Kenneth P. Eaton

Reliability of fMRI for Studies of Language in Post-Stroke Aphasia Subjects

Quantifying change in brain activation patterns associated with post-stroke recovery and reorganization of language function over time requires accurate understanding of inter-scan and inter-subject variability. Here we report inter-scan variability measures for fMRI activation patterns associated with verb generation (VG) and semantic decision/tone decision (SDTD) tasks in 4 healthy controls and 4 aphasic left middle cerebral artery (LMCA) stroke subjects. A series of 10 fMRI scans was completed on a 4T Varian scanner for each task for each subject, except for one stroke subject who completed 5 and 6 scans for SDTD and VG, thus yielding 35 and 36 total stroke subject scans for SDTD and VG, respectively. Group composite and intraclass correlation coefficient (ICC) maps were computed across all subjects and trials for each task. The patterns of reliable activation for the VG and SDTD tasks correspond well to those regions typically activated by these tasks in healthy and aphasic subjects. ICCs for activation were consistently high (R(0.05) approximately 0.8) for individual tasks among both control and aphasic subjects. These voxel-wise measures of reliability highlight regions of low inter-scan variability within language circuitry for control and post-recovery stroke subjects. ICCs computed from the combination of the SDTD/VG data were markedly reduced for both control and aphasic subjects as compared with the ICCs for the individual tasks. These quantitative measures of inter-scan variability support the proposed use of these fMRI paradigms for longitudinal mapping of neural reorganization of language processing following left hemispheric insult.

A 10-year longitudinal fMRI study of narrative comprehension in children and adolescents.

Comprehension of spoken narratives requires coordination of multiple language skills. As such, for normal children narrative skills develop well into the school years and, during this period, are particularly vulnerable in the face of brain injury or developmental disorder. For these reasons, we sought to determine the developmental trajectory of narrative processing using longitudinal fMRI scanning. 30 healthy children between the ages of 5 and 18 enrolled at ages 5, 6, or 7, were examined annually for up to 10 years. At each fMRI session, children were presented with a set of five, 30s-long, stories containing 9, 10, or 11 sentences designed to be understood by a 5 year old child. fMRI data analysis was conducted based on a hierarchical linear model (HLM) that was modified to investigate developmental changes while accounting for missing data and controlling for factors such as age, linguistic performance and IQ. Performance testing conducted after each scan indicated well above the chance (p<0.002) comprehension performance. There was a linear increase with increasing age in bilateral superior temporal cortical activation (BAs 21 and 22) linked to narrative processing. Conversely, age-related decreases in cortical activation were observed in bilateral occipital regions, cingulate and cuneus, possibly reflecting changes in the default mode networks. The dynamic changes observed in this longitudinal fMRI study support the increasing role of bilateral BAs 21 and 22 in narrative comprehension, involving non-domain-specific integration in order to achieve final story interpretation. The presence of a continued linear development of this area throughout childhood and teenage years with no apparent plateau, indicates that full maturation of narrative processing skills has not yet occurred and that it may be delayed to early adulthood.

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.

Functional magnetic resonance imaging reveals changes in language localization in children with benign childhood epilepsy with centrotemporal spikes.

In children with benign childhood epilepsy with centrotemporal spikes, centrotemporal spikes may cause language dysfunction via disruption of underlying functional neuroanatomy. Fifteen patients with benign childhood epilepsy with centrotemporal spikes and 15 healthy controls completed 3 functional magnetic resonance imaging (MRI) language paradigms; standardized cognitive and language assessments were also performed. For all paradigms, children with benign childhood epilepsy with centrotemporal spikes showed specific regional differences in activation compared to controls. Children with benign childhood epilepsy with centrotemporal spikes also differed from controls on neuropsychological testing. They did not differ in general intelligence, but children with benign childhood epilepsy with centrotemporal spikes scored significantly lower than controls on tests of language, visuomotor integration, and processing speed. These results extend previous findings of lower language and cognitive skills in patients with benign childhood epilepsy with centrotemporal spikes, and suggest epilepsy-related remodeling of language networks that may underlie these observed differences.

FMRI activation in language areas correlates with verb generation performance in children.

