Functional near-infrared spectroscopy study on inhibitory control ability of children with attention deficit hyperactivity disorder with methylphenidate therapy: An experimental, longitudinal, and neuroimaging study

doi:10.21203/rs.3.rs-4672078/v1

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Research Article

Functional near-infrared spectroscopy study on inhibitory control ability of children with attention deficit hyperactivity disorder with methylphenidate therapy: An experimental, longitudinal, and neuroimaging study

https://doi.org/10.21203/rs.3.rs-4672078/v1

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Background

Executive dysfunction, particularly impairments in inhibitory control, is a key aspect of attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPH) is the main treatment for ADHD; however, its effects on cortical activation and inhibitory control in children with ADHD have not been comprehensively studied. This study aimed to investigate the differences in functional near-infrared spectroscopy (fNIRS) outcomes related to inhibitory control improvement and cortical activation in children with ADHD.

Methods

Between May 2023 and December 2023, 14 children diagnosed with ADHD and treated with MPH were recruited, and 17 healthy children matched for age and sex were included. fNIRS was used to monitor brain activation in healthy children and children with ADHD before and after medication during Go/Nogo, Stroop, and flanker tasks. Differences in brain activation between healthy children and children with ADHD were compared before and after treatment.

Results

Swanson, Nolan, and Pelham IV rating scale revealed statistically significant improvements in inattention and hyperactivity-impulsivity in children with ADHD (P < 0.05). Behavior Rating Inventory of Executive Function Parent Edition revealed statistically significant improvements in working memory and monitoring ability after MPH treatment in children with ADHD (P < 0.05). After MPH treatment, the anterior cingulate cortex of the Stroop task significantly improved in children with ADHD (P < 0.05). The fNIRS activation levels in channels 9, 12, 21, and 42 were higher than those in healthy children during the go/no-go task before ADHD medication (P < 0.05). Before medication administration, no significant difference was observed in fNIRS activation between children with ADHD and healthy children during the Stroop and Flanker tasks (P > 0.05). When performing the Go/No-go task, the activation level of channel 7 fNIRS in children with ADHD was lower after treatment than before (P < 0.05). In the Stroop and flaker tasks, no significant differences were observed in fNIRS activation levels in children with ADHD before and after medication (P > 0.05).

Conclusions

After 8 weeks of treatment with methylphenidate, the behavioral data of children with ADHD showed improvement in the inhibition control neuropsychological test. The characteristic brain regions improved significantly when performing inhibitory control tasks and developed towards the activation direction of healthy children's brain regions.

Attention deficit hyperactivity disorder

Functional near-infrared brain imaging

Methylphenidate

Working memory

Inhibitory control

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder commonly observed in school-aged children and adolescents. The prevalence of ADHD among Chinese children and adolescents aged 6–16 years is approximately 6.4%. More than 50% of children and adolescents with ADHD have symptoms that persist into adulthood, with lasting effects on work, family, and social life^[1–3]. The symptoms of ADHD are mainly attributed to executive dysfunction, in which the impairment of inhibitory control is severe and obvious^[4]. Inhibitory control comprises three parts: conflict monitoring, conflict adaptation, and response inhibition. Many studies have been conducted on the correlation between response inhibition and ADHD symptoms; however, patients with ADHD also have defects in conflict monitoring and adaptation. The tools used to evaluate executive function include behavioral scales, neuropsychological test tasks, and neuroimaging techniques, among which neuroimaging techniques are the most objective, reliable, and closest to the cause of executive function disorders. Functional near-infrared spectroscopy (fNIRS), a new non-invasive technique, can effectively reflect the activation of brain areas and support the study of brain function. Executive dysfunction is closely related to^[5] prefrontal cortex (PFC) function and involves the activation of multiple PFC brain regions. fNIRS monitors hemodynamic response signals in real-time to accurately reflect the level of PFC activation in children with ADHD. This technique is helpful for further exploring the association between executive dysfunction in children with ADHD and specific brain functional areas and is important for understanding the cause and prognosis of executive dysfunction in ADHD. Currently, drug therapy is the main treatment for children with ADHD. Methylphenidate (MPH) increases the levels of dopamine and norepinephrine in the synaptic cleft, enhancing nerve conduction efficiency^[6–8]. Children with ADHD showed improved^[9] test scores on some executive function mental test tasks after MPH treatment. However, owing to task design and age differences, the results of executive function improvements at the brain function level are not uniform^{[7, 10]}. Therefore, this study aimed to investigate the differences in fNIRS outcomes related to inhibitory control improvement and cortical activation in children with ADHD.

