Max J. Kurz

Somatosensory dysfunction contributes substantially to mobility impairments in cerebral palsy (CP), yet their somatosensory cortical responses to rhythmic sustained input remains unstudied. This study examined somatosensory cortical entrainment in 28 ambulatory youth with CP (Gross Motor Function Classification System levels I–III; 21.9±6.3y; 14 unilateral CP) and 34 neurotypical controls (23.4±3.8y). Participants underwent magnetoencephalography while an 8 Hz cutaneous electrical stimulation was applied to the right posterior tibial nerve. Rhythmic neural responses were mapped to the contralateral somatosensory cortices using beamforming, and virtual sensor time series were extracted to quantify neural dynamics. The entrainment response declined more steeply over time in CP compared to controls, whereas the concurrent alpha response strengthened progressively in CP but changed minimally in controls (Group×Time interactions, p s<.001). Significant cross-spectral coupling of entrainment×concurrent alpha responses was observed only in CP ( p <.001) and was most pronounced in those with bilateral CP. Weaker cross-spectral coupling was associated with better functional mobility in controls ( p =.004) but brain-behavior links in CP were phenotype-specific. Finally, the second harmonic neural response in CP was weaker ( p <.001) and demonstrated a blunted temporal modulation relative to controls ( p =.003). These findings implicate disrupted somatosensory cortical entrainment responses as possible neurophysiological features of youth with CP.

Down syndrome is commonly associated with a trisomy of chromosome 21 that often presents an accelerated aging profile and higher probability of developing Alzheimer’s disease-like symptoms at a relatively early age. However, the physiological changes that may contribute to such symptoms remain poorly understood. To begin to address this knowledge gap, we used magnetoencephalographic neurophysiological imaging to assess the entrainment of occipital cortical neurons to a 15 Hz visual stimulus in a cohort of adults with DS without a dementia diagnosis (N = 26; Age = 27.65 ± 9.55 years) and a demographically matched cohort of neurotypical controls (N = 22; Age = 30.81 ± 8.02 years). Our results indicated that adults with Down syndrome exhibit substantially weaker entrainment of the occipital cortical neurons and elevated spontaneous activity during the prestimulation baseline period compared with the controls. These results suggest that there are alterations in the integrity of occipital neural populations that may be attributable to an imbalance in local GABAergic activity and/or disruption in cholinergic pathways. These changes may affect the strength of resting cortical rhythms, leading to the elevated spontaneous activity observed here, which has been linked to reductions in the dynamic range of neural populations and impairments in perceptual and cognitive processing. These novel results advance our understanding of the occipital cortical physiology seen in adults with Down syndrome and provide foundational knowledge for the development of biomarkers for the early detection of accelerated aging and cognitive decline in those with Down syndrome.

Persons with cerebral palsy (CP) exhibit diminished somatosensory cortical activity and this has been linked with the extent of their muscular performance and mobility impairments. However, the influence of physical therapy paradigms on such diminished cortical activity remains unclear. The current study evaluated the extent of mobility changes and somatosensory cortical activity in persons with CP (n = 28; Age = 21.57 ± 7.1 yr; Gross Motor Function Classification Score levels I–III) following 8 weeks of a gait training protocol that involved exploratory activities that were directed at enhancing the somatosensory experience through rich/novel movement. A paired-pulse somatosensory paradigm during magnetoencephalography was used to assess the cortical changes after undergoing the physical therapy protocol. Consistent with the literature, the group with CP had weaker somatosensory cortical responses compared to the neurotypical controls. While the participants with CP demonstrated clinically relevant mobility improvements, there were no changes in the somatosensory cortical activity. However, there was a prominent increase in neural activity within the anterior cingulate. This implies that the novel gait training protocol used here may drive beneficial improvements in the ability of persons with CP to monitor their motor errors, attend to the available sensory feedback, and discriminate different sensory intensities during gait.

Our understanding of the neurobiology underlying cognitive dysfunction in persons with cerebral palsy is very limited, especially in the neurocognitive domain of visual selective attention. This investigation utilized magnetoencephalography and an Eriksen arrow-based flanker task to quantify the dynamics underlying selective attention in a cohort of youth and adults with cerebral palsy (n = 31; age range = 9 to 47 yr) and neurotypical controls (n = 38; age range = 11 to 49 yr). The magnetoencephalography data were transformed into the time-frequency domain to identify neural oscillatory responses and imaged using a beamforming approach. The behavioral results indicated that all participants exhibited a flanker effect (greater response time for the incongruent compared to congruent condition) and that individuals with cerebral palsy were slower and less accurate during task performance. We computed interference maps to focus on the attentional component and found aberrant alpha (8 to 14 Hz) oscillations in the right primary visual cortices in the group with cerebral palsy. Alpha and theta (4 to 7 Hz) oscillations were also seen in the left and right insula, and these oscillations varied with age across all participants. Overall, persons with cerebral palsy exhibit deficiencies in the cortical dynamics serving visual selective attention, but these aberrations do not appear to be uniquely affected by age.

The altered sensorimotor cortical dynamics seen in youth with cerebral palsy appear to be tightly coupled with their motor performance errors and uncharacteristic mobility. Very few investigations have used these cortical dynamics as potential biomarkers to predict the extent of the motor performance changes that might be seen after physical therapy or in the design of new therapeutic interventions that target a youth’s specific neurophysiological deficits. This cohort investigation was directed at evaluating the practice dependent changes in the sensorimotor cortical oscillations exhibited by youth with cerebral palsy as a step towards addressing this gap. We used magnetoencephalography to image the changes in the cortical oscillations before and after youth with cerebral palsy (N = 25; age = 15.2 ± 4.5 years; Gross Motor Function Classification Score Levels I–III) and neurotypical controls (N = 18; age = 14.6 ± 3.1 years) practiced a knee extension isometric target-matching task. Subsequently, structural equation modelling was used to assess the multivariate relationship between changes in beta (16–22 Hz) and gamma (66–82 Hz) oscillations and the motor performance after practice. The structural equation modelling results suggested youth with cerebral palsy who had a faster reaction time after practice tended to also have a stronger peri-movement beta oscillation in the sensorimotor cortices following practicing. The stronger beta oscillations were inferred to reflect greater certainty in the selected motor plan. The models also indicated that youth with cerebral palsy who overshot the targets less and matched the targets sooner tended to have a stronger execution-related gamma response in the sensorimotor cortices after practice. This stronger gamma response may represent improve activation of the sensorimotor neural generators and/or alterations in the GABAergic interneuron inhibitory–excitatory dynamics. These novel neurophysiological results provide a window on the potential neurological changes governing the practice-related outcomes in the context of the physical therapy.