Task Activation Results in Regional 13 C-Lactate Signal Increase in the Human Brain.

Hyperpolarized- 13 C magnetic resonance imaging (HP- 13 C MRI) was used to image changes in 13 C-lactate signal during a visual stimulus condition in comparison to an eyes-closed control condition. Whole-brain 13 C-pyruvate, 13 C-lactate and 13 C-bicarbonate production was imaged in healthy volunteers (N=6, ages 24-33) for the two conditions using two separate hyperpolarized 13 C-pyruvate injections. BOLD-fMRI scans were used to delineate regions of functional activation. 13 C-metabolite signal was normalized by 13 C-metabolite signal from the brainstem and the percentage change in 13 C-metabolite signal conditions was calculated. A one-way Wilcoxon signed-rank test showed a significant increase in 13 C-lactate in regions of activation when compared to the remainder of the brain ( p = 0.02, V = 21). No significant increase was observed in 13 C-pyruvate ( p = 0.11, V = 17) or 13 C-bicarbonate ( p = 0.95, V = 3) signal. The results show an increase in 13 C-lactate production in the activated region that is measurable with HP- 13 C MRI.

Lateralized Functional Connectivity of the Sensorimotor Cortex and its Variations During Complex Visuomotor Tasks.

Previous studies have shown that the left hemisphere dominates motor function, often observed through homotopic activation measurements. Using a functional connectivity approach, this study investigated the lateralization of the sensorimotor cortex during handwriting and drawing, two complex visuomotor tasks with varying contextual demands. We found that both left- and right-lateralized connectivity in the primary motor cortex (M1), dorsal premotor cortex (PMd), somatosensory cortex, and visual regions were evident in adults (males and females), primarily in an interhemispheric integrative fashion. Critically, these lateralization tendencies remained highly invariant across task contexts, representing a task-invariant neural architecture for encoding fundamental motor programs consistently implemented in different task contexts. Additionally, the PMd exhibited a slight variation in lateralization degree between task contexts, reflecting the ability of the high-order motor system to adapt to varying task demands. However, connectivity-based lateralization of the sensorimotor cortex was not detected in 10-year-old children (males and females), suggesting that the maturation of connectivity-based lateralization requires prolonged development. In summary, this study demonstrates both task-invariant and task-sensitive connectivity lateralization in sensorimotor cortices that support the resilience and adaptability of skilled visuomotor performance. These findings align with the hierarchical organization of the motor system and underscore the significance of the functional connectivity-based approach in studying functional lateralization.

Measuring Brain Temperature in Youth Bipolar Disorder Using a Novel Magnetic Resonance Imaging Approach: A Proof-of-concept Study.

BACKGROUND: There is evidence of alterations in mitochondrial energy metabolism and cerebral blood flow (CBF) in adults and youth with bipolar disorder (BD). Brain thermoregulation is based on the balance of heat-producing metabolism and heat-dissipating mechanisms, including CBF. OBJECTIVE: To examine brain temperature, and its relation to CBF, in relation to BD and mood symptom severity in youth. METHODS: This study included 25 youth participants (age 17.4 ± 1.7 years; 13 BD, 12 control group (CG)). Magnetic resonance spectroscopy data were acquired to obtain brain temperature in the left anterior cingulate cortex (ACC) and the left precuneus. Regional estimates of CBF were provided by arterial spin labeling imaging. Analyses used general linear regression models, covarying for age, sex, and psychiatric medications. RESULTS: Brain temperature was significantly higher in BD compared to CG in the precuneus. A higher ratio of brain temperature to CBF was significantly associated with greater depression symptom severity in both the ACC and precuneus within BD. Analyses examining the relationship of brain temperature or CBF with depression severity score did not reveal any significant finding in the ACC or the precuneus. CONCLUSION: The current study provides preliminary evidence of increased brain temperature in youth with BD, in whom reduced thermoregulatory capacity is putatively associated with depression symptom severity. Evaluation of brain temperature and CBF in conjunction may provide valuable insight beyond what can be gleaned by either metric alone. Larger prospective studies are warranted to further evaluate brain temperature and its association with CBF concerning BD.

