Behavioral Inhibitory Control Research Articles

Maternal behavior predicts neural underpinnings of inhibitory control in preschoolers.

Separate lines of research have revealed that the rapid development of inhibitory control in the preschool period is closely tied to normative brain development and influenced by early mother-child interactions. One potential theory is that maternal behavior in the context of early interactions influences the neural underpinnings of inhibitory control in development, with implications for child behavior. The purpose of this paper was to examine whether maternal emotional support, measured during a mother-child problem-solving game, predicted child neural responses (frontal-central N2 event-related potential) and behavioral performance (discrimination index, d') in a go/no-go task of inhibitory control in a large, diverse sample of mother-child dyads (N=276) observed in children's last year of preschool (mean age=56months). Results of a structural equation model revealed significant direct effects from maternal emotional support to child right hemisphere frontal-central N2 responses to no-go (inhibitory control) trials; greater observed emotional support predicted larger N2 responses. Larger right hemisphere N2 responses to no-go trials were also associated with better overall observed task performance (d'). A test of indirect effects from maternal emotional support to child observed performance via right hemisphere N2 responses was significant, suggesting that underlying neurophysiology is one mechanism through which maternal emotional support is associated with a child's rapidly developing inhibitory control behavior in the preschool period. This work joins a growing literature demonstrating that caregiver behavior within a "normative" range is an important environmental factor contributing to the development of neural processes supporting child functioning.

Diagnosis of Attention Deficit Hyperactivity Disorder by Using MR Imaging and Radiomics: A Potential Tool for Clinicians.

Diagnosis of Attention Deficit Hyperactivity Disorder by Using MR Imaging and Radiomics: A Potential Tool for Clinicians.

Inhibitory Control Mediates the Association between Perceived Stress and Secure Relationship Quality.

Past research has demonstrated negative associations between exposure to stressors and quality of interpersonal relationships among children and adolescents. Nevertheless, underlying mechanisms of this association remain unclear. Chronic stress has been shown to disrupt prefrontal functioning in the brain, including inhibitory control abilities, and evidence is accumulating that inhibitory control may play an important role in secure interpersonal relationship quality, including peer problems and social competence. In this prospective longitudinal study, we examine whether changes in inhibitory control, measured at both behavioral and neural levels, mediate the association between stress and changes in secure relationship quality with parents and peers. The sample included 167 adolescents (53% males) who were first recruited at age 13 or 14 years and assessed annually three times. Adolescents’ inhibitory control was measured by their behavioral performance and brain activities, and adolescents self-reported perceived stress levels and relationship quality with mothers, fathers, and peers. Results suggest that behavioral inhibitory control mediates the association between perceived stress and adolescent’s secure relationship quality with their mothers and fathers, but not their peers. In contrast, given that stress was not significantly correlated with neural inhibitory control, we did not further test the mediation path. Our results highlight the role of inhibitory control as a process through which stressful life experiences are related to impaired secure relationship quality between adolescents and their mothers and fathers.

Early onset tobacco cigarette smokers exhibit deficits in response inhibition and sustained attention

BackgroundInitiation of cigarette smoking during adolescence coincides with structural and cognitive neuromaturation. Thus, early onset smokers (EOS; initiated <16 years old) may be at unique risk of altered development of executive function relative to late onset smokers (LOS; initiated >16 years old). This study quantified the effects of age of smoking onset on response impulsivity and inhibitory control using a novel smoking Go/NoGo task (Luijten et al., 2011). MethodsNicotine deprived adult EOS (n = 10) and LOS (n = 10) and adult healthy non-smokers (HNS; n = 10) were shown smoking-related and neutral images with either a blue (Go) or yellow (NoGo) frame. Participants were instructed to respond to blue-framed Go trials quickly and accurately, and withhold responding for yellow-framed NoGo trials. ResultsEOS made more Go response accuracy errors (p ≤ 0.02) and failed more frequently to inhibit responses to NoGo trials (p < 0.02) than LOS and HNS. EOS also made more errors in inhibiting responses to smoking-related (p ≤ 0.02) and neutral (p ≤ 0.02) NoGo trials. EOS reported greater baseline craving for cigarette smoking than LOS (p < 0.04), and craving was significantly associated with greater omission errors (p ≤ 0.04). ConclusionsEOS exhibited greater difficulty than LOS in responding accurately to Go stimuli and withholding responses to both smoking and neutral NoGo stimuli, indicating greater response impulsivity, poor attention, and deficits in response inhibition. These findings suggest that EO smoking, in particular, contributes to diminished task-related attention and inhibitory control behaviors in adulthood and provide support for the tobacco-induced neurotoxicity of adolescent cognitive development (TINACD) theory (DeBry and Tiffany, 2008).