Functional MRI mapping of language areas in children frequently employs a covert verb generation task. Because responses are not monitored, the relationship between fMRI activation and task performance is unknown. We compared fMRI activation during covert and overt verb generation to performance during the overt task. 15 children, ages 11-13 years, listened to concrete nouns and responded with related verbs covertly and overtly. A clustered fMRI acquisition allowed for recording of overt responses without motion artifacts. Region of interest analysis was also performed in areas that exhibited correlation between activation and performance during overt verb generation in left inferior frontal and left superior temporal gyri (along with their right hemisphere homologues). Regression analysis determined that during both covert and overt generation, left hemisphere regions showed positive correlations with average counts of verbs generated during the overt task. These results suggest that increased verb generation performance leads to increased activation. In addition, overt performance may be used as an estimator of covert performance.

Skin imaging modalities quantify progression and stage of infantile haemangiomas

DEAR EDITOR, Infantile haemangiomas (IH) are deep, superficial or mixed vascular neoplasms with rapidly proliferating endothelial cells that stabilize and involute with diminishing cellular activity, apoptosis and resolution over 7–10 years. Clinicians evaluate progression, treatment response and stage by inspection, photography (colour, size, shape) and palpation (temperature, deformability). Lightening, flattening, reduced temperature and softness signal involution. The limitations of subjective methods and need for objective metrics are recognized. Colour, infrared (IR) and three-dimensional (3D) imaging have been applied to IHs. Photographs are compared for improvement as stable/worse (0%), slight (< 25%), moderate (25–50%), good (50–75%) and excellent (> 75%) using the Visual Analog Scale. However, images may be nonstandardized (position, lighting) and results subjective as improvement criteria may be inconsistently applied. IR surface intensity and distribution are affected by tumour depth, size, metabolism, vasculature and perfusion. Dynamic IR applies a temperature stress and the rewarming pattern provides physiological information. We conducted a prospective observational proof of concept study to determine the utility of standardized skin imaging of colour, IR thermography and 3D shape for quantifying IH progression [Clinical Trial Registration: www.clinicaltrials.gov (Identifier NCT02061735)]. We compared these measurements to clinical stage (proliferating, stable, involuting). Data were stratified by age at evaluation, i.e. 1–2, 3–5, 6–9, 10–19 and ≥ 19 months corresponding to expected growth. Fifty-nine patients with 67 superficial or mixed IHs and at least two visits yielded 250 evaluations over 18 months. Deep IHs were excluded due to the small number. Clinicians from our multidisciplinary Hemangioma and Vascular Malformation Center decided the treatment: propranolol (1–2 mg kg 1 daily), topical timolol (one drop 0 5% gel twice daily) or no treatment, and assessed patients in person. The Institutional Review Board approved the research and parents/guardians provided written informed consent. Standardized colour, IR and 3D images of the IH and contralateral controls were taken (Nikon D90 camera, 60-mm lens, 12 3 megapixels, cross polarization, wireless flash; Nikon Corporation, Tokyo, Japan; FLIR T400 IR camera; FLIR Inc., Wilsonville, OR, U.S.A.; 3D scanner; Artec MHT, Artec Group, San Diego, CA, U.S.A., respectively). IR responses to 30-s cooling (18 0 2 °C, Jack Frost; Cardinal Health, McGaw Park, IL, U.S.A.) and rewarming (30 s) were quantified for a subset of evaluations. Photographs were colour corrected, separated into L*, a* and b* images (ImageJ; NIH, Washington, DC, U.S.A.), coregistered with IR images and analysed with a graphical interface employing landmark-based registration and algorithms (MATLAB ; MathWorks, Natick, MA, U.S.A.). Thresholds were applied to identify features of the IH only. Colour and IR intensities and areas were described as means and number of pixels above threshold, respectively. The highest 10% of pixels isolated the IH highest activity for dynamic IR with behaviour measured as area under the curves [AUCcooling (cool), AUCrewarming (rw)]. Height and volume were determined from 3D scans (3dMD Vultus; 3dMD, Atlanta, GA, U.S.A.). Outcomes by time and stage were analysed using univariate general linear models with treatment and depth (time) and age and treatment (stage) as covariates, post-hoc least significant difference for pairwise comparisons (P < 0 05) (SPSS; IBM, Armonk, NY, U.S.A.). Means were 7 4 months, 8 4 months in study, 3 8 evaluations and 3 months between evaluations. Fifty IHs were treated and 51 were mixed. Clinical stage discrepancies were resolved by consensus. Figure 1 shows IH progression for one subject. Lightness intensity and height were the most discriminating outcomes. Lightness increased and height decreased over time (P < 0 05) (Fig. 2a,b; see also Supporting Information). Red intensity was highest at 2 2 and 4 5 months, decreasing by 8 0 months (P < 0 05). IR intensity was higher for 2 2 and 4 5 vs. 12 8 and 27 7 months (P < 0 05) (Fig. 2b). Changes followed a logarithmic pattern. AUCcool AUCrw differences (dynamic IR) were 1 5 6 2, 17 4 3 6, 34 6 5 3, 28 4 5 5 and 20 6 7 3 for 2 2, 4 5, 8 0, 12 8 and 27 7 months, respectively. The smaller difference for 2 2 vs. all other months (P < 0 05) indicates faster recovery. AUCrw was 1109 23, 1054 12, 1009 12, 1004 18 and 1000 24, respectively and greater at 2 2 months (P < 0 05), indicating faster rewarming. The IR area consistently extended beyond the visual IH boundaries (mean visible : IR ratio of 33 18%), suggesting that a third to a half of potentially relevant information is not visible. The IR maps (Fig. 1) show the regions of greatest thermal activity. The results are consistent with the expected changes as higher proangiogenic factors during proliferation cause increased microcirculation followed by vasoconstriction

