Activity in the pontine reticular nuclei scales with handgrip force in humans.

The neural pathways that contribute to force production in humans are currently poorly understood, as the relative roles of the corticospinal tract and brainstem pathways, such as the reticulospinal tract (RST), vary substantially across species. Using functional magnetic resonance imaging (fMRI), we aimed to measure activation in the pontine reticular nuclei (PRN) during different submaximal handgrip contractions to determine the potential role of the PRN in force modulation. Thirteen neurologically intact participants (age: 28 ± 6 yr) performed unilateral handgrip contractions at 25%, 50%, 75% of maximum voluntary contraction during brain scans. We quantified the magnitude of PRN activation from the contralateral and ipsilateral sides during each of the three contraction intensities. A repeated-measures ANOVA demonstrated a significant main effect of force (P = 0.012, [Formula: see text] = 0.307) for PRN activation, independent of side (i.e., activation increased with force for both contralateral and ipsilateral nuclei). Further analyses of these data involved calculating the linear slope between the magnitude of activation and handgrip force for each region of interest (ROI) at the individual-level. One-sample t tests on the slopes revealed significant group-level scaling for the PRN bilaterally, but only the ipsilateral PRN remained significant after correcting for multiple comparisons. We show evidence of task-dependent activation in the PRN that was positively related to handgrip force. These data build on a growing body of literature that highlights the RST as a functionally relevant motor pathway for force modulation in humans.NEW & NOTEWORTHY In this study, we used a task-based functional magnetic resonance imaging (fMRI) paradigm to show that activity in the pontine reticular nuclei scales linearly with increasing force during a handgrip task. These findings directly support recently proposed hypotheses that the reticulospinal tract may play an important role in modulating force production in humans.

Comparing models of information transfer in the structural brain network and their relationship to functional connectivity: diffusion versus shortest path routing.

The relationship between structural and functional connectivity in the human brain is a core question in network neuroscience, and a topic of paramount importance to our ability to meaningfully describe and predict functional outcomes. Graph theory has been used to produce measures based on the structural connectivity network that are related to functional connectivity. These measures are commonly based on either the shortest path routing model or the diffusion model, which carry distinct assumptions about how information is transferred through the network. Unlike shortest path routing, which assumes the most efficient path is always known, the diffusion model makes no such assumption, and lets information diffuse in parallel based on the number of connections to other regions. Past research has also developed hybrid measures that use concepts from both models, which have better predicted functional connectivity from structural connectivity than the shortest path length alone. We examined the extent to which each of these models can account for the structure-function relationship of interest using graph theory measures that are exclusively based on each model. This analysis was performed on multiple parcellations of the Human Connectome Project using multiple approaches, which all converged on the same finding. We found that the diffusion model accounts for much more variance in functional connectivity than the shortest path routing model, suggesting that the diffusion model is better suited to describing the structure-function relationship in the human brain at the macroscale.

What's in a game: Video game visual-spatial demand location exhibits a double dissociation with reading speed.

This research sought to clarify the nature of the relationship between video game experience, attention, and reading. Previous studies have suggested playing action video games can improve reading ability in children with dyslexia. Other research has linked video game experience with visual-spatial attention, and visual-spatial attention with reading. We hypothesized that the visual-spatial demands of video games may drive relationships with reading through attentional processing. In this experiment we used a hybrid attention/reading task to explore the relationship between video game visual-spatial demands, reading and attention. We also developed novel visual-spatial demand measures using participants' top five played video games for an individual-specific measure of visual demands. Peripheral visual demands in video games were associated with faster reading times, while central visual demands were associated with slower reading times for both phonetic decoding and lexical reading. In addition, video game experience in terms of hours spent playing video games each week interacted with the cueing effect size in the lexical reading condition, with experienced video game players exhibiting a larger cueing effect than participants with less video game experience. These results suggest that exposure to peripheral visual spatial demands in video games may be related to both lexical and sublexical reading processes in hybrid attentional reading tasks such as ours with skilled adult readers, which has implications not only for models of how ventral and dorsal stream reading and visual-spatial attention are integrated, but also for the development of dyslexia diagnostics and remediation.