Increased glia density in the caudate nucleus in williams syndrome: Implications for frontostriatal dysfunction in autism.

Williams syndrome (WS) is a rare neurodevelopmental disorder with a well-described, known genetic etiology. In contrast to Autism Spectrum Disorders (ASD), WS has a unique phenotype characterized by global reductions in IQ and visuospatial ability, with relatively preserved language function, enhanced reactivity to social stimuli and music, and an unusual eagerness to interact socially with strangers. A duplication of the deleted region in WS has been implicated in a subset of ASD cases, defining a spectrum of genetic and behavioral variation at this locus defined by these opposite extremes in social behavior. The hypersociability characteristic of WS may be linked to abnormalities of frontostriatal circuitry that manifest as deficits in inhibitory control of behavior. Here, we examined the density of neurons and glia in associative and limbic territories of the striatum including the caudate, putamen, and nucleus accumbens regions in Nissl stained sections in five pairs of age, sex, and hemisphere-matched WS and typically-developing control (TD) subjects. In contrast to what is reported in ASD, no significant increase in overall neuron density was observed in this study. However, we found a significant increase in the density of glia in the dorsal caudate nucleus, and in the ratio of glia to neurons in the dorsal and medial caudate nucleus in WS, accompanied by a significant increase in density of oligodendrocytes in the medial caudate nucleus. These cellular abnormalities may underlie reduced frontostriatal activity observed in WS, with implications for understanding altered connectivity and function in ASD. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 531-545, 2018.

The application of the two-choice oddball paradigm to the research of behavioral inhibitory control

Behavioral inhibitory control (BIC) refers to one’s inhibitory control of impulsive, context-inappropriate behavioral patterns, which is of vital importance to humans’ adaptation to the changing environment. Go/Nogo paradigm and Stop Signal paradigm are the two widely used paradigms for the studies of behavioral inhibitory control and its cognitive neuroscience underpinnings. In a typical Go/Nogo task, the presentation of go stimulus requires a motor response, which however should be suppressed during Nogo stimulus presentation. As a result, behavioral indicators of BIC and its inter- or intra-individual differences, in most cases, depend solely on the accuracy difference between Go and Nogo conditions, which is sometimes insensitive to inhibitory processing. Also, it is difficult to control the obscuring effects of motor preparation/execution on the interpretation of BIC-related neural activities by a simple Go-Nogo comparison. On the other hand, the stop signal paradigm uses a staircase method to vary the stop-signal delay from the go signal to the stop-signal, to manipulate participants’ successful stop and erroneous response at around 50% of the trials, respectively. This method is used to compute stop-signal reaction time (SSRT), an index considered to reflect one’s behavioral inhibitory function. However, this method sacrifices the analysis and the interpretation of accuracy data and, again, the stop-signal paradigm meets difficulty in controlling the contaminations of a preceding go stimulus processing on the neural processing of the subsequent stop signal. Based on these considerations, we introduced a novel two-choice oddball paradigm for overcoming the limitations of the above paradigms, and for the acquisition of more comprehensive and sensitive behavioral markers of BIC. Using reaction time cost (RT Cost) and accuracy cost as behavioral indexes, relevant empirical studies have shown that the new paradigm can be validly used for the psychological and cognitive neuroscience studies of BIC in the following three domains: (i) to detect inter-individual differences in BIC (e.g. sex differences) by both behavioral and neurophysiological markers; (ii) to detect intra-individual differences in BIC as a function of internal state changes (e.g. emotion); (iii) to assess the impairment and the functional plasticity of impulse inhibition in drug addiction (e.g. nicotine addiction). These evidences suggest that the two-choice oddball paradigm can be widely used to assess behavioral inhibitory function and its variability, in the broad area of psychology and cognitive neuroscience research.

