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Luke Bloy

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7 papers
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7

YNICL Journal 2026 Journal Article

Myo-inositol elevation as an in vivo marker of reactive gliosis in pediatric Friedreich ataxia: evidence from HERMES-edited MR spectroscopy

  • William Gaetz
  • Muhammad G. Saleh
  • Charlotte Birnbaum
  • Luke Bloy
  • Timothy P.L. Roberts
  • David R. Lynch

BACKGROUND: Friedreich ataxia (FRDA) is a rare neurodegenerative disorder caused by frataxin deficiency and is characterized by mitochondrial dysfunction, oxidative stress, and progressive motor dysfunction. Most in vivo MRS work in FRDA has focused on the cerebellum, brainstem/pons, and spinal cord, consistently reporting abnormalities in the neuronal marker N-acetylaspartate (NAA) and the glial metabolite myo-inositol (mI). To our knowledge, the NAA/mI ratio in the primary motor cortex has not been reported in FRDA, particularly in pediatric cohorts. Additionally, in vivo edited MRS measurements of the inhibitory neurotransmitter γ-aminobutyric acid (GABA+ (GABA + macromolecular contributions)) in FRDA have not yet been reported and GSH has been examined only rarely in FRDA and, to our knowledge, has not been studied in the motor cortex in either adult or pediatric cohorts. OBJECTIVE: To assess GSH, GABA+, NAA, and mI across cerebellum and motor cortices in pediatric FRDA using HERMES-edited MRS. METHODS: We acquired HERMES MRS data from 16 children with FRDA and 15 age-matched controls. Tissue-corrected metabolite estimates were obtained using LCModel and voxel-based tissue segmentation. Linear mixed models (LMMs) were used to evaluate group and region effects, with subject as a random effect. RESULTS: LMMs revealed no significant group differences in tissue-corrected GSH or GABA + . In contrast, the tNAA/mI ratio was significantly reduced in FRDA (p < 0.001), driven by elevated mI (p < 0.001), while tNAA did not differ between groups (p = 0.150). ROI-specific analyses showed higher mI in FRDA in both motor cortices after Bonferroni correction, with a non-significant trend in cerebellum (pcorr = 0.054). CONCLUSIONS: These findings support a model of early reactive gliosis in pediatric FRDA, indexed by elevated mI and occurring without statistically significant neuronal loss, (acknowledging that significant reductions in tNAA may require larger samples to resolve), and extend prior cerebellar-focused work to the primary motor cortex. While GSH and GABA + did not differ between groups, the observed mI elevations highlight myo-inositol as a practical in vivo biomarker of astrocytic activation and a candidate marker for disease progression in FRDA. Longitudinal studies are needed to confirm its sensitivity to clinical trajectory and therapeutic response.

YNIMG Journal 2023 Journal Article

Maturation of auditory cortex neural responses during infancy and toddlerhood

  • Yuhan Chen
  • Heather L. Green
  • Mary E. Putt
  • Olivia Allison
  • Emily S. Kuschner
  • Mina Kim
  • Lisa Blaskey
  • Kylie Mol

The infant auditory system rapidly matures across the first years of life, with a primary goal of obtaining ever-more-accurate real-time representations of the external world. Our understanding of how left and right auditory cortex neural processes develop during infancy, however, is meager, with few studies having the statistical power to detect potential hemisphere and sex differences in primary/secondary auditory cortex maturation. Using infant magnetoencephalography (MEG) and a cross-sectional study design, left and right auditory cortex P2m responses to pure tones were examined in 114 typically developing infants and toddlers (66 males, 2 to 24 months). Non-linear maturation of P2m latency was observed, with P2m latencies decreasing rapidly as a function of age during the first year of life, followed by slower changes between 12 and 24 months. Whereas in younger infants auditory tones were encoded more slowly in the left than right hemisphere, similar left and right P2m latencies were observed by ∼21 months of age due to faster maturation rate in the left than right hemisphere. No sex differences in the maturation of the P2m responses were observed. Finally, an earlier left than right hemisphere P2m latency predicted better language performance in older infants (12 to 24 months). Findings indicate the need to consider hemisphere when examining the maturation of auditory cortex neural activity in infants and toddlers and show that the pattern of left–right hemisphere P2m maturation is associated with language performance.