Deep brain stimulation of the nucleus accumbens in the treatment of severe alcohol use disorder: a phase I pilot trial.

Alcohol use disorder (AUD) is a highly prevalent, often refractory, medical illness. The symptoms of AUD are driven by dysfunction in several neurocircuits centered on the nucleus accumbens (NAc). Case reports and animal studies suggest NAc-DBS may be an effective harm-reduction treatment in severe AUD. Six patients with severe, refractory AUD underwent NAc-DBS. Safety metrics and clinical outcomes were recorded. Positron emission tomography (FDG-PET) was used to measure glucose metabolism in the NAc at baseline and 6 months. Functional magnetic resonance imaging (fMRI) was used to characterize postoperative changes in NAc functional connectivity to the rest of the brain, as well as NAc and dorsal striatal reactivity to alcoholic visual cues. This study was registered with ClinicalTrials.gov, NCT03660124. All patients experienced a reduction in craving. There was a significant reduction in alcohol consumption, alcohol-related compulsivity, and anxiety at 12 months. There was no significant change in depression. FDG-PET analysis demonstrated reduced NAc metabolism by 6 months, which correlated with improvements in compulsive drinking behaviors. Clinical improvement correlated with reduced functional connectivity between the NAc and the visual association cortex. Active DBS was associated with reduced activation of the dorsal striatum during passive viewing of alcohol-containing pictures. NAc-DBS is feasible and safe in patients with severe, otherwise refractory AUD. It is associated with a reduction in cravings and addictive behavior. A potential mechanism underlying this process is a down-regulation of the NAc, a disruption of its functional connectivity to the visual association cortex, and interference of cue-elicited dorsal striatum reactivity. Trial Registration NCT03660124 ( www.clinicaltrials.gov ).

The brain basis of handwriting deficits in Chinese children with developmental dyslexia.

Abundant behavioral studies have demonstrated high comorbidity of reading and handwriting difficulties in developmental dyslexia (DD), a neurological condition characterized by unexpectedly low reading ability despite adequate nonverbal intelligence and typical schooling. The neural correlates of handwriting deficits remain largely unknown; however, as well as the extent that handwriting deficits share common neural bases with reading deficits in DD. The present work used functional magnetic resonance imaging to examine brain activity during handwriting and reading tasks in Chinese dyslexic children (n = 18) and age-matched controls (n = 23). Compared to controls, dyslexic children exhibited reduced activation during handwriting tasks in brain regions supporting sensory-motor processing (including supplementary motor area and postcentral gyrus) and visual-orthography processing (including bilateral precuneus and right cuneus). Among these regions, the left supplementary motor area and the right precuneus also showed a trend of reduced activation during reading tasks in dyslexics. Moreover, increased activation was found in the left inferior frontal gyrus and anterior cingulate cortex in dyslexics, which may reflect more efforts of executive control to compensate for the impairments of motor and visual-orthographic processing. Finally, dyslexic children exhibited aberrant functional connectivity among brain areas for cognitive control and sensory-motor processes during handwriting tasks. Together, these findings suggest that handwriting deficits in DD are associated with functional abnormalities of multiple brain regions implicated in motor execution, visual-orthographic processing, and cognitive control, providing important implications for the diagnosis and treatment of dyslexia.

Driving With Distraction: Measuring Brain Activity and Oculomotor Behavior Using fMRI and Eye-Tracking.

INTRODUCTION: Driving motor vehicles is a complex task that depends heavily on how visual stimuli are received and subsequently processed by the brain. The potential impact of distraction on driving performance is well known and poses a safety concern - especially for individuals with cognitive impairments who may be clinically unfit to drive. The present study is the first to combine functional magnetic resonance imaging (fMRI) and eye-tracking during simulated driving with distraction, providing oculomotor metrics to enhance scientific understanding of the brain activity that supports driving performance. MATERIALS AND METHODS: As initial work, twelve healthy young, right-handed participants performed turns ranging in complexity, including simple right and left turns without oncoming traffic, and left turns with oncoming traffic. Distraction was introduced as an auditory task during straight driving, and during left turns with oncoming traffic. Eye-tracking data were recorded during fMRI to characterize fixations, saccades, pupil diameter and blink rate. RESULTS: Brain activation maps for right turns, left turns without oncoming traffic, left turns with oncoming traffic, and the distraction conditions were largely consistent with previous literature reporting the neural correlates of simulated driving. When the effects of distraction were evaluated for left turns with oncoming traffic, increased activation was observed in areas involved in executive function (e.g., middle and inferior frontal gyri) as well as decreased activation in the posterior brain (e.g., middle and superior occipital gyri). Whereas driving performance remained mostly unchanged (e.g., turn speed, time to turn, collisions), the oculomotor measures showed that distraction resulted in more consistent gaze at oncoming traffic in a small area of the visual scene; less time spent gazing at off-road targets (e.g., speedometer, rear-view mirror); more time spent performing saccadic eye movements; and decreased blink rate. CONCLUSION: Oculomotor behavior modulated with driving task complexity and distraction in a manner consistent with the brain activation features revealed by fMRI. The results suggest that eye-tracking technology should be included in future fMRI studies of simulated driving behavior in targeted populations, such as the elderly and individuals with cognitive complaints - ultimately toward developing better technology to assess and enhance fitness to drive.

Trail Making Test Performance Using a Touch-Sensitive Tablet: Behavioral Kinematics and Electroencephalography.

The Trail Making Test (TMT) is widely used to probe brain function and is performed with pen and paper, involving Parts A (linking numbers) and B (alternating between linking numbers and letters). The relationship between TMT performance and the underlying brain activity remains to be characterized in detail. Accordingly, sixteen healthy young adults performed the TMT using a touch-sensitive tablet to capture enhanced performance metrics, such as the speed of linking movements, during simultaneous electroencephalography (EEG). Linking and non-linking periods were derived as estimates of the time spent executing and preparing movements, respectively. The seconds per link (SPL) was also used to quantify TMT performance. A strong effect of TMT Part A and B was observed on the SPL value as expected (Part B showing increased SPL value); whereas the EEG results indicated robust effects of linking and non-linking periods in multiple frequency bands, and effects consistent with the underlying cognitive demands of the test.

Streamlined magnetic resonance fingerprinting: Fast whole-brain coverage with deep-learning based parameter estimation.

Magnetic resonance fingerprinting (MRF) is a quantitative MRI (qMRI) framework that provides simultaneous estimates of multiple relaxation parameters as well as metrics of field inhomogeneity in a single acquisition. However, current challenges exist in the forms of (1) scan time; (2) need for custom image reconstruction; (3) large dictionary sizes; (4) long dictionary-matching time. This study aims to introduce a novel streamlined magnetic-resonance fingerprinting (sMRF) framework based on a single-shot echo-planar imaging (EPI) sequence to simultaneously estimate tissue T1, T2, and T2* with integrated B1+ correction. Encouraged by recent work on EPI-based MRF, we developed a method that combines spin-echo EPI with gradient-echo EPI to achieve T2 in addition to T1 and T2* quantification. To this design, we add simultaneous multi-slice (SMS) acceleration to enable full-brain coverage in a few minutes. Moreover, in the parameter-estimation step, we use deep learning to train a deep neural network (DNN) to accelerate the estimation process by orders of magnitude. Notably, due to the high image quality of the EPI scans, the training process can rely simply on Bloch-simulated data. The DNN also removes the need for storing large dictionaries. Phantom scans along with in-vivo multi-slice scans from seven healthy volunteers were acquired with resolutions of 1.1×1.1×3 mm3 and 1.7×1.7×3 mm3, and the results were validated against ground truth measurements. Excellent correspondence was found between our T1, T2, and T2* estimates and results obtained from standard approaches. In the phantom scan, a strong linear relationship (R = 1-1.04, R2>0.96) was found for all parameter estimates, with a particularly high agreement for T2 estimation (R2>0.99). Similar findings are reported for the in-vivo human data for all of our parameter estimates. Incorporation of DNN results in a reduction of parameter estimation time on the order of 1000 x and a reduction in storage requirements on the order of 2500 x while achieving highly similar results as conventional dictionary matching (%differences of 7.4 ± 0.4%, 3.6 ± 0.3% and 6.0 ± 0.4% error in T1, T2, and T2* estimation). Thus, sMRF has the potential to be the method of choice for future MRF studies by providing ease of implementation, fast whole-brain coverage, and ultra-fast T1/T2/T2* estimation.

