Resting state functional connectivity associated with impaired proprioception post-stroke.

Deficits in proprioception, the knowledge of limb position and movement in the absence of vision, occur in ~50% of all strokes; however, our lack of knowledge of the neurological mechanisms of these deficits diminishes the effectiveness of rehabilitation and prolongs recovery. We performed resting-state functional magnetic resonance imaging (fMRI) on stroke patients to determine functional brain networks that exhibited changes in connectivity in association with proprioception deficits determined by a Kinarm robotic exoskeleton assessment. Thirty stroke participants were assessed for proprioceptive impairments using a Kinarm robot and underwent resting-state fMRI at 1 month post-stroke. Age-matched healthy control (n = 30) fMRI data were also examined and compared to stroke data in terms of the functional connectivity of brain regions associated with proprioception. Stroke patients exhibited reduced connectivity of the supplementary motor area and the supramarginal gyrus, relative to controls. Functional connectivity of these regions plus primary somatosensory cortex and parietal opercular area was significantly associated with proprioceptive function. The parietal lobe of the lesioned hemisphere is a significant node for proprioception after stroke. Assessment of functional connectivity of this region after stroke may assist with prognostication of recovery. This study also provides potential targets for therapeutic neurostimulation to aid in stroke recovery.

Accelerated cortical thinning precedes and predicts conversion to psychosis: The NAPLS3 longitudinal study of youth at clinical high-risk.

Progressive grey matter loss has been demonstrated among clinical high-risk (CHR) individuals who convert to psychosis, but it is unknown whether these changes occur prior to psychosis onset. Identifying illness-related neurobiological mechanisms that occur prior to conversion is essential for targeted early intervention. Among participants in the third wave of the North American Prodrome Longitudinal Study (NAPLS3), this report investigated if steeper cortical thinning was observable prior to psychosis onset among CHR individuals who ultimately converted (CHR-C) and assessed the shortest possible time interval in which rates of cortical thinning differ between CHR-C, CHR non-converters (CHR-NC), and health controls (HC). 338 CHR-NC, 42 CHR-C, and 62 HC participants (age 19.3±4.2, 44.8% female, 52.5% racial/ethnic minority) completed up to 5 MRI scans across 8 months. Accelerated thinning among CHR-C compared to CHR-NC and HC was observed in multiple prefrontal, temporal, and parietal cortical regions. CHR-NC also exhibited accelerated cortical thinning compared to HC in several of these areas. Greater percent decrease in cortical thickness was observed among CHR-C compared to other groups across 2.9±1.8 months, on average, in several cortical areas. ROC analyses discriminating CHR-C from CHR-NC by percent thickness change in a left hemisphere region of interest, scanner, age, age2, and sex had an AUC of 0.74, with model predictive power driven primarily by percent thickness change. Findings indicate that accelerated cortical thinning precedes psychosis onset and differentiates CHR-C from CHR-NC and HC across short time intervals. Mechanisms underlying cortical thinning may provide novel treatment targets prior to psychosis onset.

Mesial temporal lobe spiking reveals distinct patterns of blood oxygen level-dependent functional magnetic resonance imaging activation using simultaneous intracranial electroencephalography-functional magnetic resonance imaging.

OBJECTIVE: Temporal lobe epilepsy (TLE) has a high probability of becoming drug resistant and is frequently considered for surgical intervention. However, 30% of TLE cases have nonlesional magnetic resonance imaging (MRI) scans, which is associated with worse surgical outcomes. Characterizing interactions between temporal and extratemporal structures in these patients may help understand these poor outcomes. Simultaneous intracranial electroencephalography-functional MRI (iEEG-fMRI) can measure the hemodynamic changes associated with interictal epileptiform discharges (IEDs) recorded directly from the brain. This study was designed to characterize the whole brain patterns of IED-associated fMRI activation recorded exclusively from the mesial temporal lobes of patients with nonlesional TLE. METHODS: Eighteen patients with nonlesional TLE undergoing iEEG monitoring with mesial temporal IEDs underwent simultaneous iEEG-fMRI at 3 T. IEDs were marked, and statistically significant clusters of fMRI activation were identified. The locations of IED-associated fMRI activation for each patient were determined, and patients were grouped based on the location and pattern of fMRI activation. RESULTS: Two patterns of IED-associated fMRI activation emerged: primarily localized (n = 7), where activation was primarily located within the ipsilateral temporal lobe, and primarily diffuse (n = 11), where widespread bilateral extratemporal activation was detected. The primarily diffuse group reported significantly fewer focal to bilateral tonic-clonic seizures and had better postsurgical outcomes. SIGNIFICANCE: Simultaneous iEEG-fMRI can measure the hemodynamic changes associated with focal IEDs not visible on scalp EEG, such as those arising from the mesial temporal lobe. Significant fMRI activation associated with these IEDs was observed in all patients. Two distinct patterns of IED-associated activation were seen: primarily localized to the ipsilateral temporal lobe and more widespread, bilateral activation. Patients with widespread IED associated-activation had fewer focal to bilateral tonic-clonic seizures and better postsurgical outcome, which may suggest a neuroprotective mechanism limiting the spread of ictal events.

