Intracranial EEG reveals a time- and frequency-specific role for the right inferior frontal gyrus and primary motor cortex in stopping initiated responses.

Inappropriate response tendencies may be stopped via a specific fronto/basal ganglia/primary motor cortical network. We sought to characterize the functional role of two regions in this putative stopping network, the right inferior frontal gyrus (IFG) and the primary motor cortex (M1), using electocorticography from subdural electrodes in four patients while they performed a stop-signal task. On each trial, a motor response was initiated, and on a minority of trials a stop signal instructed the patient to try to stop the response. For each patient, there was a greater right IFG response in the beta frequency band ( approximately 16 Hz) for successful versus unsuccessful stop trials. This finding adds to evidence for a functional network for stopping because changes in beta frequency activity have also been observed in the basal ganglia in association with behavioral stopping. In addition, the right IFG response occurred 100-250 ms after the stop signal, a time range consistent with a putative inhibitory control process rather than with stop-signal processing or feedback regarding success. A downstream target of inhibitory control is M1. In each patient, there was alpha/beta band desynchronization in M1 for stop trials. However, the degree of desynchronization in M1 was less for successfully than unsuccessfully stopped trials. This reduced desynchronization on successful stop trials could relate to increased GABA inhibition in M1. Together with other findings, the results suggest that behavioral stopping is implemented via synchronized activity in the beta frequency band in a right IFG/basal ganglia network, with downstream effects on M1.

Being optimally aroused matters: Effects of a weak stress manipulation on children’s executive functions are moderated by temperament and age

We tested a core assumption of the bidirectional model of executive function (EF) (Blair & Ursache, 2011) indicating that EF is dependent on arousal. From a bottom-up perspective the performance on EF tasks is assumed to be curvilinearly related to arousal, with very high or low levels of arousal impairing EF. N = 107 4-and 6-year-olds’ performance on EF tasks was explored as a function of a weak stress manipulation aiming to raise children’s emotional arousal. EF (Stroop, Flanker, Go/no-go, and Backwards Color Recall) was assessed and stress was induced in half of the children by imposing a mild social evaluative threat. Furthermore, children’s temperament was assessed as a potential moderator. We found that stress effects on children’s EF performance were moderated by age and temperament: 4-year-olds with high Inhibitory Control and high Attentional Focusing were negatively affected by the stressor. However, it is unclear whether these effects were mediated by self-reported arousal. Our findings disconfirmed the hypotheses that adverse effects of the stressor are particularly high in children high on emotional reactivity aspects of temperament and low on self-regulatory aspects of temperament. Further, 6-year-olds did not show any stress effects. Results will be discussed within the framework of the Yerkes-Dodson law and with regard to stress manipulations in children.

The association between implicit alcohol attitudes and drinking behavior is moderated by baseline activation in the lateral prefrontal cortex

OBJECTIVE Intense alcohol consumption is a risk factor for a number of health problems. Dual-process models assume that self-regulatory behavior such as drinking alcohol is guided by both reflective and impulsive processes. Evidence suggests that (a) impulsive processes such as implicit attitudes are more strongly associated with behavior when executive functioning abilities are low, and (b) higher neural baseline activation in the lateral prefrontal cortex (PFC) is associated with better inhibitory control. The present study integrates these 2 strands of research to investigate how individual differences in neural baseline activation in the lateral PFC moderate the association between implicit alcohol attitudes and drinking behavior. METHOD Baseline cortical activation was measured with resting electroencephalography (EEG) in 89 moderate drinkers. In a subsequent behavioral testing session they completed measures of implicit alcohol attitudes and self-reported drinking behavior. RESULTS Implicit alcohol attitudes were related to self-reported alcohol consumption. Most centrally, implicit alcohol attitudes were more strongly associated with drinking behavior in individuals with low as compared with high baseline activation in the right lateral PFC. CONCLUSIONS These findings are in line with predictions made on the basis of dual-process models. They provide further evidence that individual differences in neural baseline activation in the right lateral PFC may contribute to executive functioning abilities such as inhibitory control. Moreover, individuals with strongly positive implicit alcohol attitudes coupled with a low baseline activation in the right lateral PFC may be at greater risk of developing unhealthy drinking patterns than others.

Hypothalamic feedforward inhibition of thalamocortical network controls arousal and consciousness.

