Modafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder.

BACKGROUND: Modafinil, a novel cognitive enhancer, has a clinical profile similar to conventional stimulants such as methylphenidate, despite a seemingly different mechanism of action. Modafinil selectively improves neuropsychological task performance in healthy volunteers, possibly through improved inhibitory control. We examined whether modafinil induced similar improvements in adults with attention-deficit/hyperactivity disorder. METHODS: Twenty patients with a DSM-IV diagnosis of attention-deficit/hyperactivity disorder were entered into a double-blind, randomized, placebo-controlled crossover study using a single 200 mg dose of modafinil. RESULTS: Modafinil produced a similar pattern of cognitive enhancement to that observed in healthy adults, with improvements on tests of short-term memory span, visual memory, spatial planning, and stop-signal motor inhibition. On several measures, increased accuracy was accompanied by slowed response latency. This alteration in the speed-accuracy trade-off may indicate that modafinil increases the ability to "reflect" on problems coupled with decreased impulsive responding. Improvements were also seen in sustained attention, which was unaffected in healthy subjects. CONCLUSIONS: If these benefits are shown to be maintained with chronic administration, modafinil may have potential as an important therapy for attention-deficit/hyperactivity disorder with a similar effect to stimulants such as methylphenidate in improving stop-signal response inhibition but without the side effects commonly experienced with amphetamine-like drugs.     

Brain activity in cigarette smokers performing a working memory task: effect of smoking abstinence.

BACKGROUND: When nicotine-dependent human subjects abstain from cigarette smoking, they exhibit deficits in working memory. An understanding of the neural substrates of such impairments may help to understand how nicotine affects cognition. Our aim, therefore, was to identify abnormalities in the circuitry that mediates working memory in nicotine-dependent subjects after they initiate abstinence from smoking. METHODS: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study eight smokers while they performed a letter version of the N-Back working memory task under satiety (< or = 1.5 hours abstinence) and abstinence (> or = 14 hours abstinence) conditions. RESULTS: Task-related activity in the left dorsal lateral prefrontal cortex (DLPFC) showed a significant interaction between test session (satiety, abstinence) and task load (1-back, 2-back, and 3-back). This interaction reflected the fact that task-related activity in the satiety condition was relatively low during performance of the 1-back task but greater at the more difficult task levels, whereas task-related activity in the abstinence condition was relatively high at the 1-back level and did not increase at the more difficult task levels. CONCLUSIONS: We conclude that neural processing related to working memory in the left DLPFC is less efficient during acute abstinence from smoking than at smoking satiety.     

Effects of acute smoking on brain activity vary with abstinence in smokers performing the N-Back Task: A preliminary study

We previously reported that compared with a non-deprivation state, overnight abstinence from cigarette smoking was associated with higher brain activity in the left dorsolateral prefrontal cortex (L-DLPFC) during a low demanding working memory challenge, and little increase beyond this activity level during more taxing working memory conditions. In the present study, we aimed to assess how recent smoking (overnight abstinence vs. smoking ad libitum) influenced the effect of smoking a cigarette on brain activity related to a working memory challenge. Six smokers performed the N-Back working memory task during functional magnetic resonance imaging (fMRI) both before and after smoking a cigarette in each of two test sessions: one following overnight abstinence from smoking ( 13 h) and the other following ad libitum smoking. Task-related activity in L-DLPFC showed a significant interaction between the effects of acute smoking, test session, and task load. After overnight abstinence, post-smoking brain activity in L-DLPFC was lower than before smoking at low task load and higher at high task load; corresponding activity on a day of ad libitum smoking was higher at low load and lower at high task load after smoking during the session. These data suggest that the effect of acute smoking on working memory processing depends on recent prior smoking and task load. In particular, they provide preliminary evidence that functional efficiency of working memory is improved by smoking a cigarette during abstinence, while the effect of a cigarette in a non-deprived state varies with the nature and difficulty of the working memory challenge. This interaction merits further examination in larger studies specifically designed to consider this issue.     

