Mark DiFrancesco

Simultaneous EEG/Functional Magnetic Resonance Imaging at 4 Tesla: Correlates of Brain Activity to Spontaneous Alpha Rhythm During Relaxation

Summary: Simultaneous EEG and functional magnetic resonance imaging have been applied to the study of brain states associated with alpha waves using a magnetic field strength of 1.5 Tesla and has been shown in recent years to be feasible up to 3 Tesla for other applications. This study demonstrates this technique’s continued viability at a field strength of 4 Tesla, affording a proportionally greater sensitivity to changes in Blood Oxygen Level Dependent (BOLD) signal. In addition, for the study of alpha correlations, the authors used a larger number of subjects and scanning sessions than in the previous work. Random effects group regression analysis of 35 EEG/functional magnetic resonance imaging sessions against occipital alpha magnitude in a relaxed state detected bilateral widespread activation of dorsal thalamus and portions of the anterior cingulate and cerebellum. In the same group analysis, deactivations arose predominantly in the fusiform and adjacent visual association areas with a small activation cluster also detected in dorsolateral prefrontal cortex. This pattern is consistent with a correspondence between alpha magnitude variations and resting state network dynamics ascertained by recent studies of low frequency spontaneous BOLD fluctuations. The central role of the thalamus in resting state networks correlated with alpha activity is highlighted. Demonstrating the applicability of simultaneous EEG/functional magnetic resonance imaging up to 4 Tesla is particularly important for clinically relevant research involving challenging spontaneous EEG abnormalities, such as those of epilepsy.

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.

Cortical and subcortical contributions to absence seizure onset examined with EEG/fMRI

In patients with idiopathic generalized epilepsies (IGEs), bursts of generalized spike and wave discharges (GSWDs) lasting > or =2 seconds are considered absence seizures. The location of the absence seizures generators in IGEs is thought to involve interplay between various components of thalamocortical circuits; we have recently postulated that medication resistance may, in part, be related to the location of the GSWD generators [Szaflarski JP, Lindsell CJ, Zakaria T, Banks C, Privitera MD. Epilepsy Behav. 2010;17:525-30]. In the present study we hypothesized that patients with medication-refractory IGE (R-IGE) and continued absence seizures may have GSWD generators in locations other than the thalamus, as typically seen in patients with IGE. Hence, the objective of this study was to determine the location of the GSWD generators in patients with R-IGE using EEG/fMRI. Eighty-three patients with IGE received concurrent EEG/fMRI at 4 T. Nine of them (aged 15-55) experienced absence seizures during EEG/fMRI and were included; all were diagnosed with R-IGE. Subjects participated in up to three 20-minute EEG/fMRI sessions (400 volumes, TR=3 seconds) performed at 4 T. After removal of fMRI and ballistocardiographic artifacts, 36 absence seizures were identified. Statistical parametric maps were generated for each of these sessions correlating seizures to BOLD response. Timing differences between brain regions were tested using statistical parametric maps generated by modeling seizures with onset times shifted relative to the GSWD onsets. Although thalamic BOLD responses peaked approximately 6 seconds after the onset of absence seizures, other areas including the prefrontal and dorsolateral cortices showed brief and nonsustained peaks occurring approximately 2 seconds prior to the maximum of the thalamic peak. Temporal lobe peaks occurred at the same time as the thalamic peak, with a cerebellar peak occurring approximately 1 second later. Confirmatory analysis averaging cross-correlation between cortical and thalamic regions of interest across seizures corroborated these findings. Finally, Granger causality analysis showed effective connectivity directed from frontal lobe to thalamus, supporting the notion of earlier frontal than thalamic involvement. The results of this study support our original hypothesis and indicate that in the patients with R-IGE studied, absence seizures may be initiated by widespread cortical (frontal and parietal) areas and sustained in subcortical (thalamic) regions, suggesting that the examined patients have cortical onset epilepsy with propagation to thalamus.

Preliminary fMRI findings in experimentally sleep-restricted adolescents engaged in a working memory task

Here we report preliminary findings from a small-sample functional magnetic resonance imaging (fMRI) study of healthy adolescents who completed a working memory task in the context of a chronic sleep restriction experiment. Findings were consistent with those previously obtained on acutely sleep-deprived adults. Our data suggest that, when asked to maintain attention and burdened by chronic sleep restriction, the adolescent brain responds via compensatory mechanisms that accentuate the typical activation patterns of attention-relevant brain regions. Specifically, it appeared that regions that are normally active during an attention-demanding working memory task in the well-rested brain became even more active to maintain performance after chronic sleep restriction. In contrast, regions in which activity is normally suppressed during such a task in the well-rested brain showed even greater suppression to maintain performance after chronic sleep restriction. Although limited by the small sample, study results provide important evidence of feasibility, as well as guidance for future research into the functional neurological effects of chronic sleep restriction in general, the effects of sleep restriction in children and adolescents, and the neuroscience of attention and its disorders in children.

Reduced default mode network connectivity in treatment-resistant idiopathic generalized epilepsy.

Idiopathic generalized epilepsy (IGE) resistant to treatment is common, but its neuronal correlates are not entirely understood. Therefore, the aim of this study was to examine resting‐state default mode network (DMN) functional connectivity in patients with treatment‐resistant IGE.