Self-regulation as a predictor of patterns of change in externalizing behaviors from infancy to adolescence.

We examined associations between specific self-regulatory mechanisms and externalizing behavior patterns from ages 2 to 15 (N = 443). The relation between multiple self-regulatory indicators across multiple domains (i.e., physiological, attentional, emotional, and behavioral) at age 2 and at age 5 and group membership in four distinct externalizing trajectories was examined. By examining each of these self-regulatory processes in combination with one another, and therefore accounting for their shared variance, we aimed to better understand which specific self-regulatory skills were associated most strongly with externalizing behavioral patterns. Findings suggest that behavioral inhibitory control and emotion regulation are particularly important in distinguishing between children who show normative declines in externalizing behaviors across early childhood and those who demonstrate high levels through adolescence.

Aerobic exercise training ameliorates craving and inhibitory control in methamphetamine dependencies: A randomized controlled trial and event-related potential study

ObjectiveMethamphetamine (MA) usage has been recognized as a prominent substance-abuse issue. While exercise training reportedly improves fitness and mental status in the MA-dependent, how exercise training affects addiction and cognitive deficiency has yet to be established. The current study aimed to determine the effects of aerobic exercise training on both MA-associated cravings and inhibitory control among those with MA dependencies. DesignA 12-week randomized controlled trial. MethodSixty-two people with MA dependencies recruited through the Drug Rehabilitation Bureau were assigned to either an aerobic exercise or attentional control group, with 50 participants completing the trial. The aerobic exercise program involved three 30-min sessions of moderate-intensity exercise per week. Along with a pre-test assessment, craving levels were evaluated every three weeks, and data on neutral and MA-related inhibitory control as well as its elicited neuroelectric activation were collected at the end of the intervention. ResultsCompared with the control group, the exercise group experienced attenuated MA craving levels after 6 weeks of the exercise program, and the decreased trend was maintained until the termination of treatment. In the post-test, the exercise group also demonstrated more accuracy in behavioral inhibitory control as well as greater N2 amplitude in the Nogo condition of both the standard and MA-related tasks than those in the control group or pre-test. ConclusionsThe current study provides the first evidence that aerobic exercise training may be efficacious for MA-associated cravings and inhibitory control from behavioral and neuroelectric perspectives among MA-dependent individuals.

Inhibitory Control Processes and the Strategies That Support Them during Hand and Eye Movements.

Background and Aims: Adaptive behavior depends on the ability to voluntarily suppress context-inappropriate behaviors, a process referred to as response inhibition. Stop Signal tests (SSTs) are the most frequently studied paradigm used to assess response inhibition. Previous studies of SSTs have indicated that inhibitory control behavior can be explained using a common model in which GO and STOP processes are initiated independent from one and another, and the process that is completed first determines whether the behavior is elicited (GO process) or terminated (STOP process). Consistent with this model, studies have indicated that individuals strategically delay their behaviors during SSTs in order to increase their stopping abilities. Despite being controlled by distinct neural systems, prior studies have largely documented similar inhibitory control performance across eye and hand movements. Though, no existing studies have compared the extent to which individuals strategically delay behavior across different effectors is not yet clear. Here, we compared the extent to which inhibitory control processes and the cognitive strategies that support them during oculomotor and manual motor behaviors.Methods: We examined 29 healthy individuals who performed parallel oculomotor and manual motor SSTs. Participants also completed a separate block of GO trials administered prior to the Stop Signal tests to assess baseline reaction times for each effector and reaction time increases during interleaved GO trials of the SST.Results: Our results showed that stopping errors increased for both effectors as the interval between GO and STOP cues was increased (i.e., stop signal delay), but performance deteriorated more rapidly for eye compared to hand movements with increases in stop signal delay. During GO trials, participants delayed the initiation of their responses for each effector, and greater slowing of reaction times on GO trials was associated with increased accuracy on STOP trials for both effectors. However, participants delayed their eye movements to a lesser degree than their hand movements, and strategic reaction time slowing was a stronger determinant of stopping accuracy for hand compared to eye movements. Overall, stopping accuracies for eye and hand movements were only modestly correlated, and the time it took individuals to cancel a response was not related for eye and hand movements.Discussion and Conclusion: Our findings that GO and STOP processes are independent and that individuals strategically delay their behavioral responses to increase stopping accuracy regardless of effector indicate that inhibitory control of oculomotor and manual motor behaviors both follow common guiding principles. Yet, our findings document that eye movements are more difficult to inhibit than hand movements, and the timing, magnitude, and impact of cognitive control strategies used to support voluntary response inhibition are less robust for eye compared to hand movements. This suggests that inhibitory control systems also show unique characteristics that are behavior-dependent. This conclusion is consistent with neurophysiological evidence showing important differences in the architecture and functional properties of the neural systems involved in inhibitory control of eye and hand movements. It also suggests that characterizing inhibitory control processes in health and disease requires effector-specific analysis.