Structural connectome differences in pediatric mild traumatic brain and orthopedic injury.

Sophisticated network-based approaches such as structural connectomics may help to detect a biomarker of mild traumatic brain injury (mTBI) in children. This study compared the structural connectome of children with mTBI or mild orthopedic injury (OI) to that of typically developing (TD) children. Children aged 8-16.99 years with mTBI (n = 83) or OI (n = 37) were recruited from the emergency department and completed 3T diffusion MRI 2-20 days postinjury. TD children (n = 39) were recruited from the community and completed diffusion MRI. Graph theory metrics were calculated for the binarized average fractional anisotropy among 90 regions. Multivariable linear regression and linear mixed effects models were used to compare groups, with covariates age, hemisphere, and sex, correcting for multiple comparisons. The two injury groups did not differ on graph theory metrics, but both differed from TD children in global metrics (local network efficiency: TD > OI, mTBI, d = 0.49; clustering coefficient: TD < OI, mTBI, d = 0.49) and regional metrics for the fusiform gyrus (lower degree centrality and nodal efficiency: TD > OI, mTBI, d = 0.80 to 0.96; characteristic path length: TD < OI, mTBI, d = -0.75 to -0.90) and in the superior and middle orbital frontal gyrus, paracentral lobule, insula, and thalamus (clustering coefficient: TD > OI, mTBI, d = 0.66 to 0.68). Both mTBI and OI demonstrated reduced global and regional network efficiency and segregation as compared to TD children. Findings suggest a general effect of childhood injury that could reflect pre- and postinjury factors that can alter brain structure. An OI group provides a more conservative comparison group than TD children for structural neuroimaging research in pediatric mTBI.

Longitudinal white matter microstructural changes in pediatric mild traumatic brain injury: An A-CAP study.

In the largest sample studied to date, white matter microstructural trajectories and their relation to persistent symptoms were examined after pediatric mild traumatic brain injury (mTBI). This prospective, longitudinal cohort study recruited children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) from five pediatric emergency departments. Children's pre-injury and 1-month post-injury symptom ratings were used to classify mTBI with or without persistent symptoms. Children completed diffusion-weighted imaging at post-acute (2-33 days post-injury) and chronic (3 or 6 months via random assignment) post-injury assessments. Mean diffusivity (MD) and fractional anisotropy (FA) were derived for 18 white matter tracts in 560 children (362 mTBI/198 OI), 407 with longitudinal data. Superior longitudinal fasciculus FA was higher in mTBI without persistent symptoms relative to OI, d (95% confidence interval) = 0.31 to 0.37 (0.02, 0.68), across time. In younger children, MD of the anterior thalamic radiations was higher in mTBI with persistent symptoms relative to both mTBI without persistent symptoms, 1.43 (0.59, 2.27), and OI, 1.94 (1.07, 2.81). MD of the arcuate fasciculus, -0.58 (-1.04, -0.11), and superior longitudinal fasciculus, -0.49 (-0.90, -0.09) was lower in mTBI without persistent symptoms relative to OI at 6 months post-injury. White matter microstructural changes suggesting neuroinflammation and axonal swelling occurred chronically and continued 6 months post injury in children with mTBI, especially in younger children with persistent symptoms, relative to OI. White matter microstructure appears more organized in children without persistent symptoms, consistent with their better clinical outcomes.

Localization of interictal discharge origin: A simultaneous intracranial electroencephalographic-functional magnetic resonance imaging study.

