harmonic waves vary significantly in the potential growth area of the fatigue crack. Furthermore, the imaging results for the seriously fatigued specimen show that the amplitudes of fundamental waves decrease near the fatigue crack, while the amplitudes of second harmonic waves increase. These results indicate that the proposed pulse-echo method is effective for nonlinear ultrasonic imaging and early damage evaluation. The factors affecting the nonlinear waves in the lab experiments and possible problems with practical applications are also discussed for the proposed method.

Altered white matter connectivity of ventral language networks in autism spectrum disorder: An automated fiber quantification analysis with multi-site datasets

Comprehension and pragmatic deficits are prevalent in autism spectrum disorder (ASD) and are potentially linked to altered connectivity in the ventral language networks. However, previous magnetic resonance imaging studies have not sufficiently explored the microstructural abnormalities in the ventral fiber tracts underlying comprehension dysfunction in ASD. Additionally, the precise locations of white matter (WM) changes in the long tracts of patients with ASD remain poorly understood. In the current study, we applied the automated fiber-tract quantification (AFQ) method to investigate the fine-grained WM properties of the ventral language pathway and their relationships with comprehension and symptom manifestation in ASD. The analysis included diffusion/T1 weighted imaging data of 83 individuals with ASD and 83 age-matched typically developing (TD) controls. Case-control comparisons were performed on the diffusion metrics of the ventral tracts at both the global and point-wise levels. We also explored correlations between diffusion metrics, comprehension performance, and ASD traits, and conducted subgroup analyses based on age range to examine developmental moderating effects. Individuals with ASD exhibited remarkable hypoconnectivity in the ventral tracts, particularly in the temporal portions of the left inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF). These WM abnormalities were associated with poor comprehension and more severe ASD symptoms. Furthermore, WM alterations in the ventral tract and their correlation with comprehension dysfunction were more prominent in younger children with ASD than in adolescents. These findings indicate that WM disruptions in the temporal portions of the left ILF/IFOF are most notable in ASD, potentially constituting the core neurological underpinnings of comprehension and communication deficits in autism. Moreover, impaired WM connectivity and comprehension ability in patients with ASD appear to improve with age.

A rare case of giant peritoneal loose body: A case report

Peritoneal loose bodies (PLBs) are uncommon abdominal lesions, typically asymptomatic and discovered incidentally during surgery. Giant PLBs, exceeding 5 cm in size, are even rarer and can present with clinical symptoms mimicking other abdominal pathologies. We present a 57-year-old male with a giant PLB presenting as intermittent abdominal pain, distention, and rectal bleeding. Imaging studies suggested colo-colic intussusception due to a colonic lipoma. The patient underwent an exploratory laparotomy revealing a segment of the descending colon containing multiple lipomas, one causing intussusception. In addition, a separate giant PLB 6 × 5.5 cm with central calcification was identified. A segmental colectomy with primary anastomosis and resection of the PLB was performed. The patient recovered well and reported complete resolution of symptoms at follow-up. Pathology confirmed a benign lipoma and a giant PLB. This case highlights the potential for giant PLBs to cause clinical symptoms and emphasizes the importance of including them in the differential diagnosis of abdominal complaints, even in the absence of a classic presentation. Exploratory laparotomy remains a definitive approach for diagnosis and management in such cases.

Development of a Highly Specific Fluorescent Probe based on Thiol-ene Click Nucleophilic Cascade Reactions for Delving into the Action Mechanism of Serotonin in Depression.

The intrinsic correlation between depression and serotonin (5-HT) is a highly debated topic, with significant implications for the diagnosis, treatment, and advancement of drugs targeting neurological disorders. To address this important question, it is of utmost priority to understand the action mechanism of serotonin in depression through fluorescence imaging studies. However, the development of efficient molecular probes for serotonin is hindered by the lack of responsive sites with high selectivity for serotonin at the present time. Herein, we developed the first highly selective serotonin responsive site, 3-mercaptopropionate, utilizing thiol-ene click cascade nucleophilic reactions. The novel responsive site was then employed to construct the powerful molecular probe SJ-5-HT for imaging the serotonin level changes in the depression cells and brain tissues. Importantly, the imaging studies reveal that the level of serotonin in patients with depression may not be the primary factor, while the ability of neurons in patients with depression to release serotonin appears to be more critical. Additionally, this serotonin release capability correlates strongly with the levels of mTOR (intracellular mammalian target of rapamycin). These discoveries could offer valuable insights into the molecular mechanisms underpinning depression and furnish mTOR as a novel direction for the advancement of antidepressant therapies.