Predicting better performance on a college preparedness test from narrative comprehension at the age of 6 years: An fMRI study

OBJECTIVE To investigate whether high performance on college preparedness tests at 18 years of age can be predicted from brain activation patterns during narrative comprehension at 5-7 years of age. METHODS In this longitudinal study, functional MRI data during an auditory narrative-comprehension task were acquired from 15 children (5-7 years of age) who also provided their American College Testing (ACT) scores at the age of 18 years. Active voxels during the narrative-comprehension task were correlated with both composite ACT scores and the reading-comprehension component of the exam. RESULTS Higher composite ACT scores and behavioral scores for reading comprehension were positively correlated with greater activation in frontal and anterior brain regions during the narrative-comprehension task. CONCLUSIONS Our results suggest that neural circuits supporting higher ACT performance are predictable from a narrative-comprehension task at the age of 5-7 years. This supports a critical role for the anterior cingulate cortex, which is a part of the cingulo-opercular cognitive-control network early in development, as a facilitator for better ACT scores. This study highlights that shared neural circuits that support overall ACT performance and neural circuits that support reading comprehension both rely on neural circuits related to narrative comprehension in childhood, suggesting that interventions involving narrative comprehension should be considered for individuals with reading and other academic difficulties.

Infantile hemangioma status by dynamic infrared thermography: A preliminary study.

Infantile hemangiomas (IH) are initially warm due to increased proliferation and perfusion then involute with apoptosis and reduced perfusion. Objective quantitative evaluation of IH treatment response is essential for improving outcomes. We applied a functional imaging method, dynamic infrared (IR) thermography, to investigate IH status versus control skin and over time.

Maturation of Brain Regions Related to the Default Mode Network duringAdolescence Facilitates Narrative Comprehension

Objectives Although the Default Mode Network (DMN) has been examined extensively in adults, developmental characteristics of this network during childhood are not fully understood. Methods In this longitudinal study, we characterized the developmental changes in the DMN in fifteen children who were each scanned three times during a narrative comprehension task using magnetic resonance imaging. Results Despite similar brain-activation patterns along developmental ages 5 to 18 years when listening to stories, increased, widely distributed deactivation of the DMN was observed in children between the ages of 11 and 18 years. Our findings suggest that changes occurring with increased age, primarily brain maturation and cognitive development drive deactivation of the DMN, which in turn might facilitate attendance to the task. Conclusions The interpretation of our results is as a possible reference for the typical course of deactivation of the DMN and to explain the impaired patterns in this neural network associated with different language-related pathologies.