OBJECTIVE: Scalp electroencephalographic (EEG)-functional magnetic resonance imaging (fMRI) studies suggest that the maximum blood oxygen level-dependent (BOLD) response to an interictal epileptiform discharge (IED) identifies the area of IED generation. However, the maximum BOLD response has also been reported in distant, seemingly irrelevant areas. Given the poor postoperative outcomes associated with extra-temporal lobe epilepsy, we hypothesized this finding is more common when analyzing extratemporal IEDs as compared to temporal IEDs. We further hypothesized that a subjective, holistic assessment of other significant BOLD clusters to identify the most clinically relevant cluster could be used to overcome this limitation and therefore better identify the likely origin of an IED. Specifically, we also considered the second maximum cluster and the cluster closest to the electrode contacts where the IED was observed. METHODS: Maps of significant IED-related BOLD activation were generated for 48 different IEDs recorded from 33 patients who underwent intracranial EEG-fMRI. The locations of the maximum, second maximum, and closest clusters were identified for each IED. An epileptologist, blinded to these cluster assignments, selected the most clinically relevant BOLD cluster, taking into account all available clinical information. The distances between these BOLD clusters and their corresponding IEDs were then measured. RESULTS: The most clinically relevant cluster was the maximum cluster for 56% (27/48) of IEDs, the second maximum cluster for 13% (6/48) of IEDs, and the closest cluster for 31% (15/48) of IEDs. The maximum clusters were closer to IED contacts for temporal than for extratemporal IEDs (p = .022), whereas the most clinically relevant clusters were not significantly different (p = .056). SIGNIFICANCE: The maximum BOLD response to IEDs may not always be the most indicative of IED origin. We propose that available clinical information should be used in conjunction with EEG-fMRI data to identify a BOLD cluster representative of the IED origin.

Imaging functional motor connectivity in hemiparetic children with perinatal stroke.

Perinatal stroke causes lifelong disability, particularly hemiparetic cerebral palsy. Arterial ischemic strokes (AIS) are large, cortical, and subcortical injuries acquired near birth due to acute occlusion of the middle cerebral artery. Periventricular venous infarctions (PVI) are smaller, subcortical strokes acquired prior to 34 weeks gestation involving injury to the periventricular white matter. Both stroke types can damage motor pathways, thus, we investigated resulting alterations in functional motor networks and probed function. We measured blood oxygen level dependent (BOLD) fluctuations at rest in 38 participants [10 arterial patients (age = 14.7 ± 4.1 years), 10 venous patients (age = 13.5 ± 3.7 years), and 18 typically developing controls (TDCs) (age = 15.3 ± 5.1 years)] and explored strength and laterality of functional connectivity in the motor network. Inclusion criteria included MRI-confirmed, unilateral perinatal stroke, symptomatic hemiparetic cerebral palsy, and 6-19 years old at time of imaging. Seed-based functional connectivity analyses measured temporal correlations in BOLD response over the whole brain using primary motor cortices as seeds. Laterality indices based on mean z-scores in lesioned and nonlesioned hemispheres explored laterality. In AIS patients, significant differences in both strength and laterality of motor network connections were observed compared with TDCs. In PVI patients, motor networks largely resembled those of healthy controls, albeit slightly weaker and asymmetric, despite subcortical damage and hemiparesis. Functional connectivity strengths were not related to motor outcome scores for either stroke group. This study serves as a foundation to better understand how resting-state fMRI can assess motor functional connectivity and potentially be applied to explore mechanisms of interventional therapies after perinatal stroke.

Cortical Microinfarcts on 3T Magnetic Resonance Imaging in Cerebral Amyloid Angiopathy.

Background and Purpose- Cerebral microinfarcts are small ischemic lesions that are found in cerebral amyloid angiopathy (CAA) patients at autopsy. The current study aimed to detect cortical microinfarcts (CMI) on in vivo 3 Tesla (3T) magnetic resonance imaging (MRI) in CAA patients, to study the progression of CMI over a 1-year period, and to correlate CMI with markers of CAA-related vascular brain injury and cognitive functioning. Methods- Thirty-five CAA patients (mean age, 74.2±7.6 years), 13 Alzheimer disease (AD) patients (67.0±5.8 years), and 26 healthy controls (67.2±9.5 years) participated in the study. All participants underwent a standardized clinical and neuropsychological assessment as well as 3T MRI. CMI were rated according to standardized criteria. Results- CMI were present in significantly more CAA patients (57.1%; median number: 1, range 1-9) than in Alzheimer disease (7.7%) or in healthy controls (11.5%; P<0.001). Incident CMI were observed after a 1-year follow-up. CMI did not correlate with any other MRI marker of CAA nor with cognitive function. Conclusions- In vivo CMI are a frequent finding on 3T MRI in CAA patients, and incident CMI are observable after 1-year follow-up. CMI can be regarded as a new MRI marker of CAA, potentially distinct from other well-established markers. Future larger cohort studies with longitudinal follow-up are needed to elucidate the relationship between CMI and possible causes and clinical outcomes in CAA.

Statistical inference of dynamic resting-state functional connectivity using hierarchical observation modeling.

Spontaneous fluctuations of blood-oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) signals are highly synchronous between brain regions that serve similar functions. This provides a means to investigate functional networks; however, most analysis techniques assume functional connections are constant over time. This may be problematic in the case of neurological disease, where functional connections may be highly variable. Recently, several methods have been proposed to determine moment-to-moment changes in the strength of functional connections over an imaging session (so called dynamic connectivity). Here a novel analysis framework based on a hierarchical observation modeling approach was proposed, to permit statistical inference of the presence of dynamic connectivity. A two-level linear model composed of overlapping sliding windows of fMRI signals, incorporating the fact that overlapping windows are not independent was described. To test this approach, datasets were synthesized whereby functional connectivity was either constant (significant or insignificant) or modulated by an external input. The method successfully determines the statistical significance of a functional connection in phase with the modulation, and it exhibits greater sensitivity and specificity in detecting regions with variable connectivity, when compared with sliding-window correlation analysis. For real data, this technique possesses greater reproducibility and provides a more discriminative estimate of dynamic connectivity than sliding-window correlation analysis. Hum Brain Mapp 37:4566-4580, 2016. © 2016 Wiley Periodicals, Inc.

Patient specific hemodynamic response functions associated with interictal discharges recorded via simultaneous intracranial EEG-fMRI.

Simultaneous collection of scalp EEG and fMRI has become an important tool for studying the hemodynamic changes associated with interictal epileptiform discharges (IEDs) in persons with epilepsy, and has become a standard presurgical assessment tool in some centres. We previously demonstrated that performing EEG-fMRI using intracranial electrodes (iEEG-fMRI) is of low risk to patients in our research centre, and offers unique insight into BOLD signal changes associated with IEDs recorded from very discrete sources. However, it is unknown whether the BOLD response corresponding to IEDs recorded by iEEG-fMRI follows the canonical hemodynamic response. We therefore scanned 11 presurgical epilepsy patients using iEEG-fMRI, and assessed the hemodynamic response associated with individual IEDs using two methods: assessment of BOLD signal changes associated with isolated IEDs at the location of the active intracranial electrode, and by estimating subject-specific impulse response functions to isolated IEDs. We found that the hemodynamic response associated with the intracranially recorded discharges varied by patient and by spike location. The observed shape and timing differences also deviated from the canonical hemodynamic response function traditionally used in many fMRI experiments. It is recommended that future iEEG-fMRI studies of IEDs use a flexible hemodynamic response model when performing parametric tests to accurately characterize these data.

Deep EEG source localization via EMD-based fMRI high spatial frequency.

Brain imaging with a high-spatiotemporal resolution is crucial for accurate brain-function mapping. Electroencephalography (EEG) and functional Magnetic Resonance Imaging (fMRI) are two popular neuroimaging modalities with complementary features that record brain function with high temporal and spatial resolution, respectively. One popular non-invasive way to obtain data with both high spatial and temporal resolutions is to combine the fMRI activation map and EEG data to improve the spatial resolution of the EEG source localization. However, using the whole fMRI map may cause spurious results for the EEG source localization, especially for deep brain regions. Considering the head's conductivity, deep regions' sources with low activity are unlikely to be detected by the EEG electrodes at the scalp. In this study, we use fMRI's high spatial-frequency component to identify the local high-intensity activations that are most likely to be captured by the EEG. The 3D Empirical Mode Decomposition (3D-EMD), a data-driven method, is used to decompose the fMRI map into its spatial-frequency components. Different validation measurements for EEG source localization show improved performance for the EEG inverse-modeling informed by the fMRI's high-frequency spatial component compared to the fMRI-informed EEG source-localization methods. The level of improvement varies depending on the voxels' intensity and their distribution. Our experimental results also support this conclusion.

Structural network topology associated with naming improvements following intensive aphasia therapy in post-stroke aphasia.