Aim, design, and setting

This study aimed to investigate the differences in fNIRS outcomes related to inhibitory control improvement and cortical activation in children with ADHD. This study used a longitudinal, pre-post treatment design. This study was conducted in a clinical setting, involving children diagnosed with ADHD and a control group of healthy children.

Ethics compliance

This study was approved by the Ethics Committee of the Capital Institute of Pediatrics (ethics number: SHERLL2023005).

Study population

Participants were enrolled in the neurology outpatient department and multidisciplinary combined ADHD outpatient Department of Children's Hospital Affiliated to Capital Institute of Pediatrics between May 2023 and December 2023, according to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders Children with ADHD Disorders 5th (DSM-5). Children diagnosed with ADHD according to the DSM-5 criteria by a physician with the title of associate director or above and whose guardians agreed to use MPH for treating the children were included. Fourteen children with ADHD were enrolled based on the inclusion and exclusion criteria. The inclusion criteria of the group with ADHD were as follows: (1) children aged 7–12 years; (2) meeting the diagnostic criteria for ADHD in DSM-5; (3) no drug treatment or non-drug treatment related to ADHD in the past 2 months; (4) Wechsler children's intelligence test results showing an IQ ≥ 80; (5) right-handedness; (6) children with good cooperation and ability to complete relevant neuropsychological tests under guidance; (7) Good compliance, able to take medications on time and return to the doctor when required; (8) Parents or guardians provided informed consent. The exclusion criteria were as follows: (1) poor cooperation of the child; (2) inability to complete all tests and cognitive function training; (3) suffering from organic brain and physical diseases; and (4) children with extensive developmental disorders, mental retardation, and other mental disorders. The inclusion criteria of the 17 healthy children matched by sex and age in the control group were as follows: (1) children aged 7–12 years; (2) not meeting the diagnostic criteria for ADHD in DSM-5; (3) Wechsler child intelligence test results showing an IQ ≥ 80; (4) right-handedness; (5) children with good cooperation and ability to complete relevant neuropsychological tests under guidance; (6) Parents or guardians providing informed consent.

Research methods

General information collection

The outpatient medical records of the Children's Hospital Affiliated with the Capital Institute of Pediatrics were used to collect data, including demographic data, history, development history, family history, allergy history, and pregnancy history.

Scale assessment

(1) Core Symptom Severity Rating Scale for Children with ADHD Swanson, Nolan, and Pelham IV (SNAP-IV): In this study, 26 versions of the parental SNAP-IV were adopted after strict screening and verification to scientifically and systematically assess the severity of core symptoms in children with ADHD. (2) Evaluation of executive function-related behaviors: In this study, 86 versions of the Behavior Rating Inventory of Executive Function (BRIEF) were used to conduct a comprehensive assessment of the executive function-related symptoms of children with ADHD to reflect their behaviors related to executive function. (3) Inhibition control task: A response inhibition task. The Go/No-go paradigm was used to test the response inhibition ability of children with ADHD. Conflict monitoring task: The Stroop task paradigm was used to test the conflict-monitoring ability of children with ADHD. Conflict adaptation task: The flanker task paradigm was used to test the conflict-monitoring ability of children with ADHD.

