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William Gaetz

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6 papers
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6

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 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.

YNIMG Journal 2019 Journal Article

Magnetoencephalography and the infant brain

  • Yu-Han Chen
  • Joni Saby
  • Emily Kuschner
  • William Gaetz
  • J. Christopher Edgar
  • Timothy P.L. Roberts

Magnetoencephalography (MEG) is a non-invasive neuroimaging technique that provides whole-head measures of neural activity with millisecond temporal resolution. Over the last three decades, MEG has been used for assessing brain activity, most commonly in adults. MEG has been used less often to examine neural function during early development, in large part due to the fact that infant whole-head MEG systems have only recently been developed. In this review, an overview of infant MEG studies is provided, focusing on the period from birth to three years. The advantages of MEG for measuring neural activity in infants are highlighted (See Box 1), including the ability to assess activity in brain (source) space rather than sensor space, thus allowing direct assessment of neural generator activity. Recent advances in MEG hardware and source analysis are also discussed. As the review indicates, efforts in this area demonstrate that MEG is a promising technology for studying the infant brain. As a noninvasive technology, with emerging hardware providing the necessary sensitivity, an expected deliverable is the capability for longitudinal infant MEG studies evaluating the developmental trajectory (maturation) of neural activity. It is expected that departures from neuro-typical trajectories will offer early detection and prognosis insights in infants and toddlers at-risk for neurodevelopmental disorders, thus paving the way for early targeted interventions.

YNICL Journal 2017 Journal Article

Neuromagnetic responses to tactile stimulation of the fingers: Evidence for reduced cortical inhibition for children with Autism Spectrum Disorder and children with epilepsy

  • William Gaetz
  • Michael T. Jurkiewicz
  • Sudha Kilaru Kessler
  • Lisa Blaskey
  • Erin S. Schwartz
  • Timothy P.L. Roberts

The purpose of this study was to compare somatosensory responses from a group of children with epilepsy and a group of children with autism spectrum disorder (ASD), with age matched TD controls. We hypothesized that the magnitude of the tactile "P50m" somatosensory response would be reduced in both patient groups, possibly due to reduced GABAergic signaling as has been implicated in a variety of previous animal models and in vivo human MRS studies. We observed significant (~ 25%) decreases in tactile P50m dipole moment values from the source localized tactile P50m response, both for children with epilepsy and for children with ASD. In addition, the latency of the tactile P50m peak was observed to be equivalent between TD and ASD groups but was significantly delayed in children with epilepsy by ~ 6 ms. Our data support the hypothesis of impaired GABAergic signaling in both children with ASD and children with epilepsy. Further work is needed to replicate these findings and directly relate them to both in vivo measures of GABA via e.g. magnetic resonance spectroscopy and psychophysical assessments of somatosensory function, and behavioral indices.

YNIMG Journal 2008 Journal Article

Self-paced movements induce high-frequency gamma oscillations in primary motor cortex

  • Douglas Cheyne
  • Sonya Bells
  • Paul Ferrari
  • William Gaetz
  • Andreea C. Bostan

There has been increasing interest in the functional role of high-frequency (>30 Hz) cortical oscillations accompanying various sensorimotor and cognitive tasks in humans. Similar “high gamma” activity has been observed in the motor cortex, although the role of this activity in motor control is unknown. Using whole-head MEG recordings combined with advanced source localization methods, we identified high-frequency (65 to 80 Hz) gamma oscillations in the primary motor cortex during self-paced movements of the upper and lower limbs. Brief bursts of gamma activity were localized to the contralateral precentral gyrus (MI) during self-paced index finger abductions, elbow flexions and foot dorsiflexions. In comparison to lower frequency (10–30 Hz) sensorimotor rhythms that are bilaterally suppressed prior to and during movement (Jurkiewicz et al. , 2006), high gamma activity increased only during movement, reaching maximal increase 100 to 250 ms following EMG onset, and was lateralized to contralateral MI, similar to findings from intracranial EEG studies. Peak frequency of gamma activity was significantly lower during foot dorsiflexion (67. 4±5. 2 Hz) than during finger abduction (75. 3±4. 4 Hz) and elbow flexion (73. 9±3. 7 Hz) although markedly similar for left and right movements of the same body part within subjects, suggesting activation of a common underlying network for gamma oscillations in the left and right motor cortex. These findings demonstrate that voluntary movements elicit high-frequency gamma oscillations in the primary motor cortex that are effector specific, and possibly reflect the activation of cortico-subcortical networks involved in the feedback control of discrete movements.

YNIMG Journal 2006 Journal Article

Localization of sensorimotor cortical rhythms induced by tactile stimulation using spatially filtered MEG

  • William Gaetz
  • Douglas Cheyne

We applied the synthetic aperture magnetometry (SAM) spatial filtering method to localize sensorimotor mu (8–14 Hz) and beta (15–35 Hz) rhythms following tactile (brush) stimulation. Neuromagnetic activity was recorded from 10 adult subjects. Transient brush stimuli were applied separately to the right index finger, medial right toe and lower right lip. Differential images of mu and beta band source power were created for periods during (event-related desynchronization; ERD) or following (event-related synchronization; ERS) tactile stimulation, relative to prestimulus baseline activity. Mu ERD to finger brushing was localized to the contralateral somatosensory cortex and was organized somatotopically. Mu ERS, however, was not consistently observed for each subject. Beta ERD was consistently localized to sensory cortical areas and organized somatotopically in the post-central gyrus (SI), and beta ERS was observed to be organized motorotopically in the precentral gyrus (MI). Longer duration (2–3 s) stimulation of the index finger also produced beta ERS in the primary motor cortex, and its time course demonstrated that these oscillatory changes are an off-response to the termination of the presented sensory stimulus. Interestingly, lip and toe stimulation also produced post-stimulus increases in beta rhythms in the bilateral motor hand areas for all subjects, suggesting that common neural systems in the primary motor cortex are activated during tactile stimulation of different body regions.

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