A novel relative-equilibrium graphical plot for rapid reversible tracer studies in dynamic PET imaging.

This study aims to address the issue of long scan durations required by traditional graphical analysis methods, such as the Logan plot and its variant, the reversible equilibrium (RE) Logan plot, for dynamic PET imaging of tracer kinetics. 
Approach: We propose a relative RE Logan model that builds on the principles of the Logan plot and its variant to significantly reduce scan time without compromising the accuracy of tracer kinetics analysis. The model is supported by theoretical evidence and experimental validations, including two computer simulations and one clinical data analysis. 
Main results: The proposed model demonstrates a significant linear relationship between the variable x and the slope DV_T of the RE Logan plot, and the variable x' and the slope DV_T' of the relative RE Logan plot. The Pearson correlation coefficients (r) of the linear fitting of the x' to the x equal 0.9849 in the simulated data and 0.9912 in the clinical data. Similarly, the r value for the linear fitting of DV_T' to DV_T equal 0.9989 and 0.9988 in the simulated data, and 0.9954 in the clinical data. 
Significance: These results demonstrate the model's capability to maintain strong linear relationships and produce parametric images comparable to those of the traditional RE Logan plot, but with the considerable advantage of shorter scan durations. This innovation holds significant potential for enhancing the efficiency and feasibility of PET imaging in clinical settings.

Genetic and multi-omic resources for Alzheimer disease and related dementia from the Knight Alzheimer Disease Research Center

The Knight-Alzheimer Disease Research Center (Knight-ADRC) at Washington University in St. Louis has pioneered and led worldwide seminal studies that have expanded our clinical, social, pathological, and molecular understanding of Alzheimer Disease. Over more than 40 years, research volunteers have been recruited to participate in cognitive, neuropsychologic, imaging, fluid biomarkers, genomic and multi-omic studies. Tissue and longitudinal data collected to foster, facilitate, and support research on dementia and aging. The Genetics and high throughput -omics core (GHTO) have collected of more than 26,000 biological samples from 6,625 Knight-ADRC participants. Samples available include longitudinal DNA, RNA, non-fasted plasma, cerebrospinal fluid pellets, and peripheral blood mononuclear cells. The GHTO has performed deep molecular profiling (genomic, transcriptomic, epigenomic, proteomic, and metabolomic) from large number of brain (n = 2,117), CSF (n = 2,012) and blood/plasma (n = 8,265) samples with the goal of identifying novel risk and protective variants, identify novel molecular biomarkers and causal and druggable targets. Overall, the resources available at GHTO support the increase of our understanding of Alzheimer Disease.

Stationary prospective cardiac gated computed tomography-dynamic study in phantoms and in vivo.

This study explores the feasibility of a stationary gantry cardiac gated computed tomography (CT) with carbon nanotube (CNT) linear x-ray source arrays. Conventional rotational CTs are limited by the rotational forces on the rapidly spinning gantries. We have recently developed a stationary gantry CT system utilizing the multipixel CNT x-ray sources. As these sources also enable straightforward x-ray pulse control, we sought to explore the potential for performing gated prospective imaging with our stationary CT system. Prospective respiratory and cardiac gating control was implemented and the system was evaluated with dynamic phantom imaging studies followed by imaging of a porcine model with cardiac and respiratory gating. The findings revealed minimal motion artifacts, confirming successful physiologic gated acquisition in stationary gantry cardiac CT, showing the potential of this imaging approach.&#xD.