YNIMG Journal 2020 Journal Article

Evaluating motor cortical oscillations and age-related change in autism spectrum disorder

  • William Gaetz
  • Edward Rhodes
  • Luke Bloy
  • Lisa Blaskey
  • Carissa R. Jackel
  • Edward S. Brodkin
  • Amy Waldman
  • David Embick

Autism spectrum disorder (ASD) is primarily characterized by impairments in social communication and the appearance of repetitive behaviors with restricted interests. Increasingly, evidence also points to a general deficit of motor tone and coordination in children and adults with ASD; yet the neural basis of motor functional impairment in ASD remains poorly characterized. In this study, we used magnetoencephalography (MEG) to (1) assess potential group differences between typically developing (TD) and ASD participants in motor cortical oscillatory activity observed on a simple button-press task and (2) to do so over a sufficiently broad age-range so as to capture age-dependent changes associated with development. Event-related desynchronization was evaluated in Mu (8–13 Hz) and Beta (15–30 Hz) frequency bands (Mu-ERD, Beta-ERD). In addition, post-movement Beta rebound (PMBR), and movement-related gamma (60–90 Hz) synchrony (MRGS) were also assessed in a cohort of 123 participants (63 typically developing (TD) and 59 with ASD) ranging in age from 8 to 24. 9 years. We observed significant age-dependent linear trends in Beta-ERD and MRGS power with age for both TD and ASD groups; which did not differ significantly between groups. However, for PMBR, in addition to a significant effect of age, we also observed a significant reduction in PMBR power in the ASD group (p < 0. 05). Post-hoc tests showed that this omnibus group difference was driven by the older cohort of children >13. 2 years (p < 0. 001) and this group difference was not observed when assessing PMBR activity for the younger PMBR groups (ages 8–13. 2 years; p = 0. 48). Moreover, for the older ASD cohort, hierarchical regression showed a significant relationship between PMBR activity and clinical scores of ASD severity (Social Responsiveness Scale (SRS T scores)), after regressing out the effect of age (p < 0. 05). Our results show substantial age-dependent changes in motor cortical oscillations (Beta-ERD and MRGS) occur for both TD and ASD children and diverge only for PMBR, and most significantly for older adolescents and adults with ASD. While the functional significance of PMBR and reduced PMBR signaling remains to be fully elucidated, these results underscore the importance of considering age as a factor when assessing motor cortical oscillations and group differences in children with ASD.

YNICL Journal 2016 Journal Article

Maturation of auditory neural processes in autism spectrum disorder — A longitudinal MEG study

  • Russell G. Port
  • J. Christopher Edgar
  • Matthew Ku
  • Luke Bloy
  • Rebecca Murray
  • Lisa Blaskey
  • Susan E. Levy
  • Timothy P.L. Roberts

BACKGROUND: Individuals with autism spectrum disorder (ASD) show atypical brain activity, perhaps due to delayed maturation. Previous studies examining the maturation of auditory electrophysiological activity have been limited due to their use of cross-sectional designs. The present study took a first step in examining magnetoencephalography (MEG) evidence of abnormal auditory response maturation in ASD via the use of a longitudinal design. METHODS: Initially recruited for a previous study, 27 children with ASD and nine typically developing (TD) children, aged 6- to 11-years-old, were re-recruited two to five years later. At both timepoints, MEG data were obtained while participants passively listened to sinusoidal pure-tones. Bilateral primary/secondary auditory cortex time domain (100 ms evoked response latency (M100)) and spectrotemporal measures (gamma-band power and inter-trial coherence (ITC)) were examined. MEG measures were also qualitatively examined for five children who exhibited "optimal outcome", participants who were initially on spectrum, but no longer met diagnostic criteria at follow-up. RESULTS: M100 latencies were delayed in ASD versus TD at the initial exam (~ 19 ms) and at follow-up (~ 18 ms). At both exams, M100 latencies were associated with clinical ASD severity. In addition, gamma-band evoked power and ITC were reduced in ASD versus TD. M100 latency and gamma-band maturation rates did not differ between ASD and TD. Of note, the cohort of five children that demonstrated "optimal outcome" additionally exhibited M100 latency and gamma-band activity mean values in-between TD and ASD at both timepoints. Though justifying only qualitative interpretation, these "optimal outcome" related data are presented here to motivate future studies. CONCLUSIONS: Children with ASD showed perturbed auditory cortex neural activity, as evidenced by M100 latency delays as well as reduced transient gamma-band activity. Despite evidence for maturation of these responses in ASD, the neural abnormalities in ASD persisted across time. Of note, data from the five children whom demonstrated "optimal outcome" qualitatively suggest that such clinical improvements may be associated with auditory brain responses intermediate between TD and ASD. These "optimal outcome" related results are not statistically significant though, likely due to the low sample size of this cohort, and to be expected as a result of the relatively low proportion of "optimal outcome" in the ASD population. Thus, further investigations with larger cohorts are needed to determine if the above auditory response phenotypes have prognostic utility, predictive of clinical outcome.

