Matthew L. White

Broadband neurophysiological abnormalities in the medial prefrontal region of the default-mode network in adults with ADHD.

Previous investigations of the default‐mode network (DMN) in persons with attention‐deficit/hyperactivity disorder (ADHD) have shown reduced functional connectivity between the anterior and posterior aspects. This finding was originally demonstrated in adults with ADHD, then in youth with ADHD, and has been tentatively linked to ultra low frequency oscillations within the DMN. The current study evaluates the specificity of DMN abnormalities to neuronal oscillations in the ultra low frequency range, and examines the regional specificity of these DMN aberrations in medicated and unmedicated adults with, and those without ADHD. An individually matched sample of adults with and without ADHD completed 6‐minute sessions of resting‐state magnetoencephalography (MEG). Participants with ADHD were known responders to stimulant medications and completed two sessions (predrug/postdrug). MEG data were coregistered to the participants MRI, corrected for head motion, fitted to a regional‐level source model, and subjected to spectral analyses to extract neuronal population activity in regions of the DMN. The unmedicated adults with ADHD exhibited broadband deficits in medial prefrontal cortices (MPFC), but not other DMN regions compared to adults without ADHD. Unmedicated patients also showed abnormal cross‐frequency coupling in the gamma range between the MPFC and posterior cingulate areas, and disturbed balance within the DMN as activity in posterior regions was stronger than frontal regions at beta and lower frequencies, which dissipated at higher γ‐frequencies. Administration of pharmacotherapy significantly increased prefrontal alpha activity (8–14 Hz) in adults with ADHD, and decreased the cross‐frequency gamma coupling. These results indicate that neurophysiological aberrations in the DMN of patients with ADHD are not limited to ultra slow oscillations, and that they may be primarily attributable to abnormal broadband activity in the MPFC. Hum Brain Mapp, 2013.

Atypical coupling between posterior regions of the default mode network in attention-deficit/hyperactivity disorder: a pharmaco-magnetoencephalography study.

BACKGROUND Dysfunction in the default mode network (DMN), a group of cortical areas more active during the resting state, has been linked to attentional deficits and symptoms associated with attention-deficit/hyperactivity disorder (ADHD). Prior imaging studies have shown decreased functional connectivity between DMN nodes in patients with ADHD, primarily between anterior and posterior regions. Using magnetoencephalography (MEG), we evaluated phase coherence (i.e., functional connectivity) among regions of the DMN in healthy controls and adults with ADHD before and after stimulant therapy. METHODS We obtained a resting-state MEG recording for all participants. Magnetoencephalography data were transformed into a ~30 node regional source model using inverse spatial filtering, including regions corresponding to the DMN. We computed the zero-lag phase coherence between these regions pairwise for 5 distinct frequency bands, and we assessed group and medication effects. RESULTS Twelve adults with and 13 without ADHD participated in our study. Functional connectivity was stronger between particular node pairs and showed frequency-specific effects. Unmedicated patients showed reduced phase locking between posterior cingulate/precuneus regions (PCC) and right inferior parietal cortices (RIPL), and between medial prefrontal regions (MPFC) and the left inferior parietal region (LIPL) and the PCC. Unmedicated patients had increased phase locking between the RIPL and LIPL regions compared with controls. Administration of stimulants improved phase locking abnormalities along the MPFC-PCC and LIPL-RIPL pathways in patients with ADHD. LIMITATIONS Modest sample size and lack of duration of patient treatment history may limit the generalizability of our findings. CONCLUSION Adults with ADHD exhibit hyper- and hypoconnectivity between regions of the DMN during rest, which were suppressed after stimulant medication administration.

Multimodal neuroimaging evidence of alterations in cortical structure and function in HIV-infected older adults.

Combination antiretroviral therapy transformed human immunodefiency virus (HIV)‐infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV‐infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high‐resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV‐related cognitive impairments. HIV‐infected adults and individually matched controls completed 3‐Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel‐based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV‐infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV‐infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV‐associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV‐associated cognitive impairment, and may hold promise as a potential disease marker. Hum Brain Mapp 36:897–910, 2015.

Cervical spinal cord multiple sclerosis: evaluation with 2D multi-echo recombined gradient echo MR imaging

Abstract Objective: The two-dimensional multi-echo recombined gradient echo (MERGE) technique automatically acquires and sums multiple gradient echoes at various echo times in cervical spine magnetic resonance (MR) imaging. This technique increases the grey–white matter contrast within the spinal cord and should also improve the depiction of cervical cord lesions. The aim of this study was to qualitatively and quantitatively evaluate MERGE imaging compared with T2-weighted fast spin-echo (T2WFSE) imaging for depicting multiple sclerosis (MS) lesions in the cervical cord. Methods: Nineteen consecutive patients (10 males and 9 females; age range 22–62 years, mean age 43.6 years) with clinically diagnosed MS were examined with cervical spinal cord MR imaging at 3 T including both MERGE and T2WFSE imaging. Qualitative evaluation for MS lesion conspicuity was performed. The quantitative criterion utilized to compare MERGE imaging with T2WFSE imaging was the lesion-to-background contrast-to-noise ratio (CNR). Results: MERGE imaging showed 79 lesions and missed 1 that was depicted on T2WFSE imaging. T2WFSE imaging showed 46 lesions and missed 34 that were depicted on MERGE imaging. MERGE imaging was markedly superior to T2WFSE imaging in rendering greater lesion conspicuity. In the quantitative evaluation, the lesion-to-background CNR upon MERGE imaging was significantly higher than that upon T2WFSE imaging (P < 0.001, paired t-test). Conclusions: MERGE imaging in the cervical spinal cord increases detection and conspicuity of MS lesions. Strong consideration should be given to utilizing axial MERGE images in the diagnosis and follow-up study of cervical cord MS.

