Conflict processing networks: A directional analysis of stimulus-response compatibilities using MEG.

The suppression of distracting information in order to focus on an actual cognitive goal is a key feature of executive functions. The use of brain imaging methods to investigate the underlying neurobiological brain activations that occur during conflict processing have demonstrated a strong involvement of the fronto-parietal attention network (FPAN). Surprisingly, the directional interconnections, their time courses and activations at different frequency bands remain to be elucidated, and thus, this constitutes the focus of this study. The shared information flow between brain areas of the FPAN is provided for frequency bands ranging from the theta to the lower gamma band (4-40 Hz). We employed an adaptation of the Simon task utilizing Magnetoencephalography (MEG). Granger causality was applied to investigate interconnections between the active brain regions, as well as their directionality. Following stimulus onset, the middle frontal precentral cortex and superior parietal cortex were significantly activated during conflict processing in a time window of between 300 to 600ms. Important differences in causality were found across frequency bands between processing of conflicting stimuli in the left as compared to the right visual hemifield. The exchange of information from and to the FPAN was most prominent in the beta band. Moreover, the anterior cingulate cortex and the anterior insula represented key areas for conflict monitoring, either by receiving input from other areas of the FPAN or by generating output themselves. This indicates that the salience network is at least partly involved in processing conflict information. The present study provides detailed insights into the underlying neural mechanisms of the FPAN, especially regarding its temporal characteristics and directional interconnections.

Changes in brain activation related to visuo-spatial memory after real-time fMRI neurofeedback training in healthy elderly and Alzheimer's disease.

Cognitive decline is a symptom of healthy ageing and Alzheimer's disease. We examined the effect of real-time fMRI based neurofeedback training on visuo-spatial memory and its associated neuronal response. Twelve healthy subjects and nine patients of prodromal Alzheimer's disease were included. The examination spanned five days (T1-T5): T1 contained a neuropsychological pre-test, the encoding of an itinerary and a fMRI-based task related that itinerary. T2-T4 hosted the real-time fMRI neurofeedback training of the parahippocampal gyrus and on T5 a post-test session including encoding of another itinerary and a subsequent fMRI-based task were done. Scores from neuropsychological tests, brain activation and task performance during the fMRI-paradigm were compared between pre and post-test as well as between healthy controls and patients. Behavioural performance in the fMRI-task remained unchanged, while cognitive testing showed improvements in visuo-spatial memory performance. Both groups displayed task-relevant brain activation, which decreased in the right precentral gyrus and left occipital lobe from pre to post-test in controls, but increased in the right occipital lobe, middle frontal gyrus and left frontal lobe in the patient group. While results suggest that the training has affected brain activation differently between controls and patients, there are no pointers towards a behavioural manifestation of these changes. Future research is required on the effects that can be induced using real-time fMRI based neurofeedback training and the required training duration to elicit broad and lasting effects.

Chronotype differences in cortical thickness: grey matter reflects when you go to bed.

Based on individual circadian cycles and associated cognitive rhythms, humans can be classified via standardised self-reports as being early (EC), late (LC) and intermediate (IC) chronotypes. Alterations in neural cortical structure underlying these chronotype differences have rarely been investigated and are the scope of this study. 16 healthy male ECs, 16 ICs and 16 LCs were measured with a 3 T MAGNETOM TIM TRIO (Siemens, Erlangen) scanner using a magnetization prepared rapid gradient echo sequence. Data were analysed by applying voxel-based morphometry (VBM) and vertex-wise cortical thickness (CTh) analysis. VBM analysis revealed that ECs showed significantly lower grey matter volumes bilateral in the lateral occipital cortex and the precuneus as compared to LCs, and in the right lingual gyrus, occipital fusiform gyrus and the occipital pole as compared to ICs. CTh findings showed lower grey matter volumes for ECs in the left anterior insula, precuneus, inferior parietal cortex, and right pars triangularis than for LCs, and in the right superior parietal gyrus than for ICs. These findings reveal that chronotype differences are associated with specific neural substrates of cortical thickness, surface areas, and folding. We conclude that this might be the basis for chronotype differences in behaviour and brain function. Furthermore, our results speak for the necessity of considering "chronotype" as a potentially modulating factor in all kinds of structural brain-imaging experiments.

Blunted Frontostriatal Blood Oxygen Level-Dependent Signals Predict Stimulant and Marijuana Use.