During non-rapid eye movement (NREM) sleep, synchronous synaptic activity in the thalamocortical network generates predominantly low-frequency oscillations (<4 Hz) that are modulated by inhibitory inputs from the thalamic reticular nucleus (TRN). Whether TRN cells integrate sleep-wake signals from subcortical circuits remains unclear. We found that GABA neurons from the lateral hypothalamus (LHGABA) exert a strong inhibitory control over TRN GABA neurons (TRNGABA). We found that optogenetic activation of this circuit recapitulated state-dependent changes of TRN neuron activity in behaving mice and induced rapid arousal during NREM, but not REM, sleep. During deep anesthesia, activation of this circuit induced sustained cortical arousal. In contrast, optogenetic silencing of LHGABA-TRNGABA transmission increased the duration of NREM sleep and amplitude of delta (1-4 Hz) oscillations. Collectively, these results demonstrate that TRN cells integrate subcortical arousal inputs selectively during NREM sleep and may participate in sleep intensity.

Selective effects of methylphenidate in attention deficit hyperactivity disorder: A functional magnetic resonance study

Functional MRI revealed differences between children with Attention Deficit Hyperactivity Disorder (ADHD) and healthy controls in their frontal–striatal function and its modulation by methylphenidate during response inhibition. Children performed two go/no-go tasks with and without drug. ADHD children had impaired inhibitory control on both tasks. Off-drug frontal–striatal activation during response inhibition differed between ADHD and healthy children: ADHD children had greater frontal activation on one task and reduced striatal activation on the other task. Drug effects differed between ADHD and healthy children: The drug improved response inhibition in both groups on one task and only in ADHD children on the other task. The drug modulated brain activation during response inhibition on only one task: It increased frontal activation to an equal extent in both groups. In contrast, it increased striatal activation in ADHD children but reduced it in healthy children. These results suggest that ADHD is characterized by atypical frontal–striatal function and that methylphenidate affects striatal activation differently in ADHD than in healthy children.

An anatomical substrate for experience-dependent plasticity of the rat barrel field cortex.

The objective of this study was to examine the influence of sensory experience on the synaptic circuitry of the cortex. For this purpose, the quantitative distribution of the overall and of the gamma-aminobutyric acid (GABA) population of synaptic contacts was investigated in each layer of the somatosensory barrel field cortex of rats which were sensory deprived from birth by continuously removing rows of whiskers. Whereas there were no statistically significant changes in the quantitative distribution of the overall synaptic population, the number and proportion of GABA-immunopositive synaptic contacts were profoundly altered in layer IV of the somatosensory cortex of sensory-deprived animals. These changes were attributable to a specific loss of as many as two-thirds of the GABA contacts targeting dendritic spines. Thus, synaptic contacts made by GABA terminals in cortical layer IV and, in particular, those targeting dendritic spines represent a structural substrate of experience-dependent plasticity. Furthermore, since in this model of cortical plasticity the neuronal receptive-field properties are known to be affected, we propose that the inhibitory control of dendritic spines is essential for the elaboration of these functional properties.

Proactive and reactive inhibition during overt and covert actions. An electrical neuroimaging study.

