The Functional Near-infrared Spectroscopy Study Of Response Inhibition And Working Memory In Children With Different Subtypes Of ADHD

Background:Attention deficit hyperactivity disorder（ADHD）is a common neurodevelopmental disorder in children,which can be divided into three subtypes,inattention subtype of ADHD（ADHD-I）,hyperactivity impulsive subtype of ADHD（ADHD-HI）and combined subtype of ADHD（ADHD-C）.The pathogenesis of ADHD is still unclear and may be related to cognitive dysfunction,especially executive dysfunction.And response inhibition and working memory have an important place in etiological models of ADHD.Functional near-infrared brain imaging（fNIRS）is an emerging optical brain functional instrument that can detect cortical activation and reflect cognitive function in subjects.With noninvasive,noise-free,and insensitive to movement artifacts,fNIRS is particularly suitable for children with ADHD.Previously,our group used fNIRS to explore executive dysfunction in children with ADHD.The results showed positional differences in activated damaged brain regions and brain regions that improved after medication in children with ADHD.There were also inconsistencies in location among relevant studies from other investigators.The reason for the discrepancy may be related to the small sample size and the absence of distinguishing subtypes.Therefore,the present study aimed to investigate whether there are differences in the activation of the cerebral cortex in different subtypes of ADHD children when performing executive function tasks.Part One:The functional near-infrared spectroscopy study of inhibition control in children with different subtypes of ADHDObjective:To understand the differences in the activation of functional near-infrared spectroscopy（fNIRS）of the cerebral cortex when performing a response inhibition task in children with different subtypes of ADHD.Methods:75 children with ADHD attending children’s Hospital of Capital Institute of Pediatrics between August 2019 and February 2021 were included.Among them,39 were inattention subtype of ADHD（ADHD-I）,12 were hyperactivity impulsive subtype of ADHD（ADHD-HI）,24 were combined subtype of ADHD（ADHD-C）,and 28 healthy controls were included.Enrolled children were divided into four groups based on three different subtypes and healthy controls.Cerebral cortical activations were recorded with fNIRS while subjects performed the go/no go task.Results:（1）There was no significant difference in reaction time and accuracy rate between different subtypes of ADHD children and healthy children during the performance of go task.The fNIRS results also showed that none of the four groups showed significantly enhanced activation during the go task compared with baseline.（2）The enhanced activation during the no go task compared to that during the go task represents the response inhibition function.The fNIRS results showed that healthy children showed predominantly enhanced activation in the right prefrontal cortex,with significantly greater activation in the right middle and inferior frontal gyri（P<0.05）.Enhanced activation in the right prefrontal cortex was also present in children with ADHD,but the range and extent of activation enhancement was diminished.The right middle and inferior frontal gyrus activation was significantly enhanced（P<0.05）in ADHD-I compared with healthy children in the same brain regions with increased activation,but with a reduced range.The behavioral results showed no statistically significant differences in the accuracy rate and reaction time on the no go task between ADHD-I and healthy children.No significant enhancement of activation was observed in ADHD-HI type brain regions.The activation in the right middle frontal gyrus of ADHD-C type was significantly enhanced（P<0.05）,and the range of activation was narrower than that in healthy children.The behavioral results also showed that the correct rate of the no go task was significantly higher in healthy children than in ADHD-HI type and ADHD-C type.The results of intergroup comparison showed that the activation enhancement of ADHD-I type in the right precentral gyrus and middle frontal gyrus was significantly lower than that in the other three groups（P<0.05）.The activation enhancement of ADHD-I and ADHD-C was significantly attenuated in the left middle temporal gyrus compared with healthy children（P<0.05）.（3）Correlation analysis revealed that all three subtypes were associated with enhanced activation of channel 34（right inferior frontal gyrus）during the no go task compared with the go task,and the ADHD-I was significantly negatively correlated with the hyperactivity impulsivity dimension of the Conners parent questionnaire（r_s=-0.337,P<0.05）and the attention deficit subscale in SNAP-IV（r_s=-0.396,P<0.05）;In the ADHD-HI type,a significant negative correlation was observed with the performance of the Conners parent questionnaire（rs=-0.871,P<0.01）,anxiety（r_s=-0.715,P<0.05）,hyperactivity index（r_s=-0.737,P<0.01）,and total score（r_s=-0.818,P<0.01）;A significant negative correlation was found between ADHD-C type and IVA parent Symptom Inventory score（r_s=-0.482,P<0.05）.In ADHD-HI type,the enhanced activation of channel52（middle temporal gyrus）was significantly correlated with the IVA hyperactivity quotient（r_s=0.795,P<0.05）.In ADHD-C,enhanced activation in channel 25（right middle frontal gyrus）was significantly and positively correlated with scores on the Conners parent questionnaire（r_s=0.485,P<0.05）,the SNAP-IV oppositional defiant subscale score（r_s=0.479,P<0.05）,and the