Dataset Information

Dorsal-to-ventral imbalance in the superior longitudinal fasciculus mediates methylphenidate's effect on beta oscillations in ADHD.

ABSTRACT: While pharmacological treatment with methylphenidate (MPH) is a first line intervention for ADHD, its mechanisms of action have yet to be elucidated. We here seek to identify the white matter tracts that mediate MPH's effect on beta oscillations. We implemented a double-blind placebo-controlled crossover design, where boys diagnosed with ADHD underwent behavioral and MEG measurements during a spatial attention task while on and off MPH. The results were compared with an age/IQ-matched control group. Estimates of white matter tracts were obtained using diffusion tensor imaging (DTI). Via a stepwise model selection strategy, we identified the fiber tracts (regressors) significantly predicting values of the dependent variables of interest (i.e., oscillatory power, behavioral performance, and clinical symptoms): the anterior thalamic radiation (ATR), the superior longitudinal fasciculus ("parietal endings") (SLFp), and superior longitudinal fasciculus ("temporal endings") (SLFt). ADHD symptoms severity was associated with lower fractional anisotropy (FA) within the ATR. In addition, individuals with relatively higher FA in SLFp compared to SLFt, led to stronger behavioral effects of MPH in the form of faster and more accurate responses. Furthermore, the same parietotemporal FA gradient explained the effects of MPH on beta modulation: subjects with ADHD exhibiting higher FA in SLFp compared to SLFt also displayed greater effects of MPH on beta power during response preparation. Our data suggest that the behavioral deficits and aberrant oscillatory modulations observed in ADHD depend on a possibly detrimental structural connectivity imbalance within the SLF, caused by a diffusivity gradient in favor of parietal rather than temporal, fiber tracts.

SUBMITTER: Mazzetti C

PROVIDER: S-EPMC9287074 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:AimTo understand the relationship between cognition and white-matter structure in adolescents born preterm without obvious brain injury.MethodsThirty-two adolescents from a longitudinal study of child development were selected according to risk of developmental disorders at birth (born at term: eight males, five females; median age 16y 1mo, interquartile range 10mo; low risk preterm: four males, five females, median age 16y, range 4mo; high risk preterm: three males, seven females, median age 16y 2mo, range 1y 2mo) and reading ability (good: three males, eight females, median age 16y, range 7mo; average: six males, three females, median age 16y 10mo, range 1y; poor: six males, six females, median age 16y, range 6mo). Preterm birth was defined as a gestational age of 36 weeks or less and a birthweight of 1600g or less. All participants had normal clinical neuroimaging findings. We examined fractional anisotropy, radial diffusivity, and volume of three major white-matter fasciculi. The relationship between structural measures and birth risk, hemisphere, and cognitive ability (attention, lexical and sublexical decoding, auditory phonological awareness, and processing speed) were analysed using mixed-model regression.ResultsLeft-hemisphere superior longitudinal fasciculus (SLF) fractional anisotropy and radial diffusivity were linked to reading-related skills (fractional anisotropy vs letter-word identification, r((30))=-0.37, p<0.05; fractional anisotropy vs phoneme reversal, r((30))=-0.34, p=0.05; radial diffusivity vs letter-word identification, r((30))=0.31, p<0.10; radial diffusivity vs phoneme reversal, r((30))=0.40, p<0.05), whereas right-hemisphere SLF fractional anisotropy was related to attention skills (fractional anisotropy vs inattentiveness, r((30))=-0.38, p<0.05). SLF volume decreased as these skills declined for adolescents born preterm (volume vs phoneme reversal, r((17))=0.58, p<0.01; volume vs inattentiveness, r((17))=-0.69, p<0.01), but not for those born at term.InterpretationThe relationship between cognitive skills and SLF volume suggests that in adolescents born preterm, cryptic white-matter injury may exist, possibly related to oligodendrocyte or axonal loss, despite normal clinical neuroimaging.