Structure can predict function in the human brain: a graph neural network deep learning model of functional connectivity and centrality based on structural connectivity.

Although functional connectivity and associated graph theory measures (e.g., centrality; how centrally important to the network a region is) are widely used in brain research, the full extent to which these functional measures are related to the underlying structural connectivity is not yet fully understood. Graph neural network deep learning methods have not yet been applied for this purpose, and offer an ideal model architecture for working with connectivity data given their ability to capture and maintain inherent network structure. Here, we applied this model to predict functional connectivity from structural connectivity in a sample of 998 participants from the Human Connectome Project. Our results showed that the graph neural network accounted for 89% of the variance in mean functional connectivity, 56% of the variance in individual-level functional connectivity, 99% of the variance in mean functional centrality, and 81% of the variance in individual-level functional centrality. These results represent an important finding that functional centrality can be robustly predicted from structural connectivity. Regions of particular importance to the model's performance as determined through lesioning are discussed, whereby regions with higher centrality have a higher impact on model performance. Future research on models of patient, demographic, or behavioural data can also benefit from this graph neural network method as it is ideally-suited for depicting connectivity and centrality in brain networks. These results have set a new benchmark for prediction of functional connectivity from structural connectivity, and models like this may ultimately lead to a way to predict functional connectivity in individuals who are unable to do fMRI tasks (e.g., non-responsive patients).

Unique, Shared, and Dominant Brain Activation in Visual Word Form Area and Lateral Occipital Complex during Reading and Picture Naming.

Identifying printed words and pictures concurrently is ubiquitous in daily tasks, and so it is important to consider the extent to which reading words and naming pictures may share a cognitive-neurophysiological functional architecture. Two functional magnetic resonance imaging (fMRI) experiments examined whether reading along the left ventral occipitotemporal region (vOT; often referred to as a visual word form area, VWFA) has activation that is overlapping with referent pictures (i.e., both conditions significant and shared, or with one significantly more dominant) or unique (i.e., one condition significant, the other not), and whether picture naming along the right lateral occipital complex (LOC) has overlapping or unique activation relative to referent words. Experiment 1 used familiar regular and exception words (to force lexical reading) and their corresponding pictures in separate naming blocks, and showed dominant activation for pictures in the LOC, and shared activation in the VWFA for exception words and their corresponding pictures (regular words did not elicit significant VWFA activation). Experiment 2 controlled for visual complexity by superimposing the words and pictures and instructing participants to either name the word or the picture, and showed primarily shared activation in the VWFA and LOC regions for both word reading and picture naming, with some dominant activation for pictures in the LOC. Overall, these results highlight the importance of including exception words to force lexical reading when comparing to picture naming, and the significant shared activation in VWFA and LOC serves to challenge specialized models of reading or picture naming.

Ipsilesional Motor Cortex Activation with High-force Unimanual Handgrip Contractions of the Less-affected Limb in Participants with Stroke.

Stroke is a leading cause of severe disability that often presents with unilateral motor impairment. Conventional rehabilitation approaches focus on motor practice of the affected limb and aim to suppress brain activity in the contralesional hemisphere. Conversely, exercise of the less-affected limb promotes contralesional brain activity which is typically viewed as contraindicated in stroke recovery due to the interhemispheric inhibitory influence onto the ipsilesional hemisphere. Yet, high-force unimanual handgrip contractions are known to increase ipsilateral brain activation in control participants, and it remains to be determined if high-force contractions with the less-affected limb would promote ipsilateral brain activation in participants with stroke (i.e., the ipsilesional hemisphere). Therefore, this study aimed to determine how parametric increases in handgrip force during repeated contractions with the less-affected limb impacts brain activity bilaterally in participants with stroke and in a cohort of neurologically intact controls. Participants performed repeated submaximal contractions at 25%, 50%, and 75% of their maximum voluntary contraction during separate functional magnetic resonance imaging brain scans. Brain activation during the tasks was quantified as the percent change from resting levels. In this study, higher force contractions were found to increase brain activation in the ipsilesional (stroke)/ipsilateral (controls) hemisphere in both groups (p = .002), but no between group differences were observed. These data suggest that high-force exercise with the less-affected limb may promote ipsilesional cortical plasticity to promote motor recovery of the affected-limb in participants with stroke.