fNIR brain spectral imaging equipment

We used a fNIR brain imager (ETG-4000; Hitachi, Japan). The device used near-infrared light with wavelengths of 695 and 830 nm to detect 1–3 cm of tissue under the children’s scalp and measured the activation of the brain region of the children through the spectral absorption rate. ETG-4000 contains 33 light probes, including 17 emission and 16 absorption probes. The distance between the probes was 3 cm, and 52 channels were formed in the viewing area between adjacent probes. The synchronous sampling rate of the channel is 10 Hz, and the data unit is mM•mm. The probes were arranged according to the electroencephalogram 10–20 system. The bottom central probe (channel 26) was located at Fpz, and the remaining channels were on both sides along the T3 and T4 directions. Changes in brain tissue activation lead to changes in absorption and scattering coefficients in the optical path, which are translated into changes in oxygenated hemoglobin concentration in the brain tissue according to the Beer-Lambert law, reflecting the activation of the cerebral cortex during working memory and inhibitory control tasks in children with ADHD and healthy children before and after MPH treatment. Mapping of the 52 channels corresponding to fNIRS was completed at the State Key Laboratory of Cognitive Neuroscience, Beijing Normal University.

Statistical analysis

Behavioral data analysis

SPSS 23.0 was used for data analysis, and data are presented as mean ± standard deviation (Χ ± SD). A paired T-test was used to compare the accuracy and reaction time of the Go, No-go, same-color meaning, different-color meaning, no-side interference, and side interference tasks of children with ADHD before and after treatment. Statistical significance was set at P < 0.05.

fNIRS data analysis

We conducted bad guide marking, dedrift, head motion correction, and filter pre-processing (0.01–0.08 Hz) for NIR data and fractional amplitude of low-frequency fluctuations (fALFF) analysis. fALFF calculates the amplitude in a given frequency range as a proportion of the total amplitude range, not just the amplitude in that frequency range. This method helps reduce the effect of high-frequency signals and better reflects true low-frequency oscillating signals, improving the accuracy of the measurement of brain functional connectivity. A Z-transform was applied to the results to conform to the parameter test standards. An independent samples T-test was used to compare the differences in HbO2 in the brain regions of children with ADHD before MPH treatment. A paired t-test was used to compare the HbO2 levels in children with ADHD before and after MPH treatment. Owing to repeated comparisons, false discovery rate correction was used, and statistical significance was set at P < 0.05.

Basic information

Fourteen children with ADHD were included in this study (10 males and 4 females), ranging in age from 7.50 to 10.58 years, with an average age of 8.71 ± 1.35 years. The control group included 17 children (12 males, 5 females). No difference was observed in the sex ratio of children between the groups (χ² = 0.003, P = 0.959). The healthy children ranged in age from 7.08 to 10.33 years, with an average age of 8.01 ± 1.56 years. No significant difference was observed in age between the groups (t = 1.331, P = 0.193).

SNAP-IV scale results

The SNAP-IV scale results of the children with ADHD before and after MPH treatment revealed statistically significant improvements after MPH treatment in inattention and hyperactivity-impulsivity (P < 0.05). The oppositional defiance dimension showed no statistically significant improvement (P > 0.05) (Table 1).

Table 1

SNAP-IV scores before and after methylphenidate in children with ADHD
Dimensions	Children with ADHD pre-treatment	Children with ADHD post-treatment	t/\(\:{\chi\:}^{2}\)	P
Lack of concentration	19.53 ± 3.62	11.53 ± 4.96	5.02	< 0.001
Hyperactivity – impulsive	15.67 ± 6.45	9.27 ± 5.73	8.39	0.002
Oppositional defiance	9.67 ± 4.37	8.00 (6.50–9.50)	0.85	0.394

SNAP-IV, Swanson, Nolan, and Pelham IV; ADHD, Attention deficit hyperactivity disorder

BRIEF parent edition executive function rating scale results

The BRIEF parental version executive function of the children with ADHD before and after MPH treatment revealed statistically significant improvement in working memory and monitoring ability (P < 0.05) (Table 2).

Table 2

BRIEF parental version executive function rating scores before and after methylphenidate in children with ADHD
Dimensions	Children with ADHD pre-treatment	Children with ADHD post-treatment	t/\(\:{\chi\:}^{2}\)	P
Suppress	19.53 ± 4.81	17.87 ± 5.85	0.88	0.395
Conversion	11.00 (9.50–13.50)	11.20 ± 2.48	0.39	0.694
Emotional control	15.60 ± 3.27	14.00 (11.50–18.00)	0.51	0.614
Starting	15.07 ± 4.01	14.47 ± 4.03	0.36	0.722
Working memory	24.00 ± 3.59	19.20 ± 4.33	4.11	0.001
Plan	25.67 ± 5.77	23.20–±6.16	1.03	0.322
Tissue	16.00 (12.50–16.00)	13.60 ± 3.02	0.60	0.549
Monitoring	21.47 ± 4.22	15.00 (14.50–19.50)	2.51	0.012
Behavior Management Index	47.07 ± 7.99	44.20 ± 11.45	0.70	0.493
Metacognition	100.47 ± 15.45	87.47 ± 19.52	1.83	0.089
Total points	147.53 ± 21.61	131.67 ± 29.10	1.51	0.154

