Jennifer Vannest

Functional MRI of language lateralization during development in children.

Changes in the distribution of language function in the brain have been documented from infancy through adulthood. Even macroscopic measures of language lateralization reflect a dynamic process of language development. In this review, we summarize a series of functional MRI studies of language skills in children ages of five to 18 years, both typically-developing children and children with brain injuries or neurological disorders that occur at different developmental stages with different degrees of severity. These studies used a battery of fMRI-compatible language tasks designed to tap sentential and lexical language skills that develop early and later in childhood. In typically-developing children, lateralization changes with age are associated with language skills that have a protracted period of development, reflecting the developmental process of skill acquisition rather than general maturation of the brain. Normative data, across the developmental period, acts as a reference for disentangling developmental patterns in brain activation from changes due to developmental or acquired abnormalities. This review emphasizes the importance of considering age and child development in neuroimaging studies of language.

Excitatory repetitive transcranial magnetic stimulation induces improvements in chronic post-stroke aphasia

Summary Background Aphasia affects 1/3 of stroke patients with improvements noted only in some of them. The goal of this exploratory study was to provide preliminary evidence regarding safety and efficacy of fMRI-guided excitatory repetitive transcranial magnetic stimulation (rTMS) applied to the residual left-hemispheric Broca’s area for chronic aphasia treatment. Material/Methods We enrolled 8 patients with moderate or severe aphasia >1 year after LMCA stroke. Linguistic battery was administered pre-/post-rTMS; a semantic decision/tone decision (SDTD) fMRI task was used to localize left-hemispheric Broca’s area. RTMS protocol consisted of 10 daily treatments of 200 seconds each using an excitatory stimulation protocol called intermittent theta burst stimulation (iTBS). Coil placement was targeted individually to the left Broca’s. Results 6/8 patients showed significant pre-/post-rTMS improvements in semantic fluency (p=0.028); they were able to generate more appropriate words when prompted with a semantic category. Pre-/post-rTMS fMRI maps showed increases in left fronto-temporo-parietal language networks with a significant left-hemispheric shift in the left frontal (p=0.025), left temporo-parietal (p=0.038) regions and global language LI (p=0.018). Patients tended to report subjective improvement on Communicative Activities Log (mini-CAL; p=0.075). None of the subjects reported ill effects of rTMS. Conclusions FMRI-guided, excitatory rTMS applied to the affected Broca’s area improved language skills in patients with chronic post-stroke aphasia; these improvements correlated with increased language lateralization to the left hemisphere. This rTMS protocol appears to be safe and should be further tested in blinded studies assessing its short- and long-term safety/efficacy for post-stroke aphasia rehabilitation.

Comparison of fMRI data from passive listening and active‐response story processing tasks in children

To use functional MRI (fMRI) methods to visualize a network of auditory and language‐processing brain regions associated with processing an aurally‐presented story. We compare a passive listening (PL) story paradigm to an active‐response (AR) version including online performance monitoring and a sparse acquisition technique.

Recovered vs. not-recovered from post-stroke aphasia: the contributions from the dominant and non-dominant hemispheres.

PURPOSE Several adult studies have documented the importance of the peri-stroke areas to aphasia recovery. But, studies examining the differences in patterns of cortical participation in language comprehension in patients who have (LMCA-R) or have not recovered (LMCA-NR) from left middle cerebral artery infarction have not been performed up to date. METHODS In this study, we compare cortical correlates of language comprehension using fMRI and semantic decision/tone decision task in 9 LMCA-R and 18 LMCA-NR patients matched at the time of stroke for age and handedness. We examine the cortical correlates of language performance by correlating intra- and extra-scanner measures of linguistic performance with fMRI activation and stroke volumes. RESULTS Our analyses show that LMCA-R at least 1 year after stroke show a return to typical fMRI language activation patterns and that there is a compensatory reorganization of language function in LMCA-NR patients with shifts to the right hemispheric brain regions. Further, with increasing strength of the left-hemispheric fMRI signal shift there are associated improvements in performance as tested with standardized linguistic measures. A negative correlation between the size of the stroke and performance on some of the linguistic tests is also observed. CONCLUSIONS This right-hemispheric shift as a mechanism of post-stroke recovery in adults appears to be an ineffective mode of language function recovery with increasing right-hemispheric shift associated with lower language performance. Thus, normalization of the post-stroke language activation patterns is needed for better language performance while shifts of the activation patterns to the non-dominant (right) hemisphere and/or large stroke size are associated with decreased linguistic abilities after stroke.

Medial temporal fMRI activation reflects memory lateralization and memory performance in patients with epilepsy

Memory difficulties are a frequent cognitive complaint of patients with chronic epilepsy. Previous studies have suggested that the presence of a seizure focus causes reorganization of brain mechanisms underlying memory function. Here we examine whether seizure onset in the left hemisphere and onset in the right hemisphere have different effects on memory lateralization and whether longer duration of epilepsy is associated with increased lateralization of memory functions to the unaffected hemisphere. We hypothesized that hemisphere of onset and duration of epilepsy would influence plasticity of memory mechanisms, similar to the plasticity observed for language mechanisms. Healthy controls (HC, N = 10) and patients with epilepsy (N = 23, 11 with a left- and 12 with a right-hemisphere focus) performed a scene-encoding fMRI task at 4 T. Active voxels (relative to scrambled image viewing) were identified for each participant. Memory laterality indices (LIs) were calculated in three regions of interest (ROIs) designed on the basis of HC group data: a functional ROI, an anatomical-hippocampal ROI, and an anatomical-medial temporal ROI encompassing hippocampus and parahippocampal gyrus. In healthy controls, LIs were suggestive of slight left lateralization of encoding memory for pictures. Patients with right hemisphere epilepsy showed a nonsignificant increase in degree of left lateralization. In contrast, patients with left hemispheric epilepsy showed right-lateralized activation, differing significantly from controls and from patients with right hemispheric epilepsy. Neuropsychological measures of memory (WMS-III Story Recall) across epilepsy patients predicted LIs in the anatomical ROIs: higher scores were associated with more left-lateralized medial temporal fMRI activation. Neither age of onset nor duration of epilepsy was significantly related to LI. These results indicate that focal epilepsy may influence the functional neuroanatomy of memory function.