An fMRI, DTI and Neurophysiological Examination of Atypical Organization of Motor Cortex in Ipsilesional Hemisphere Following Post-Stroke Recovery.

OBJECTIVES: We report a 61-year-old woman who developed left hemiparesis following a right frontal stroke. She underwent rehabilitation and regained function of the left side of her body. Three years after her first stroke, she developed a large left subdural hematoma and again presented with left hemiparesis. MATERIALS AND METHODS: Prior to the cranioplasty, an fMRI scan involving left and right hand movement, arm movement, and foot peddling were conducted in order to determine whether the patient showed ipsilateral activation for the motor tasks, thus explaining the left hemiparesis following the left subdural hematoma. Diffusion tensor imaging (DTI) tractography was also collected to visualize the motor and sensory tracts. RESULTS: The fMRI results revealed activation in the expected contralateral left primary motor cortex (M1) for the right-sided motor tasks, and bilateral M1 activation for the left-sided motor tasks. Intraoperative neurophysiology confirmed these findings, whereby electromyography revealed left-sided (i.e., ipsilateral) responses for four of the five electrode locations. The DTI results indicated that the corticospinal tracts and spinothalamic tracts were within normal limits and showed no displacement or disorganization. CONCLUSIONS: These results suggest that there may have been reorganization of the M1 following her initial stroke, and that the left hemisphere may have become involved in moving the left side of the body thereby leading to left hemiparesis following the left subdural hematoma. The findings suggest that cortical reorganization may occur in stroke patients recovering from hemiparesis, and specifically, that components of motor processing subserved by M1 may be taken over by ipsilateral regions.

High Force Unimanual Handgrip Contractions Increase Ipsilateral Sensorimotor Activation and Functional Connectivity.

Imaging and brain stimulation studies seem to correct the classical understanding of how brain networks, rather than contralateral focal areas, control the generation of unimanual voluntary force. However, the scaling and hemispheric-specificity of network activation remain less understood. Using fMRI, we examined the effects of parametrically increasing right-handgrip force on activation and functional connectivity among the sensorimotor network bilaterally with 25%, 50%, and 75% maximal voluntary contractions (MVC). High force (75% MVC) unimanual handgrip contractions resulted in greater ipsilateral motor activation and functional connectivity with the contralateral hemisphere compared to a low force 25% MVC condition. The ipsilateral motor cortex activation and network strength correlated with relative handgrip force (% MVC). Increases in unimanual handgrip force resulted in greater ipsilateral sensorimotor activation and greater functional connectivity between hemispheres within the sensorimotor network.

Language lateralization differences between left and right temporal lobe epilepsy as measured by overt word reading fMRI activation and DTI structural connectivity.

In cases of brain disease such as temporal lobe epilepsy (TLE), damage may lead to functional reorganization and a shift in language dominance to homolog regions in the other hemisphere. If the effects of TLE on language dominance are hemisphere-focused, then brain regions and connections involved in word reading should be less left-lateralized in left temporal lobe epilepsy (lTLE) than right temporal lobe epilepsy (rTLE) or healthy controls, and the opposite effect should be observed in patients with rTLE. In our study, functional magnetic resonance imaging (fMRI) showed that patients with rTLE had more strongly lateralized left hemisphere (LH) activation than patients with lTLE and healthy controls in language-related brain regions (pars opercularis and fusiform gyrus (FuG)). Corresponding with this difference, diffusion tensor imaging (DTI) found differences in connectivity indicative of patients with lTLE having greater tract integrity than patients with rTLE in the right hemisphere (RH) uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), and inferior fronto-occipital fasciculus (IFOF) using the network-based statistic analysis method. The UF, ILF, and IFOF tract integrity have previously been associated with lexical (whole-word) processing abilities. Multivariate distance matrix regression provided converging evidence for regions of the IFOF having different connectivity patterns between groups with lTLE and rTLE. This research demonstrates language lateralization differences between patient groups with lTLE and rTLE, and corresponding differences in the connectivity strength of the ILF, IFOF, and UF. This research provides a novel approach to measuring lateralization of language in general, and the fMRI and DTI findings were integral for guiding the neurosurgeons performing the TLE resections. This approach should inform future studies of language lateralization and language reorganization in patients such as those with TLE.

The Concept of an Epilepsy Brain Bank.

Epilepsy comprises more than 40 clinical syndromes affecting millions of patients and families worldwide. To decode the molecular and pathological framework of epilepsy researchers, need reliable human epilepsy and control brain samples. Brain bank organizations collecting and supplying well-documented clinically and pathophysiologically tissue specimens are important for high-quality neurophysiology and neuropharmacology studies for epilepsy and other neurological diseases. New development in molecular mechanism and new treatment methods for neurological disorders have evoked increased demands for human brain tissue. An epilepsy brain bank is a storage source for both the frozen samples as well as the formaldehyde fixed paraffin embedded (FFPE) tissue from epilepsy surgery resections. In 2014, the University of Saskatchewan have started collecting human epilepsy brain tissues for the first time in Canada. This review highlights the necessity and importance of Epilepsy Brain bank that provides unique access for research to valuable source of brain tissue and blood samples from epilepsy patients.

Structural connectivity predicts functional activation during lexical and sublexical reading.

A critical question in neuroscience is the extent to which structural connectivity of the brain predicts localization of brain function. Recent research has suggested that anatomical connectivity can predict functional magnetic resonance imaging (fMRI) responses in several cognitive domains, including face, object, scene, and body processing, and development of word recognition skills (Osher et al., 2016; Saygin et al., 2016). However, this technique has not yet been extended to skilled word reading. Thus, we developed a computational model that relates anatomical connectivity (measured using probabilistic tractography) of individual cortical voxels to fMRI responses of the same voxels during lexical and sublexical reading tasks. Our results showed that the model built from structural connectivity was able to accurately predict functional responses of individual subjects based on their structural connectivity alone. This finding was apparent across the cortex, as well as to specific regions of interest associated with reading, language, and spatial attention. Further, we identified the structural connectivity networks associated with different aspects of skilled reading using connectivity analyses, and showed that interconnectivity between left hemisphere language and right hemisphere attentional areas underlies both lexical and sublexical reading. This work has important implications for understanding how structural connectivity contributes to reading and suggests that there is a relationship between skilled reading and neuroanatomical brain connectivity that future research should continue to explore.

Brain Structural Connectivity Predicts Brain Functional Complexity: Diffusion Tensor Imaging Derived Centrality Accounts for Variance in Fractal Properties of Functional Magnetic Resonance Imaging Signal.

The complexity of brain activity has recently been investigated using the Hurst exponent (H), which describes the extent to which functional magnetic resonance imaging (fMRI) blood oxygen-level dependent (BOLD) activity is simple vs. complex. For example, research has demonstrated that fMRI activity is more complex before than after consumption of alcohol and during task than resting state. The measurement of H in fMRI is a novel method that requires the investigation of additional factors contributing to complexity. Graph theory metrics of centrality can assess how centrally important to the brain network each region is, based on diffusion tensor imaging (DTI) counts of probabilistic white matter (WM) tracts. DTI derived centrality was hypothesized to account for the complexity of functional activity, based on the supposition that more sources of information to integrate should result in more complex activity. FMRI BOLD complexity as measured by H was associated with five brain region centrality measures: degree, eigenvector, PageRank, current flow betweenness, and current flow closeness centrality. Multiple regression analyses demonstrated that eigenvector centrality was the most robust predictor of complexity, whereby greater centrality was associated with increased complexity (lower H). Regions known to be highly connected, including the thalamus and hippocampus, notably were among the highest in centrality and complexity. This research has led to a greater understanding of how brain region characteristics such as DTI centrality relate to the novel Hurst exponent approach for assessing brain activity complexity, and implications for future research that employ these measures are discussed.