ADHD, Attention deficit hyperactivity disorder; BRIEF, Behavior Rating Inventory of Executive Function

Response suppression task

Behavioral results of response inhibition task

No statistically significant differences were observed in the Go task response time (RT), anterior cingulate cortex (ACC) Go task, No-go task RT, and ACC No-go task among children with ADHD in the Go/No-go tasks before and after MPH treatment (P > 0.05) (Table 3).

Table 3

Behavioral results of Go/Nogo tasks in children with ADHD before and after methylphenidate
Dimensions	Children with ADHD before treatment	Children with ADHD after treatment	t/\(\:{\chi\:}^{2}\)	P
GoRT	359.73 ± 96.41	353.08 ± 110.26	0.224	0.826
NogoACC	444.10 ± 110.27	400.63 ± 79.23	1.449	0.169
GoRT	88.06 ± 7.56	87.16 ± 8.94	0.269	0.791
NogoACC	77.85 ± 14.86	90.48 (82.34–95.68)	1.647	0.100

ADHD, Attention deficit hyperactivity disorder; ACC, Anterior cingulate cortex

Response inhibition task fNIRS results

Go/No-go task activation in healthy children and children with ADHD before MPH treatment

Before MPH treatment in children with ADHD, channels 9 (BA8 includes the frontal oculomotor area, left medial frontal gyrus of LPBA[Lobe- and Tract-based Parcellation of the Brain Atlas]), 12 (BA3 somatosensory cortex (SC), right posterior central gyrus of LPBA), 21 (BA40 superior limbic gyrus, left superior limbic gyrus of LPBA), 42 (BA42 auditory association cortex, Left superior temporal gyrus) had significant activation enhancement (P < 0.05) (Table 4). The T-value diagram is shown in Fig. 1. The different channels for the coordinates and Brodmann areas (BAs) are listed in Table 5.

Table 4

fNIRS results of Go/Nogo tasks between children with ADHD and healthy children before methylphenidate treatment
Channel	Healthy children	Children with ADHD pre-treatment	t	P	P_FDR
9	0.55 ± 0.58	0.51 ± 1.06	3.829	< 0.001	0.005
12	0.63 ± 0.75	0.54 ± 1.00	4.356	< 0.001	0.002
21	0.51 ± 0.75	0.53 ± 0.92	4.164	< 0.001	0.002
42	0.55 ± 0.78	0.48 ± 1.11	3.465	0.001	0.012

ADHD, Attention deficit hyperactivity disorder; fNIRS, Functional near-infrared spectroscopy

Table 5

Different channel coordinates and corresponding BA in Go/Nogo task between healthy children and children with ADHD before methylphenidate treatment
Channel	Mean Montreal Neurological Institute coordinates				BA	LPBA partition
Channel	X	Y	Z	Standard deviation	BA	LPBA partition
9	53.38	4.32	43.78	6.43	BA8 includes the frontal eye movement area	Left medial frontal gyrus
12	66.24	12.77	33.42	5.62	BA3 somatosensory cortex	Right posterior central gyrus
21	65.57	34.02	38.29	4.94	BA40 margin superior gyrus	Left superior marginal gyrus
42	69.51	29.81	8.19	5.38	BA42 Auditory Association Cortex	Left superior temporal gyrus

BA, Brodmann area; ADHD, Attention deficit hyperactivity disorder

Changes in brain area activation during Go/No-go tasks in children with ADHD before and after MPH treatment

Channel 7 (BA8 frontal oculomotor area, LPBA left medial frontal gyrus) activation decreased after MPH treatment (P < 0.05) (Table 6). The T-value diagram is shown in Fig. 2. The coordinates of the differential channels and corresponding BA regions are listed in Table 7.