YNIMG Journal 2012 Journal Article

White matter atlas generation using HARDI based automated parcellation

  • Luke Bloy
  • Madhura Ingalhalikar
  • Harini Eavani
  • Robert T. Schultz
  • Timothy P.L. Roberts
  • Ragini Verma

Most diffusion imaging studies have used subject registration to an atlas space for enhanced quantification of anatomy. However, standard diffusion tensor atlases lack information in regions of fiber crossing and are based on adult anatomy. The degree of error associated with applying these atlases to studies of children for example has not yet been estimated but may lead to suboptimal results. This paper describes a novel technique for generating population-specific high angular resolution diffusion imaging (HARDI)-based atlases consisting of labeled regions of homogenous white matter. Our approach uses a fiber orientation distribution (FOD) diffusion model and a data driven clustering algorithm. White matter regional labeling is achieved by our automated data driven clustering algorithm that has the potential to delineate white matter regions based on fiber complexity and orientation. The advantage of such an atlas is that it is study specific and more comprehensive in describing regions of white matter homogeneity as compared to standard anatomical atlases. We have applied this state of the art technique to a dataset consisting of adolescent and preadolescent children, creating one of the first examples of a HARDI-based atlas, thereby establishing the feasibility of the atlas creation framework. The white matter regions generated by our automated clustering algorithm have lower FOD variance than when compared to the regions created from a standard anatomical atlas.

YNIMG Journal 2011 Journal Article

Diffusion based abnormality markers of pathology: Toward learned diagnostic prediction of ASD

  • Madhura Ingalhalikar
  • Drew Parker
  • Luke Bloy
  • Timothy P.L. Roberts
  • Ragini Verma

This paper presents a paradigm for generating a quantifiable marker of pathology that supports diagnosis and provides a potential biomarker of neuropsychiatric disorders, such as autism spectrum disorder (ASD). This is achieved by creating high-dimensional nonlinear pattern classifiers using support vector machines (SVM), that learn the underlying pattern of pathology using numerous atlas-based regional features extracted from diffusion tensor imaging (DTI) data. These classifiers, in addition to providing insight into the group separation between patients and controls, are applicable on a single subject basis and have the potential to aid in diagnosis by assigning a probabilistic abnormality score to each subject that quantifies the degree of pathology and can be used in combination with other clinical scores to aid in diagnostic decision. They also produce a ranking of regions that contribute most to the group classification and separation, thereby providing a neurobiological insight into the pathology. As an illustrative application of the general framework for creating diffusion based abnormality classifiers we create classifiers for a dataset consisting of 45 children with ASD (mean age 10. 5±2. 5yr) as compared to 30 typically developing (TD) controls (mean age 10. 3±2. 5yr). Based on the abnormality scores, a distinction between the ASD population and TD controls was achieved with 80% leave one out (LOO) cross-validation accuracy with high significance of p<0. 001, ~84% specificity and ~74% sensitivity. Regions that contributed to this abnormality score involved fractional anisotropy (FA) differences mainly in right occipital regions as well as in left superior longitudinal fasciculus, external and internal capsule while mean diffusivity (MD) discriminates were observed primarily in right occipital gyrus and right temporal white matter.

YNIMG Journal 2005 Journal Article

Spatial sensitivity and temporal response of spin echo and gradient echo bold contrast at 3 T using peak hemodynamic activation time

  • Justin Hulvershorn
  • Luke Bloy
  • Eugene E. Gualtieri
  • John S. Leigh
  • Mark A. Elliott

Recent theoretical and experimental work has suggested that spin echo (SE) functional MRI (fMRI) has improved localization of neural activity compared to gradient echo (GE) fMRI at high field strengths, albeit with a decrease in blood oxygenation level-dependent (BOLD) contrast. The present study investigated spatial and temporal variations in GE and SE fMRI at 3 T in response to a brief visual stimulus. The results demonstrate that SE BOLD contrast reaches its maximum amplitude more quickly than does GE contrast at long echo times. We have called this metric the peak hemodynamic activation time (PHAT). Because BOLD changes in response to increased neuronal activity occur earlier in the microvasculature and then later propagate into the venous compartment, these results provide further evidence that SE-based BOLD contrast provides superior localization to the site of activation at 3 T. Spatial overlay of SE and GE PHAT maps onto structural images reveal markedly different spatial profiles and further support the interpretation that shorter peak times correlate to improved spatial sensitivity.

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