Reduced temporal and spatial stability of neural activity patterns predict cognitive control deficits in children with ADHD

Abstract

This study explores the neural underpinnings of cognitive control deficits in ADHD, focusing on overlooked aspects of trial-level variability of neural coding. We employed a novel computational approach to neural decoding on a single-trial basis alongside a cued stop-signal task which allowed us to distinctly probe both proactive and reactive cognitive control. Typically developing (TD) children exhibited stable neural response patterns for efficient proactive and reactive dual control mechanisms. However, neural coding was compromised in children with ADHD. Children with ADHD showed increased temporal variability and diminished spatial stability in neural responses in salience and frontal-parietal network regions, indicating disrupted neural coding during both proactive and reactive control. Moreover, this variability correlated with fluctuating task performance and with more severe symptoms of ADHD. These findings underscore the significance of modeling single-trial variability and representational similarity in understanding distinct components of cognitive control in ADHD, highlighting new perspectives on neurocognitive dysfunction in psychiatric disorders.

Keywords: ADHD; proactive control; reactive control; representational similarity analysis; stability; variability.

Figure 1.. Experimental design, analysis pipeline, and hypotheses.

a. CSST paradigm involved Certain Go, Uncertain Go and Stop trials. b. Dual control model decomposed reactive control and proactive control processes in the CSST. c. We hypothesized that children with ADHD will show higher temporal variability and lower spatial stability of trial-evoked brain responses than TD children. d. The Gaussian model was applied to assess temporal variability of trial-evoked neural responses. e. Representational similarity analysis (RSA) was used to examine spatial stability of trial-evoked activation patterns. f. ICP index was computed to measure the extent to which proactive control was implemented in Certain and Uncertain Go trials, which modulates trial-wise behavioral fluctuation. g. Inter-subject pattern similarity analysis was used to investigate group-specificity of neural coding during proactive and reactive control. h. Core regions of interests (ROIs) in the salience and frontal-parietal network, defined from an independent meta-analysis study (Shirer et al., 2012). CSST, stop-signal task; SSD, stop-signal delay; SSRT: stop-signal reaction time; ICP: inhibitory control pattern; rAI, right anterior insula; dmPFC, dorsal medial prefrontal cortex; rdlPFC, right dorsal lateral prefrontal cortex; rPPC, right posterior parietal cortex; RT: reaction time; RSA: representational similarity analysis.

Figure 2.. Heightened temporal variability of neural responses in children with ADHD.

a. Children with ADHD showed significantly greater variability, measured using standard deviation (std), than typically developing (TD) controls (p<0.05, corrected). b. Children with ADHD also showed significantly greater kurtosis than TD children (p<0.05, corrected). std: standard deviation.

Figure 3.. Weakened spatial stability of trial-evoked neural responses in children with ADHD.

a. Typically developing (TD) children showed greater spatial stability than children with ADHD in salience and frontoparietal networks during Uncertain Go, Certain Go and SuccStop trials. b. Highly stable recruitment of salience and frontoparietal networks during proactive and reactive control was found in TD children (p<0.05, corrected) but not in children with ADHD.

Figure 4.. Atypical neural dynamics underlie impaired behavioral regulation in children ADHD.

a. Inhibitory control pattern (ICP) index of the salience and frontoparietal networks during Certain and Uncertain Go trials modulates trial-wise reaction time (RT) in TD children and children with ADHD (p<0.05, corrected). b. TD children demonstrated significantly greater association between ICP index of ROIs from the salience network and trial-wise RT fluctuation than children with ADHD (p<0.05, corrected). c. Data from an exemplary participant illustrated a positive association between ICP of the dmPFC and RT. dmPFC: dorsomedial prefrontal cortex.

Figure 5.. Heterogeneity of trial-evoked neural responses in children with ADHD.

a. Within-group inter-subject spatial pattern stability analyses revealed between group differences during Certain Go, Uncertain Go and Stop trials (p<0.05, corrected). b. Within-group inter-subject spatial pattern stability during proactive and reactive control. c. Group-specificity of inter-subject spatial pattern similarity analyses revealed more heterogeneous trial-evoked neural response during proactive and reactive control in children with ADHD than typically developing (TD) children (p<0.05, corrected).

Figure 6.. Neural variability of the rAI predicts ADHD symptom severity.

ADHD-like activation pattern during proactive control in the right anterior insula (rAI) was significantly correlated with inattention scores (r=0.436, p=0.007).