J. Leon Kenemans

A meta-analytic review of stopping performance in attention-deficit/hyperactivity disorder: deficient inhibitory motor control?

This review discusses whether deficient inhibitory motor control is the core deficit of attention-deficit/hyperactivity disorder (ADHD). Inhibitory motor control is commonly assessed using the stop-signal paradigm. Since the last meta-analysis that was performed, 33 new studies have appeared. The current meta-analysis revealed a significant difference between ADHD patients and matched controls in stop latency (stop-signal reaction time) in both children and adults. Basic reaction time was significantly longer in children with ADHD, but not in adults, and there was a significant interaction between the elongation of the latency to stop and to respond in adults, but not in children. Deficient inhibitory motor control may be less crucial in children than in adults with ADHD.

Stroop Interference and Attention-Deficit/Hyperactivity Disorder: A Review and Meta-Analysis

Previous reviews and meta-analyses that addressed abnormal Stroop interference in attention-deficit/hyperactivity disorder (ADHD) yielded mixed results. The authors of the present study argue that the inconsistencies may reflect the problematic nature of 2 frequently used methods to quantify Stroop interference-the difference score and Goldens method (C. J. Golden, 1978). Goldens method correction for base-word reading is inadequate, and the difference score is sensitive to the nature of the outcome variable. The latter can be remedied with a ratio score. Contrasting previous meta-analyses, this meta-analysis covers all age groups and all Stroop test variants, and it excludes studies using the Golden quantification method. Mean effect sizes for interference in ADHD as quantified by difference scores relative to control scores were 0.24 across all studies but 1.11 for time-per-item studies; outcome variable was a significant moderator variable, reflecting the sensitivity of the difference score to this variable. Consistency analysis of ratio scores across 19 studies reveals more interference for the ADHD groups relative to the control groups. It is concluded that interference control is consistently compromised in individuals with ADHD.

Inhibition in children with attention-deficit/hyperactivity disorder: a psychophysiological study of the stop task.

BACKGROUND The purpose of the study was to investigate and identify abnormal brain activity, as revealed by event-related potentials (ERPs) concurring with deficient inhibitory control in children with attention-deficit/hyperactivity disorder (ADHD). METHODS Performance and ERPs from 16 children with ADHD and 16 control subjects were compared in the stop-signal paradigm. RESULTS The ADHD children showed a lower inhibition percentage and their (estimated) response time to the stop signal was disproportionally longer compared to the slowing of reaction times to primary-task stimuli. In normal control subjects, fronto-central positivity (100-400 msec) after the onset of the stop-signal was larger in case of successful inhibition, relative to failed inhibition; this was less so in ADHD children. A late positive wave (500-700 msec), maximal at Oz on failed inhibition trials, and possibly related to error-detection, was smaller in ADHD children. CONCLUSIONS These results point to abnormalities in brain processes involved in motor inhibition and error-detection in ADHD children.

Associations Between Event-Related Potentials and Measures of Attention and Inhibition in the Continuous Performance Task in Children With ADHD and Normal Controls

OBJECTIVES First, to differentiate between inattention and impulsivity based on type of errors made in the AX version of the Continuous Performance Task (CPT), and second, to investigate whether differences in performance between children with attention-deficit hyperactivity disorder (ADHD) and normal controls also occur in specific forms of brain activity, namely event-related potentials (ERPs), presumably related to inattention and impulsivity or inhibition. METHOD Sixteen ADHD and 16 normal control children performed the CPT-AX. ERPs were recorded at occipital (Oz), parietal (Pz), central (Cz), and frontal (Fz) leads. RESULTS The ADHD children had a higher CPT-Inattention score and showed smaller parietal positive waves at a latency of approximately 300 msec in reaction to target stimuli, target P3s, likewise indicating less attention. In contrast, they showed neither higher CPT-Impulsivity nor a smaller frontocentral negative wave at about 200 msec (N2); the N2 is generally seen as reflecting inhibition. A subgroup of children with ADHD and oppositional defiant disorder (n = 6) had smaller N2 waves than controls, however. CONCLUSIONS The ADHD group studied showed deficits in attention but not in impulsivity (or inhibition).

Exogenous testosterone attenuates the integrated central stress response in healthy young women.

Animal research has shown that the androgen steroid testosterone, the end product of the hypothalamic-pituitary-gonadal (HPG) axis, down regulates the integrated stress response at multiple levels. These effects have been demonstrated at the level of the amygdala and the bed nucleus of the stria terminalis, and along the different nodes of the hypothalamic-pituitary-adrenal (HPA) axis. The present study was designed to assess effects of exogenous testosterone upon reactivity of the autonomic nervous system and modulation of the acoustic startle reflex in humans. Twenty healthy female participants received double-blind, placebo-controlled sublingual administrations of .5mg testosterone. Measurements were made of phasic electrodermal activity, cardiac responses, and startle reflexes to acoustic probes while participants were exposed to pictures with strongly aversive, neutral, or positive content. Subjective reports of mood and picture evaluations were also obtained. Results support the hypothesis of a generally decreased responsiveness of the stress system by showing reduced skin conductance responses as well as reduced affective startle modulation in anxiety-prone participants after administration of testosterone. Candidate neurobiological mechanisms of action are outlined and discussed, and it is argued that androgens promote dynamic regulation of the stress system through actions upon central neuropeptidergic pathways that control corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) expression. The present findings highlight the importance of further investigation of the possible role of the HPG axis in disorders that are associated with HPA axis dysfunctions.

