John Ostuni

Evidence of Left Inferior Frontal–Premotor Structural and Functional Connectivity Deficits in Adults Who Stutter

The neurophysiological basis for stuttering may involve deficits that affect dynamic interactions among neural structures supporting fluid speech processing. Here, we examined functional and structural connectivity within corticocortical and thalamocortical loops in adults who stutter. For functional connectivity, we placed seeds in the left and right inferior frontal Brodmann area 44 (BA44) and in the ventral lateral nucleus (VLN) of the thalamus. Subject-specific seeds were based on peak activation voxels captured during speech and nonspeech tasks using functional magnetic resonance imaging. Psychophysiological interaction (PPI) was used to find brain regions with heightened functional connectivity with these cortical and subcortical seeds during speech and nonspeech tasks. Probabilistic tractography was used to track white matter tracts in each hemisphere using the same seeds. Both PPI and tractrography supported connectivity deficits between the left BA44 and the left premotor regions, while connectivity among homologous right hemisphere structures was significantly increased in the stuttering group. No functional connectivity differences between BA44 and auditory regions were found between groups. The functional connectivity results derived from the VLN seeds were less definitive and were not supported by the tractography results. Our data provide strongest support for deficient left hemisphere inferior frontal to premotor connectivity as a neural correlate of stuttering.

Functional but not structural networks of the human laryngeal motor cortex show left hemispheric lateralization during syllable but not breathing production

The laryngeal motor cortex (LMC) is indispensible for the vocal motor control of speech and song production. Patients with bilateral lesions in this region are unable to speak and sing, although their nonverbal vocalizations, such as laughter and cry, are preserved. Despite the importance of the LMC in the control of voluntary voice production in humans, the literature describing its connections remains sparse. We used diffusion tensor probabilistic tractography and functional magnetic resonance imaging-based functional connectivity analysis to identify LMC networks controlling two tasks necessary for speech production: voluntary voice as repetition of two different syllables and voluntary breathing as controlled inspiration and expiration. Peaks of activation during all tasks were found in the bilateral ventral primary motor cortex in close proximity to each other. Functional networks of the LMC during voice production but not during controlled breathing showed significant left-hemispheric lateralization (p < 0.0005). However, structural networks of the LMC associated with both voluntary voice production and controlled breathing had bilateral hemispheric organization. Our findings indicate the presence of a common bilateral structural network of the LMC, upon which different functional networks are built to control various voluntary laryngeal tasks. Bilateral organization of functional LMC networks during controlled breathing supports its indispensible role in all types of laryngeal behaviors. Significant left-hemispheric lateralization of functional networks during simple but highly learned voice production suggests the readiness of the LMC network for production of a complex voluntary behavior, such as human speech.

Study of relapsing remitting experimental allergic encephalomyelitis SJL mouse model using MION-46L enhanced in vivo MRI: Early histopathological correlation

MION‐46L, a superparamagnetic iron oxide contrast agent, was investigated for its ability to increase the sensitivity of in vivo 3D MRI in the detection of brain lesions in a chronic experimental allergic encephalomyelitis (crEAE) mouse model. Lesion conspicuity on postcontrast 3D MRI was dramatically enhanced as compared to precontrast images corresponding to areas of inflammatory and demyelinating lesions. MION‐46L could be detected on Prussian blue iron stain in the vascular endothelium, the perivascular space, and in macrophages within perivascular cuffs and areas of inflammation and demyelination. By taking advantage of the MION‐46L induced macroscopic susceptibility effect, acute early lesions measuring only 100 μm in diameter could be detected. MION‐46L enhanced MRI may be used to 1) provide a unique sensitivity in EAE lesion detection and correlate imaging to histopathology; 2) help to understand EAE lesion development and its underlying pathophysiology; and 3) eventually assist in preclinical screening of new experimental therapies directed at patients with multiple sclerosis (MS). J. Neurosci. Res. 52:549–558, 1998. Published 1998 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.