A stroke can disrupt the finely tuned language network resulting in aphasia, a language impairment. Though many stroke survivors with aphasia recover within the first 6 months, a significant proportion have lasting deficits. The factors contributing to optimal treatment response remain unclear. Some evidence suggests that increased modularity or fragmentation of brain networks may underlie post-stroke aphasia severity and the extent of recovery. We examined associations between network organization and aphasia recovery in sixteen chronic stroke survivors with non-fluent aphasia following 35 h of Multi-Modality Aphasia Therapy over 10 days and 20 healthy controls who underwent imaging at a single timepoint. Using diffusion-weighted scans obtained before and after treatment, we constructed whole-brain structural connectomes representing the number of probabilistic streamlines between brain regions. Graph theory metrics were quantified for each connectome using the Brain Connectivity Toolbox. Correlations were examined between graph metrics and speech performance measured using the Boston Naming Test (BNT) at pre-, post- and 3-months post-intervention. Compared to controls, participants with stroke demonstrated higher whole-brain modularity at pre-treatment. Modularity did not differ between pre- and post-treatment. In individuals who responded to therapy, higher pre-treatment modularity was associated with worse performance on the BNT. Moreover, higher pre-treatment participation coefficients (i.e., how well a region is connected outside its own module) for the left IFG, planum temporale, and posterior temporal gyri were associated with greater improvements at post-treatment. These results suggest that pre-treatment network topology may impact therapeutic gains, highlighting the influence of network organization on post-stroke aphasia recovery.

Association of Psychological Resilience, Cognitive Reserve, and Brain Reserve with Post-Concussive Symptoms in Children with Mild Traumatic Brain Injury and Orthopedic Injury: An A-CAP Study.

Protective factors, including psychological resilience, cognitive reserve, and brain reserve, may be positively associated with recovery after pediatric mild traumatic brain injury (mTBI) but are yet to be studied concurrently. We sought to examine these factors as moderators of post-concussive symptoms (PCS) in pediatric mTBI compared with mild orthopedic injury (OI). Participants included 967 children (633 mTBI, 334 OI) aged 8-16.99 years, recruited from 5 Canadian pediatric emergency departments as part of a prospective longitudinal cohort study. At 10 days post-injury, psychological resilience was measured using the Connor-Davidson Resilience Scale and brain reserve was measured using total brain volume derived from structural magnetic resonance imaging. Cognitive reserve was measured at 3 months post-injury using IQ scores from the Wechsler Abbreviated Scale of Intelligence-Second Edition. Cognitive and somatic PCS were measured using child and parent ratings on the Health and Behavior Inventory, completed weekly for 3 months and biweekly to 6 months. Analyses involved generalized least-squares regression models using restricted cubic splines. Covariates included age at injury, sex, racialized identity, material and social deprivation, pre-injury migraine and concussion history, and retrospective pre-injury PCS. Psychological resilience moderated group differences in parent-reported PCS. At 30 days post-injury, estimated group differences in parent-reported cognitive and somatic PCS (mTBI > OI) were larger at higher (75th percentile) resilience scores (Est = 2.25 [0.87, 3.64] and Est = 2.38 [1.76, 3.00], respectively) than at lower (25th percentile) resilience scores (Est = 1.44 [0.01, 2.86] and Est = 2.08 [1.45, 2.71], respectively). Resilience did not moderate group differences in child-reported PCS but was negatively associated with child-reported PCS in both groups (ps ≤ 0.001). Brain reserve (i.e., total brain volume [TBV]) also moderated group differences, but only for parent-reported somatic PCS (p = 0.018). Group difference (mTBI > OI) at 30 days was larger at smaller (25th percentile) TBV (Est = 2.78 [2.17, 3.38]) than at larger (75th percentile) TBV (Est = 1.95 [1.31, 2.59]). TBV was not associated with parent-reported cognitive PCS or child-reported PCS. IQ did not moderate PCS in either group but had a significant non-linear association in both groups with child-reported somatic PCS (p = 0.018) and parent-reported PCS (p < 0.001), with higher PCS scores at both lower and higher IQs. These findings suggest that higher resilience predicts fewer PCS, but less strongly after mTBI than OI; greater brain reserve may reduce the effect of mTBI on somatic PCS; and cognitive reserve has an unexpected curvilinear association with PCS across injury types. The results highlight the importance of protective factors as predictors of recovery and potential targets for intervention following pediatric mTBI.