A group independent component analysis of covert verb generation in children: A functional magnetic resonance imaging study

Semantic language skills are an integral part of early childhood language development. The semantic association between verbs and nouns constitutes an important building block for the construction of sentences. In this large-scale functional magnetic resonance imaging (fMRI) study, involving 336 subjects between the ages of 5 and 18 years, we investigated the neural correlates of covert verb generation in children. Using group independent component analysis (ICA), seven task-related components were identified including the mid-superior temporal gyrus, the most posterior aspect of the superior temporal gyrus, the parahippocampal gyrus, the inferior frontal gyrus, the angular gyrus, and medial aspect of the parietal lobule (precuneus/posterior cingulate). A highly left-lateralized component was found including the medial temporal gyrus, the frontal gyrus, the inferior frontal gyrus, and the angular gyrus. The associated independent component (IC) time courses were analyzed to investigate developmental changes in the neural elements supporting covert verb generation. Observed age effects may either reflect specific local neuroplastic changes in the neural substrates supporting language or a more global transformation of neuroplasticity in the developing brain. The results are analyzed and presented in the framework of two theoretical models for neurocognitive brain development. In this context, group ICA of fMRI data from our large sample of children aged 5-18 years provides strong evidence in support of the regionally weighted model for cognitive neurodevelopment of language networks.

Cognitive and behavioral outcomes in benign childhood epilepsy with centrotemporal spikes

We review the evidence that BECTS may be associated with cognitive dysfunction and behavioral problems, the extent to which these problems may be associated with patterns of EEG abnormalities in BECTS, and the impact of antiepileptic medication on cognition and behavior in BECTS. A growing literature examining cognitive and behavioral outcomes suggests that children with BECTS perform below the level of their peers. Consistent with this, neuroimaging studies reveal that BECTS has an impact on structural and functional brain development, but the potential influence of frequency and lateralization of centrotemporal spikes (CTS) on cognition and behavior is not well understood. Treatment with AEDs is an option in BECTS, but existing studies have not clearly shown a clear relationship between elimination of CTS and improved cognitive or behavioral outcomes.

Language networks in children: Evidence from functional MRI studies

OBJECTIVE The purpose of our study was to review functional MRI and other neuroimaging studies of language skills in children from infancy to adulthood. CONCLUSION Functional MRI (fMRI) and other neuroimaging studies show developmental changes in the networks of brain regions supporting language, which can be affected by brain injuries or neurologic disorders. Particular aspects of language rely on networks that lateralize to the dominant hemisphere; others rely on bilateral or nondominant mechanisms. Multiple fMRI tasks for pediatric patients characterize functional brain reorganization that may accompany language deficits.

Low‐ and high‐frequency oscillations reveal distinct absence seizure networks

The aim of this study was to determine the frequency‐dependent, spatiotemporal involvement of corticothalamic networks to the generation of absence seizures.

Functional MRI-navigated Repetitive Transcranial Magnetic Stimulation Over Supplementary Motor Area in Chronic Tic Disorders

BACKGROUND Open label studies have shown repetitive transcranial magnetic stimulation to be effective in reducing tics. OBJECTIVES To determine whether 8 sessions of continuous theta burst stimulation (cTBS) over supplementary motor area (SMA) given over 2 days may reduce tics and motor cortical network activity in Tourette syndrome/chronic tic disorders. METHODS This was a randomized (1:1), double-blind, sham-controlled trial of functional MRI (fMRI)-navigated, 30 Hz cTBS at 90% of resting motor threshold (RMT) over SMA in 12 patients ages 10-22 years. Comorbid ADHD (n = 8), OCD (n = 8), and stable concurrent medications (n = 9) were permitted. Neuro-navigation utilized each individuals event-related fMRI signal. Primary clinical and cortical outcomes were: 1) Yale Global Tic Severity Scale (YGTSS) at one week; 2) fMRI event-related signal in SMA and primary motor cortex (M1) during a finger-tapping motor task. RESULT Baseline characteristics were not statistically different between groups (age, current tic/OCD/ADHD severities, tic-years, number of prior medication trials, RMT). Mean YGTSS scores decreased in both active (27.5 ± 7.4 to 23.2 ± 9.8) and sham (26.8 ± 4.8 to 21.7 ± 7.7) groups. However, no significant difference in video-based tic severity rating was detected between the two groups. Two-day post-treatment fMRI activation during finger tapping decreased significantly in active vs. sham groups for SMA (P = 0.02), left M1 (P = 0.0004), and right M1 (P < 0.0001). No serious adverse events occurred. CONCLUSION Active, fMRI-navigated cTBS administered in 8 sessions over 2 days to the SMA induced significant inhibition in the motor network (SMA, bilateral M1). However, both groups on average experienced tic reduction at 7 days. Larger sample size and protocol modifications may be needed to produce clinically significant tic reduction beyond placebo effect.