increased activation in Channel35（right inferior frontal gyrus）was significantly and positively correlated with the hyperactivity index of the Conners parent questionnaire（r_s=0.440,P<0.05）.Conclusion:Children with ADHD have impaired response inhibition;Impaired activation of the right middle and inferior frontal gyri was present in children with different subtypes of ADHD during performance of a response inhibition task.And different subtypes of ADHD children have their respective brain region activation profiles.Impaired activation of the right precentral gyrus and left middle temporal gyrus is present in ADHD-I type.Impaired left middle temporal gyrus activation is present in ADHD-C type.Enhanced activation of brain regions in children with different subtypes of ADHD is correlated with their core symptoms and behavioral problems.Part Two:The functional near-infrared spectroscopy study of working memory in children with different subtypes of ADHDObjective:To understand the differences in the activation of functional near-infrared spectroscopy（fNIRS）of the cerebral cortex in different subtypes of ADHD children during working memory tasks.Methods:82 children with ADHD attending children’s Hospital of Capital Institute of Pediatrics between August 2019 and February 2021 were included.Among them,43 were inattention subtype of ADHD（ADHD-I）,12 were hyperactivity impulsive subtype of ADHD（ADHD-HI）,27 were combined subtype of ADHD（ADHD-C）,and 28 healthy controls were included.Enrolled children were divided into four groups based on three different subtypes and healthy controls.Cerebral cortical activations were recorded with fNIRS while subjects performed the N-back task.Results:（1）Behavioral results:under the 0-back task,the reaction time of ADHD-C type was significantly longer than that of healthy children and ADHD-I type,and the accuracy rates of different subtypes of ADHD children were significantly lower than that of healthy children.Under the 1-back task,there was no significant difference in reaction time among the four groups,and the accuracy rates of the different subtypes of ADHD children were lower than those of the healthy children.（2）fNIRS results:neither healthy nor ADHD children showed significantly enhanced activation during the 0-back task compared to baseline.There was a trend towards increased activation in the frontopolar regions（right superior and bilateral middle frontal gyri）of the ADHD-I prefrontal cortex（P<0.1）and decreased activation in the right postcentral gyrus（P<0.1）.There was a trend towards increased activation in the frontopolar region（left middle frontal gyrus）of the prefrontal cortex in ADHD-C type（P<0.1）.The results of intergroup comparisons showed that children with the three subtypes of ADHD showed significantly enhanced activation in the frontopolar region（left middle frontal gyrus）of the prefrontal cortex compared with healthy children,while there was no significant difference in activation among the three subtypes.Healthy children,ADHD-HI type and ADHD-C type activations were not significantly enhanced during the 1-back task compared to baseline.ADHD-I showed significantly（P<0.05）enhanced activation in the frontal oculomotor areas,frontal polar areas of the prefrontal cortex,dorsolateral prefrontal lobes（left superior frontal gyrus,right middle frontal gyrus）,primary motor energy cortex（right precentral gyrus）,and frontal polar areas of the prefrontal cortex（left middle frontal gyrus）,with a trend of increased activation in the precuneus region.The results of intergroup comparisons showed that the ADHD-HI type was more activated in the dorsolateral prefrontal lobe（left middle frontal gyrus）than the other 3 groups.（3）Correlation analysis:during the 0-back task,there was no significant relationship between the increased activation in the three subtypes of ADHD and the scale results.During the1-back task,the activations in ADHD-HI type and ADHD-C type were not significantly correlated with the scale results.The activation of channel 5（right superior frontal gyrus）in ADHD-I was negatively correlated with the hyperactivity index of the Conners parent symptom questionnaire（r_s=-0.334,P<0.05）to a low degree.The activation of channel 8（left superior frontal gyrus）of ADHD-I showed a low positive correlation with the Conners’parent symptom questionnaire for psychosomatic problems（r_s=0.336,P<0.05）and total score（r_s=0.456,P<0.05）.The activation of channel 15（right middle frontal gyrus）of ADHD-I showed a low positive correlation with the Conners parent symptom questionnaire for psychosoma（r_s=0.338,P<0.05）.The activation of channel 36（right middle frontal gyrus）of ADHD-I showed a low positive correlation with the Conners parent symptom questionnaire for psychosoma（r_s=0.376,P<0.05）,anxiety（r_s=0.339,P<0.05）.The activation of channel 38（left middle frontal gyrus）of ADHD-I showed a low positive correlation with anxiety（r_s=0.384,P<0.05）on the Conners parent symptom questionnaire.Conclusion:Children with ADHD have deficits in working memory functioning in both parts of the phonological circuit and the central executive system.During working memory tasks,children with different subtypes of ADHD are all compensated by enhanced activation（or trends towards enhancement）in the prefrontal cortex.Meanwhile,the right postcentral gyrus activation is impaired in ADHD-I type and the right supramarginal gyrus and dorsolateral prefrontal activation are impaired in ADHD-C type.Enhanced activation in brain regions of ADHD-I correlates with their core symptoms and behavioral problems.