Clinical role of genetic testing for the Brugada syndrome overlapping with arrhythmogenic cardiomyopathy

BackgroundBrugada syndrome (BrS) and arrhythmogenic cardiomyopathy (ACM) are inherited cardiac diseases that may predispose to ventricular arrhythmia. Although overlapping features between BrS and ACM have been demonstrated previously, it remains to be determined whether genetic testing for ACM-related genes is needed in BrS probands.MethodBased on a single-center, retrospective registry of BrS, we aimed to verify genetic profiles of BrS using a next-generation sequencing panel, and further analyzed genetic testing of ACM-related variants in Brugada phenotypes.ResultsAmong a total of 119 Brugada phenotypes, 114 patients (95.8%) were male and the mean age of onset was 43.6 years. Genetic variants were identified in 25 of the 42 patients who underwent genetic testing. Fifteen patients had BrS-related genotypes, including SCN5A in 6 patients, and non-SCN5A genes in 9 patients (SCN10A, HCN4, SCN3B, and KCNE3). Nineteen patients underwent additional genetic testing with cardiomyopathy panel, which revealed ACM-related genotypes (2 PKP2, 1 DSG2, 1 TMEM43, 1 JUP, and 1 DSP) present in 6 patients (31.5%). None of the patients had structural or electrocardiographic features that fulfilled the diagnostic criteria for ACM.ConclusionsIn clinical setting, ACM-related genes were identified in a significant proportion of Brugada phenotypes, supporting the argument that genetic testing of ACM overlapping is needed. Follow-up imaging studies should be considered to monitor if the disease progresses to ACM.

Brain neuroplasticity in multiple sclerosis patients in functional magnetic resonance imaging studies. Part 2: Effect of aerobic training

PurposeThe aim of this study was to evaluate the effects of aerobic training on motor cortical areas in multiple sclerosis (MS) patients, based on task-based functional magnetic resonance imaging (t-fMRI) as well as on brain activity at rest, according to resting state functional MRI (rs-fMRI) studies.Material and methodsMultiple sclerosis patients were divided into 2 groups consisting of 14 participants each: the MS study group and the MS control group. All MS patients underwent clinical assessment and MRI examination, twice: in the MS study group at the time of inclusion in the study and after a 4-week period of aerobic training, whereas in the MS control group it happened at the time of inclusion and after a period of one month without exercise rehabilitation. The MRI study protocol included rs-fMRI and t-fMRI sequences, which were the grounds for an analysis of resting state networks (RSN) as well as peak level and cluster level parameters within motor cortex areas – the primary motor cortex, premotor area, and supplementary motor area, respectively.ResultsIn the MS study group, aerobic training improved the clinical condition and decreased the functional correlation between the sensorimotor network and the salience network. Also, significant decreases of the mean cluster level (72.42 vs. 38.35) and peak level values (10.89 vs. 7.64) were observed in the contralateral primary motor cortex in this group of patients between examinations.ConclusionsAerobic training not only improves physical performance but also contributes to changes in brain activity – both within RSN and motor cortex areas in MS patients.

Synthetic MRI and MR Fingerprinting-Derived Relaxometry of Antenatal Human Brainstem Myelination: A Postmortem-Based Quantitative Imaging Study.

The radiologic evaluation of ongoing myelination is currently limited prenatally. Novel quantitative MR imaging modalities provide relaxometric properties that are linked to myelinogenesis. In this retrospective postmortem imaging study, the capability of Synthetic MR imaging and MR fingerprinting-derived relaxometry for tracking fetal myelin development was investigated. Moreover, the consistency of results for both MR approaches was analyzed. In 26 cases, quantitative postmortem fetal brain MR data were available (gestational age range, 15 + 1 to 32 + 1; female/male ratio, 14/12). Relaxometric measurements (T1-/T2-relexation times) were determined in the medulla oblongata and the midbrain using Synthetic MR imaging/MR fingerprinting-specific postprocessing procedures (Synthetic MR imaging and MR Robust Quantitative Tool for MR fingerprinting). The Pearson correlations were applied to detect relationships between T1-relaxation times/T2-relaxation times metrics and gestational age at MR imaging. Intraclass correlation coefficients were calculated to assess the consistency of the results provided by both modalities. Both modalities provided quantitative data that revealed negative correlations with gestational age at MR imaging: Synthetic MR imaging-derived relaxation times (medulla oblongata [r = -0.459; P = .021]; midbrain [r = -0.413; P = .040]), T2-relaxation times (medulla oblongata [r = -0.625; P < .001]; midbrain [r = -0.571; P = .003]), and MR fingerprinting-derived T1-relaxation times (medulla oblongata [r = -0.433; P = .035]; midbrain [r = -0.386; P = .062]), and T2-relaxation times (medulla oblongata [r =-0.883; P < .001]; midbrain [r = -0.890; P < .001]).The intraclass correlation coefficient analysis for result consistency between both MR approaches ranged between 0.661 (95% CI, 0.351-0.841) (T2-relaxation times: medulla oblongata) and 0.920 (95% CI, 0.82-0.965) (T1-relaxation times: midbrain). There is a good-to-excellent consistency between postmortem Synthetic MR imaging and MR fingerprinting myelin quantifications in fetal brains older than 15 + 1 gestational age. The strong correlations between quantitative myelin metrics and gestational age indicate the potential of quantitative MR imaging to identify delayed or abnormal states of myelination at prenatal stages of cerebral development.