Atypical language localization in right temporal lobe epilepsy: An fMRI case report.

We report a 41- year-old, left-handed patient with drug-resistant right temporal lobe epilepsy (TLE). Presurgical fMRI was conducted to examine whether the patient had language functioning in the right hemisphere given that left-handedness is associated with a higher prevalence of right hemisphere dominance for language. The fMRI results revealed bilateral activation in Broca's and Wernicke's areas and activation of eloquent cortex near the region of planned resection in the right temporal lobe. Due to right temporal language-related activation, the patient underwent an awake right-sided temporal lobectomy with intraoperative language mapping. Intraoperative direct cortical stimulation (DCS) was conducted in the regions corresponding to the fMRI activation, and the patient showed language abnormalities, such as paraphasic errors, and speech arrest. The decision was made to abort the planned anterior temporal lobe procedure, and the patient instead underwent a selective amygdalohippocampectomy via the Sylvian fissure at a later date. Post-operatively the patient was seizure-free with no neurological deficits. Taken together, the results support previous findings of right hemisphere language activation in left-handed individuals, and should be considered in cases in which presurgical localization is conducted for left-hand dominant patients undergoing neurosurgical procedures.

FMRI of shared-stream priming of lexical identification by object semantics along the ventral visual processing stream.

Distributed sub-systems of the brain's semantic network have been shown to process semantics associated with visual features of objects (e.g., shape, colour) in the ventral visual processing stream, whereas semantics associated with actions are processed in the dorsal stream. Orthographic lexical processing has also been shown to occur in the ventral stream. Past research from our lab (Neudorf et al., 2019) has demonstrated a temporal (i.e., reaction time) priming advantage for object primes over action primes in the lexical decision task consistent with ventral shared-stream processing of visual feature object semantics and orthographic lexical identification, whereby object primes produced larger priming effects than action primes. The current experiment explored this paradigm using functional magnetic resonance imaging (fMRI) and identified the potential loci of shared-stream processing to regions in the ventral stream just anterior to colour sensitive visual area V4 cortex in the left fusiform gyrus and anterior to lexical and shape sensitive regions in the left fusiform gyrus, as well as in cerebellar lobule VI. Action priming showed more activation than object priming in dorsal stream motion related regions of the right parietal occipital junction, right superior occipital gyrus, and bilateral visual area V3. The fMRI activation observed in this experiment supports the theory that spatially shared-stream activation occurs in the ventral stream during object (but not action) priming of lexical identification, which is consistent with our earlier behavioural research showing that these processes are also temporally shared.

How words and space collide: Lexical and sublexical reading are reliant on separable reflexive and voluntary attention regions in hybrid tasks.

Reading ability requires the coordination of many cognitive processes to be effective, including spatial attention. Recent functional magnetic resonance imaging (fMRI) evidence from Ekstrand et al. (2019) suggests that lexical reading is more associated with reflexive attentional orienting regions, whereas sublexical reading is more associated with voluntary attentional orienting regions. The current research sought to further examine the neuroanatomical relationship between reading and attention using a novel experimental design in fMRI. Participants performed four hybrid attentional orienting and reading-aloud tasks, where a reflexive or voluntary spatial cue preceded a lexical or sublexical target. Results indicated that lexical reading resulted in greater activation in the right temporoparietal junction, a reflexive orienting region. Sublexical reading resulted in greater activation in the left inferior frontal gyrus, left fusiform and inferior temporal gyrus, and right superior parietal lobule and intraparietal sulcus (voluntary orienting regions). Further, we found an interaction between reading and attention in the middle occipital gyrus. This study provides the most direct evidence to date that lexical and sublexical reading recruit differential attentional orienting regions during single-word reading in skilled readers. Implications for models of reading and attention, as well as for strategic remediation of their dysfunction, are discussed.