Effects of tobacco smoking on topographic EEG and Stroop test in smoking deprived smokers

1. Quantitative electroencephalography (EEG) was used to measure human brain electrical changes produced by tobacco deprivation and smoking. Sixteen scalp cortical recording sites monitored regional changes in brain activity. 2. The quantitative EEG was subdivided into delta, theta, alpha1, alpha2, beta1 and beta2 bands for topographic mapping. A demanding version of the Stroop test was used to determine tobacco smoking effects on attention. The version used was more difficult than that used in previously reported studies. 3. Healthy drug and substance free adult male and female volunteers were divided into nonsmoker (n=7) and smoker (n=7) groups according to their smoking status. They were instructed to abstain from tobacco products for at least 12 hr overnight before the next morning's experiment. 4. EEG was recorded before and after smoking either a fake placebo cigarette for nonsmokers or the cigarette of their choice for smokers. Subjects were also asked to perform the Stroop test before and after smoking the placebo or tobacco cigarette. 5. The results showed that tobacco smoking significantly depressed delta and increased alpha2 and beta1 activity and slightly increased the Stroop effect. Although smoking one cigarette stimulated brain electrical activity of smoking deprived smokers, it did not improve performance on a difficult Stroop test.     

Neuropsychological functioning in adolescent children of mothers with a history of bipolar or major depressive disorders.

BACKGROUND: Growing evidence demonstrates an association of neuropsychological deficits with mood disorders, but it is not yet clear whether these deficits are risk factors or are concomitant with the symptoms. This study examines the neuropsychological functioning of a group of adolescent offspring who are at risk for a mood disorder by virtue of being raised by mothers who have been diagnosed with major depressive disorder (MDD) or bipolar disorder (BPD). METHODS: Adolescent offspring of mothers with BPD (n = 43) or MDD (n = 72) and of psychiatrically well parents (n = 50) completed a battery of neuropsychological tests to assess executive functioning, memory, and attention. RESULTS: Children of mothers with BPD showed deficits in executive functioning and selective deficits in spatial memory and attention, in comparison with children of well mothers. Deficits were not found for children of MDD mothers. CONCLUSIONS: Knowledge of these neurocognitive processes could aid ultimately in determining whether neurocognitive deficits precede BPD, whether unique profiles are associated with various types of mood disorders, and who may benefit from interventions.     

Adverse Effects of 24 Hours of Sleep Deprivation on Cognition and Stress Hormones

Background and Purpose

The present study was designed to investigate whether 24 h of SD negatively affects the attention and working memory and increases the serum concentrations of stress hormones, glucose, and inflammatory markers.

Methods

The acute effects of sleep deprivation (SD) on cognition and the stress hormones were evaluated in six healthy volunteers (all men, age 23-27 years). All were good sleepers, had no history of medical or neuropsychiatric diseases, and were not taking any kind of medication. All of the volunteers were subjected to the Continuous Performance Test (CPT) for attention and working memory of cognition and blood tests both before and after 24 h of SD. Electroencephalographic monitoring was performed during the study to confirm the wakefulness of the subjects.

Results

SD significantly elevated the serum concentrations of stress hormones (cortisol, epinephrine, and norepinephrine), but serum levels of glucose and inflammatory markers were not changed compared to baseline. For easier steps of the CPT the subjects performed well in giving correct responses after SD; the correct response scores decreased only at the most difficult step of the CPT. However, the subjects performed consistently poor for the error responses at all steps after SD. There was no correlation between the CPT scores and stress hormone levels.

Conclusions

The 24 h of SD significantly heightened the levels of stress hormones and lowered attention and working memory. The acute SD condition seems to render the subject more susceptible to making errors.     

The contribution of working memory to divided attention

Previous studies have indicated that increasing working memory (WM) load can affect the attentional selection of signals originating from one object/location. Here we assessed whether WM load affects also the selection of multiple objects/locations (divided attention). Participants monitored either two object‐categories (vs. one category; object‐based divided attention) or two locations (vs. one location; space‐based divided attention) while maintaining in WM either a variable number of objects (object‐based WM load) or locations (space‐based WM load). Behavioural results showed that WM load affected attentional performance irrespective of divided or focused attention. However, fMRI results showed that the activity associated with object‐based divided attention increased linearly with increasing object‐based WM load in the left and right intraparietal sulcus (IPS); while, in the same areas, activity associated with space‐based divided attention was not affected by any type of WM load. These findings support the hypothesis that WM contributes to the maintenance of resource‐demanding attentional sets in a domain‐specific manner. Moreover, the dissociable impact of WM load on performance and brain activity suggests that increased IPS activation reflects a recruitment of additional, domain‐specific processing resources that enable dual‐task performance under conditions of high WM load and high attentional demand. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Common and distinct neural regions for the guidance of selection by visuoverbal information held in memory: converging evidence from fMRI and rTMS

Recent research indicates that working memory (WM) and attention interact, with attention automatically biased to stimuli that match the contents of WM. Though there is behavioral evidence for verbal guidance (written words) as well as guidance by more visual cues in WM, we have limited understanding of how these two representational formats influence the guidance of visual selection at a neural level. Here, we present converging evidence from functional MRI and transcranial magnetic stimulation (TMS), which indicates that both common and distinct neural regions mediate the influence of visuoverbal representations on WM. Colored shapes, but not words, in WM activated the superior frontal gyrus (SFG) and recognition memory areas in the temporal lobe when the contents of WM matched a stimulus in a subsequent search display. rTMS to the SFG disrupted WM effects from colored shapes. The lateral occipital cortex, however, tended to be more activated with written word cues, and rTMS to the lateral occipital complex tended to disrupt effects from written words more than from colored shapes in WM. There was also evidence for cue validity effects from colored shapes and written stimuli operating through different subthalamic nuclei. We discuss the evidence for understanding the neural systems mediating attention effects from WM.     

Effects of acute smoking on brain activity vary with abstinence in smokers performing the N-Back task: a preliminary study

We previously reported that compared with a non-deprivation state, overnight abstinence from cigarette smoking was associated with higher brain activity in the left dorsolateral prefrontal cortex (L-DLPFC) during a low demanding working memory challenge, and little increase beyond this activity level during more taxing working memory conditions. In the present study, we aimed to assess how recent smoking (overnight abstinence vs. smoking ad libitum) influenced the effect of smoking a cigarette on brain activity related to a working memory challenge. Six smokers performed the N-Back working memory task during functional magnetic resonance imaging (fMRI) both before and after smoking a cigarette in each of two test sessions: one following overnight abstinence from smoking ( approximately 13 h) and the other following ad libitum smoking. Task-related activity in L-DLPFC showed a significant interaction between the effects of acute smoking, test session, and task load. After overnight abstinence, post-smoking brain activity in L-DLPFC was lower than before smoking at low task load and higher at high task load; corresponding activity on a day of ad libitum smoking was higher at low load and lower at high task load after smoking during the session. These data suggest that the effect of acute smoking on working memory processing depends on recent prior smoking and task load. In particular, they provide preliminary evidence that functional efficiency of working memory is improved by smoking a cigarette during abstinence, while the effect of a cigarette in a non-deprived state varies with the nature and difficulty of the working memory challenge. This interaction merits further examination in larger studies specifically designed to consider this issue.     

Working memory and everyday cognition in adults with Down's syndrome

A number of previous studies have suggested that young people with Down's syndrome (DS) have a specific deficit of the phonological loop component of the working memory. However, there have also been studies which have proposed a specific deficit of the central executive component of working memory and suggested similarities of working memory functioning with patients with Alzheimer's disease. Fifteen middle‐aged people with DS were matched for their individual scores of non‐verbal intelligence to 15 individuals with mixed aetiology of intellectual disability. A versatile range of tasks was used in order to evaluate the functioning of working memory components. In addition, several everyday cognition skills were assessed. The subjects with DS performed significantly more poorly in all tasks assessing the phonological loop. Performance in other working memory tasks and compound variables representing different working memory components was equal in the groups. In addition, both groups had equal everyday cognition skills. The functioning of the phonological loop seems to be clearly deficient in people with DS. Interestingly, the deficit does not seem to affect the vocabulary or other everyday cognition skills in individuals with DS. No signs of specific deficit of the central executive component of working memory were found.     

The focus of attention as observed in visual working memory tasks: making sense of competing claims

Recent behavioral and neuroscientific evidence speaks to the question of whether the human focus of attention is limited to a single item or can accommodate several items. This issue is fundamental to an understanding of the nature of human cognition and brain function. Here I review evidence from visual working memory tasks and suggest that it supports the concept of a focus of attention that can include several items at once as a core vehicle of working memory, regardless of the stimulus modality. One brain area in particular, the left intraparietal sulcus (IPS), seems critically important in the network underlying the focus of attention as a working memory storage mechanism. This view is reconciled with evidence previously taken to indicate that the focus of attention only includes a single item at a time, which is reinterpreted here.     

The Impact of Prefrontal Cortex for Selective Attention in a Visual Working Memory Task

In this study, a variant of the n-back task was used to investigate electrophysiological correlates of top-down processes in visual-object working memory. Event-related potentials were used to replicate results concerning an attention related modulation of neural processes and to investigate the involvement of prefrontal cortex in this modulation. 16 healthy subjects executed an n-back task with sequentially presented faces and scenes. Attention was selectively directed to only one stimulus category. We found an enhancement of the N170 amplitudes for relevant stimuli compared to irrelevant or neutral stimuli. Late frontal amplitudes were stronger positive for relevant compared to neutral stimuli indicating selective attention processes of working memory. Evidence for selective inhibition was not found.     

Domain-specific relationships of subjective and objective cognition in epilepsy

Objective

Many people with epilepsy report subjective cognitive impairment (SCI), i.e., problems with memory, attention, or executive functions, reducing quality of life. Nevertheless, overlap with objective cognitive impairment (OCI) is often weak. One reason may be a domain-specific mismatch between subjective reports and objective tests. We aimed to evaluate relations between SCI and OCI of corresponding domains and to assess whether these differ between persons who over- or underestimate their performance.

Methods

In this prospective, cross-sectional sample of 104 adult inpatients with epilepsy, we performed multiple regression analyses predicting SCI in the domains attention, memory, and executive functions. We tested relationships with measures of psychomotor speed, short-term memory, verbal learning, verbal delayed recall, and word fluency while controlling for age, sex, seizure frequency, structural lesions, mono- versus polytherapy and adverse events of antiseizure medication (ASM), depressive and anxiety symptoms, level of education, and employment status. Furthermore, we tested whether these relationships differed between realistic raters and over- and underestimators.

Results

We found domain-specific relations for attention and executive functions for the full sample, explaining a small proportion of variance of SCI (general dominance index = .03 and .004), whereas ASM adverse events and psychological variables were more important predictors. When dividing the sample according to the concordance of SCI and OCI, we found high frequencies of both over- (23%–46%) and underestimation (31%–35%) depending on the domain. The explanatory power of OCI for SCI was stronger within the subgroups compared to the full sample, suggesting nonlinear relationships and different underlying mechanisms for realistic raters, underestimators, and overestimators.

Significance

Domain-specific SCI and OCI are related, and both should be assessed with standardized instruments. These relationships differ between over- and underestimators as well as realistic raters. Based on the concordance of self-ratings and objective measures, tailored counseling and treatment should be offered.     

Functional correlates of verbal memory deficits emerging during nicotine withdrawal in abstinent adolescent cannabis users.

BACKGROUND: Cannabis remains the most widely used illicit substance by adolescents and is typically consumed by this population in the context of ongoing tobacco use. Human studies have shown that both cannabis and tobacco exert effects on cognitive function; however, little is known about possible interacting effects of these drugs on brain function and cognition during adolescent development. METHODS: Verbal learning and memory were assessed in 20 adolescent users of tobacco and cannabis and 25 adolescent tobacco users with minimal history of cannabis use. Functional magnetic resonance imaging was used to examine brain function and functional connectivity while a subset of these subjects performed a verbal working memory task. RESULTS: Delayed recall of verbal stimuli deteriorated during nicotine withdrawal among cannabis users but not among comparison subjects. During high verbal working memory load, nicotine withdrawal selectively increased task-related activation of posterior cortical regions and was associated with disruption of frontoparietal connectivity in adolescent cannabis users relative to comparison subjects. CONCLUSIONS: These observations suggest that cannabis use during adolescent development may disrupt neurocircuitry supporting verbal memory formation and that deficits associated with disruption of these neurocircuits are unmasked during nicotine withdrawal.     