Arterial Spin-Labeling MR Imaging in the Detection of Intracranial Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease that causes vascular malformations in a variety of organs and tissues, including brain AVMs. Because brain AVMs have the potential to cause disabling or fatal intracranial hemorrhage, detection of these lesions before rupture is the goal of screening MR imaging/MRA examinations in patients with HHT. Prior studies have demonstrated superior sensitivity for HHT-related brain AVMs by using postcontrast MR imaging sequences as compared with MRA alone. We now present data regarding the incremental benefit of including arterial spin-labeling (ASL) perfusion sequences as part of MR imaging/MRA screening in patients with this condition. We retrospectively analyzed 831 patients at the UCSF Hereditary Hemorrhagic Telangiectasia Center of Excellence. Of these, 42 patients had complete MR imaging/MRA, ASL perfusion scans, and criterion-standard DSA data. Two neuroradiologists reviewed imaging studies and a third provided adjudication when needed. Eight patients had no brain AVMs detected on DSA. The remaining 34 patients had 57 brain AVMs on DSA. Of the 57 identified AVMs, 51 (89.5%) were detected on ASL and 43 (75.4%) were detected on conventional MR imaging/MRA sequences (P = .049), with 8 lesions detected on ASL perfusion but not on conventional MR imaging. ASL provides increased sensitivity for brain AVMs in patients with HHT. Inclusion of ASL should be considered as part of comprehensive MR imaging/MRA screening protocols for institutions taking care of patients with HHT.

Hue and Orientation Pinwheels in Macaque Area V4.

Area V4 is an intermediate-level area of the macaque visual cortical hierarchy that serves key functions in cortical visual processing by integrating feedforward inputs from multiple functional compartments in lower areas such as V1 and V2 and providing feedforward inputs to many areas in inferotemporal, parietal, and prefrontal cortex. While many previous imaging studies of V4 have analyzed the differential responses to color, orientation, disparity, and motion stimuli, many details of the spatial organization of significant hue and orientation tuning have not been fully described. The Support Vector Machine (SVM) decoding of intrinsic cortical single-condition responses was used to generate high-resolution maps of hue and orientation tuning in V4. Like V1 and V2, V4 contains maps of iso-orientation domains organized around pinwheel centers. V4 contains maps of hue that consist of iso-hue domains surrounding pinwheel centers. The circular organization of these pinwheels more closely represents the perception of hue than is observed in antecedent cortical areas. Domains significantly tuned for hue occupy roughly four times the surface of the orientation domains, are largely segregated from each other, and overlap by roughly 5%. The spatial organization of hue and orientation pinwheels and their domains are largely consistent with the largely segregated inputs arising from the thin and interstripe compartments of V2. This modular segregation of processing suggests that further integration of color and shape must occur in inferotemporal cortical areas that receive direct projections from V4.

Medical imaging in melioidosis - 20-year experience in a non-endemic Australian city.

Melioidosis may occasionally be encountered in non-endemic areas and medical imaging is frequently used to identify and characterise sites of disease. The purpose of this study is to describe the spectrum of imaging findings encountered in melioidosis patients treated in the tertiary public hospitals of Perth, Western Australia, between 2002 and 2022. A database search and electronic medical record review was used to identify cases. Cases were included if they had Burkholderia pseudomallei isolated on culture and if they had at least one diagnostic imaging study performed at a Perth public tertiary hospital. The relevant imaging studies were reviewed, and imaging findings were recorded. Thirty-six cases were identified. The most common disease manifestation was bacteraemia (72%, 26 cases), followed by pulmonary infection (58%, 21 cases), skin and soft tissue infection (22%, eight cases), prostate abscess (14%, five cases) and septic arthritis (6%, two cases). A previously unreported case of isolated melioid pleural effusion was identified, as was a case of reactivated chronic latent pulmonary melioidosis with an apparent delay of over 20 years between the onset of symptoms and the time of infection. In cases with pulmonary melioidosis, the major lung abnormalities on CT chest could be categorised into one of two distinct patterns: nodular-predominant (78%) or consolidation-predominant (22%). Further research is required to assess the utility of the pattern-based categorisation of lung abnormalities on CT chest seen in the pulmonary melioidosis cases of this series.

Prospective longitudinal cohort study of quantitative muscle magnetic resonance imaging in a healthy control population.

Quantitative muscle magnetic resonance imaging (qMRI) is a valuable methodology for assessing muscular injuries and neuromuscular disorders. Notably, muscle diffusion tensor imaging (DTI) gives insights into muscle microstructural and macrostructural characteristics. However, the long-term reproducibility and robustness of these measurements remain relatively unexplored. The purpose of this prospective longitudinal cohort study was to assess the long-term robustness and range of variation of qMRI parameters, especially DTI metrics, in the lower extremity muscles of healthy controls under real-life conditions. Twelve volunteers (seven females, age 44.1 ± 12.1 years, body mass index 23.3 ± 2.0 kg/m2) underwent five leg muscle MRI sessions every 20 ± 4 weeks over a total period of 1.5 years. A multiecho gradient-echo Dixon-based sequence, a multiecho spin-echo T2-mapping sequence, and a spin-echo echo planar imaging diffusion-weighted sequence were acquired bilaterally with a Philips 3-T Achieva MR System using a 16-channel torso coil. Fifteen leg muscles were segmented in both lower extremities. qMRI parameters, including fat fraction (FF), water T2 relaxation time, and the diffusion metrics fractional anisotropy (FA) and mean diffusivity (MD), were evaluated. Coefficients of variance (wsCV) and intraclass correlation coefficients (ICCs) were calculated to assess the reproducibility of qMRI parameters. The standard error of measurement (SEM) and the minimal detectable change (MDC) were calculated to determine the range of variation. All tests were applied to all muscles and, subsequently, to each muscle separately. wsCV showed good reproducibility (≤ 10%) for all qMRI parameters in all muscles. The ICCs revealed excellent agreement between time points (FF = 0.980, water T2 = 0.941, FA = 0.952, MD = 0.948). Random measurement errors assessed by SEM and the MDC were low (< 12%). In conclusion, in this study, we showed that qMRI parameters in healthy volunteers living normal lives are stable over 18 months, thereby defining a benchmark for the expected range of variation over time.

Synthesis and preliminary evaluation of novel PET probes for GSK-3 imaging

Non-invasive imaging of GSK-3 expression in the brain will help to understand the role of GSK-3 in disease pathology and progression. Herein, we report the radiosynthesis and evaluation of two novel isonicotinamide based 18F labeled PET probes, [18F]2 and [18F]6 for noninvasive imaging of GSK3. Among the developed PET probes, the in vitro blood–brain permeability coefficient of 2 (38 ± 20 × 10–6 cm/s, n = 3) was found to be better than 6 (8.75 ± 3.90 × 10–6 cm/s, n = 5). The reference compounds 2 and 6 showed nanomolar affinity towards GSK-3α and GSK-3β. PET probe [18F]2 showed higher stability (100%) in mouse and human serums compared to [18F]6 (67.01 ± 4.93%, n = 3) in mouse serum and 66.20 ± 6.38%, n = 3) in human serum at 120 min post incubation. The in vivo imaging and blocking studies were performed in wild-type mice only with [18F]2 due to its observed stability. [18F]2 showed a SUV of 0.92 ± 0.28 (n = 6) in mice brain as early as 5 min post-injection followed by gradual clearance over time.

