Altered white matter connectivity in children with congenital heart disease with single ventricle physiology.

Children born with congenital heart disease (CHD) have seen a dramatic decrease in mortality thanks to surgical innovations. However, there are numerous risk factors associated with CHD that can disrupt neurodevelopment. Recent studies have found that psychological deficits and structural brain abnormalities persist into adulthood. The goal of the current study was to investigate white matter connectivity in early school-age children (6-11 years), born with complex cyanotic CHD (single ventricle physiology), who have undergone Fontan palliation, compared to a group of heart-healthy, typically developing controls (TPC). Additionally, we investigated associations between white matter tract connectivity and measures on a comprehensive neuropsychological battery within each group. Our results suggest CHD patients exhibit widespread decreases in white matter connectivity, and the extent of these decreases is related to performance in several cognitive domains. Analysis of network topology showed that hub distribution was more extensive and bilateral in the TPC group. Our results are consistent with previous studies suggesting perinatal ischemia leads to white matter lesions and delayed maturation.

Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case-Control Pilot Study.

OBJECTIVE: This case-control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long-term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD. METHODS: We studied youth with ASD aged 11-18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor-evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS. RESULTS: Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons. CONCLUSION: In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of ASD based on behavioral and cognitive testing.

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects.

BACKGROUND: Although single- and paired-pulse (sp/pp) transcranial magnetic stimulation (TMS) studies are considered minimal risk in adults and children, the safety profile for theta-burst TMS (TBS) is unknown. OBJECTIVE: In this comparative analysis, we explored the rate, severity, and specific symptoms of TMS-related adverse effects (AEs) between sp/ppTMS and TBS in subjects between ages 6 and 18 years. METHOD: Data from 165 participants from 2009 to 2014 were analyzed. Assessment of AEs was performed based on baseline and post-TMS administration of a symptom-based questionnaire that rated AEs on a 5-level ordinal scale (minimal, mild, moderate, marked, severe). AE rates and severity were compared using Chi Square or Fisher's Exact Test depending on data characteristics. RESULT: Overall, no seizures or severe-rated AEs were reported by 165 pediatric participants. The rate of AE in all TBS sessions was 10.5% (n = 76, 95% CI: 4.7-19.7%), whereas the rate of AE in all sp/ppTMS sessions was 12.4% (n = 89, 95% CI: 6.3-21.0%). There was no statistical difference in AE rates between TBS and sp/ppTMS (p = 0.71). In all sp/ppTMS and TBS sessions, 20 subjects reported a total of 35 AEs, among these 31 (~88.6%) were rated as "minimal" or "mild". There was no difference in the severity of AE between TBS and sp/ppTMS (p = 1.0). Only one of 76 TBS participants reported an AE rated as more than minimal/mild. CONCLUSION: Our comparative analysis showed that TBS appears to be as safe as sp/ppTMS in terms of AE rate and severity. This report supports further investigation of TBS in children.

Effect of 30 Hz theta burst transcranial magnetic stimulation on the primary motor cortex in children and adolescents.

Fourteen healthy children (13.8 ± 2.2 years, range 10-16; M:F = 5:9) received 30 Hz intermittent theta burst transcranial magnetic stimulation (iTBS) with a stimulation intensity of 70% of resting motor threshold (RMT) with a total of 300 (iTBS300) pulses. All volunteers were free of neurologic, psychiatric and serious medical illnesses, not taking any neuropsychiatric medications, and did not have any contraindications to transcranial magnetic stimulation. Changes in the mean amplitudes of motor-evoked potentials from baseline following iTBS were expressed as a ratio and assessed from 1 to 10 min (BLOCK1) and 1-30 min (BLOCK2) using repeated-measures analysis of variance. All 14 subjects completed iTBS300 over the dominant primary motor cortex (M1) without any clinically reported adverse events. ITBS300 produced significant M1 facilitation [F (5, 65) = 3.165, p = 0.01] at BLOCK1 and trend level M1 facilitation at BLOCK2 [F (10, 129) = 1.69, p = 0.089]. Although iTBS300 (stimulation duration of 92 s at 70% RMT) delivered over M1 in typically developed children was well-tolerated and produced on average significant facilitatory changes in cortical excitability, the post-iTBS300 neurophysiologic response was variable in our small sample. ITBS300-induced changes may represent a potential neuroplastic biomarker in healthy children and those with neuro-genetic or neuro-psychiatric disorders. However, a larger sample size is needed to address safety and concerns of response variability.