Estimating the passage of minutes: deviant oscillatory frontal activity in medicated and unmedicated ADHD.

OBJECTIVE Attention-deficit/hyperactivity disorder (ADHD) is a common and extensively treated psychiatric disorder in children, which often persists into adulthood. The core diagnostic symptoms include inappropriate levels of hyperactivity, impulsivity, and/or pervasive inattention. Another crucial aspect of the disorder involves aberrations in temporal perception, which have been well documented in behavioral studies and, recently, have been the focus of neuroimaging studies. These functional magnetic resonance imaging studies have shown reduced activation in anterior cingulate and prefrontal cortices in ADHD using a time-interval discrimination task, whereby participants distinguish intervals differing by only hundreds of milliseconds. METHOD We used magnetoencephalography (MEG) to evaluate the cortical network serving temporal perception during a continuous, long-duration (in minutes) time estimation experiment. Briefly, medicated and unmedicated persons with ADHD, and a control group responded each time they estimated 60 s had elapsed for an undisclosed amount of time in two separate MEG sessions. All MEG data were transformed into regional source activity, and subjected to spectral analyses to derive amplitude estimates of gamma-band activity. RESULTS Compared to controls, unmedicated patients were less accurate time estimators and had weaker gamma activity in the anterior cingulate, supplementary motor area, and left prefrontal cortex. After medication, these patients exhibited small but significant increases in gamma across these same neural regions and significant improvements in time estimation accuracy, which correlated with the gamma activity increases. CONCLUSION We found deficient gamma activity in brain areas known to be crucial for timing functions, which may underlie the day-to-day abnormalities in time perception that are common in ADHD.

Pharmaco-MEG evidence for attention related hyper-connectivity between auditory and prefrontal cortices in ADHD.

The ability to attend to particular stimuli while ignoring others is crucial in goal-directed activities and has been linked with prefrontal cortical regions, including the dorsolateral prefrontal cortex (DLPFC). Both hyper- and hypo-activation in the DLPFC has been reported in patients with attention-deficit/hyperactivity disorder (ADHD) during many different cognitive tasks, but the network-level effects of such aberrant activity remain largely unknown. Using magnetoencephalography (MEG), we examined functional connectivity between regions of the DLPFC and the modality-specific auditory cortices during an auditory attention task in medicated and un-medicated adults with ADHD, and those without ADHD. Participants completed an attention task in two separate sessions (medicated/un-medicated), and each session consisted of two blocks (attend and no-attend). All MEG data were coregistered to structural MRI, corrected for head motion, and projected into source space. Subsequently, we computed the phase coherence (i.e., functional connectivity) between DLPFC regions and the auditory cortices. We found that un-medicated adults with ADHD exhibited greater phase coherence in the beta (14-30Hz) and gamma frequency (30-56Hz) range in attend and no-attend conditions compared to controls. Stimulant medication attenuated these differences, but did not fully eliminate them. These results suggest that aberrant bottom-up processing may engulf executive resources in ADHD.

Primary angiitis of the central nervous system: apparent diffusion coefficient lesion analysis

Apparent diffusion coefficients (ADCs) of the brain lesions in primary angiitis of the central nervous system (PACNS) patients were analyzed in this study. The mean ADC ratios for acute/subacute phase lesions were significantly lower than that for chronic phase lesions. However, some acute/subacute phase lesions had elevated ADCs and these lesions disappeared overtime, implicating a nonischemic mechanism in PACNS.

Three-tesla diffusion tensor imaging of Meyer's loop by tractography, color-coded fractional anisotropy maps, and eigenvectors

The aim of this study was to evaluate Meyers loop by 3-T MRI with fiber tractography, color-coded fractional anisotropy maps, and eigenvector maps. The anteroposterior distance from the anterior bundle of the Meyers loop to temporal pole ranged from 26.3 to 34 mm, overlapping with the previously published anatomical dissection studies. Diffusion tensor imaging with fiber tractography, color-coded FA maps, and color maps of the principal eigenvector at 3 T appear to be promising techniques for the virtual dissection of Meyers loop.

Sinonasal secretions: evaluation by diffusion-weighted imaging and apparent diffusion coefficients.

This study retrospectively reviewed magnetic resonance images of 20 patients with sinonasal inflammatory diseases. Forty-four areas of sinonasal secretions were analyzed with correlation between the signal ratios on T2-weighted images and the diffusion-weighted imaging signal ratios or apparent diffusion coefficients (ADCs). ADCs decreased in direct proportion to the signal ratios on the T2-weighted images (P<.001, r=.56). Given the correlation between the ADCs and the physiological state of sinonasal secretions, ADCs may provide quantitative information useful to the diagnosis of sinonasal inflammatory disease.

Multinodular and Vacuolating Neuronal Tumor: A Rare Seizure-associated Entity

Multinodular and vacuolating neuronal tumor is a recently described seizure-associated entity with overlapping features of a malformative and neoplastic process. We report a case of multinodular and vacuolating neuronal tumor in a 29-year-old man with a history of recent headaches and complex partial seizures. Neuroimaging revealed a nonenhancing, T2 and T2 fluid-attenuated inversion recovery hyperintense multinodular lesion in the right temporal lobe. Lesional tissue demonstrated well-demarcated nodules of ganglioid cells with vacuolation of both the perikarya and the fibrillary neuropil-like background. The ganglioid cells showed weak cytoplasmic reactivity for synaptophysin and were nonreactive for neurofilament and chromogranin. CD34-positive stellate cells were present within the nodules. A 50-gene next-generation sequencing panel did not identify any somatic mutations in genomic DNA extracted from the tumor.