Approach and inhibition responses to external food cues among average-weight women who binge eat and weight-matched controls

Despite laboratory evidence linking impulsivity to binge-eating (BE) among people with obesity, it is unclear whether such inhibitory control deficits extend to average-weight persons who binge eat or influence actual calories consumed when such opportunities present. Towards clarifying these issues, women with higher (n = 31) and lower (n = 31) BE levels engaged in a visual Go/No-Go task comprising images of high-calorie foods, low-calorie foods, and household objects, after which they completed a self-report battery in an environment conducive to snacking. Analyses indicated these groups did not differ in task-based false alarm rates (i.e., responding when response inhibition was required) but the higher BE group reported more trait-based impulsivity, was faster and more accurate in responding to “Go” trials involving high-calorie food images, and was more likely to eat at least one snack during post-task questionnaire completion. Within the entire sample, faster “Go” trial reaction times and higher false alarm rates across image types predicted higher post-task calorie intake levels while BE status and trait impulsivity did not. In sum, average weight women who binge eat were more responsive to high calorie food cues but showed no evidence of behavioral inhibitory control deficits compared to weight-matched controls.

Evidence for superior neurobiological and behavioral inhibitory control abilities in non-offending as compared to offending pedophiles.

Neurobehavioral models of pedophilia and child sexual offending suggest a pattern of temporal and in particular prefrontal disturbances leading to inappropriate behavioral control and subsequently an increased propensity to sexually offend against children. However, clear empirical evidence for such mechanisms is still missing. Using a go/nogo paradigm in combination with functional magnetic resonance imaging (fMRI) we compared behavioral performance and neural response patterns among three groups of men matched for age and IQ: pedophiles with (N = 40) and without (N = 37) a history of hands-on sexual offences against children as well as healthy non-offending controls (N = 40). As compared to offending pedophiles, non-offending pedophiles exhibited superior inhibitory control as reflected by significantly lower rate of commission errors. Group-by-condition interaction analysis also revealed inhibition-related activation in the left posterior cingulate and the left superior frontal cortex that distinguished between offending and non-offending pedophiles, while no significant differences were found between pedophiles and healthy controls. Both areas showing distinct activation pattern among pedophiles play a critical role in linking neural networks that relate to effective cognitive functioning. Data therefore suggest that heightened inhibition-related recruitment of these areas as well as decreased amount of commission errors is related to better inhibitory control in pedophiles who successfully avoid committing hands-on sexual offences against children. Hum Brain Mapp 38:1092-1104, 2017. © 2016 Wiley Periodicals, Inc.

Changes in frontal EEG coherence across infancy predict cognitive abilities at age 3: The mediating role of attentional control.

Theoretical perspectives of cognitive development have maintained that functional integration of the prefrontal cortex across infancy underlies the emergence of attentional control and higher cognitive abilities in early childhood. To investigate these proposed relations, we tested whether functional integration of prefrontal regions across the second half of the first year predicted observed cognitive performance in early childhood 1 year prior indirectly through observed attentional control (N = 300). Results indicated that greater change in left-but not right-frontal EEG coherence between 5 and 10 months was positively associated with attentional control, cognitive flexibility, receptive language, and behavioral inhibitory control. Specifically, a larger increase in coherence between left frontal regions was positively associated with accuracy on a visual search task at Age 2, and visual search accuracy was positively associated with receptive vocabulary, performance on a set-shifting task (DCCS), and delay of gratification at Age 3. Finally, the indirect effects from the change in left frontal EEG coherence to 3-year cognitive flexibility, receptive language, and behavioral inhibitory control were significant, suggesting that internally controlled attention is a mechanism through which early neural maturation influences children's cognitive development. (PsycINFO Database Record

Response inhibition of cigarette-related cues in male light smokers: behavioral evidence using a two-choice oddball paradigm.