The Ins and Outs of Consciousness

In Enchanted Looms, Rodney Cotterill defends the hypothesisthat conscious sensory experience depends on motor response. Thepositive evidence for this hypothesis is inconclusive, andnegative evidence can be marshaled against it. I present analternative hypothesis according to which consciousness involvesintermediate level sensory processing, attention, and workingmemory. The circuitry of consciousness can be dissociated fromaction systems and may mark an evolutionary advance from a priorphylogenetic stage in which motor outputs and sensory inputswere more intimately bound.     

Effects of tobacco smoking on the topographic EEG II.

1. Tobacco smokers are well aware of the long term hazards of tobacco smoking, yet they continue to smoke. Presumably people smoke because of short term gains due to nicotine. 2. The mechanism by which nicotine is a drug reinforcer still needs a great deal of study. The specific aim of the present study was to determine the effects of tobacco smoking on the topographic EEG of 12 hr deprived heavy tobacco smokers. 3. Seven normal adult tobacco smokers of mixed sex were recruited into the study and compared with six normal nonsmokers of similar age and sex. 4. A Grass Model 8-24D EEG and 16 different scalp monopolar electrodes were used to record the EEG using both ears as reference before and after smoking. EKG lead II was recorded on channel 17. Blood pressure was measured by auscultation. Exhaled CO was measured using a CO detector. Computer analysis of the EEG data was run of line on a Zenith 386/25 microcomputer using RHYTHM 7.1. The same system was used to store the EEG in digitized form. The maximum number of 4 sec artifact free epochs in a 3 min recording period with eyes open and then closed was used before and after low and high nicotine tobacco or sham smoking. 5. The hypothesis of this research was confirmed, i.e., that tobacco smoking of high nicotine cigarettes (about 2.0 mg/cigarette) would cause a shift in EEG alpha rhythm to higher frequencies in more diffuse midline cortical structures. In other studies an increase in alpha rhythm has been correlated with an awake relaxed behavioral state. 6. A heart rate increase was a more sensitive index of tobacco smoking than an increase in arterial blood pressure. Exhaled smoking CO levels correlated with the nicotine and tar content of the cigarette.     

Effects of tobacco smoking on the kinetics of the pupillary light reflex: a comparison between smokers and non-smokers

BACKGROUND: The time course of the pupillary light reflex (PLR) is determined by the successive activation of parasympathetic and sympathetic innervations of the iris, latency and amplitude reflecting parasympathetic activity and recovery time showing mainly sympathetic activity. OBJECTIVE: To determine the effects of tobacco cigarette smoking on the PLR in smokers after an abstinence period of at least 12 h. METHODS: Ten smokers (mean 15.7 cigarettes/day) and 10 non-smokers participated in a randomised, non-intervention controlled, cross-over study that included a parallel control group. Smokers underwent two sessions with a time interval between 3 and 8 days; two recordings were taken at each session, separated by 20 min: session 1, without smoking, and session 2, smoking 3 cigarettes within a 30-min period. Non-smokers underwent one session; two recordings were taken separated by 20 min. At each recording, in both groups, PLR was elicited with four light flashes of increasing luminance. RESULTS: The relationship between PLR parameters and light intensity was linear in each subject. The slope of the regression line for relative amplitude increase versus intensity was significantly flatter in abstinent smokers than in non-smokers (p=0.033); the slope returned significantly after smoking (p=0.043). No other significant effects were obtained. CONCLUSIONS: Kinetic parameters of PLR provide a sensitive pharmacological test to detect cholinergic neurotransmission manipulation effects, as they seem to detect changes in moderate smokers after 12 h of abstinence, and their reversal on return to smoking. These results suggest an enhancement in the suppression of the parasympathetic oculomotor reflex arc rather than a facilitation of the sympathetic drive to the iris.