Tablet Technology for Writing and Drawing during Functional Magnetic Resonance Imaging: A Review.

Functional magnetic resonance imaging (fMRI) is a powerful modality to study brain activity. To approximate naturalistic writing and drawing behaviours inside the scanner, many fMRI-compatible tablet technologies have been developed. The digitizing feature of the tablets also allows examination of behavioural kinematics with greater detail than using paper. With enhanced ecological validity, tablet devices have advanced the fields of neuropsychological tests, neurosurgery, and neurolinguistics. Specifically, tablet devices have been used to adopt many traditional paper-based writing and drawing neuropsychological tests for fMRI. In functional neurosurgery, tablet technologies have enabled intra-operative brain mapping during awake craniotomy in brain tumour patients, as well as quantitative tremor assessment for treatment outcome monitoring. Tablet devices also play an important role in identifying the neural correlates of writing in the healthy and diseased brain. The fMRI-compatible tablets provide an excellent platform to support naturalistic motor responses and examine detailed behavioural kinematics.

Three-Tesla Magnetic Resonance Imaging of Patients With Deep Brain Stimulators: Results From a Phantom Study and a Pilot Study in Patients.

BACKGROUND: Deep brain stimulation (DBS) is a standard of care treatment for multiple neurologic disorders. Although 3-tesla (3T) magnetic resonance imaging (MRI) has become the gold-standard modality for structural and functional imaging, most centers refrain from 3T imaging in patients with DBS devices in place because of safety concerns. 3T MRI could be used not only for structural imaging, but also for functional MRI to study the effects of DBS on neurocircuitry and optimize programming. OBJECTIVE: To use an anthropomorphic phantom design to perform temperature and voltage safety testing on an activated DBS device during 3T imaging. METHODS: An anthropomorphic 3D-printed human phantom was constructed and used to perform temperature and voltage testing on a DBS device during 3T MRI. Based on the phantom assessment, a cohort study was conducted in which 6 human patients underwent MRI with their DBS device in an activated (ON) state. RESULTS: During the phantom study, temperature rises were under 2°C during all sequences, with the DBS in both the deactivated and activated states. Radiofrequency pulses from the MRI appeared to modulate the electrical discharge from the DBS, resulting in slight fluctuations of voltage amplitude. Six human subjects underwent MRI with their DBS in an activated state without any serious adverse events. One patient experienced stimulation-related side effects during T1-MPRAGE scanning with the DBS in an ON state because of radiofrequency-induced modulation of voltage amplitude. CONCLUSION: Following careful phantom-based safety testing, 3T structural and functional MRI can be safely performed in subjects with activated deep brain stimulators.

Functional magnetic resonance imaging of the trail-making test in older adults.

The trail-making test (TMT) is a popular neuropsychological test, which is used extensively to measure cognitive impairment associated with neurodegenerative disorders in older adults. Behavioural performance on the TMT has been investigated in older populations, but there is limited research on task-related brain activity in older adults. The current study administered a naturalistic version of the TMT to a healthy older-aged population in an MRI environment using a novel, MRI-compatible tablet. Functional MRI was conducted during task completion, allowing characterization of the brain activity associated with the TMT. Performance on the TMT was evaluated using number of errors and seconds per completion of each link. Results are reported for 36 cognitively healthy older adults between the ages of 52 and 85. Task-related activation was observed in extensive regions of the bilateral frontal, parietal, temporal and occipital lobes as well as key motor areas. Increased age was associated with reduced brain activity and worse task performance. Specifically, older age was correlated with decreased task-related activity in the bilateral occipital, temporal and parietal lobes. These results suggest that healthy older aging significantly affects brain function during the TMT, which consequently may result in performance decrements. The current study reveals the brain activation patterns underlying TMT performance in a healthy older aging population, which functions as an important, clinically-relevant control to compare to pathological aging in future investigations.