Longitudinal Functional Connectome in Pediatric Concussion: An Advancing Concussion Assessment in Pediatrics Study.

Advanced magnetic resonance imaging (MRI) techniques indicate that concussion (i.e., mild traumatic brain injury) disrupts brain structure and function in children. However, the functional connectivity of brain regions within global and local networks (i.e., functional connectome) is poorly understood in pediatric concussion. This prospective, longitudinal study addressed this gap using data from the largest neuroimaging study of pediatric concussion to date to study the functional connectome longitudinally after concussion as compared with mild orthopedic injury (OI). Children and adolescents (n = 967) 8-16.99 years with concussion or mild OI were recruited from pediatric emergency departments within 48 h post-injury. Pre-injury and 1-month post-injury symptom ratings were used to classify concussion with or without persistent symptoms based on reliable change. Subjects completed a post-acute (2-33 days) and chronic (3 or 6 months via random assignment) MRI scan. Graph theory metrics were derived from 918 resting-state functional MRI scans in 585 children (386 concussion/199 OI). Linear mixed-effects modeling was performed to assess group differences over time, correcting for multiple comparisons. Relative to OI, the global clustering coefficient was reduced at 3 months post-injury in older children with concussion and in females with concussion and persistent symptoms. Time post-injury and sex moderated group differences in local (regional) network metrics of several brain regions, including degree centrality, efficiency, and clustering coefficient of the angular gyrus, calcarine fissure, cuneus, and inferior occipital, lingual, middle occipital, post-central, and superior occipital gyrus. Relative to OI, degree centrality and nodal efficiency were reduced post-acutely, and nodal efficiency and clustering coefficient were reduced chronically after concussion (i.e., at 3 and 6 months post-injury in females; at 6 months post-injury in males). Functional network alterations were more robust and widespread chronically as opposed to post-acutely after concussion, and varied by sex, age, and symptom recovery at 1-month post-injury. Local network segregation reductions emerged globally (across the whole brain network) in older children and in females with poor recovery chronically after concussion. Reduced functioning between neighboring regions could negatively disrupt specialized information processing. Local network metric alterations were demonstrated in several posterior regions that are involved in vision and attention after concussion relative to OI. This indicates that functioning of superior parietal and occipital regions could be particularly susceptibile to the effects of concussion. Moreover, those regional alterations were especially apparent at later time periods post-injury, emerging after post-concussive symptoms resolved in most and persisted up to 6 months post-injury, and differed by biological sex. This indicates that neurobiological changes continue to occur up to 6 months after pediatric concussion, although changes emerge earlier in females than in males. Changes could reflect neural compensation mechanisms.

Presurgical language fMRI and postsurgical deficits: a single centre experience.

BACKGROUND: In this study, we conducted a retrospective investigation of our initial single-centre experience with the clinical use of functional magnetic resonance imaging (fMRI) of hemisphere dominance for language processing (i.e., language lateralization). We demonstrated its association with surgical outcome and its potential impact on surgical planning and patient management. METHODS: Fifty-two cases were reviewed, covering the period from July 2007 to July 2010. Clinical fMRI reports were examined to determine the hemisphere dominance for language processing. Neurological reports were examined to determine if new language deficits were present post-surgery. Neurosurgeon notes were also reviewed to determine if fMRI had an impact on surgical planning. RESULTS: Of the cases reviewed, 49 (94%) generated conclusive fMRI. Eleven (22%) patients exhibited fMRI language lateralization contralateral to pathology; zero of nine of these patients that had surgery experienced post-surgical deficits. Twenty-two (44%) patients exhibited fMRI language lateralization ipsilateral to pathology; three of 13 of these patients that had surgery experienced post-surgical deficits. Sixteen (34%) patients exhibited bilateral lateralization of language; five of 13 of these patients that had surgery experienced post-surgery deficits. Several post-fMRI reports indicated that fMRI results had an impact on surgical planning. CONCLUSIONS: Our results suggest that fMRI demonstrations of language processing within the hemisphere ipsilateral to pathology (either ipsilateral alone or bilateral) is associated with a greater risk for post-surgical language deficits, and in these cases, fMRI results should be taken into consideration for pre-surgical planning.IRMf du langage avant la chirurgie et déficits après la chirurgie : expérience d'un centre.

Impact of averaging fNIRS regional coherence data when monitoring people with long term post-concussion symptoms.