Table 6

fNIRS results of Go/Nogo tasks in children with ADHD before and after methylphenidate intervention
Channel	Healthy children	Children with ADHD after treatment	t	P	P_FDR
7	0.72 ± 0.80	1.25 ± 0.59	3.762	< 0.001	0.045

fNIRS, Functional near-infrared spectroscopy; ADHD, Attention deficit hyperactivity disorder; FDR, False discovery rate

Table 7

Differential channel coordinates and corresponding BA in Go/Nogo tasks before and after methylphenidate treatment
Channel	Mean Montreal Neurological Institute coordinates				BA	LPBA regions
Channel	X	Y	Z	Standard deviation	BA	LPBA regions
7	26.35	41.60	41.19	5.51	BA8 includes the frontal eye movement area	Left medial frontal gyrus
BA, Brodmann areas

Conflict monitoring tasks

Behavioral results of conflict monitoring tasks

Before and after MPH treatment, the ACC of the Stroop task with different color meanings was significantly improved in children with ADHD (P < 0.05), whereas the ACC of the same-color meaning, RT of the same-color meaning, and RT of the different-color meaning tasks were not significantly improved (P > 0.05) (Table 8).

Table 8

Behavioral results of Stroop task before and after methylphenidate intervention in children with ADHD
	Children with ADHD before treatment	Children with ADHD after treatment	t/	P
Color meaning the same RT	367.44 ± 80.29	372.5 ± 109.80	0.184	0.857
Color meaning the same ACC	956.06 ± 210.49	858.43 ± 158.64	1.340	0.201
Color meaning different RT	81.96 ± 6.99	83.65 ± 8.01	0.615	0.549
Color meaning different ACC	51.70 ± 15.09	65.55 ± 12.03	2.417	0.030

ADHD, Attention deficit hyperactivity disorder; RT, Response time; ACC, Anterior cingulate cortex

fNIRS activation in children with ADHD before MPH treatment and healthy children

No significant difference was observed in brain activation between healthy children and children with ADHD before MPH treatment (Fig. 3).

Differences in fNIRS activation in the brain regions of children with ADHD before and after MPH treatment

No significant difference was observed in brain activation of children with ADHD before and after MPH treatment (Fig. 4).

Conflict adaptation task

Behavioral results of conflict adaptation tasks

The intervention treatment of children with ADHD in the flanker task showed no significant improvement (P > 0.05) (Table 9).

Table 9

Behavioral results of Flanker task before and after methylphenidate treatment in children with ADHD
	Children with ADHD before treatment	Children with ADHD after treatment	t/	P
Interference-free RT	349.67 ± 79.48	356.19 ± 76.86	0.291	0.775
No interference ACC	652.18 ± 121.54	582.56 ± 138.72	1.874	0.082
Have interference RT	78.27 ± 13.10	81.62 ± 13.97	1.144	0.272
Have interference ACC	61.90 ± 8.01	67.45 ± 13.08	1.202	0.249

ADHD, Attention deficit hyperactivity disorder; RT, Response time; ACC, Anterior cingulate cortex

fNIRS activation in children with ADHD before treatment with MPH and healthy children

No significant difference was observed in brain activity between healthy children and children with MPH before treatment (Fig. 5).

Differences in fNIRS activation in the brain areas of children with ADHD before and after MPH treatment

No significant difference was observed in the activation of brain areas in children with ADHD before and after MPH treatment (Fig. 6).

ADHD is a common neurodevelopmental disorder affecting children's learning and life. Executive function impairment is the core manifestation of ADHD, and inhibitory control is an important part of executive function. In this study, under the inhibition control tasks, such as Go/No-go, Stroop, and Flanker, fNIRS was used to analyze the differences between children with ADHD and healthy children before and after treatment, and the changes of fNIRS in children with ADHD before and after MPH treatment. The multiple inhibition control task paradigm was used to conduct multiple analyses. These results suggest that brain activation in children with ADHD is different from that in healthy children when performing inhibitory control tasks. After 8 weeks of MPH treatment, the behavioral data of children with ADHD improved significantly in inhibition control neuropsychological tests, and the characteristic brain areas of children with ADHD improved significantly in inhibition control tasks, resembling those seen in healthy children.