Where words and space collide: The overlapping neural activation of lexical and sublexical reading with voluntary and reflexive spatial attention.

Recent research has shown a relationship between reading and attention, however the neuroanatomical overlap of these two processes has remained relatively unexplored. Therefore, we sought to investigate the overlapping neural mechanisms of spatial attention and reading using functional magnetic resonance imaging. Participants performed two attentional orienting tasks (reflexive and voluntary), and two overt word-reading tasks (lexical and sublexical). We hypothesized that there would be greater unique activation overlap of reflexive attention with lexical reading, and of voluntary attention with sublexical reading. Results indicated that lexical reading had greater overlapping activation in reflexive orienting areas compared to sublexical reading, suggesting that lexical reading may employ more automatic attentional mechanisms. In contrast, sublexical reading had greater overlapping activation with voluntary attention areas compared to lexical reading, suggesting that phonetic decoding may rely more heavily on voluntary attention. This research broadens our understanding of the neural overlap that underlies the relationship between reading and spatial attention.

The Effect of Tumor Neovasculature on Functional Magnetic Resonance Imaging Blood Oxygen Level-Dependent Activation.

BACKGROUND: We report the case of a 40-year-old patient with a large, World Health Organization grade III oligodendroglioma in the left parietal lobe. CASE DESCRIPTION: Presurgical planning included functional magnetic resonance imaging (fMRI) localization of language, motor, and somatosensory processing. fMRI results for motor and somatosensory tasks revealed activation in perilesional regions near the surgical resection as well as deactivation in the tumor for the sensory task, suggesting decreased autoregulation in the region owing to the glioma. fMRI results showed left-hemisphere dominance for language and activation in perilesional regions for all 3 speech tasks (i.e., word reading, picture naming, and semantic questions). In addition, the results demonstrated that the high vascularity of the lesion altered the blood oxygen level-dependent function, resulting in false-positive and false-negative activation in the semantic questions and leg/foot rubbing task, respectively. Intraoperative direct cortical stimulation was conducted in the regions corresponding to fMRI activation while the patient performed motor, sensory, and language tasks and showed no loss of function. Follow-up fMRI revealed that there was no longer activation in the tumor or in perilesional regions, presumably owing to the resection of the vascularized tumor. CONCLUSIONS: This case highlights the importance of presurgical fMRI to inform the neurosurgical approach and emphasizes the need for careful interpretation of fMRI data, especially in cases of malignant glioma, which can decrease autoregulation in surrounding regions, affecting fMRI blood oxygen level-dependent signal.

Reorganized neural activation in motor cortex following subdural fluid collection: an fMRI and DTI study.

We report a patient with a cavernous malformation involving the right lentiform nucleus. Pre-surgical planning included fMRI localization of language, motor, and sensory processing, and DTI of white matter tracts. fMRI results revealed no activation near the planned resection zone. However, post-surgery the patient developed a subdural fluid collection, which applied pressure to the primary motor cortex (M1). Follow-up scans revealed that motor activation had shifted due to pressure, and then shifted to a new location after the fluid collection subsided. This case report suggests that long-term neural reorganization can occur in response to short term compression in the cortex.

More than a feeling: The bidirectional convergence of semantic visual object and somatosensory processing.

Prevalent theories of semantic processing assert that the sensorimotor system plays a functional role in the semantic processing of manipulable objects. While motor execution has been shown to impact object processing, involvement of the somatosensory system has remained relatively unexplored. Therefore, we developed two novel priming paradigms. In Experiment 1, participants received a vibratory hand prime (on half the trials) prior to viewing a picture of either an object interacted primarily with the hand (e.g., a cup) or the foot (e.g., a soccer ball) and reported how they would interact with it. In Experiment 2, the same objects became the prime and participants were required to identify whether the vibratory stimulation occurred to their hand or foot. In both experiments, somatosensory priming effects arose for the hand objects, while foot objects showed no priming benefits. These results suggest that object semantic knowledge bidirectionally converges with the somatosensory system.