Thalamic Involvement and Its Impact on Clinical Disability in Patients with Multiple Sclerosis: A Diffusion Tensor Imaging Study at 3T

BACKGROUND AND PURPOSE: Several studies suggest that grey matter involvement may play a role in multiple sclerosis (MS) pathology. Diffusion tensor imaging (DTI) at 3T was used to investigate the presence of damage to the normal-appearing thalamus in MS and its relationship with disability. MATERIALS AND METHODS: Twenty-four patients with relapsing-remitting (RR, n = 13, age = 41.7 ± 6.1, Expanded Disability Status Scale [EDSS] score = 2.2 ± 1.2) and secondary-progressive (n = 11, age = 46.9 ± 9.6, EDSS = 5.9 ± 1.0) MS and 24 age- and sex-matched healthy volunteers were studied. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in regions of interest of normal-appearing thalamus. We examined group differences in MD and FA and correlations between DTI-derived metrics and clinical or imaging measures of disease. RESULTS: Patients with MS had higher thalamic FA (P < .0001) and MD (P = .035) than volunteers. MD values correlated with the Paced Auditory Serial Addition Task (r = −0.43, P = .034) and motor EDSS (r = 0.47, P = .021) scores. In patients with RRMS, MD values correlated with global EDSS (r = 0.75, P = .003) and motor EDSS (r = 0.68, P = .010). Correlations were found between MD values and T1 and T2 lesion load (r = 0.58, P < .05) and brain parenchymal fraction (r = −0.46, P < .05). CONCLUSIONS: DTI was able to detect abnormalities in normal-appearing thalamus of patients with MS. The strength of association between thalamic DTI measures and functional impairment was in the same range as those seen with standard MR imaging disease measures. The assessment of the integrity of the thalamus with DTI is a promising metric as a marker of disease for future studies.

Analysis of interpolation effects in the reslicing of functional MR images

PURPOSE Typically, the final step in volume registration is the reslicing of the volume of interest. The purpose of this work is to examine the effects of this reslicing on functional MRI (fMRI) data using different interpolation methods. METHOD Functional whole-brain echo planar imaging (EPI) volumes were resliced using six different interpolation methods: trilinear, tricubic splines, and a 3D sinc function using a rectangular and a Hanning window, both with half-window lengths of 3 and 4 voxels. RESULTS Interpolation by tricubic spline and 3D sinc using a Hanning window had comparable errors, although tricubic spline interpolation was computationally the fastest. Interpolation by trilinear and 3D sinc using a rectangular window had relatively large errors, although the speed of trilinear makes it desirable for some applications. CONCLUSION Interpolations using all of the tested methods adversely affected the fMRI data, although these effects differed for each method.

Relationship between inflammatory lesions and cerebral atrophy in multiple sclerosis.

Objective: To investigate the temporal relationship between inflammation and cerebral atrophy in a longitudinal study of 19 patients with relapsing-remitting multiple sclerosis (RRMS) using serial monthly contrast enhanced MRI examinations and monthly measurements of brain fractional volume (BFV) for an average of 4 (range 2.4 to 10) years. Methods: In this retrospective study, all patients had an active MRI scan at entry with a minimum of two new contrast enhancing lesions (CEL) on baseline MRI examinations. Patients were followed for a minimum of 3 months during a baseline (pretreatment) phase and subsequently followed during treatment with recombinant interferon β (IFN) and various other immunomodulatory agents. Pre- and post contrast axial images were obtained using 3-mm slice thickness and a gadolinium contrast dose of 0.1 mmol/kg. Monthly CEL were sequentially numbered on hardcopy films and monthly BFV was determined on precontrast T1W images using a semiautomated program. For BFV measurements, all T1W scans were registered to the entry examination, which served as a mask image. Cerebral atrophy was measured as percent brain fractional volume change (PBVC) compared to the entry baseline scan. Results: The results demonstrate that cerebral atrophy paralleled that of contrast enhancing lesion accumulation. The correlation between cumulative CEL and PBVC ranged from R2 = 0.47 to 0.81. Immunomodulatory agents that effectively reduced CEL accumulation also slowed the rate of atrophy. Conclusions: The correlation between contrast enhancing lesions (CEL) and atrophy suggests that patients who are not responding to therapy with a decrease in CEL may also be at risk for developing increased atrophy.