Response inhibition is the ability to suppress inadequate but automatically activated, prepotent or ongoing response tendencies. In the framework of motor inhibition, two distinct operating strategies have been described: “proactive” and “reactive” control modes. In the proactive modality, inhibition is recruited in advance by predictive signals, and actively maintained before its enactment. Conversely, in the reactive control mode, inhibition is phasically enacted after the detection of the inhibitory signal. To date, ample evidence points to a core cerebral network for reactive inhibition comprising the right inferior frontal gyrus (rIFG), the presupplementary motor area (pre-SMA) and the basal ganglia (BG). Moreover, fMRI studies showed that cerebral activations during proactive and reactive inhibition largely overlap. These findings suggest that at least part of the neural network for reactive inhibition is recruited in advance, priming cortical regions in preparation for the upcoming inhibition. So far, proactive and reactive inhibitory mechanisms have been investigated during tasks in which the requested response to be stopped or withheld was an “overt” action execution (AE) (i.e., a movement effectively performed). Nevertheless, inhibitory mechanisms are also relevant for motor control during “covert actions” (i.e., potential motor acts not overtly performed), such as motor imagery (MI). MI is the conscious, voluntary mental rehearsal of action representations without any overt movement. Previous studies revealed a substantial overlap of activated motor-related brain networks in premotor, parietal and subcortical regions during overtly executed and imagined movements. Notwithstanding this evidence for a shared set of cerebral regions involved in encoding actions, whether or not those actions are effectively executed, the neural bases of motor inhibition during MI, preventing covert action from being overtly performed, in spite of the activation of the motor system, remain to be fully clarified. Taking into account this background, we performed a high density EEG study evaluating cerebral mechanisms and their related sources elicited during two types of cued Go/NoGo task, requiring the execution or withholding of an overt (Go) or a covert (MI) action, respectively. The EEG analyses were performed in two steps, with different aims: 1) Analysis of the “response phase” of the cued overt and covert Go/NoGo tasks, for the evaluation of reactive inhibitory control of overt and covert actions. 2) Analysis of the “preparatory phase” of the cued overt and covert Go/NoGo EEG datasets, focusing on cerebral activities time-locked to the preparatory signals, for the evaluation of proactive inhibitory mechanisms and their related neural sources. For these purposes, a spatiotemporal analysis of the scalp electric fields was applied on the EEG data recorded during the overt and covert Go/NoGo tasks. The spatiotemporal approach provide an objective definition of time windows for source analysis, relying on the statistical proof that the electric fields are different and thus generated by different neural sources. The analysis of the “response phase” revealed that key nodes of the inhibitory circuit, underpinning inhibition of the overt movement during the NoGo response, were also activated during the MI enactment. In both cases, inhibition relied on the activation of pre-SMA and rIFG, but with different temporal patterns of activation in accord with the intended “covert” or “overt” modality of motor performance. During the NoGo condition, the pre-SMA and rIFG were sequentially activated, pointing to an early decisional role of pre-SMA and to a later role of rIFG in the enactment of inhibitory control of the overt action. Conversely, a concomitant activation of pre-SMA and rIFG emerged during the imagined motor response. This latter finding suggested that an inhibitory mechanism (likely underpinned by the rIFG), could be prewired into a prepared “covert modality” of motor response, as an intrinsic component of the MI enactment. This mechanism would allow the rehearsal of the imagined motor representations, without any overt movement. The analyses of the “preparatory phase”, confirmed in both overt and covert Go/NoGo tasks the priming of cerebral regions pertaining to putative inhibitory network, reactively triggered in the following response phase. Nonetheless, differences in the preparatory strategies between the two tasks emerged, depending on the intended “overt” or “covert” modality of the possible incoming motor response. During the preparation of the overt Go/NoGo task, the cue primed the possible overt response programs in motor and premotor cortex. At the same time, through preactivation of a pre-SMA-related decisional mechanism, it triggered a parallel preparation for the successful response selection and/or inhibition during the subsequent response phase. Conversely, the preparatory strategy for the covert Go/NoGo task was centred on the goal-oriented priming of an inhibitory mechanism related to the rIFG that, being tuned to the instructed covert modality of the motor performance and instantiated during the subsequent MI enactment, allowed the imagined response to remain a potential motor act. Taken together, the results of the present study demonstrate a substantial overlap of cerebral networks activated during proactive recruitment and subsequent reactive enactment of motor inhibition in both overt and covert actions. At the same time, our data show that preparatory cues predisposed ab initio a different organization of the cerebral areas (in particular of the pre-SMA and rIFG) involved with sensorimotor transformations and motor inhibitory control for executed and imagined actions. During the preparatory phases of our cued overt and covert Go/NoGo tasks, the different adopted strategies were tuned to the “how” of the motor performance, reflecting the intended overt and covert modality of the possible incoming action.

Estudo das relações entre maus tratos na infância, prejuízo em funções executivas e transtornos do comportamento disruptivo em uma amostra comunitária de crianças

Evidências apontam para forte relação independente entre maus tratos na infância, comportamentos disruptivos e prejuízos em funções executivas. No entanto, ainda não é completamente compreendido como estes três fatores se relacionam entre si. Esta pesquisa avaliou a relação entre maus-tratos na infância e transtornos do comportamento disruptivo, testando desempenho em funções executivas como possível mediador e moderador desta relação. A presente pesquisa está inserida no estudo \"Coorte de escolares de alto risco para o desenvolvimento de psicopatologia e resiliência na infância e adolescência - projeto Prevenção\", projeto integrante do Instituto Nacional de Ciência e Tecnologia de Psiquiatria do Desenvolvimento para Infância e Adolescência (INCT-INPD), o qual incluiu 2500 crianças em idade escolar de São Paulo e Porto Alegre (Brasil). As crianças foram extensamente avaliadas com entrevistas diagnósticas, relatos de pais e da própria criança sobre maus tratos e com testes neuropsicológicos. Resultados indicam associação de maus tratos na infância e transtornos do comportamento disruptivo, porém não foi encontrada associação entre maus tratos e funções executivas. Crianças com transtornos do comportamento disruptivo apresentaram pior desempenho em teste específico para avaliação de flexibilidade cognitiva. Desempenho em funções executivas não agiu como mediador ou moderador da associação entre maus tratos e transtornos do comportamento disruptivo. Desta forma, os resultados indicam que a associação entre experiências de maus tratos e transtornos do comportamento disruptivo ocorre independentemente do desempenho em funções executivas. Futuros estudos longitudinais são fundamentais para confirmar estes resultados e elucidar os mecanismos cognitivos envolvidos nesta associação causal

Étude des liens entre l’orientation mentale paternelle et le développement des manifestations morales à l’âge préscolaire

Essai présenté à la Faculté des arts et des sciences en vue de l’obtention du doctorat en psychologie (D.Psy.)