BACKGROUND: Occasional recreational stimulant (amphetamine and cocaine) use is an important public health problem among young adults because 16% of those who experiment develop stimulant use disorder. This study aimed to determine whether behavioral and/or neural processing measures can forecast the transition from occasional to problematic stimulant use. METHODS: Occasional stimulant users completed a Risky Gains Task during functional magnetic resonance imaging and were followed up 3 years later. Categorical analyses tested whether blood oxygen level-dependent (BOLD) responses differentiated occasional stimulant users who became problem stimulant users (n = 35) from those who desisted from stimulant use (n = 75) at follow-up. Dimensional analyses (regardless of problem stimulant user or desisted stimulant use status; n = 144) tested whether BOLD responses predicted baseline and follow-up stimulant and marijuana use. RESULTS: Categorical results indicated that relative to those who desisted from stimulant use, problem stimulant users 1) made riskier decisions after winning feedback; 2) exhibited lower frontal, insular, and striatal BOLD responses to win/loss feedback after making risky decisions; and 3) displayed lower thalamic but greater temporo-occipital BOLD responses to risky losses than to risky wins. In comparison, dimensional results indicated that lower BOLD signals to risky choices than to safe choices in frontal, striatal, and additional regions predicted greater marijuana use at follow-up. CONCLUSIONS: Taken together, blunted frontostriatal signals during risky choices may quantify vulnerability to future marijuana consumption, whereas blunted frontostriatal signals to risky outcomes mark risk for future stimulant use disorder. These behavioral and neural processing measures may prove to be useful for identifying ultra-high risk individuals prior to onset of problem drug use.

Cognitive Improvement and Brain Changes after Real-Time Functional MRI Neurofeedback Training in Healthy Elderly and Prodromal Alzheimer's Disease.

BACKGROUND: Cognitive decline is characteristic for Alzheimer's disease (AD) and also for healthy ageing. As a proof-of-concept study, we examined whether this decline can be counteracted using real-time fMRI neurofeedback training. Visuospatial memory and the parahippocampal gyrus (PHG) were targeted. METHODS: Sixteen healthy elderly subjects (mean age 63.5 years, SD = 6.663) and 10 patients with prodromal AD (mean age 66.2 years, SD = 8.930) completed the experiment. Four additional healthy subjects formed a sham-feedback condition to validate the paradigm. The protocol spanned five examination days (T1-T5). T1 contained a neuropsychological pre-test, the encoding of a real-world footpath, and an anatomical MRI scan of the brain. T2-T4 included the fMRI neurofeedback training paradigm, in which subjects learned to enhance activation of the left PHG while recalling the path encoded on T1. At T5, the neuropsychological post-test and another anatomical MRI brain scan were performed. The neuropsychological battery included the Montreal Cognitive Assessment (MoCA); the Visual and Verbal Memory Test (VVM); subtests of the Wechsler Memory Scale (WMS); the Visual Patterns Test; and Trail Making Tests (TMT) A and B. RESULTS: Healthy elderly and patients with prodromal AD showed improved visuospatial memory performance after neurofeedback training. Healthy subjects also performed better in a working-memory task (WMS backward digit-span) and in the MoCA. Both groups were able to elicit parahippocampal activation during training, but no significant changes in brain activation were found over the course of the training. However, Granger-causality-analysis revealed changes in cerebral connectivity over the course of the training, involving the parahippocampus and identifying the precuneus as main driver of activation in both groups. Voxel-based morphometry showed increases in grey matter volumes in the precuneus and frontal cortex. Neither cognitive enhancements, nor parahippocampal activation were found in the control group undergoing sham-feedback. CONCLUSION: These findings suggest that cognitive decline, either related to prodromal AD or healthy ageing, could be counteracted using fMRI-based neurofeedback. Future research needs to determine the potential of this method as a treatment tool.

Chronotype Modulates Language Processing-Related Cerebral Activity during Functional MRI (fMRI).