Spatiotemporal overlap between brain activation related to saccade preparation and attentional orienting

Recent brain imaging studies provided evidence that the brain areas involved with attentional orienting and the preparation of saccades largely overlap, which may indicate that focusing attention at a specific location can be considered as an unexecuted saccade towards that location (i.e. the premotor theory of attention). Alternatively, it may be proposed that attentional orienting is simply relevant for preparing saccades, but the two processes may also be completely unrelated. In two experiments, we examined temporal activation of brain areas by measuring the electroencephalogram. Central cues indicated the likely side (left or right) at which a to-be-attended target would occur, or to which a saccade had to be prepared. Cue direction-related activity was determined, time-locked to cue onset. In addition, in our second experiment, delayed saccades had to be carried out, which allows to focus on processes strongly related to saccade execution. In nearly all tasks, an early directing attention negativity (EDAN), an anterior directing attention negativity (ADAN), and a late directing attention positivity (LDAP) were observed, time-locked to cue onset. Source analyses supported the view that this activity probably originates from areas within the ventral intraparietal sulcus (vIPS) and the frontal eye fields (FEF). The saccade-locked analysis also indicated that the FEF plays an important role in triggering saccades, but the role of vIPS appears to be minimal. The latter finding disfavors the premotor theory of attention, as it suggests that the relation between attention and action is less direct.

Detection of visual change: mismatch or rareness?

How do we detect changes in our visual environment? By continuously comparing visual inputs to templates of experiences in the immediate past? Or by determining their rareness, how infrequently a visual event occurred previously? Recent results from event-related potentials have been interpreted in favour of the first hypothesis, as in the case of the auditory mismatch negativity. Here we demonstrate that rareness, rather than mismatch with a template, underlies visual change detection. Such rareness is detected through a dedicated mechanism in human visual cortex about 100 ms after the rare event occurs, reflected in the rareness-related negativity (RRN).

Prepulse inhibition and P50 suppression: Commonalities and dissociations

Patients with schizophrenia exhibit reduced levels of both prepulse inhibition of the startle reflex (PPI) and condition-test suppression of the P50 event-related potential. This study investigated the extent to which PPI and P50 suppression, which exhibit similar parametric sensitivities, are intrinsically auditory phenomena or can be induced cross-modally, and reflect common or distinct neural mechanisms of inhibition. PPI, N100, and P50 were assessed in 20 healthy male volunteers, using auditory test probes and both visual and auditory lead stimuli, separated by 100- or 500-ms interstimulus intervals (ISIs). PPI was found in the auditory-lead condition across the complete group, and with visual-lead stimuli in approximately half of the subjects. Intra-modal auditory PPI was significantly higher with the 100-ms ISI than with the 500-ms ISI. P50 suppression was found only with the 500-ms ISI, with no difference between the auditory and visual conditions. Source analyses revealed that suppression was associated with frontal cortical activity. N100 suppression was found only in the auditory condition, with no difference between 100- and 500-ms ISIs. Although both phenomena are considered to provide operational measures of gating, PPI and P50 suppression are differentially sensitive to ISI and therefore reflect partly different neural mechanisms. They are not intrinsically auditory phenomena, and both appear to involve frontal cortical activity. In contrast, N100 suppression is most likely based on refractory mechanisms intrinsic to the auditory system.

How Human Electrophysiology Informs Psychopharmacology: from Bottom-up Driven Processing to Top-Down Control

This review surveys human event-related brain potential (ERP) and event-related magnetic field (ERF) approaches to psychopharmacology and psychopathology, and the way in which they complement behavioral studies and other neuroimaging modalities. The major paradigms involving ERP/ERF are P50 suppression, loudness-dependent auditory evoked potential (LDAEP), mismatch negativity (MMN), P300, mental chronometry, inhibitory control, and conflict processing (eg, error-related negativity (ERN)). Together these paradigms cover a range of more bottom-up driven to more top-down controlled processes. A number of relationships between the major neurotransmitter systems and electrocortical mechanisms are highlighted. These include the role of dopamine in conflict processing, and perceptual processing vs motor preparation; the role of serotonin in P50 suppression, LDAEP, and MMN; glutamate/NMDA and MMN; and the role of acetylcholine in P300 generation and memory-related processes. A preliminary taxonomy for these relationships is provided, which should be helpful in attuning possible new treatments or new applications of existing treatments to various disorders.

Neurophysiological predictors of non-response to rTMS in depression.

BACKGROUND The application of rTMS in Depression has been very well investigated over the last few years. However, little is known about predictors of non-response associated with rTMS treatment. OBJECTIVE This study examined neurophysiological parameters (EEG and ERP) in 90 depressed patients treated with rTMS and psychotherapy and sought to identify predictors of non-response. METHODS This study is a multi-site open-label study assessing pre-treatment EEG and ERP measures associated with non-response to rTMS treatment. RESULTS Non-responders were characterized by 1) Increased fronto-central theta EEG power, 2) a slower anterior individual alpha peak frequency, 3) a larger P300 amplitude, and 4) decreased pre-frontal delta and beta cordance. A discriminant analysis yielded a significant model, and subsequent ROC curve demonstrated an area under the curve of 0.814. CONCLUSIONS Several EEG variables demonstrated clear differences between R and NR such as the anterior iAPF, fronto-central Theta and pre-frontal cordance in the Delta and Beta band (representative of increased relative pre-frontal perfusion). The increased P300 amplitude as a predictor for non-response requires further study, since this was the opposite as hypothesized and there were no correlations of this measure with clinical improvement for the whole sample. Combining these biomarkers in a discriminant analysis resulted in a reliable identification of non-responders with low false positive rates. Future studies should prospectively replicate these findings and also further investigate appropriate treatments for the sub-groups of non-responders identified in this study, given that most of these biomarkers have also been found in antidepressant medication studies.