TY - JOUR
T1 - Neurophysiological and behavioral effects of multisession prefrontal tDCS and concurrent cognitive remediation training in patients with autism spectrum disorder (ASD)
T2 - A double-blind, randomized controlled fNIRS study
AU - Han, Yvonne M.Y.
AU - Chan, Melody M.Y.
AU - Shea, Caroline K.S.
AU - Lai, Oscar Long hin
AU - Krishnamurthy, Karthikeyan
AU - Cheung, Mei chun
AU - Chan, Agnes S.
N1 - Funding Information:
Extensive research has shown that executive functioning (EF), a series of cognitive processes required for monitoring goal-directed behavior [9], is impaired in ASD [10]. Specifically, cognitive flexibility (CF), often defined as the capacity to adjust behaviors according to different environmental demands so that appropriate responses can be generated for goal attainment [11], has been shown to be key for ?cold? EF (i.e., EF that involves purely cognitive processing [12]), and contributes to the behavioral manifestation of ASD individuals [13]. Daily examples of CF, such as updating one's beliefs when facing new information and shifting from one conversation to another [14], are impaired in these individuals. Furthermore, Ewing et al. [15] reported that children with ASD demonstrated reduced perceptual updating of faces, while Mo et al. [16] revealed that children with ASD have problems disengaging from and shifting between the social and nonsocial visual stimuli. More importantly, a number of studies have demonstrated that CF deficits are associated with impaired social interaction skills such as emotion recognition, which is regarded as ?hot? EF (i.e., EF that involves affective processing [12]). For example, using a variant of the Wisconsin Card Sorting Test (WCST), Fabio et al. [17] showed that the performance of children with ASD decreased after the card sorting rule had changed, and this impaired performance was positively correlated with impaired emotion recognition abilities. Moreover, Strang et al. [18] showed that slower performance on the Trail Making Test (which involves rule switching) significantly correlated with more inflexible behaviors in daily life. In addition, using the Cambridge Neuropsychological Test Automated Battery (CANTAB) multitasking test (MTT), Krishnamurthy et al. [19] demonstrated that children with ASD produced more errors than TD controls after the rule changed. Taken together, these studies support the notion that both cold and hot EF are impaired in ASD, and these impairments are mediated by individuals' speed of processing during task performance.Although the exact neurophysiological mechanism by which ASD influences EF and overall social functioning remains unclear, a prominent theory postulates that an excitation-inhibition (E:I) imbalance in local neural networks that support cognitive and affective processes impedes global brain signaling; thus, individuals with ASD may experience difficulties in modulating flexible and goal-directed behaviors [ 20?22]. Converging evidence from multiple neurophysiological and neuroimaging studies has shown that an E:I imbalance is evident in different regions of the prefrontal cortex (PFC) in ASD. Notably, a magnetic resonance spectroscopy (MRS) study reported that ASD individuals had a higher E:I ratio due to a higher glutamate concentration in the left frontal cortex but not the right frontal cortex [23]. Moreover, neurophysiological studies have shown that the heightened E:I ratio in ASD is specifically found in the left dorsolateral prefrontal cortex (dlPFC) during ?cold? EF tasks [24] and that this heightened E:I ratio is modifiable by repeated inhibitory (low-frequency) transcranial magnetic stimulation [25,26]. Another resting-state neuroimaging study showed that a higher E:I ratio was also evident in the ventromedial PFC (vmPFC) in ASD [27]; a higher E:I ratio in this region has been associated with decreased inhibitory neurotransmitter gamma-aminobutyric acid (GABA) functioning [28] and impaired synaptic information processing and social behavior in rodent ASD models [29]. The local E:I ratio has recently been shown to play a major role in the organization of resting-state functional connectivity (rsFC [30]). Specifically, Gu et al. [31] have shown that a higher regional E:I ratio is associated with lower functional connectivity within the default mode network (DMN), a network with medial PFC as a core hub [32,33], which supports CF [14] and social-cognitive functions [34]. Structural and functional alterations in individuals with ASD were found to be associated with social-cognitive dysfunctions in these individuals [21].Health and Medical Research Fund (HMRF06173096)This study was supported by the Health and Medical Research Fund (HMRF06173096) from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region. The authors would like to thank Ms. Coco Choi for her efforts in assisting with subject recruitment and data collection, Mr. Ming Chung Chan for his efforts in data collection, and the participants and their parents who enrolled in this study.
Funding Information:
This study was supported by the Health and Medical Research Fund ( HMRF06173096 ) from the Food and Health Bureau , The Government of the Hong Kong Special Administrative Region. The authors would like to thank Ms. Coco Choi for her efforts in assisting with subject recruitment and data collection, Mr. Ming Chung Chan for his efforts in data collection, and the participants and their parents who enrolled in this study.