Project description:Birth defects are among the leading causes of infant mortality and contribute substantially to illness and long-term disability. Defects in Bone Morphogenetic Protein (BMP) signaling are associated with cleft lip/palate. Many craniofacial syndromes are caused by defects in signaling pathways that pattern the cranial neural crest cells (CNCCs) along the dorsal-ventral axis. For example, auriculocondylar syndrome is caused by impaired Endothelin-1 (Edn1) signaling, and Alagille syndrome is caused by defects in Jagged-Notch signaling. The BMP, Edn1, and Jag1b pathways intersect because BMP signaling is required for ventral edn1 expression that, in turn, restricts jag1b to dorsal CNCC territory. In zebrafish, the scaffolding protein Wdr68 is required for edn1 expression and subsequent formation of the ventral Meckel's cartilage as well as the dorsal Palatoquadrate. Here we report that wdr68 activity is required between the 17-somites and prim-5 stages, that edn1 functions downstream of wdr68, and that wdr68 activity restricts jag1b, hey1, and grem2 expression from ventral CNCC territory. Expression of dlx1a and dlx2a was also severely reduced in anterior dorsal and ventral 1st arch CNCC territory in wdr68 mutants. We also found that the BMP agonist isoliquiritigenin (ISL) can partially rescue lower jaw formation and edn1 expression in wdr68 mutants. However, we found no significant defects in BMP reporter induction or pSmad1/5 accumulation in wdr68 mutant cells or zebrafish. The Transforming Growth Factor Beta (TGF-?) signaling pathway is also known to be important for craniofacial development and can interfere with BMP signaling. Here we further report that TGF-? interference with BMP signaling was greater in wdr68 mutant cells relative to control cells. To determine whether interference might also act in vivo, we treated wdr68 mutant zebrafish embryos with the TGF-? signaling inhibitor SB431542 and found partial rescue of edn1 expression and craniofacial development. While ISL treatment failed, SB431542 partially rescued dlx2a expression in wdr68 mutants. Together these findings reveal an indirect role for Wdr68 in the BMP-Edn1-Jag1b signaling hierarchy and dorso-anterior expression of dlx1a/2a.

Project description:BackgroundWearable devices have been found effective in training ankle control in patients with neurological diseases. However, the neural mechanisms associated with using wearable devices for ankle training remain largely unexplored. This study aimed to investigate the ankle tracking performance and brain white matter changes associated with ankle tracking learning using a wearable-device system and the behavior-brain structure relationships in middle-aged and older adults.MethodsTwenty-six middle-aged and older adults (48-75 years) participated in this study. Participants underwent 5-day ankle tracking learning with their non-dominant foot using a custom-built ankle tracking system equipped with a wearable sensor and a sensor-computer interface for real-time visual feedback and data acquisition. Repeated and random sequences of target tracking trajectories were both used for learning and testing. Ankle tracking performance, calculated as the root-mean-squared-error (RMSE) between the target and actual ankle trajectories, and brain diffusion spectrum MR images were acquired at baseline and retention tests. The general fractional anisotropy (GFA) values of eight brain white matter tracts of interest were calculated to indicate their integrity. Two-way (Sex × Time) mixed repeated measures ANOVA procedures were used to investigate Sex and Time effects on RMSE and GFA. Correlations between changes in RMSE and those in GFA were analyzed, controlling for age and sex.ResultsAfter learning, both male and female participants reduced the RMSE of tracking repeated and random sequences (both p < 0.001). Among the eight fiber tracts, the right superior longitudinal fasciculus II (R SLF II) was the only one which showed both increased GFA (p = 0.039) after learning and predictive power of reductions in RMSE for random sequence tracking with its changes in GFA [β = 0.514, R2 change = 0.259, p = 0.008].ConclusionsOur findings implied that interactive tracking movement learning using wearable sensors may place high demands on the attention, sensory feedback integration, and sensorimotor transformation functions of the brain. Therefore, the SLF II, which is known to perform these brain functions, showed corresponding neural plasticity after such learning, and its plasticity also predicted the behavioral gains. The SLF II appears to be a very important anatomical neural correlate involved in such learning paradigms.

Dataset Information

Dorsal-to-ventral imbalance in the superior longitudinal fasciculus mediates methylphenidate's effect on beta oscillations in ADHD.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets