Prefrontal activation during inhibitory control measured by near-infrared spectroscopy for differentiating between autism spectrum disorders and attention deficit hyperactivity disorder in adults.
ABSTRACT: The differential diagnosis of autism spectrum disorders (ASDs) and attention deficit hyperactivity disorder (ADHD) based solely on symptomatic and behavioral assessments can be difficult, even for experts. Thus, the development of a neuroimaging marker that differentiates ASDs from ADHD would be an important contribution to this field. We assessed the differences in prefrontal activation between adults with ASDs and ADHD using an entirely non-invasive and portable neuroimaging tool, near-infrared spectroscopy. This study included 21 drug-naïve adults with ASDs, 19 drug-naïve adults with ADHD, and 21 healthy subjects matched for age, sex, and IQ. Oxygenated hemoglobin concentration changes in the prefrontal cortex were assessed during a stop signal task and a verbal fluency task. During the stop signal task, compared to the control group, the ASDs group exhibited lower activation in a broad prefrontal area, whereas the ADHD group showed underactivation of the right premotor area, right presupplementary motor area, and bilateral dorsolateral prefrontal cortices. Significant differences were observed in the left ventrolateral prefrontal cortex between the ASDs and ADHD groups during the stop signal task. The leave-one-out cross-validation method using mean oxygenated hemoglobin changes yielded a classification accuracy of 81.4% during inhibitory control. These results were task specific, as the brain activation pattern observed during the verbal fluency task did not differentiate the ASDs and ADHD groups significantly. This study therefore provides evidence of a difference in left ventrolateral prefrontal activation during inhibitory control between adults with ASDs and ADHD. Thus, near-infrared spectroscopy may be useful as an auxiliary tool for the differential diagnosis of such developmental disorders.
Project description:The stimulant methylphenidate (MPX) and the nonstimulant atomoxetine (ATX) are the most commonly prescribed medications for attention deficit hyperactivity disorder (ADHD). However, no functional magnetic resonance imaging (fMRI) study has as yet investigated the effects of ATX on inhibitory or any other brain function in ADHD patients or compared its effects with those of MPX. A randomized, double-blind, placebo-controlled, crossover pharmacological design was used to compare the neurofunctional effects of single doses of MPX, ATX, and placebo during a stop task, combined with fMRI within 19 medication-naive ADHD boys, and their potential normalization effects relative to 29 age-matched healthy boys. Compared with controls, ADHD boys under placebo showed bilateral ventrolateral prefrontal, middle temporal, and cerebellar underactivation. Within patients, MPX relative to ATX and placebo significantly upregulated right ventrolateral prefrontal activation, which correlated with enhanced inhibitory capacity. Relative to controls, both drugs significantly normalized the left ventrolateral prefrontal underactivation observed under placebo, while MPX had a drug-specific effect of normalizing right ventrolateral prefrontal and cerebellar underactivation observed under both placebo and ATX. The findings show shared and drug-specific effects of MPX and ATX on performance and brain activation during inhibitory control in ADHD patients with superior upregulation and normalization effects of MPX.
Project description:Children with attention-deficit/hyperactivity disorder (ADHD) have deficits in performance monitoring often improved with the indirect catecholamine agonist methylphenidate (MPH). We used functional magnetic resonance imaging to investigate the effects of single-dose MPH on activation of error processing brain areas in medication-naive boys with ADHD during a stop task that elicits 50% error rates.Twelve medication-naive boys with ADHD were scanned twice, under either a single clinical dose of MPH or placebo, in a randomized, double-blind design while they performed an individually adjusted tracking stop task, designed to elicit 50% failures. Brain activation was compared within patients under either drug condition. To test for potential normalization effects of MPH, brain activation in ADHD patients under either drug condition was compared with that of 13 healthy age-matched boys.During failed inhibition, boys with ADHD under placebo relative to control subjects showed reduced brain activation in performance monitoring areas of dorsomedial and left ventrolateral prefrontal cortices, thalamus, cingulate, and parietal regions. MPH, relative to placebo, upregulated activation in these brain regions within patients and normalized all activation differences between patients and control subjects. During successful inhibition, MPH normalized reduced activation observed in patients under placebo compared with control subjects in parietotemporal and cerebellar regions.MPH normalized brain dysfunction in medication-naive ADHD boys relative to control subjects in typical brain areas of performance monitoring, comprising left ventrolateral and dorsomedial frontal and parietal cortices. This could underlie the amelioration of MPH of attention and academic performance in ADHD.
Project description:Previous studies on working memory (WM) function in adults with attention-deficit/hyperactivity disorder (ADHD) suggested aberrant activation of the prefrontal cortex and the cerebellum. Although it has been hypothesized that activation differences in these regions most likely reflect aberrant frontocerebellar circuits, the functional coupling of these brain networks during cognitive performance has not been investigated so far. In this study, functional magnetic resonance imaging (fMRI) and both univariate and multivariate analytic techniques were used to investigate regional activation changes and functional connectivity differences during cognitive processing in healthy controls (n = 12) and ADHD adults (n = 12). Behavioral performance during a parametric verbal WM paradigm did not significantly differ between adults with ADHD and healthy controls. During the delay period of the activation task, however, ADHD patients showed significantly less activation in the left ventrolateral prefrontal cortex (VLPFC), as well as in cerebellar and occipital regions compared with healthy control subjects. In both groups, independent component analyses revealed a functional network comprising bilateral lateral prefrontal, striatal, and cingulate regions. ADHD adults had significantly lower connectivity in the bilateral VLPFC, the anterior cingulate cortex, the superior parietal lobule, and the cerebellum compared with healthy controls. Increased connectivity in ADHD adults was found in right prefrontal regions, the left dorsal cingulate cortex and the left cuneus. These findings suggest both regional brain activation deficits and functional connectivity changes of the VLPFC and the cerebellum as well as functional connectivity abnormalities of the anterior cingulate and the parietal cortex in ADHD adults during WM processing.
Project description:Deficient response inhibition in situations involving a trade-off between response execution and response stopping is a hallmark of attention deficit hyperactive disorder (ADHD). There are two key components of response inhibition; reactive inhibition where one attempts to cancel an ongoing response and prospective inhibition is when one withholds a response pending a signal to stop. Prospective inhibition comes into play prior to the presentation of the stop signal and reactive inhibition follows the presentation of a signal to stop a particular action. The aim of this study is to investigate the neural activity evoked by prospective and reactive inhibition in adolescents with and without ADHD.Twelve adolescents with ADHD and 12 age-matched healthy controls (age range 9-18) were imaged while performing the stop signal task (SST).Reactive inhibition activated right inferior frontal gyrus (IFG) in both groups. ADHD subjects activated IFG bilaterally. In controls, prospective inhibition invoked preactivation of the same part of right IFG that activated during reactive inhibition. In ADHD subjects, prospective inhibition was associated with deactivation in this region. Controls also deactivated the medial prefrontal cortex (MPFC) during prospective inhibition, whereas ADHD subjects activated the same area.This pattern of activity changes in the same structures, but in opposite directions, was also evident across all phases of the task in various task-specific areas like the superior and middle temporal gyrus and other frontal areas.Differences between ADHD and control participants in task-specific and default mode structures (IFG and MPFC) were evident during prospective, but not during reactive inhibition.
Project description:Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders in children and affects 3 to 5% of school-aged children. This study is to demonstrate whether functional near-infrared spectroscopy (fNIRS) can detect the changes in the concentration of oxygenated hemoglobin (oxy-HB) in children with ADHD and typically developing children (TD children). Method: In this study, 14 children with ADHD and 15 TD children were studied. Metabolic signals of functional blood oxygen were recorded by using fNIRS during go/no-go task. A statistic method is used to compare the fNIRS between the ADHD children and controls. Results: A significant oxy-HB increase in the left frontopolar cortex (FPC) in control subjects but not in children with ADHD during inhibitory tasks. Moreover, ADHD children showed reduced activation in left FPC relative to TD children. Conclusion: Functional brain imaging using fNIRS showed reduced activation in the left prefrontal cortex (PFC) of children with ADHD during the inhibition task. The fNIRS could be a promising tool for differentiating children with ADHD and TD children.
Project description:BACKGROUND:Autism spectrum disorders (ASDs) involve impairments in cognitive control. In typical development (TYP), neural systems underlying cognitive control undergo substantial maturation during adolescence. Development is delayed in adolescents with ASD. Little is known about the neural substrates of this delay. METHODS:We used event-related functional magnetic resonance imaging and a cognitive control task involving overcoming a prepotent response tendency to examine the development of cognitive control in young (ages 12-15; n = 13 with ASD and n = 13 with TYP) and older (ages 16-18; n = 14 with ASD and n = 14 with TYP) adolescents with whole-brain voxelwise univariate and task-related functional connectivity analyses. RESULTS:Older ASD and TYP showed reduced activation in sensory and premotor areas relative to younger ones. The older ASD group showed reduced left parietal activation relative to TYP. Functional connectivity analyses showed a significant age by group interaction with the older ASD group exhibiting increased functional connectivity strength between the ventrolateral prefrontal cortex and the anterior cingulate cortex, bilaterally. This functional connectivity strength was related to task performance in ASD, whereas that between dorsolateral prefrontal cortex and parietal cortex (Brodmann areas 9 and 40) was related to task performance in TYP. CONCLUSIONS:Adolescents with ASD rely more on reactive cognitive control, involving last-minute conflict detection and control implementation by the anterior cingulate cortex and ventrolateral prefrontal cortex, versus proactive cognitive control requiring processing by dorsolateral prefrontal cortex and parietal cortex. Findings await replication in larger longitudinal studies that examine their functional consequences and amenability to intervention.
Project description:PURPOSE: Although flow experience is positively associated with motivation to learn, the biological basis of flow experience is poorly understood. Accumulation of evidence on the underlying brain mechanisms related to flow is necessary for a deeper understanding of the motivation to learn. The purpose of this study is to investigate the relationship between flow experience and brain function using near-infrared spectroscopy (NIRS) during the performance of a cognitive task. METHODS: Sixty right-handed occupational therapy (OT) students participated in this study. These students performed a verbal fluency test (VFT) while 2-channel NIRS was used to assess changes in oxygenated hemoglobin concentration (oxygenated hemoglobin [oxy-Hb]) in the prefrontal cortex. Soon after that, the OT students answered the flow questionnaire (FQ) to assess the degree of flow experience during the VFT. RESULTS: Average oxy-Hb in the prefrontal cortex had a significant negative correlation with the satisfaction scores on the FQ. CONCLUSION: Satisfaction during the flow experience correlated with prefrontal hemodynamic suppression. This finding may assist in understanding motivation to learn and related flow experience.
Project description:Delirium is a common and serious psychiatric syndrome caused by an underlying medical condition. It is associated with significant mortality and increased healthcare resource utilization. There are few biological markers of delirium, perhaps related to the etiologic heterogeneity of the syndrome. Functional near-infrared spectroscopy (fNIRS) is an optical topography system to measure changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the cerebral cortex. We examined whether altered cortical brain activity in delirious patients with end stage liver disease (ESLD) is detected by fNIRS. We found that the [oxy-Hb] change during the verbal fluency task (VFT) was reduced in patients with ESLD compared with healthy controls (HC) in the prefrontal and bi-temporal regions. The [oxy-Hb] change during the sustained attention task (SAT) was elevated in patients with ESLD compared to HC in the prefrontal and left temporal regions. Notably, [oxy-Hb] change in the left dorsolateral prefrontal cortex during SAT showed a positive correlation with the severity of delirium. Our results suggest that [oxy-Hb] change in the prefrontal cortex during the sustained attention task measured with fNIRS might serve as a biological marker associated with delirium in ESLD patients.
Project description:Preparing to stop an inappropriate action requires keeping in mind the task goal and using this to influence the action control system. We tested the hypothesis that different subregions of prefrontal cortex show different temporal profiles consistent with dissociable contributions to preparing-to-stop, with dorsolateral prefrontal cortex (DLPFC) representing the task goal and ventrolateral prefrontal cortex (VLPFC) implementing action control. Five human subjects were studied using electrocorticography recorded from subdural grids over right lateral frontal cortex. On each trial, a task cue instructed the subject whether stopping might be needed or not (Maybe Stop [MS] or No Stop [NS]), followed by a go cue, and on some MS trials, a subsequent stop signal. We focused on go trials, comparing MS with NS. In the DLPFC, most subjects had an increase in high gamma activity following the task cue and the go cue. In contrast, in the VLPFC, all subjects had activity after the go cue near the time of the motor response on MS trials, related to behavioral slowing, and significantly later than the DLPFC activity. These different temporal profiles suggest that DLPFC and VLPFC could have dissociable roles, with DLPFC representing task goals and VLPFC implementing action control.
Project description:Attention-deficit/hyperactivity disorder (ADHD) is associated with difficulty inhibiting impulsive, hyperactive, and off-task behavior. However, no studies have examined whether a distinct pattern of brain activity precedes inhibitory errors in typically developing (TD) children and children with ADHD. In healthy adults, increased activity in the default mode network, a set of brain regions more active during resting or internally focused states, predicts commission errors, suggesting that momentary lapses of attention are related to inhibitory failures.Event-related functional magnetic resonance imaging and a go/no-go paradigm were used to explore brain activity preceding errors in 13 children with ADHD and 17 TD controls.Comparing pre-error with pre-correct trials, TD children showed activation in the precuneus/posterior cingulate cortex and parahippocampal and middle frontal gyri. In contrast, children with ADHD demonstrated activation in the cerebellum, dorsolateral prefrontal cortex (DLPFC), and basal ganglia. Between-group comparison for the pre-error versus pre-correct contrast showed that children with ADHD showed greater activity in the cerebellum, DLPFC, and ventrolateral PFC compared with TD controls. Results of region-of-interest analysis confirmed that the precuneus/posterior cingulate cortex are more active in TD children compared with children with ADHD.These preliminary data suggest that brain activation patterns immediately preceding errors differ between children with ADHD and TD children. In TD children, momentary lapses of attention precede errors, whereas pre-error activity in children with ADHD may be mediated by different circuits, such as those involved in response selection and control.