Significance: Functional near-infrared spectroscopy (fNIRS), with its measure of delta hemoglobin concentration, has shown promise as a monitoring tool for the functional assessment of neurological disorders and brain injury. Analysis of fNIRS data often involves averaging data from several channel pairs in a region. Although this greatly reduces the processing time, it is uncertain how it affects the ability to detect changes post injury. Aim: We aimed to determine how averaging data within regions impacts the ability to differentiate between post-concussion and healthy controls. Approach: We compared interhemispheric coherence data from 16 channel pairs across the left and right dorsolateral prefrontal cortex during a task and a rest period. We compared the statistical power for differentiating groups that was obtained when undertaking no averaging, vs. averaging data from 2, 4, or 8 source detector pairs. Results: Coherence was significantly reduced in the concussion group compared with controls when no averaging was undertaken. Averaging all 8 channel pairs before undertaking the coherence analysis resulted in no group differences. Conclusions: Averaging between fiber pairs may eliminate the ability to detect group differences. It is proposed that even adjacent fiber pairs may have unique information, so averaging must be done with caution when monitoring brain disorders or injury.

Repetitive transcranial magnetic stimulation (rTMS) combined with multi-modality aphasia therapy for chronic post-stroke non-fluent aphasia: A pilot randomized sham-controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) shows promise in improving speech production in post-stroke aphasia. Limited evidence suggests pairing rTMS with speech therapy may result in greater improvements. Twenty stroke survivors (>6 months post-stroke) were randomized to receive either sham rTMS plus multi-modality aphasia therapy (M-MAT) or rTMS plus M-MAT. For the first time, we demonstrate that rTMS combined with M-MAT is feasible, with zero adverse events and minimal attrition. Both groups improved significantly over time on all speech and language outcomes. However, improvements did not differ between rTMS or sham. We found that rTMS and sham groups differed in lesion location, which may explain speech and language outcomes as well as unique patterns of BOLD signal change within each group. We offer practical considerations for future studies and conclude that while combination therapy of rTMS plus M-MAT in chronic post-stroke aphasia is safe and feasible, personalized intervention may be necessary.

Multimodal Brain MRI of Deep Gray Matter Changes Associated With Inflammatory Bowel Disease.

BACKGROUND: Behavioral symptoms, including mood disorders, substantially impact the quality of life of patients with inflammatory bowel disease (IBD), even when clinical remission is achieved. Here, we used multimodal magnetic resonance imaging (MRI) to determine if IBD is associated with changes in the structure and function of deep gray matter brain regions that regulate and integrate emotional, cognitive, and stress responses. METHODS: Thirty-five patients with ulcerative colitis (UC) or Crohn's disease (CD) and 32 healthy controls underwent 3 Tesla MRIs to assess volume, neural activity, functional connection strength (connectivity), inflammation, and neurodegeneration of key deep gray matter brain regions (thalamus, caudate, pallidum, putamen, amygdala, hippocampus, and hypothalamus) involved in emotional, cognitive and stress processing. Associations with sex, presence of pain, disease activity, and C-reactive protein (CRP) concentration were examined. RESULTS: Significantly increased activity and functional connectivity were observed in cognitive and emotional processing brain regions, including parts of the limbic system, basal ganglia, and hypothalamus of IBD patients compared with healthy controls. Inflammatory bowel disease patients exhibited significantly increased volumes of the amygdala and hypothalamus, as well as evidence of neurodegeneration in the putamen and pallidum. Hippocampal neural activity was increased in IBD patients with active disease. The volume of the thalamus was positively correlated with CRP concentration and was increased in females experiencing pain. CONCLUSIONS: Patients with IBD exhibit functional and structural changes in the limbic and striatal systems. These changes may be targets for assessing or predicting the response to therapeutic interventions aimed at improving comorbid emotional and cognitive symptoms.

Magnetic resonance imaging revealed structural and functional changes within the brains of inflammatory bowel disease patients, in regions known to be involved in processing brain signals associated with behavioral symptoms, anxiety, pain, stress, and cognitive deficits.