OBJECTIVE: Based on individual daily physiological cycles, humans can be classified as early (EC), late (LC) and intermediate (IC) chronotypes. Recent studies have verified that chronotype-specificity relates to performance on cognitive tasks: participants perform more efficiently when tested in the chronotype-specific optimal time of day than when tested in their non-optimal time. Surprisingly, imaging studies focussing on the underlying neural mechanisms of potential chronotype-specificities are sparse. Moreover, chronotype-specific alterations of language-related semantic processing have been neglected so far. METHODS: 16 male, healthy ECs, 16 ICs and 16 LCs participated in a fast event-related functional Magnetic Resonance Imaging (fMRI) paradigm probing semantic priming. Subjects read two subsequently presented words (prime, target) and were requested to determine whether the target word was an existing word or a non-word. Subjects were tested during their individual evening hours when homeostatic sleep pressure and circadian alertness levels are high to ensure equal entrainment. RESULTS: Chronotype-specificity is associated with task-performance and brain activation. First, ECs exhibited slower reaction times than LCs. Second, ECs showed attenuated BOLD responses in several language-related brain areas, e.g. in the left postcentral gyrus, left and right precentral gyrus and in the right superior frontal gyrus. Additionally, increased BOLD responses were revealed for LCs as compared to ICs in task-related areas, e.g. in the right inferior parietal lobule and in the right postcentral gyrus. CONCLUSIONS: These findings reveal that even basic language processes are associated with chronotype-specific neuronal mechanisms. Consequently, results might change the way we schedule patient evaluations and/or healthy subjects in e.g. experimental research and adding "chronotype" as a statistical covariate.

Attenuated Neural Processing of Risk in Young Adults at Risk for Stimulant Dependence.

OBJECTIVE: Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate), which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing. METHODS: 158 occasional stimulants users (OSU) and 50 comparison subjects (CS) performed a "risky gains" decision making task during which they could select safe options (cash in 20 cents) or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, "risky decisions"). The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42), or <50 lifetime marijuana uses (n = 32), were compared to CS with <50 lifetime uses (n = 46) to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed. RESULTS: There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC) and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options. DISCUSSION: Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions critical for performance monitoring, reward processing and interoceptive awareness. Marijuana had additive effects by diminishing neural risk differentiation.

fMRI identifies chronotype-specific brain activation associated with attention to motion--why we need to know when subjects go to bed.

Human cognition relies on attentional capacities which, among others, are influenced by factors like tiredness or mood. Based on their inherent preferences in sleep and wakefulness, individuals can be classified as specific "chronotypes". The present study investigated how early, intermediate and late chronotypes (EC, IC, LC) differ neurally on an attention-to-motion task. Twelve EC, 18 IC and 17 LC were included into the study. While undergoing functional magnetic resonance imaging (fMRI) scans, subjects looked at vertical bars in an attention-to-motion task. In the STATIONARY condition, subjects focused on a central fixation cross. During Fix-MOVING and Attend-MOVING, bars were moving horizontally. Only during the Attend-MOVING, subjects were required to attend to changes in the velocity of bars and indicate those by button presses. A two-way repeated measures ANOVA probed group by attentional load effects. The dorsolateral prefrontal cortex (DLPFC), insula and anterior cingulate cortex showed group by attention specific activations. Specifically, EC and LC presented attenuated DLPFC activation under high attentional load (Attend-MOVING), while EC showed less anterior insula activation than IC. LC compared to IC exhibited attenuation of superior parietal cortex. Our study reveals that individual sleep preferences are associated with characteristic brain activation in areas crucial for attention and bodily awareness. These results imply that considering sleep preferences in neuroimaging studies is crucial when administering cognitive tasks. Our study also has socio-economic implications. Task performance in non-optimal times of the day (e.g. shift workers), may result in cognitive impairments leading to e.g. increased error rates and slower reaction times.

Specific and disease stage-dependent episodic memory-related brain activation patterns in Alzheimer's disease: a coordinate-based meta-analysis.

Episodic memory is typically affected during the course of Alzheimer's disease (AD). Due to the pronounced heterogeneity of functional neuroimaging studies on episodic memory impairments in mild cognitive impairment (MCI) and AD regarding their methodology and findings, we aimed to delineate consistent episodic memory-related brain activation patterns. We performed a systematic, quantitative, coordinate-based whole-brain activation likelihood estimation meta-analysis of 28 functional magnetic resonance imaging (fMRI) studies comprising 292 MCI and 102 AD patients contrasted to 409 age-matched control subjects. We included episodic encoding and/or retrieval phases, investigated the effects of group, verbal or image stimuli and correlated mean Mini-Mental-Status-Examination (MMSE) scores with the modelled activation estimates. MCI patients presented increased right hippocampal activation during memory encoding, decreased activation in the left hippocampus and fusiform gyrus during retrieval tasks, as well as attenuated activation in the right anterior insula/inferior frontal gyrus during verbal retrieval. In AD patients, however, stronger activation within the precuneus during encoding tasks was accompanied by attenuated right hippocampal activation during retrieval tasks. Low cognitive performance (MMSE scores) was associated with stronger activation of the precuneus and reduced activation of the right (para)hippocampus and anterior insula/inferior frontal gyrus. This meta-analysis provides evidence for a specific and probably disease stage-dependent brain activation pattern related to the pathognomonic AD characteristic of episodic memory loss.

Transferring cognitive tasks between brain imaging modalities: implications for task design and results interpretation in FMRI studies.

As cognitive neuroscience methods develop, established experimental tasks are used with emerging brain imaging modalities. Here transferring a paradigm (the visual oddball task) with a long history of behavioral and electroencephalography (EEG) experiments to a functional magnetic resonance imaging (fMRI) experiment is considered. The aims of this paper are to briefly describe fMRI and when its use is appropriate in cognitive neuroscience; illustrate how task design can influence the results of an fMRI experiment, particularly when that task is borrowed from another imaging modality; explain the practical aspects of performing an fMRI experiment. It is demonstrated that manipulating the task demands in the visual oddball task results in different patterns of blood oxygen level dependent (BOLD) activation. The nature of the fMRI BOLD measure means that many brain regions are found to be active in a particular task. Determining the functions of these areas of activation is very much dependent on task design and analysis. The complex nature of many fMRI tasks means that the details of the task and its requirements need careful consideration when interpreting data. The data show that this is particularly important in those tasks relying on a motor response as well as cognitive elements and that covert and overt responses should be considered where possible. Furthermore, the data show that transferring an EEG paradigm to an fMRI experiment needs careful consideration and it cannot be assumed that the same paradigm will work equally well across imaging modalities. It is therefore recommended that the design of an fMRI study is pilot tested behaviorally to establish the effects of interest and then pilot tested in the fMRI environment to ensure appropriate design, implementation and analysis for the effects of interest.

"Early to bed, early to rise": diffusion tensor imaging identifies chronotype-specificity.

Sleep and wakefulness are crucial prerequisites for cognitive efficiency, the disturbances of which severely impact performance and mood as present e.g. after time zone traveling, in shift workers or patients with sleep or affective disorders. Based on their individual disposition to sleep and wakefulness, humans can be categorized as early (EC), late (LC) or intermediate (IC) chronotypes. While ECs tend to wake up early in the morning and find it difficult to remain awake beyond their usual bedtime, LCs go to bed late and have difficulties getting up. Beyond sleep/wake timings, chronotypes show distinct patterns of cognitive performance, gene expression, endocrinology and lifestyle. However, little is known about brain structural characteristics potentially underlying differences. Specifically, white matter (WM) integrity is crucial for intact brain function and has been related to various lifestyle habits, suggesting differences between chronotypes. Hence, the present study draws on Diffusion Tensor Imaging as a powerful tool to non-invasively probe WM architecture in 16 ECs, 23 LCs and 20 ICs. Track-based spatial statistics highlight that LCs were characterized by WM differences in the frontal and temporal lobes, cingulate gyrus and corpus callosum. Results are discussed in terms of findings reporting late chronotypes to exhibit a chronic form of jet lag accompanied with sleep disturbances, vulnerability to depression and higher consumption of nicotine and alcohol. This study has far-reaching implications for health and the economy. Ideally, work schedules should fit in with chronotype-specificity whenever possible.

Do EEG paradigms work in fMRI? Varying task demands in the visual oddball paradigm: Implications for task design and results interpretation.

We investigate the effects of variations in response requirements on BOLD activation in a visual oddball task and consider implications for fMRI task designs. Sixteen healthy subjects completed 3 runs of a visual oddball task: passive, count and respond. Besides expected activation patterns during passive viewing, we identified joint activations, but more importantly crucial differences between the count and respond versions of the task. Middle frontal gyrus activation was seen in the respond but not the count condition suggesting that this region is associated with action execution rather than the decision-making aspect of the task. In addition, activation observed in the central opercular cortex and parietal operculum in the respond (but not count) condition is likely to reflect integration of the sensory, decision and response processes. We also observed activation in the supplementary motor area (SMA) during count as well as respond. Since the count condition requires no motor planning or response our data provide evidence for an SMA involvement in decision-making. Our study clearly shows that the count and respond versions of the visual oddball task result in different patterns of BOLD activation that could both be attributed to 'target detection' if information on the respective other condition was not available. We also show that considering the elements of a complex task is crucial when transferring it from one imaging modality to another and that a motor response is not always necessary in fMRI studies when the task has been set up appropriately.

Parallel imaging acceleration of EPIK for reduced image distortions in fMRI.

EPI with Keyhole (EPIK) is a hybrid imaging technique used to improve the performance of EPI in dynamic MRI applications. The method had been previously validated at 1.5 T with both phantom and in vivo images; EPIK was able to provide a higher temporal resolution and less image distortions than single-shot EPI. The data presented here demonstrate that the performance of EPIK can be further improved by accelerating it with the parallel imaging. For this work, this combination was tested at 3 T. After initial evaluation using phantom images, use of the method in functional MRI was verified with visual fMRI measurements as well as MRI simulation results. The results showed that accelerated EPIK had increased temporal resolution with favorable robustness against susceptibility artifacts when compared with EPI or non-accelerated EPIK.

Young adults at risk for stimulant dependence show reward dysfunction during reinforcement-based decision making.

BACKGROUND: While stimulant-dependent individuals continue to make risky decisions, in spite of poor outcomes, much less is known about decision-making characteristics of occasional stimulant users (OSU) at risk for developing stimulant dependence. This study examines whether OSU exhibit inefficient learning and execution of reinforced decision-outcome contingencies. METHODS: Occasional stimulant users (n = 161) and stimulant-naïve comparison subjects (CTL) (n = 48) performed a Paper Scissors Rock task during functional magnetic resonance imaging. Selecting a particular option was associated with a predetermined probability of winning, which was altered repeatedly to examine neural and behavioral characteristics of reinforced contingencies. RESULTS: Occasional stimulant users displayed greater anterior insula, inferior frontal gyrus, and dorsal striatum activation than CTL during late trials when contingencies were familiar (as opposed to being learned) in the presence of comparable behavioral performance in both groups. Follow-up analyses demonstrated that during late trials: 1) OSU with high cannabis use displayed greater activation in these brain regions than CTL, whereas OSU with low cannabis use did not differ from the other two groups; and 2) OSU preferring cocaine exhibited greater anterior insula, inferior frontal gyrus, and dorsal striatum activation than CTL and also displayed higher activation in the former two regions than OSU who preferred prescription stimulants. CONCLUSIONS: Occasional stimulant users exhibit inefficient resource allocation during the execution of reinforced contingencies that may be a result of additive effects of cocaine and cannabis use. A critical next step is to establish whether this inefficiency predicts transition to stimulant dependence.

EEG acquisition in ultra-high static magnetic fields up to 9.4 T.

The simultaneous acquisition of electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) data has gained momentum in recent years due to the synergistic effects of the two modalities with regard to temporal and spatial resolution. Currently, only EEG-data recorded in fields of up to 7 T have been reported. We investigated the feasibility of recording EEG inside a 9.4 T static magnetic field, specifically to determine whether meaningful EEG information could be recovered from the data after removal of the cardiac-related artefact. EEG-data were recorded reliably and reproducibly at 9.4 T and the cardiac-related artefact increased in amplitude with increasing B0, as expected. Furthermore, we were able to correct for the cardiac-related artefact and identify auditory event related responses at 9.4 T in 75% of subjects using independent component analysis (ICA). Also by means of ICA we detected event related spectral perturbations (ERSP) in subjects at 9.4 T in response to opening/closing the eyes comparable with the response at 0 T. Overall our results suggest that it is possible to record meaningful EEG data at ultra-high magnetic fields. The simultaneous EEG-fMRI approach at ultra-high-fields opens up the horizon for investigating brain dynamics at a superb spatial resolution and a temporal resolution in the millisecond domain.

Cholinergic blockade under working memory demands encountered by increased rehearsal strategies: evidence from fMRI in healthy subjects.

The connection between cholinergic transmission and cognitive performance has been established in behavioural studies. The specific contribution of the muscarinic receptor system on cognitive performance and brain activation, however, has not been evaluated satisfyingly. To investigate the specific contribution of the muscarinic transmission on neural correlates of working memory, we examined the effects of scopolamine, an antagonist of the muscarinic receptors, using functional magnetic resonance imaging (fMRI). Fifteen healthy male, non-smoking subjects performed a fMRI scanning session following the application of scopolamine (0.4 mg, i.v.) or saline in a placebo-controlled, repeated measure, pseudo-randomized, single-blind design. Working memory was probed using an n-back task. Compared to placebo, challenging the cholinergic transmission with scopolamine resulted in hypoactivations in parietal, occipital and cerebellar areas and hyperactivations in frontal and prefrontal areas. These alterations are interpreted as compensatory strategies used to account for downregulation due to muscarinic acetylcholine blockade in parietal and cerebral storage systems by increased activation in frontal and prefrontal areas related to working memory rehearsal. Our results further underline the importance of cholinergic transmission to working memory performance and determine the specific contribution of muscarinic transmission on cerebral activation associated with executive functioning.

Latencies in BOLD response during visual attention processes.

One well-investigated division of attentional processes focuses on alerting, orienting and executive control, which can be assessed applying the attentional network test (ANT). The goal of the present study was to add further knowledge about the temporal dynamics of relevant neural correlates. As a right hemispheric dominance for alerting and orienting has previously been reported for intrinsic but not for phasic alertness, we additionally addressed a potential impact of this lateralization of attention by employing a lateralized version of the ANT, capturing phasic alertness processes. Sixteen healthy subjects underwent event-related functional magnetic resonance imaging (fMRI) while performing the ANT. Analyses of BOLD magnitude replicated the engagement of a fronto-parietal network in the attentional subsystems. The amplitudes of the attentional contrasts interacted with visual field presentation in the sense that the thalamus revealed a greater involvement for spatially cued items presented in the left visual field. Comparisons of BOLD latencies in visual cortices, first, verified faster BOLD responses following contra-lateral stimulus presentation. Second and more importantly, we identified attention-modulated activation in secondary visual and anterior cingulate cortices. Results are discussed in terms of bottom-up and lateralization processes. Although intrinsic and phasic alertness are distinct cognitive processes, we propose that neural substrates of intrinsic alertness may be accessed by phasic alertness provided that the attention-dominant (i.e., the right) hemisphere is activated directly by a warning stimulus.

Evidence for subtle verbal fluency deficits in occasional stimulant users: quick to play loose with verbal rules.

Psychostimulants like cocaine and amphetamine are commonly abused by young adults who often state that they take these drugs to increase social or cognitive performance. The current study tested the hypothesis that individuals at early stages of occasional stimulant use show subtle executive dysfunctions such as verbal fluency deficits. 155 young (age 18-25), non-dependent occasional users of stimulants and 49 stimulant naïve comparison subjects performed the Delis-Kaplan Verbal Fluency test. Correlation and median split analyses were conducted to account for stimulant history and co-drug use. Compared to stimulant naïve subjects, occasional stimulant users generated significantly more responses on an over-learned verbal fluency task (Category Fluency), but at the expense of increased error rates (Set Loss and Repetition Errors). These performance differences were not related to lifetime uses of stimulants or marijuana. Taken together, these results support the hypothesis that individuals who are using stimulants occasionally exhibit subtle executive dysfunctions when required to generate verbal sets under time pressure. In particular, occasional stimulant users apply quickly but inaccurately verbal rules, which may represent a mix of diminished cognitive flexibility along with increased rigidity and impulsivity. This specific executive dysfunction may help to identify individuals at risk for stimulant use or dependence.

Cognitive performance and cholinergic transmission: influence of muscarinic and nicotinic receptor blockade.

The cholinergic system is essential in mediating cognitive processes. Although there has been extensive research regarding cholinergic receptor subsystems, the specific contribution of the muscarinic and nicotinic receptor system to cognitive processes still has not been sufficiently explored. In the present study, we examined the selective contribution of muscarinic and nicotinic antagonism to cognitive performance in healthy human subjects. A single-blind, double-dummy, time-elapsed, repeated measures cross-over design was used on 15 healthy males. Subjects completed a neuropsychological test battery assessing a wide range of cognitive domains after 0.4 mg scopolamine (intravenous), 0.2 mg/kg mecamylamine (max. 15 mg; oral) or placebo. Subjects were tested under three conditions: placebo/placebo (PP), scopolamine/placebo (SP) and mecamylamine/placebo (MP). Results show that scopolamine significantly impaired the free recall and recognition performance in the verbal learning test. No other cognitive domain was affected, neither by scopolamine nor by mecamylamine. In line with the existing literature, antagonism of muscarinic receptors resulted in specific cognitive impairments, predominantly memory performance.