Analysis of core symptoms and behavior problems in children with ADHD

In this study, the SNAP-IV scale was used to assess the severity of core symptoms in children with ADHD and was completed by parents of children according to their children's behavior in the past 6 months, with good reliability and validity. The results showed that, regarding core symptoms, the performance of inattention and hyperactivity-impulsivity in children with ADHD significantly improved after MPH treatment (P < 0.01). Currently, MPH is the preferred treatment for children with ADHD; therefore, its effect on the core symptoms is evident. In previous studies, the efficacy rate of MPH after 6 weeks of treatment was 83.3%, and the complete remission rate was 44%. In this study, 13 of the 14 children with ADHD had lower core symptom scores after 8 weeks of MPH treatment. The effective rate was 92.9%, of which six children had complete remission (42.9%), indicating that the children with ADHD in this study responded well to MPH. Therefore, exploring improvements in executive function in children with ADHD treated with MPH is important.

Analysis of executive function-related behavior treatment in children with ADHD

In this study, the BRIEF Scale was used to assess changes in executive function after MPH treatment in children with ADHD. The BRIEF scale evaluates the executive function-related performance of school-aged children in eight dimensions. This evaluation tool is closely integrated with Chinese culture and life background, has good reliability and validity, and is suitable for evaluating executive function-related behavioral performance of Chinese school-age children. In this study, after MPH treatment, the working memory and monitoring-related symptoms of children with ADHD were significantly improved (P < 0.05). Working memory mainly includes short-term memory, memory capacity, sustained attention, and anti-interference ability impairments, while monitoring is reflected in insufficient self-knowledge and the inability to arrange and coordinate tasks. Their self-control abilities were poor.

Previous studies have found that children with ADHD treated with MPH have a significant improvement in memory capacity and a decrease in behavioral scores related to memory capacity concerning working memory performance. Combined with the improvement in MPH for children's attention, the score of related dimensions of working memory in this study significantly improved, which is consistent^[11] with the results of another study. There is no relevant neuropsychological test to support the improvement of monitoring ability; however, MPH can improve the overall information-processing ability of children with ADHD. Therefore, the overall control ability of children in learning and life tasks improves, and the scores for self-control and self-knowledge-related performance decrease ^[12]. However, improvement in children's behavior regarding inhibition, conversion, emotional control, initiation, planning, and organization was not evident. According to the detailed analysis of the scale items, differences were observed among the dimensions and a certain crossover. These dimensions were significantly related to children's adaptive ability, fear of difficulty, and emotional stability and required more behavioral and psychological interventions.

Analysis of fNIRS in healthy children and children with ADHD before MDH treatment

The Go/No-go task was mainly used to reflect the response inhibition function of the tested children, in which the Go task was used to test their ability to perform operations, and the No-go task was used to test their response inhibition ability^[13]. In this study, compared with healthy children, fNIRS results in pretreated children with ADHD during the Go/No-go task suggested that channel 9 in the left medial frontal gyrus, including the frontal eye field (FEF), was located in the right posterior central gyrus, and channel 12 in the somatosensory cortex was located in the left superior marginal gyrus. Channels 21 in the superior limbic gyrus, 42 in the left superior temporal gyrus, and 42 in the auditory association cortex were more activated than those in healthy children.

The FEF controls visual attention. In the task paradigm, only a stimulus appeared at the center of the screen. The load is low in healthy children, while it may be high in children with ADHD, who require more FEF activation to maintain attention^[14]. The SC is mainly responsible for the processing of physical sensory information, and some studies have found that the SC is associated with emotional control problems in various mental disorders. The Go/No-go task used in this study was characterized by repeated problems. Children with ADHD are more impatient and anxious and may exhibit increased^[15] SC activation. The main function of the Supramarginal gyrus (SmG) is to determine the optimal operating load. With an increase in operating load, SmG activation becomes more evident^[16]. Children with ADHD have impaired response inhibition abilities, and the interfering factors before the keystroke response are more complicated. The load of choosing whether to keystroke was also higher than that in healthy children, and the degree of SmG activation was also higher. The Primary Association Cortex (PAC) is responsible for the reception, recognition, and preprocessing of auditory information. In the Go/No-go task, the field environment was relatively quiet; however, there were signals and sounds unique to the instrument markers. Children with ADHD have poor sustained attention and anti-interference abilities. They are easily disturbed by external sounds, and the PAC is more likely to be activated ^[17]. Owing to the impairment of attention, inhibition, and emotional control in children with ADHD, compensatory enhancement of FEF, SC, and SmG activation occurs when performing go/no-go tasks with a low task load and enhancement of PAC activation owing to auditory interference.