Theory of mind and relational complexity

Cognitive complexity and control theory and relational complexity theory attribute developmental changes in theory of mind (TOM) to complexity. In 3 studies, 3-, 4-, and 5-year-olds performed TOM tasks (false belief, appearance-reality), less complex connections (Level 1 perspective-taking) tasks, and transformations tasks (understanding the effects of location changes and colored filters) with content similar to TOM. There were also predictor tasks at binary-relational and ternary-relational complexity levels, with different content. Consistent with complexity theories: (a) connections and transformations were easier and mastered earlier than TOM; (b) predictor tasks accounted for more than 80% of age-related variance in TOM; and (c) ternary-relational items accounted for TOM variance, before and after controlling for age and binary-relational items. Prediction did not require hierarchically structured predictor tasks.

Genetic influences on cognitive processes associated with distraction: An event-related potential study of the slow wave

The efficiency of inhibitory control processes has been proposed as a mechanism constraining working-memory capacity. In order to investigate genetic influences on processes that may reflect interference control, event-related potential (ER-P) activity recorded at frontal sites, during distracting and nondistracting conditions of a working-memory task, in a sample of 509 twin pairs was examined. The ERP component of interest was the slow wave (SW). Considerable overlap in source of genetic influence was found, with a common genetic factor accounting for 37 - 45% of SW variance irrespective of condition. However, 3 - 8 % of SW variance in the distracting condition was influenced by an independent genetic source. These results suggest that neural responses to irrelevant and distracting information, that may disrupt working-memory performance, differ in a fundamental way from perceptual and memory-based processing in a working-memory task. Furthermore, the results are consistent with the view that cognition is a complex genetic trait influenced by numerous genes of small influence.

Intentional forgetting in depressed states

The aim of this thesis was to extend previous research on intentional forgetting in depressed states. The first experiment used the think/no-think paradigm, and found that although dysphoric individuals were significantly worse at suppressing emotional (positive and negative) words than non-dysphoric individuals, both groups were unsuccessful at direct thought suppression. However, there was no effect of rumination on dysphoric individuals' ability to intentionally forget material. Furthermore, there was also no group differences in attentional measures of Stroop and IDEO. The second experiment involved modifying the TNT task, by including the use of substitute words in the suppression phase, in order to determine whether recalling substitute words during suppression would increase the level of forgetting. The findings from the study revealed that both dysphoric and non-dysphoric individuals were successful at intentionally forgetting neutral words using a thought substitution strategy. However, both groups were impaired at suppressing words in the direct thought substitution condition. The third experiment investigated the influence of thought substitution on intentional forgetting of emotional words in dysphoria. The study replicated experiment two, but used emotional (i.e. positive and depression-relevant) words instead of neutral words. The study found that dysphoric individuals were still impaired in their ability to suppress emotional material. Furthermore, dysphoric individuals were recalling significantly more depression­ relevant respond and previously-suppressed words. The fourth experiment examined the role of executive control in intentional forgetting. In the study, dysphoric and non­ dysphoric participants were categorised as having good or poor executive control based on their scores on the operation span with words task (OSPAN). The study found that non-dysphoric individuals with good control demonstrated successful suppression. However, dysphoric individuals with good control were unsuccessful at suppression. The fifth experiment investigated whether experimentally induced changes in mood state would alter an individual's ability to intentionally forget emotional material. Non-dysphoric healthy participants were given a positive or negative autobiographical memory and music mood induction. They completed two modified think/no-think tasks, one prior to the mood induction and one after the mood induction. The study found that transient negative mood state impaired intentional forgetting of depression-relevant material. Summary: Taken together, the findings suggest that individuals in a depressed mood are impaired in their ability to intentionally forget emotional material, even with the use of a thought substitution strategy. Furthermore, the findings implicate poor executive control and negative mood state in impaired intentional forgetting. An important theme emerging from the findings was the role of an inhibitory mechanism in intentional forgetting. The findings reported in this thesis suggest that thought substitution involves engaging an inhibitory control mechanism that contributes to successful intentional forgetting. The findings have clear implications on depressed individuals everyday functioning, and suggest that even with the presence of effective distraction, dysphoric indivduals are imapired in their ability to suppress emotional material. Furthermore, it is suggested that impaired intentional forgetting of emotional material may contribute to the maintenance of depressed mood, and could potentially worsen ongoing depression.