Technical Note: An anthropomorphic phantom with implanted neurostimulator for investigation of MRI safety.

PURPOSE: The objective of this work was to design and construct an improved anthropomorphic phantom for use in studying magnetic resonance imaging (MRI) radiofrequency (RF) safety at 3 T related to deep brain stimulation (DBS), and especially the role of DBS lead trajectories. METHOD: Based on a computer-aided design including reasonable representation of human features, the phantom was fabricated by three-dimensional (3D) printing and then fully assembled with a human skull, a commercial DBS device implanted using the surgical standard at our institution, and fiber-optic temperature sensors embedded in two tissue mimicking solutions (e.g., the heterogeneous setup). Preliminary MRI safety experiments were conducted using turbo spin-echo (TSE) imaging with the device powered on and powered off. These results were then compared to analogous results for a homogeneous phantom setup that filled the structure with a standard body average solution. RESULT: Both phantom setups produced temperature increases of ~1.0°C, with a maximum increase of 1.1 ± 0.2°C recorded during imaging of the heterogeneous phantom setup. The preliminary experimental results suggest that improved phantom structures capable of replicating actual DBS lead trajectories may be advisable when conducting DBS-related MRI safety studies. CONCLUSION: An anthropomorphic phantom was constructed with promising initial results indicating different DBS lead trajectories and phantom setups may impact temperature elevations along an implanted DBS lead. Although additional work will be necessary to validate its efficacy over conventional phantoms, the anthropomorphic phantom can likely be used in the future to assess different procedures for DBS lead placement, the RF power deposition of MRI protocols applicable to DBS patients, and to validate novel methods to reduce localized heating effects associated with DBS devices, such as parallel RF transmission.

Men and women differ in the neural basis of handwriting.

There is an ongoing debate about whether, and to what extent, males differ from females in their language skills. In the case of handwriting, a composite language skill involving language and motor processes, behavioral observations consistently show robust sex differences but the mechanisms underlying the effect are unclear. Using functional magnetic resonance imaging (fMRI) in a copying task, the present study examined the neural basis of sex differences in handwriting in 53 healthy adults (ages 19-28, 27 males). Compared to females, males showed increased activation in the left posterior middle frontal gyrus (Exner's area), a region thought to support the conversion between orthographic and graphomotor codes. Functional connectivity between Exner's area and the right cerebellum was greater in males than in females. Furthermore, sex differences in brain activity related to handwriting were independent of language material. This study identifies a novel neural signature of sex differences in a hallmark of human behavior, and highlights the importance of considering sex as a factor in scientific research and clinical applications involving handwriting.

Brain activation during laparoscopic tasks in high- and low-performing medical students: a pilot fMRI study.

BACKGROUND: Up to 20% of medical students are unable to reach competency in laparoscopic surgery. It is unknown whether these difficulties arise from heterogeneity in neurological functioning across individuals. We sought to examine the differences in neurological functioning during laparoscopic tasks between high- and low-performing medical students using functional magnetic resonance imaging (fMRI). METHODS: This prospective cohort study enrolled North American medical students who were within the top 20% and bottom 20% of laparoscopic performers from a previous study. Brain activation was recorded using fMRI while participants performed peg-pointing, intracorporeal knot tying (IKT), and the Pictorial Surface Orientation (PicSOr) test. Brain activation maps were created and areas of activation were compared between groups. RESULTS: In total, 9/12 high and 9/13 low performers completed the study. High performers completed IKT faster and made more successful knot ties than low performers [standing: 23.5 (5.0) sec vs. 37.6 (18.4) sec, p = 0.03; supine: 23.2 (2.5) sec vs. 72.7 (62.8) sec, p = 0.02; number of successful ties supine, 3 ties vs. 1 tie, p = 0.01]. Low performers showed more brain activation than high performers in the peg-pointing task (q < 0.01), with no activation differences in the IKT task. There were no behavioral differences in the PiCSOr task. CONCLUSIONS: This study is the first to show differences between low and high performers of laparoscopic tasks at the brain level. This pilot study has shown the feasibility of using fMRI to examine laparoscopic surgical skills. Future studies are needed for further exploration of our initial findings.

Visualization of Brain Shift Corrected Functional Magnetic Resonance Imaging Data for Intraoperative Brain Mapping.

BACKGROUND: Brain tumor surgery requires careful balance between maximizing tumor excision and preserving eloquent cortex. In some cases, the surgeon may opt to perform an awake craniotomy including intraoperative mapping of brain function by direct cortical stimulation (DCS) to assist in surgical decision-making. Preoperatively, functional magnetic resonance imaging (fMRI) facilitates planning by identification of eloquent brain areas, helping to guide DCS and other aspects of the surgical plan. However, brain deformation (shift) limits the usefulness of preoperative fMRI during surgery. To address this, an integrated visualization method for fMRI and DCS results is developed that is intuitive for the surgeon. METHODS: An image registration pipeline was constructed to display preoperative fMRI data corrected for brain shift overlaid on images of the exposed cortical surface at the beginning and completion of DCS mapping. Preoperative fMRI and DCS data were registered for a range of misalignments, and the residual registration errors were calculated. The pipeline was validated on imaging data from five brain tumor patients who underwent awake craniotomy. RESULTS: Registration errors were well under 5 mm (the approximate spatial resolution of DCS) for misalignments of up to 25 mm and approximately 10-15°. For rotational misalignments up to 20°, the success rate was 95% for an error tolerance of 5 mm. Failures were negligible for rotational misalignments up to 10°. Good quality registrations were observed for all five patients. CONCLUSIONS: A proof-of-concept image registration pipeline is presented with acceptable accuracy for intraoperative use, providing multimodality visualization with potential benefits for intraoperative brain mapping.

Spatial reorganisation of the somatosensory cortex in a patient with a low-grade glioma.

Multiple authors have speculated that functional plasticity of the neural networks required for speech and motor function may occur in the setting of low-grade brain tumours. Here, we present the case of a 39-year-old right-handed woman found on presentation for intermittent right-hand tingling and twitching to have a low-grade glioma involving the somatosensory cortex on both structural and functional MRI. Intraoperative awake mapping identified gyral dissociation of the somateosensory areas for right arm and leg sensation. These findings demonstrate that brain plasticity may be dramatic in the setting of a low-grade glioma, and emphasise the critical need for careful brain mapping when considering tumour resection in these patients.

Functional MRI of Letter Cancellation Task Performance in Older Adults.

The Letter Cancellation Task (LCT) is a widely used pen-and-paper probe of attention in clinical and research settings. Despite its popularity, the neural correlates of the task are not well understood. The present study uses functional magnetic resonance imaging (fMRI) and specialized tablet technology to identify the neural correlates of the LCT in 32 healthy older adults between 50-85 years of age, and further investigates the effect of healthy aging on performance. Subjects performed the LCT in its standard pen-and-paper administration and with the tablet during fMRI. Performance on the tablet was significantly slower than on pen-and-paper, with both response modes showing slower performance as a function of age. Across all ages, bilateral brain activation was observed in the cerebellum, superior temporal lobe, precentral gyrus, frontal gyrus, and occipital and parietal areas. Increasing age correlated with reduced brain activity in the supplementary motor area, middle occipital gyrus, medial and inferior frontal gyrus, cerebellum and putamen. Better LCT performance was correlated with increased activity in the middle frontal gyrus, and reduced activity in the cerebellum. The brain regions activated are associated with visuospatial attention and motor control, and are consistent with the neural correlates of LCT performance previously identified in lesion studies.

The Neural Correlates of the Clock-Drawing Test in Healthy Aging.