The Stroop task is a common neuropsychological paradigm that assesses children's ability to control conflicting information^[18]. Compared with other Stroop studies based on functional magnetic resonance imaging (fMRI) and fNIRS, in this study, no significant difference was observed in the activation degree of the fNIRS when performing the Stroop task between healthy children and children with ADHD before medication administration, which may be mainly owing to the incomplete curing degree of text knowledge in schoolchildren aged 7–12 years. Therefore, the degree of conflict between common sense and color is not evident^{[19,20 ]}. In the follow-up task design, the anti-Stroop task, which is more sensitive to school-age children, should be adopted to test conflict-monitoring ability in school-age children^[21].

The Flanker task is also a traditional psychological paradigm mainly used to test conflict adaptability^[22]. In this study, No significant difference was observed in the activation degree of fNIRS during the flanker task between healthy children and children with ADHD before treatment. Flanker tasks can be divided into two design methods. The first is a design whose main indicators are accuracy and response. This method is widely used in assessing preschool children's conflict adaptability; however, the sensitivity of outcome indicators is^[23] poor. The other is the pre- and post-control design, which compares the difference in behavioral data at different stages during the task and has a strong sensitivity to outcome indicators. In this study, the flanker task reference was used for design alone, and the difficulty was not significantly adjusted; therefore, no significant difference was observed in brain region activation. In a follow-up experiment, the stimulation duration, interval time, and interference intensity should be adjusted, and a before-and-after control design should be used to better detect the conflict adaptability of school-age children with ADHD.

Analysis of fNIRS before and after MPH treatment in children with ADHD

The children with ADHD enrolled in this study were 8.71 ± 1.35 years old. With increasing age, children's reaction inhibition ability gradually increased, and the difficulty of the Go/No-go task was relatively low. Therefore, the detection sensitivity of reaction inhibition ability in older children with ADHD was poor, and it was not easy to show a significant improvement in behavioral results. However, in the fNIRS results of children with ADHD after MPH treatment, channel 7 activation, located in the left middle frontal gyrus, including the frontal eye movement area, decreased, suggesting that behavioral changes could be detected using fNIRS. FEF activation was decreased in children with ADHD after MPH treatment, indicating that visual attention load and mobilization levels were reduced during Go/No-go tasks. This indicates that after MPH treatment, the brain activation of children with ADHD becomes more similar to that of healthy children when performing a response inhibition task.

The behavioral results of the Stroop task revealed that children with ADHD had a significantly improved rate of correct responses in different color-related tasks after receiving MPH treatment, indicating that their conflict-monitoring ability improved. Improvement in conflict monitoring ability can help children with ADHD process information faster, maintain attention, reduce interference from external distractions, and improve^[41] the core symptoms of children with ADHD. Therefore, MPH can improve the core symptoms and behavioral problems of children with ADHD by improving their ability to monitor conflict.

However, no significant difference was observed in the fNIRS results between the two groups, which could be attributed to two reasons. In a combined Stroop task and fMRI study, the dorsal ACC (DACC) in children with ADHD showed increased activation after MPH intervention, with no significant changes in a separate brain region. However, the DACC correlated with and affected^[21] the overall activation of the frontopolar cortex (FPC). The monitoring depth of fNIRS under the skull is approximately 1–3 cm; therefore, detecting specific changes in DACC hemoglobin or observing the correlation between DACC and FPC in various brain regions is impossible. According to current theories, after MPH treatment in children with ADHD, the control effect of the striatum on the DACC is improved, and the function of each brain region on the FPC is improved by the DACC by improving^[24] the connection properties and transmission efficiency of each brain region. However, school-age ADHD children do not have a deep impression of the solidification of general knowledge of words, and the conflict-monitoring load is low, which fails to cause definite changes in brain function. In a follow-up study, in addition to changing the Stroop task to an anti-Stroop task, which is more suitable for school-age children, increasing the brain depth and breadth measurement and exploring the two dimensions of brain activation and connectivity is necessary.