Publisher Copyright:
© 2022 The Authors
PY - 2022/3/1
Y1 - 2022/3/1
N2 - Background: The clinical effects and neurophysiological mechanisms of prefrontal tDCS and concurrent cognitive remediation training in individuals with autism spectrum disorder (ASD) remain unclear. Objective: This two-armed, double-blind, randomized, sham-controlled trial aimed to investigate the beneficial effects of tDCS combined with concurrent cognitive remediation training on adolescents and young adults with ASD. Methods: Participants were randomly assigned to either active or sham tDCS groups and received 1.5 mA prefrontal tDCS with left dorsolateral prefrontal cortex (dlPFC) cathode placement and right supraorbital region anode placement for 20 minutes over two consecutive weeks. tDCS was delivered concurrently with a computerized cognitive remediation training program. Social functioning and its underlying cognitive processes, as well as prefrontal resting-state functional connectivity (rsFC), were measured. Results: The results from 41 participants indicated that multisession prefrontal tDCS, compared to sham tDCS, significantly enhanced the social functioning of ASD individuals [F(1,39) = 4.75, p =.035, ηp2 = 0.11]. This improvement was associated with enhanced emotion recognition [F(1,39) = 8.34, p =.006, ηp2 = 0.18] and cognitive flexibility [F(1,39) = 4.91, p =.033, ηp2 = 0.11]. Specifically, this tDCS protocol optimized information processing efficiency [F(1,39) = 4.43, p =.042, ηp2 = 0.10], and the optimization showed a trend to be associated with enhanced rsFC in the right medial prefrontal cortex (ρ = 0.339, pFDR =.083). Conclusion: Multisession tDCS with left dlPFC cathode placement and right supraorbital region anode placement paired with concurrent cognitive remediation training promoted social functioning in individuals with ASD. This appeared to be associated with the enhancement of the functional connectivity of the right medial PFC, a major hub for flexible social information processing, allowing these individuals to process information more efficiently in response to different social situations. Trial registration: ClinicalTrials.gov (ID: NCT03814083)
AB - Background: The clinical effects and neurophysiological mechanisms of prefrontal tDCS and concurrent cognitive remediation training in individuals with autism spectrum disorder (ASD) remain unclear. Objective: This two-armed, double-blind, randomized, sham-controlled trial aimed to investigate the beneficial effects of tDCS combined with concurrent cognitive remediation training on adolescents and young adults with ASD. Methods: Participants were randomly assigned to either active or sham tDCS groups and received 1.5 mA prefrontal tDCS with left dorsolateral prefrontal cortex (dlPFC) cathode placement and right supraorbital region anode placement for 20 minutes over two consecutive weeks. tDCS was delivered concurrently with a computerized cognitive remediation training program. Social functioning and its underlying cognitive processes, as well as prefrontal resting-state functional connectivity (rsFC), were measured. Results: The results from 41 participants indicated that multisession prefrontal tDCS, compared to sham tDCS, significantly enhanced the social functioning of ASD individuals [F(1,39) = 4.75, p =.035, ηp2 = 0.11]. This improvement was associated with enhanced emotion recognition [F(1,39) = 8.34, p =.006, ηp2 = 0.18] and cognitive flexibility [F(1,39) = 4.91, p =.033, ηp2 = 0.11]. Specifically, this tDCS protocol optimized information processing efficiency [F(1,39) = 4.43, p =.042, ηp2 = 0.10], and the optimization showed a trend to be associated with enhanced rsFC in the right medial prefrontal cortex (ρ = 0.339, pFDR =.083). Conclusion: Multisession tDCS with left dlPFC cathode placement and right supraorbital region anode placement paired with concurrent cognitive remediation training promoted social functioning in individuals with ASD. This appeared to be associated with the enhancement of the functional connectivity of the right medial PFC, a major hub for flexible social information processing, allowing these individuals to process information more efficiently in response to different social situations. Trial registration: ClinicalTrials.gov (ID: NCT03814083)
KW - Autism
KW - Cognitive
KW - fNIRS
KW - RCT
KW - Social
KW - tDCS
UR - http://www.scopus.com/inward/record.url?scp=85125124147&partnerID=8YFLogxK
U2 - 10.1016/j.brs.2022.02.004
DO - 10.1016/j.brs.2022.02.004
M3 - Journal article
C2 - 35181532
AN - SCOPUS:85125124147
SN - 1935-861X
VL - 15
SP - 414
EP - 425
JO - Brain Stimulation
JF - Brain Stimulation
IS - 2
ER -