A Magnetization Transfer Imaging Study of Corpus Callosum Myelination in Young Children with Autism

BACKGROUND Several lines of evidence suggest that autism may be associated with abnormalities in white matter development. However, inconsistencies remain in the literature regarding the nature and extent of these abnormalities, partly because of the limited types of measurements that have been used. Here, we used magnetization transfer imaging to provide insight into the myelination of the corpus callosum in children with autism. METHODS Magnetization transfer imaging scans were obtained in 101 children with autism and 35 typically developing children who did not significantly differ with regard to gender or age. The midsagittal area of the corpus callosum was manually traced and the magnetization transfer ratio (MTR) was calculated for each voxel within the corpus callosum. Mean MTR and height and location of the MTR histogram peak were analyzed. RESULTS Mean MTR and MTR histogram peak height and location were significantly higher in children with autism than in typically developing children, suggesting abnormal myelination of the corpus callosum in autism. CONCLUSIONS The differences in callosal myelination suggested by these results may reflect an alteration in the normally well-regulated process of myelination of the brain, with broad implications for neuropathology, diagnosis, and treatment of autism.

Similarities in speech and white matter characteristics in idiopathic developmental stuttering and adult-onset stuttering

Adult-onset stuttering (AS) typically occurs following neurological and/or psychological trauma, considered different from developmental stuttering (DS), which starts during early childhood with few if any new cases reported after adolescence. Here we report four cases of AS, two with apparent psychological trigger and two without, none with evidence of neurological injury, and none conforming to previously reported characteristics of psychogenic stuttering. We asked whether this group of AS would have similar speech and neuroanatomical characteristics to those with DS. We conducted blinded analyses of speech samples in both AS cases and 14 cases of DS on type, frequency, and loci of disfluencies. Diffusion tensor imaging (DTI) was conducted to compare white matter tracts using fractional anisotropy (FA). We found that AS did not differ significantly from DS in any of the speech characteristics measured. On DTI, DS had significantly increased FA relative to controls in the right superior longitudinal tract. AS cases showed a similar trend for increases in these regions when compared to controls. The results of this study suggest that symptoms of idiopathic stuttering can begin during adulthood, and that similar neuroanatomical differences from controls may be associated with both developmental and adult onset idiopathic stuttering.

Comparison of methods for obtaining longitudinal whole-brain magnetization transfer measurements †

To investigate whether the method of applying image masks can alter quantifiable measures determined from whole‐brain MTR calculations.

Multimodality image registration based on hierarchical shape representation

Image registration is a correlation procedure that allows either the complementary study of images obtained from different modalities, or enables the analysis of images obtained by the same modality but at different times. Applied to a variety of clinical and investigational problems, image registration can offer a major advance in diagnostic imaging. In this paper, we present an automated multi-modality registration algorithm based on hierarchical feature extraction. Two kinds of shape representations -- edges and surfaces (skin surface, inner skull surface, and outer brain surface) -- are extracted hierarchically from different image modalities. The registration is then performed using the user- specified (but automatically extracted) corresponding features. Both the robustness of the algorithm and the registration accuracy using different registration features are compared in this paper. The preliminary results show that the use of edge and surface features could succeed over a large range of geometric displacements. The results also indicate that neither the edge nor the surface feature is clearly superior in terms of registration accuracy. Using the edge feature could, however, have the advantage of eliminating the surface segmentation step which requires extra complexity, variability, and time cost. We have shown the proposed 3D registration algorithm provides a simple and fast method for automatic registration of CT and MR image modalities. Preliminary results using our registration algorithm are comparable to those obtained by other techniques.