Longitudinal Gray Matter Trajectories in Pediatric Mild Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: This prospective, longitudinal cohort study examined trajectories of brain gray matter macrostructure after pediatric mild traumatic brain injury (mTBI). METHODS: Children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) were recruited from 5 pediatric emergency departments. Reliable change between preinjury and 1 month postinjury symptom ratings was used to classify mTBI with or without persistent symptoms. Children completed postacute (2-33 days) and/or chronic (3 or 6 months) postinjury T1-weighted MRI, from which macrostructural metrics were derived using automated segmentation. Linear mixed-effects models were used, with multiple comparisons correction. RESULTS: Groups (N = 623; 407 mTBI/216 OI; 59% male; age mean = 12.03, SD = 2.38 years) did not differ in total brain, white, or gray matter volumes or regional subcortical gray matter volumes. However, time postinjury, age at injury, and biological sex-moderated differences among symptom groups in cortical thickness of the angular gyrus, basal forebrain, calcarine cortex, gyrus rectus, medial and posterior orbital gyrus, and the subcallosal area all corrected p < 0.05. Gray matter macrostructural metrics did not differ between groups postacutely. However, cortical thinning emerged chronically after mTBI relative to OI in the angular gyrus in older children (d [95% confidence interval] = -0.61 [-1.15 to -0.08]); and in the basal forebrain (-0.47 [-0.94 to -0.01]), subcallosal area (-0.55 [-1.01 to -0.08]), and the posterior orbital gyrus (-0.55 [-1.02 to -0.08]) in females. Cortical thinning was demonstrated for frontal and occipital regions 3 months postinjury in males with mTBI with persistent symptoms vs without persistent symptoms (-0.80 [-1.55 to -0.05] to -0.83 [-1.56 to -0.10]) and 6 months postinjury in females and younger children with mTBI with persistent symptoms relative to mTBI without persistent symptoms and OI (-1.42 [-2.29 to -0.45] to -0.91 [-1.81 to -0.01]). DISCUSSION: These findings signal little diagnostic and prognostic utility of postacute gray matter macrostructure in pediatric mTBI. However, mTBI altered the typical course of cortical gray matter thinning up to 6 months postinjury, even after symptoms typically abate in most children. Collapsing across symptom status obscured the neurobiological heterogeneity of discrete clinical outcomes after pediatric mTBI. The results illustrate the need to examine neurobiology in relation to clinical outcomes and within a neurodevelopmental framework.

Altered longitudinal structural connectome in paediatric mild traumatic brain injury: an Advancing Concussion Assessment in Paediatrics study.

Advanced diffusion-weighted imaging techniques have increased understanding of the neuropathology of paediatric mild traumatic brain injury (i.e. concussion). Most studies have examined discrete white-matter pathways, which may not capture the characteristically subtle, diffuse and heterogenous effects of paediatric concussion on brain microstructure. This study compared the structural connectome of children with concussion to those with mild orthopaedic injury to determine whether network metrics and their trajectories across time post-injury differentiate paediatric concussion from mild traumatic injury more generally. Data were drawn from of a large study of outcomes in paediatric concussion. Children aged 8-16.99 years were recruited from five paediatric emergency departments within 48 h of sustaining a concussion (n = 360; 56% male) or mild orthopaedic injury (n = 196; 62% male). A reliable change score was used to classify children with concussion into two groups: concussion with or without persistent symptoms. Children completed 3 T MRI at post-acute (2-33 days) and/or chronic (3 or 6 months, via random assignment) post-injury follow-ups. Diffusion-weighted images were used to calculate the diffusion tensor, conduct deterministic whole-brain fibre tractography and compute connectivity matrices in native (diffusion) space for 90 supratentorial regions. Weighted adjacency matrices were constructed using average fractional anisotropy and used to calculate global and local (regional) graph theory metrics. Linear mixed effects modelling was performed to compare groups, correcting for multiple comparisons. Groups did not differ in global network metrics. However, the clustering coefficient, betweenness centrality and efficiency of the insula, cingulate, parietal, occipital and subcortical regions differed among groups, with differences moderated by time (days) post-injury, biological sex and age at time of injury. Post-acute differences were minimal, whereas more robust alterations emerged at 3 and especially 6 months in children with concussion with persistent symptoms, albeit differently by sex and age. In the largest neuroimaging study to date, post-acute regional network metrics distinguished concussion from mild orthopaedic injury and predicted symptom recovery 1-month post-injury. Regional network parameters alterations were more robust and widespread at chronic timepoints than post-acutely after concussion. Results suggest that increased regional and local subnetwork segregation (modularity) and inefficiency occurs across time after concussion, emerging after post-concussive symptom resolve in most children. These differences persist up to 6 months after concussion, especially in children who showed persistent symptoms. While prognostic, the small to modest effect size of group differences and the moderating effects of sex likely would preclude effective clinical application in individual patients.