Behavioral inhibitory control has been shown to play an important role in a variety of addictive behaviors. A number of studies involving the use of Go/NoGo and stop-signal paradigms have shown that smokers have reduced response inhibition for cigarette-related cues. However, it is not known whether male light smokers’ response inhibition for cigarette-related cues is lower than that of non-smokers in the two-choice oddball paradigm. The objective of the current study was to provide further behavioral evidence of male light smokers’ impaired response inhibition for cigarette-related cues, using the two-choice oddball paradigm. Sixty-two male students (31 smokers, 31 non-smokers), who were recruited via an advertisement, took part in this two-choice oddball experiment. Cigarette-related pictures (deviant stimuli) and pictures unrelated to cigarettes (standard stimuli) were used. Response inhibition for cigarette-related cues was measured by comparing accuracy (ACC) and reaction time (RT) for deviant and standard stimuli in the two groups of subjects. An analysis of variance (ANOVA) showed that in all the participants, ACC was significantly lower for deviant stimuli than for standard stimuli. For deviant stimuli, the RTs were significantly longer for male light smokers than for male non-smokers; however, there was no significant difference in RTs for standard stimuli. Compared to male non-smokers, male light smokers seem to have a reduced ability to inhibit responses to cigarette-related cues.

Brain and behavioral inhibitory control of kindergartners facing negative emotions.

Inhibitory control (IC) - one of the most critical functions underlying a child's ability to self-regulate - develops significantly throughout the kindergarten years. Experiencing negative emotions imposes challenges on executive functioning and may specifically affect IC. In this study, we examined kindergartners' IC and its related brain activity during a negative emotional situation: 58 children (aged 5.5-6.5years) performed an emotion-induction Go/NoGo task. During this task, we recorded children's performance and brain activity, focusing on the fronto-central N2 component in the event-related potential (ERP) and the power of its underlying theta frequency. Compared to Go trials, inhibition of NoGo trials was associated with larger N2 amplitudes and theta power. The negative emotional experience resulted in better IC performance and, at the brain level, in larger theta power. Source localization of this effect showed that the brain activity related to IC during the negative emotional experience was principally generated in the posterior frontal regions. Furthermore, the band power measure was found to be a more sensitive index for children's inhibitory processes than N2 amplitudes. This is the first study to focus on kindergartners' IC while manipulating their emotional experience to induce negative emotions. Our findings suggest that a kindergartner's experience of negative emotion can result in improved IC and increases in associated aspects of brain activity. Our results also suggest the utility of time-frequency analyses in the study of brain processes associated with response inhibition in young children.

Inhibitory behavioral control: A stochastic dynamic causal modeling study comparing cocaine dependent subjects and controls.

Cocaine dependence is associated with increased impulsivity in humans. Both cocaine dependence and impulsive behavior are under the regulatory control of cortico-striatal networks. One behavioral laboratory measure of impulsivity is response inhibition (ability to withhold a prepotent response) in which altered patterns of regional brain activation during executive tasks in service of normal performance are frequently found in cocaine dependent (CD) subjects studied with functional magnetic resonance imaging (fMRI). However, little is known about aberrations in specific directional neuronal connectivity in CD subjects. The present study employed fMRI-based dynamic causal modeling (DCM) to study the effective (directional) neuronal connectivity associated with response inhibition in CD subjects, elicited under performance of a Go/NoGo task with two levels of NoGo difficulty (Easy and Hard). The performance on the Go/NoGo task was not significantly different between CD subjects and controls. The DCM analysis revealed that prefrontal–striatal connectivity was modulated (influenced) during the NoGo conditions for both groups. The effective connectivity from left (L) anterior cingulate cortex (ACC) to L caudate was similarly modulated during the Easy NoGo condition for both groups. During the Hard NoGo condition in controls, the effective connectivity from right (R) dorsolateral prefrontal cortex (DLPFC) to L caudate became more positive, and the effective connectivity from R ventrolateral prefrontal cortex (VLPFC) to L caudate became more negative. In CD subjects, the effective connectivity from L ACC to L caudate became more negative during the Hard NoGo conditions. These results indicate that during Hard NoGo trials in CD subjects, the ACC rather than DLPFC or VLPFC influenced caudate during response inhibition.