Long-range inhibition from prelimbic to cingulate areas of the medial prefrontal cortex enhances network activity and response execution

It is well established that the medial prefrontal cortex (mPFC) exerts top-down control of many behaviors, but little is known regarding how cross-talk between distinct areas of the mPFC influences top-down signaling. We performed virus-mediated tracing and functional studies in male mice, homing in on GABAergic projections whose axons are located mainly in layer 1 and that connect two areas of the mPFC, namely the prelimbic area (PrL) with the cingulate area 1 and 2 (Cg1/2). We revealed the identity of the targeted neurons that comprise two distinct types of layer 1 GABAergic interneurons, namely single-bouquet cells (SBCs) and neurogliaform cells (NGFs), and propose that this connectivity links GABAergic projection neurons with cortical canonical circuits. In vitro electrophysiological and in vivo calcium imaging studies support the notion that the GABAergic projection neurons from the PrL to the Cg1/2 exert a crucial role in regulating the activity in the target area by disinhibiting layer 5 output neurons. Finally, we demonstrated that recruitment of these projections affects impulsivity and mechanical responsiveness, behaviors which are known to be modulated by Cg1/2 activity.

Congenital absence of the appendix in a 21-year-old male with clinical presentation of acute appendicitis: a diagnostic challenge at Prince Ali Military Hospital

Acute appendicitis is commonly associated with right lower quadrant abdominal pain and is a leading cause of emergent abdominal surgeries, carrying a significant morbidity risk. The rarity of anatomical deviations, such as appendix agenesis, complicates diagnosis and can exacerbate clinical outcomes due to diagnostic delays or mismanagement. We report the case of a 21-year-old male, who was surgically explored at prince Ali military hospital for suspected acute appendicitis based on clinical symptoms and an Alvarado score of 7. Despite strong clinical indications, imaging studies, including ultrasound and computed tomography, failed to visualize the appendix. Intraoperatively, appendix agenesis was confirmed, a finding seldom reported in medical literature. This case underscores the challenges of diagnosing congenital appendix absence and highlights the need for heightened awareness among clinicians to prevent unnecessary surgical interventions. Such awareness could potentially improve patient outcomes by sparing them from unnecessary surgical risks and complications.

Selective recruitment of the cerebellum evidenced by task-dependent gating of inputs

Functional magnetic resonance imaging (fMRI) studies have documented cerebellar activity across a wide array of tasks. However, the functional contribution of the cerebellum within these task domains remains unclear because cerebellar activity is often studied in isolation. This is problematic, as cerebellar fMRI activity may simply reflect the transmission of neocortical activity through fixed connections. Here, we present a new approach that addresses this problem. Rather than focus on task-dependent activity changes in the cerebellum alone, we ask if neocortical inputs to the cerebellum are gated in a task-dependent manner. We hypothesize that input is upregulated when the cerebellum functionally contributes to a task. We first validated this approach using a finger movement task, where the integrity of the cerebellum has been shown to be essential for the coordination of rapid alternating movements but not for force generation. While both neocortical and cerebellar activity increased with increasing speed and force, the speed-related changes in the cerebellum were larger than predicted by an optimized cortico-cerebellar connectivity model. We then applied the same approach in a cognitive domain, assessing how the cerebellum supports working memory. Enhanced gating was associated with the encoding of items in working memory, but not with the manipulation or retrieval of the items. Focusing on task-dependent gating of neocortical inputs to the cerebellum offers a promising approach for using fMRI to understand the specific contributions of the cerebellum to cognitive function.

Selective recruitment of the cerebellum evidenced by task-dependent gating of inputs.

Functional magnetic resonance imaging (fMRI) studies have documented cerebellar activity across a wide array of tasks. However, the functional contribution of the cerebellum within these task domains remains unclear because cerebellar activity is often studied in isolation. This is problematic, as cerebellar fMRI activity may simply reflect the transmission of neocortical activity through fixed connections. Here, we present a new approach that addresses this problem. Rather than focus on task-dependent activity changes in the cerebellum alone, we ask if neocortical inputs to the cerebellum are gated in a task-dependent manner. We hypothesize that input is upregulated when the cerebellum functionally contributes to a task. We first validated this approach using a finger movement task, where the integrity of the cerebellum has been shown to be essential for the coordination of rapid alternating movements but not for force generation. While both neocortical and cerebellar activity increased with increasing speed and force, the speed-related changes in the cerebellum were larger than predicted by an optimized cortico-cerebellar connectivity model. We then applied the same approach in a cognitive domain, assessing how the cerebellum supports working memory. Enhanced gating was associated with the encoding of items in working memory, but not with the manipulation or retrieval of the items. Focusing on task-dependent gating of neocortical inputs to the cerebellum offers a promising approach for using fMRI to understand the specific contributions of the cerebellum to cognitive function.