Moderating effects of music on resting state networks

Resting state networks (RSNs) are spontaneous, synchronous, low-frequency oscillations observed in the brains of subjects who are awake but at rest. A particular RSN called the default mode network (DMN) has been shown to exhibit changes associated with neurological disorders such as temporal lobe epilepsy or Alzheimers disease. Previous studies have also found that differing experimental conditions such as eyes-open versus eyes-closed can produce measurable changes in the DMN. These condition-associated changes have the potential of confounding the measurements of changes in RSNs related to or caused by disease state(s). In this study, we use fMRI measurements of resting-state connectivity paired with EEG measurements of alpha rhythm and employ independent component analysis, undirected graphs of partial spectral coherence, and spatiotemporal regression to investigate the effect of music-listening on RSNs and the DMN in particular. We observed similar patterns of DMN connectivity in subjects who were listening to music compared with those who were not, with a trend toward a more introspective pattern of resting-state connectivity during music-listening. We conclude that music-listening is a valid condition under which the DMN can be studied.

Sweet/Dessert Foods Are More Appealing to Adolescents after Sleep Restriction

Study Objective Examine the effect of experimental sleep restriction (SR) on adolescents’ subjective hunger and perceived appeal of sweet/dessert foods versus other foods. A secondary goal was to replicate previous findings on the effects of SR on dietary intake. Design Randomized cross-over sleep restriction-extension paradigm. Setting Sleep was obtained and monitored at home. Outcome measures were gathered during office visits. Participants 31 typically-developing adolescents aged 14–17 years. Interventions The three-week protocol consisted of a baseline week, followed randomly by five consecutive nights of SR (6.5 hours in bed) versus healthy sleep duration (HS; 10 hours in bed), a 2-night wash-out period, and a 5-night cross-over. Measurements Sleep was monitored via actigraphy. The morning after each experimental condition, teens rated their hunger, underwent a 24-hour diet recall interview, and rated the appeal of a series of pictures of sweet/dessert foods (e.g., ice cream, candy) and non-sweets (meat, eggs, fruits, vegetables). Results Teens rated pictures of sweet/dessert foods to be more appealing after SR than after HS (Cohen’s d = .41, t = 2.07, p = .045). The sleep manipulation did not affect self-reported hunger or the appeal of non-sweet foods (p >.10). Consistent with our prior work, intake of overall calories was 11% higher and consumption of sweet/dessert servings was 52% greater during SR than HS. Conclusions Adolescent SR appears to increase the subjective appeal of sweet/dessert foods, indicating a potential mechanism by which SR might contribute to weight gain and the risk for obesity and chronic illness.

Brain morphometric changes associated with childhood-onset systemic lupus erythematosus and neurocognitive deficit

ObjectiveTo use structural magnetic resonance imaging (MRI) to characterize changes in gray matter and white matter volumes between patients with childhood-onset systemic lupus erythematosus (SLE) and matched controls, between patients with childhood-onset SLE with and those without neurocognitive deficit, and in relation to disease duration and treatment with steroids. MethodsTwenty-two patients with childhood-onset SLE and 19 healthy controls underwent high-resolution structural MRI. Probability density maps for gray matter and white matter were compared between groups. ResultsNeuropsychological testing confirmed the presence of neurocognitive deficit in 8 patients with childhood-onset SLE. Multiple brain regions had reduced gray matter volume in the patients with childhood- onset SLE with neurocognitive deficit versus controls or patients with childhood-onset SLE without neurocognitive deficit. Neither disease duration nor cumulative oral or intravenous steroid doses accounted for decreases in gray matter. White matter volume was also reduced in patients with childhood-onset SLE with neurocognitive deficit, and the reduction was positively associated with both disease duration and cumulative oral steroid dose. Conversely, higher cumulative intravenous steroid doses were associated with higher white matter volumes. ConclusionNeurocognitive deficit in patients with childhood-onset SLE is associated with multifocal decreases in both gray and white matter volumes. Since only white matter volume changes are related to disease duration and cumulative oral steroid use, this may suggest that gray and white matter alterations relate to different underlying mechanisms. Further work is needed to understand the relationship between gray and white matter alterations in childhood-onset SLE, whether the underlying mechanisms relate to immunologic, vascular, or other causes, and whether the changes are reversible or preventable. Likewise, the protective properties of intravenous steroids in maintaining white matter volumes require confirmation in larger cohorts.

BOLD fMRI in infants under sedation: Comparing the impact of pentobarbital and propofol on auditory and language activation

To elucidate differences in the disruption of language network function, as measured by blood oxygenation level‐dependent (BOLD) contrast functional MRI (fMRI), attributable to two common sedative agents administered to infants under clinical imaging protocols.

Increased Resting-State Functional Connectivity in the Cingulo-Opercular Cognitive-Control Network after Intervention in Children with Reading Difficulties

Dyslexia, or reading difficulty, is characterized by slow, inaccurate reading accompanied by executive dysfunction. Reading training using the Reading Acceleration Program improves reading and executive functions in both children with dyslexia and typical readers. This improvement is associated with increased activation in and functional connectivity between the anterior cingulate cortex, part of the cingulo-opercular cognitive-control network, and the fusiform gyrus during a reading task after training. The objective of the current study was to determine whether the training also has an effect on functional connectivity of the cingulo-opercular and fronto-parietal cognitive-control networks during rest in children with dyslexia and typical readers. Fifteen children with reading difficulty and 17 typical readers (8-12 years old) were included in the study. Reading and executive functions behavioral measures and resting-state functional magnetic resonance imaging data were collected before and after reading training. Imaging data were analyzed using a graphical network-modeling tool. Both reading groups had increased reading and executive-functions scores after training, with greater gains among the dyslexia group. Training may have less effect on cognitive control in typical readers and a more direct effect on the visual area, as previously reported. Statistical analysis revealed that compared to typical readers, children with reading difficulty had significantly greater functional connectivity in the cingulo-opercular network after training, which may demonstrate the importance of cognitive control during reading in this population. These results support previous findings of increased error-monitoring activation after reading training in children with dyslexia and confirm greater gains with training in this group.