Inhibitory behavioral control: a stochastic dynamic causal modeling study using network discovery analysis.

This study employed functional magnetic resonance imaging (fMRI)-based dynamic causal modeling (DCM) to study the effective (directional) neuronal connectivity underlying inhibitory behavioral control. fMRI data were acquired from 15 healthy subjects while they performed a Go/NoGo task with two levels of NoGo difficulty (Easy and Hard NoGo conditions) in distinguishing spatial patterns of lines. Based on the previous inhibitory control literature and the present fMRI activation results, 10 brain regions were postulated as nodes in the effective connectivity model. Due to the large number of potential interconnections among these nodes, the number of models for final analysis was reduced to a manageable level for the whole group by conducting DCM Network Discovery, which is a recently developed option within the Statistical Parametric Mapping software package. Given the optimum network model, the DCM Network Discovery analysis found that the locations of the driving input into the model from all the experimental stimuli in the Go/NoGo task were the amygdala and the hippocampus. The strengths of several cortico-subcortical connections were modulated (influenced) by the two NoGo conditions. Specifically, connectivity from the middle frontal gyrus (MFG) to hippocampus was enhanced by the Easy condition and further enhanced by the Hard NoGo condition, possibly suggesting that compared with the Easy NoGo condition, stronger control from MFG was needed for the hippocampus to discriminate/learn the spatial pattern in order to respond correctly (inhibit), during the Hard NoGo condition.

Behavioral response inhibition in psychotic disorders: Diagnostic specificity, familiality and relation to generalized cognitive deficit

Difficulty inhibiting context-inappropriate behavior is a common deficit in psychotic disorders. The diagnostic specificity of this impairment, its familiality, and its degree of independence from the generalized cognitive deficit associated with psychotic disorders remain to be clarified. Schizophrenia, schizoaffective and bipolar patients with history of psychosis (n=523), their available first-degree biological relatives (n=656), and healthy participants (n=223) from the multi-site B-SNIP study completed a manual Stop Signal task. A nonlinear mixed model was used to fit logistic curves to success rates on Stop trials as a function of parametrically varied Stop Signal Delay. While schizophrenia patients had greater generalized cognitive deficit than bipolar patients, their deficits were similar on the Stop Signal task. Further, only bipolar patients showed impaired inhibitory control relative to healthy individuals after controlling for generalized cognitive deficit. Deficits accounted for by the generalized deficit were seen in relatives of schizophrenia and schizoaffective patients, but not in relatives of bipolar patients. In clinically stable patients with psychotic bipolar disorder, impaired inhibitory behavioral control was a specific cognitive impairment, distinct from the generalized neuropsychological impairment associated with psychotic disorders. Thus, in bipolar disorder with psychosis, a deficit in inhibitory control may contribute to risk for impulsive behavior. Because the deficit was not familial in bipolar families and showed a lack of independence from the generalized cognitive deficit in schizophrenia spectrum disorders, it appears to be a trait related to illness processes rather than one tracking familial risk factors.