In this study, no significant differences were observed in the behavioral results of tasks in flanker and results of fNIRS monitoring of cerebral cortex blood oxygen changes before and after the MPH intervention. The main reason is that the study used the flanker task reference alone, the difficulty was not significantly adjusted, and no significant differences were observed in brain region activation. In subsequent experiments, the stimulation duration, interval time, and interference intensity should be adjusted, and a reference should be made to the before-and-after control design to better detect conflict adaptability in school-aged children with ADHD. The limitations of this study are the small number of cases, and further cases will be increased in the future.

The effectiveness and extent of executive function improvement caused by various treatments for children with ADHD remain controversial ^[25]. Neuroimaging can be used to further explore the etiology of executive dysfunction in children with ADHD by monitoring brain function. In this study, fNIRS was used to monitor the brain regions of children with ADHD after MPH intervention. MPH reduced the activation of brain regions with enhanced compensatory activation. Previous studies have shown that, after MPH intervention, the activity of brain regions develops similarly to that of healthy children ^[26]. However, there were problems with task design, difficulty, and selection in this study, and the small sample size made it impossible to stratify and type the study for different phenotypes, sexes, and ages. In subsequent experiments, the task paradigm should be adjusted, and the sample size should be expanded to include a stratified grouping design for conducting further research.

SNAP-IV, Swanson, Nolan, and Pelham IV

ADHD, Attention deficit hyperactivity disorder

BRIEF, Behavior Rating Inventory of Executive Function

fNIRS, Functional near-infrared spectroscopy

RT, Response time

ACC, Anterior cingulate cortex

PFC, Prefrontal cortex

DSM-5, Diagnostic and Statistical Manual of Mental Disorders Children with ADHD Disorders 5

fALFF, Fractional amplitude of low-frequency fluctuations

MPH, Methylphenidate

SC, Somatosensory cortex

SmG, Supramarginal gyrus

PAC, Primary Association Cortex

fMRI, Functional magnetic resonance imaging

DACC, Dorsal anterior cingulate cortex

FPC, Frontopolar cortex

FEF, Frontal eye field

Ethics approval and consent to participate

All methods were performed in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards. Parents or guardians provided informed consent. This study was approved by the Ethics Committee of the Capital Institute of Pediatrics (ethics number: SHERLL2023005).

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Conflict of interest

The authors declare that they have no competing interests.

Funding

Open-access funding was provided by the National Natural Science Foundation of China (project approval number 82271579).

Author contributions

JY organized and analyzed the data and was a major contributor to writing the manuscript. ZL and YR organized and analyzed the data. XW prepared the figure and table. GL and MT have been involved in the management of the children. JZ supervised the research and revised the manuscript. All authors read and approved the final manuscript.

Acknowledgments

We thank all the physicians, patients, and families who provided clinical information.

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31 Jul, 2024
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Functional near-infrared spectroscopy study on inhibitory control ability of children with attention deficit hyperactivity disorder with methylphenidate therapy: An experimental, longitudinal, and neuroimaging study

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Abstract

Background

Methods

Results

Conclusions

Figures

Background

Methods

Aim, design, and setting

Ethics compliance

Study population

Research methods

Statistical analysis

Results

Basic information

SNAP-IV scale results

BRIEF parent edition executive function rating scale results

Response suppression task

Conflict monitoring tasks

Conflict adaptation task

Discussion

Analysis of core symptoms and behavior problems in children with ADHD

Analysis of executive function-related behavior treatment in children with ADHD

Analysis of fNIRS in healthy children and children with ADHD before MDH treatment

Analysis of fNIRS before and after MPH treatment in children with ADHD

Conclusions

Abbreviations

Declarations

References

Status:

Version 1