Importance: The clock-drawing test (CDT) is an important neurocognitive assessment tool, widely used as a screening test for dementia. Behavioral performance on the test has been studied extensively, but there is scant literature on the underlying neural correlates. Purpose: To administer the CDT naturalistically to a healthy older aging population in an MRI environment, and characterize the brain activity associated with test completion. Main Outcome and Measure: Blood-oxygen-level dependent (BOLD) functional MRI was conducted as participants completed the CDT using novel tablet technology. Brain activity during CDT performance was contrasted to rest periods of visual fixation. Performance on the CDT was evaluated using a standardized scoring system (Rouleau score) and time to test completion. To assess convergent validity, performance during fMRI was compared to performance on a standard paper version of the task, administered in a psychometric testing room. Results: Study findings are reported for 33 cognitively healthy older participants aged 52-85. Activation was observed in the bilateral frontal, occipital and parietal lobes as well as the supplementary motor area and precentral gyri. Increased age was significantly correlated with Rouleau scores on the clock number drawing (R2) component (rho = -0.55, p < 0.001); the clock hand drawing (R3) component (rho = -0.50, p < 0.005); and the total clock (rho = -0.62, p < 0.001). Increased age was also associated with decreased activity in the bilateral parietal and occipital lobes as well as the right temporal lobe and right motor areas. Conclusion and Relevance: This imaging study characterizes the brain activity underlying performance of the CDT in a healthy older aging population using the most naturalistic version of the task to date. The results suggest that the functions of the occipital and parietal lobe are significantly altered by the normal aging process, which may lead to performance decrements.

Functional MRI of Handwriting Tasks: A Study of Healthy Young Adults Interacting with a Novel Touch-Sensitive Tablet.

Handwriting is a complex human activity that engages a blend of cognitive and visual motor skills. Current understanding of the neural correlates of handwriting has largely come from lesion studies of patients with impaired handwriting. Task-based fMRI studies would be useful to supplement this work. To address concerns over ecological validity, previously we developed a fMRI-compatible, computerized tablet system for writing and drawing including visual feedback of hand position and an augmented reality display. The purpose of the present work is to use the tablet system in proof-of-concept to characterize brain activity associated with clinically relevant handwriting tasks, originally developed to characterize handwriting impairments in Alzheimer's disease patients. As a prelude to undertaking fMRI studies of patients, imaging was performed of twelve young healthy subjects who copied sentences, phone numbers, and grocery lists using the fMRI-compatible tablet. Activation maps for all handwriting tasks consisted of a distributed network of regions in reasonable agreement with previous studies of handwriting performance. In addition, differences in brain activity were observed between the test subcomponents consistent with different demands of neural processing for successful task performance, as identified by investigating three quantitative behavioral metrics (writing speed, stylus contact force and stylus in air time). This study provides baseline behavioral and brain activity results for fMRI studies that adopt this handwriting test to characterize patients with brain impairments.

Tablet-Based Functional MRI of the Trail Making Test: Effect of Tablet Interaction Mode.

The Trail Making Test (TMT) is widely used for assessing executive function, frontal lobe abilities, and visual motor skills. Part A of this pen-and-paper test (TMT-A) involves linking numbers randomly distributed in space, in ascending order. Part B (TMT-B) alternates between linking numbers and letters. TMT-B is more demanding than TMT-A, but the mental processing that supports the performance of this test remains incompletely understood. Functional MRI (fMRI) may help to clarify the relationship between TMT performance and brain activity, but providing an environment that supports real-world pen-and-paper interactions during fMRI is challenging. Previously, an fMRI-compatible tablet system was developed for writing and drawing with two modes of interaction: the original cursor-based, proprioceptive approach, and a new mode involving augmented reality to provide visual feedback of hand position (VFHP) for enhanced user interaction. This study characterizes the use of the tablet during fMRI of young healthy adults (n = 22), with half of the subjects performing TMT with VFHP and the other half performing TMT without VFHP. Activation maps for both TMT-A and TMT-B performance showed considerable overlap between the two tablet modes, and no statistically differences in brain activity were detected when contrasting TMT-B vs. TMT-A for the two tablet modes. Behavioral results also showed no statistically different interaction effects for TMT-B vs. TMT-A for the two tablet modes. Tablet-based TMT scores showed reasonable convergent validity with those obtained by administering the standard pen-and-paper TMT to the same subjects. Overall, the results suggest that despite the slightly different mechanisms involved for the two modes of tablet interaction, both are suitable for use in fMRI studies involving TMT performance. This study provides information for using tablet-based TMT methods appropriately in future fMRI studies involving patients and healthy individuals.