Prenatal tobacco exposure and response inhibition in school-aged children: An event-related potential study

Prenatal cigarette smoke exposure (PCSE) has been linked to problems in behavioral inhibition and attention deficit hyperactivity disorder in children in several epidemiological studies. We used event-related potentials (ERPs) to examine the effects of PCSE on neural correlates of inhibitory control of behavior. In a prospective longitudinal study on child development in the Canadian Arctic, we assessed 186 Inuit children (mean age=11.3years) on a visual Go/No-go response inhibition paradigm. PCSE was assessed through maternal recall. Potential confounders were documented from a maternal interview, and exposure to neurotoxic environmental contaminants was assessed from umbilical cord and child blood samples. PCSE was not related to behavioral performance on this simple response inhibition task. Nevertheless, this exposure was associated with smaller amplitudes of the N2 and P3 components elicited by No-go stimuli, suggesting an impairment in the neural processes underlying response inhibition. Amplitude of the No-go P3 component was also inversely associated with behavioral measures of externalizing problems and hyperactivity/impulsivity in the classroom. This study is the first to report neurophysiological evidence of impaired response inhibition in school-aged children exposed to tobacco smoke in utero. Effects were found on ERP components associated with conflict processing and inhibition of a prepotent response, indicating neurophysiological deficits that may play a critical role in the attention and behavior problems observed in children with PCSE.

Adolescent alcohol exposure reduces behavioral flexibility, promotes disinhibition, and increases resistance to extinction of ethanol self-administration in adulthood.

The prefrontal cortex (PFC) is a brain region that is critically involved in cognitive function and inhibitory control of behavior, and adolescence represents an important period of continued PFC development that parallels the maturation of these functions. Evidence suggests that this period of continued development of the PFC may render it especially vulnerable to environmental insults that impact PFC function in adulthood. Experimentation with alcohol typically begins during adolescence when binge-like consumption of large quantities is common. In the present study, we investigated the effects of repeated cycles of adolescent intermittent ethanol (AIE) exposure (postnatal days 28-42) by vapor inhalation on different aspects of executive functioning in the adult rat. In an operant set-shifting task, AIE-exposed rats exhibited deficits in their ability to shift their response strategy when the rules of the task changed, indicating reduced behavioral flexibility. There were no differences in progressive ratio response for the reinforcer suggesting that AIE did not alter reinforcer motivation. Examination of performance on the elevated plus maze under conditions designed to minimize stress revealed that AIE exposure enhanced the number of entries into the open arms, which may reflect either reduced anxiety and/or disinhibition of exploratory-like behavior. In rats that trained to self-administer ethanol in an operant paradigm, AIE increased resistance to extinction of ethanol-seeking behavior. This resistance to extinction was reversed by positive allosteric modulation of mGluR5 during extinction training, an effect that is thought to reflect promotion of extinction learning mechanisms within the medial PFC. Consistent with this, CDPPB was also observed to reverse the deficits in behavioral flexibility. Finally, diffusion tensor imaging with multivariate analysis of 32 brain areas revealed that while there were no differences in the total brain volume, the volume of a subgroup of regions (hippocampus, thalamus, dorsal striatum, neocortex, and hypothalamus) were significantly different in AIE-exposed adults compared with litter-matched Control rats. Taken together, these findings demonstrate that binge-like exposure to alcohol during early to middle adolescence results in deficits in PFC-mediated behavioral control in adulthood.

Prenatal origins of temperament: fetal growth, brain structure, and inhibitory control in adolescence.

ObjectiveIndividual differences in the temperamental dimension of effortful control are constitutionally based and have been associated with an adverse prenatal developmental environment, with structural brain alterations presenting a potential mechanism. We investigated this hypothesis for anatomically defined brain regions implicated in cognitive and inhibitory motor control.MethodsTwenty-seven 15–16 year old participants with low, medium, or high fetal growth were selected from a longitudinal birth cohort to maximize variation and represent the full normal spectrum of fetal growth. Outcome measures were parent ratings of attention and inhibitory control, thickness and surface area of the orbitofrontal cortex (lateral (LOFC) and medial (MOFC)) and right inferior frontal gyrus (rIFG), and volumetric measures of the striatum and amygdala.ResultsLower birth weight was associated with lower inhibitory control, smaller surface area of LOFC, MOFC and rIFG, lower caudate volume, and thicker MOFC. A mediation model found a significant indirect effect of birth weight on inhibitory control via caudate volume.ConclusionsOur findings support a neuroanatomical mechanism underlying potential long-term consequences of an adverse fetal developmental environment for behavioral inhibitory control in adolescence and have implications for understanding putative prenatal developmental origins of externalizing behavioral problems and self-control.