Autonomic, biometric and oculomotor correlates of myopia in young adults

The principal work reported in this thesis is the examination of autonomic profile of ciliary muscle innervation as a risk factor in myopia development. Deficiency in sympathetic inhibitory control of accommodation has been proposed as a contributory factor in the development of late onset myopia (LOM). Complementary measurements of ocular biometry, oculomotor function and dynamic accommodation response were carried out on the same subject cohort, thus allowing cross-correlation of these factors with. autonomic profile. Subjects were undergraduate and postgraduate students of Aston University. A 2.5 year longitudinal study of refractive error progression in 40 subjects revealed the onset of LOM in 10, initially emmetropic, young adult subjects (age range 18-24 years) undertaking substantial amounts of near work. A controlled, double blind experimental protocol was conducted concurrently to measure post-task open-loop accommodative regression following distance (0 D) or near (3 D above baseline tonic accommodation) closed-loop tasks of short (10 second) or long (3 minute) duration. Closed-loop tasks consisted of observation of a high contrast Maltese cross target; open-loop conditions were imposed by observation of a 0.2 c/deg Difference of Gaussian target. Accommodation responses were recorded continuously at 42 Hz using a modified Shin-Nippon SRW-5000 open-view infra-red optometer. Blockade of the sympathetic branch of accommodative control was achieved by topical instillation of the non-selective b-adrenoceptor antagonist timolol maleate. Betaxolol hydrochloride (non-selective b1-adrenoceptor antagonist) and normal saline were employed as control agents. Retarded open-loop accommodative regression under b2 blockade following the 3 minute near task indicated the presence of sympathetic facility. Sympathetic inhibitory facility in accommodation control was found in similar proportions between LOM and stable emmetropic subjects. A cross-sectional study (N=60) of autonomic profile showed that sympathetic innervation of ciliary muscle is present in similar proportions between emmetropes, early-, and late-onset myopes. Sympathetic facility was identified in 27% of emmetropes, 21% of EOMs and 29% of LOMs.

Familial and disease specific abnormalities in the neural correlates of the Stroop Task in Bipolar Disorder

Patients with Bipolar Disorder (BD) perform poorly on tasks of selective attention and inhibitory control. Although similar behavioural deficits have been noted in their relatives, it is yet unclear whether they reflect dysfunction in the same neural circuits. We used functional magnetic resonance imaging and the Stroop Colour Word Task to compare task related neural activity between 39 euthymic BD patients, 39 of their first-degree relatives (25 with no Axis I disorders and 14 with Major Depressive Disorder) and 48 healthy controls. Compared to controls, all individuals with familial predisposition to BD, irrespective of diagnosis, showed similar reductions in neural responsiveness in regions involved in selective attention within the posterior and inferior parietal lobules. In contrast, hypoactivation within fronto-striatal regions, implicated in inhibitory control, was observed only in BD patients and MDD relatives. Although striatal deficits were comparable between BD patients and their MDD relatives, right ventrolateral prefrontal dysfunction was uniquely associated with BD. Our findings suggest that while reduced parietal engagement relates to genetic risk, fronto-striatal dysfunction reflects processes underpinning disease expression for mood disorders. © 2011 Elsevier Inc.

Sorting Test, Tower Test, and BRIEF-SR do not predict school performance of healthy adolescents in preuniversity education

Executive functions (EF) such as self-monitoring, planning, and organizing are known to develop through childhood and adolescence. They are of potential importance for learning and school performance. Earlier research into the relation between EF and school performance did not provide clear results possibly because confounding factors such as educational track, boy-girl differences, and parental education were not taken into account. The present study therefore investigated the relation between executive function tests and school performance in a highly controlled sample of 173 healthy adolescents aged 12–18. Only students in the pre-university educational track were used and the performance of boys was compared to that of girls. Results showed that there was no relation between the report marks obtained and the performance on executive function tests, notably the Sorting Test and the Tower Test of the Delis-Kaplan Executive Functions System (D-KEFS). Likewise, no relation was found between the report marks and the scores on the Behavior Rating Inventory of Executive Function—Self-Report Version (BRIEF-SR) after these were controlled for grade, sex, and level of parental education. The findings indicate that executive functioning as measured with widely used instruments such as the BRIEF-SR does not predict school performance of adolescents in preuniversity education any better than a student's grade, sex, and level of parental education.