Peter Bublak

Effects of modafinil on working memory processes in humans

RationaleModafinil is a well-tolerated psychostimulant drug with low addictive potential that is used to treat patients with narcolepsy or attention deficit disorders and to enhance vigilance in sleep-deprived military personal. So far, understanding of the cognitive enhancing effects of modafinil and the relevant neurobiological mechanisms are incomplete.ObjectivesThe aim of this study was to investigate the effects of modafinil on working memory processes in humans and how they are related to noradrenergic stimulation of the prefrontal cortex.MethodsSixteen healthy volunteers (aged 20–29 years) received either modafinil 200xa0mg or placebo using a double blind crossover design. Two computerized working memory tasks were administered, a numeric manipulation task that requires short-term maintenance of digit-sequences and different degrees of manipulation as well as delayed matching task that assesses maintenance of visuo-spatial information over varying delay lengths. The battery was supplemented by standardized paper pencil tasks of attentional functions.ResultsModafinil significantly reduced error rates in the long delay condition of the visuo-spatial task and in the manipulation conditions, but not in the maintenance condition of the numeric task. Analyses of reaction times showed no speed-accuracy trade-off. Attentional control tasks (letter cancellation, trail-making, catch trials) were not affected by modafinil.ConclusionsIn healthy volunteers without sleep deprivation modafinil has subtle stimulating effects on maintenance and manipulation processes in relatively difficult and monotonous working memory tasks, especially in lower performing subjects. Overlapping attentional and working memory processes have to be considered when studying the noradrenergic modulation of the prefrontal cortex.

Effects of modafinil and methylphenidate on visual attention capacity: a TVA-based study

IntroductionTheory of visual attention (TVA; Bundesen 1990) whole report tasks allow the independent measurement of visual perceptual processing speed and visual short-term memory (vSTM) storage capacity, unconfounded by motor speed. This study investigates how cognitive enhancing effects of psychostimulants depend on baseline performance and individual plasma levels.Materials and methodsEighteen healthy volunteers (aged 20–35xa0years) received single oral doses of either 40xa0mg methylphenidate, 400xa0mg modafinil or placebo in a counterbalanced, double-blind crossover design. A whole report of visually presented letter arrays was performed 2.5–3.5xa0h after drug administration, and blood samples for plasma level analysis were taken.ResultsMethylphenidate and modafinil both enhanced perceptual processing speed in participants with low baseline (placebo) performance. These improvements correlated with subjective alertness. Furthermore, we observed differential plasma level-dependent effects of methylphenidate in lower and higher performing participants: higher plasma levels led to a greater improvement in low-performing participants and to decreasing improvement in high-performing participants. Modafinil enhanced visual short-term memory storage capacity in low-performing participants.ConclusionsThis is the first pharmacological investigation demonstrating the usefulness of a TVA task for high-resolution and repeated cognitive parameter estimation after cognitive-enhancing medication. Our results confirm previous findings of attentional capacity improvements in low performers and extend the baseline dependency model to methylphenidate. Plasma level-dependent effects of psychostimulants can be modelled on an inverted U-shaped dose–response relationship, which is highly relevant to predict cognitive enhancing and detrimental effects of psychostimulants in patients with cognitive deficits (e.g., attention deficit hyperactivity disorder) and healthy volunteers (e.g., self-medicating academics).

Manipulation of working memory information is impaired in Parkinson's disease and related to working memory capacity

It has been suggested that in patients with Parkinsons disease (PD), difficulties in the manipulation of information, which result in problems in executive tasks, are related to a reduction of working memory capacity (J. D. E. Gabrieli, J. Singh, G. T. Stebbins, & C. G. Goetz, 1996). The present study selectively varied the manipulation demand irrespective of the maintenance requirement. In a group of 14 PD patients, performance declined overproportionally with the increasing task demand and was significantly correlated with a measure of working memory capacity. These results suggest that the complexity of working memory processing may decisively contribute to the exhaustion of resources in PD patients. Increasing complexity may either affect their manipulation ability directly or impede the management of inhibitory control requirements inherent to the task.

Cortical areas and the control of self-determined finger movements: an fMRI study.

WE investigated cortical areas involved in the control of self-determined finger movements. In a tapping task, subjects tapped with different movement frequencies in two different movement conditions (predetermined vs self-determined). fMRI provided evidence for the involvement of the horizontal and ascending parts of the intraparietal sulcus (IPS), the left superior frontal gyrus and the posterior cingulate gyrus in the control of self-determined finger movements. Higher movement frequency increased the extent of activated area only in the horizontal part of IPS. The results suggest a major role of the IPS in controlling sequences of finger movements. This area probably serves as a region for integration of motor, sensory and sensorimotor feedback information used for movement control.

Noradrenergic blockade and numeric working memory in humans

To investigate the noradrenergic modulation of working memory in humans single doses of two β-blockers [either 25 mg of propranolol (lipophilic) or 50 mg of atenolol (hydrophilic)] or placebo were administered to young healthy volunteers (16 subjects per drug condition) performing a numerical working memory task that requires either short-term maintenance or maintenance plus manipulation of visually presented four-number sequences. Higher manipulation costs (i.e. process-specific slowing of reaction times in the manipulation conditions compared to the control condition) were observed after propranolol but not after atenolol. The propranolol effect was mainly observed in subjects with low emotional arousal (i.e. low state anxiety rating at baseline). Because both β-blockers induced a comparable decrease of blood pressure and pulse, the propranolol effect on the ‘working component’ of working memory is considered to be a central, presumably prefrontal one.

Differential demands on working memory for guiding a simple action sequence: evidence from closed-head-injured subjects.

In the present study, a working memory paradigm was used to assess coordinative abilities required for the flexible control of a sequence of actions. Subjects had to maintain and recall a list of digits that functioned as an ensemble of activity cues used for guiding a sequence of forced-choice responses. In three task conditions, the demand on the selection of the activity cues was varied parametrically to manipulate the requirement of coordinating maintenance and processing operations of working memory for guiding the response sequences. A comparison between subjects suffering from severe closed head injury (CHI) and matched controls in a blocked presentation of task conditions revealed that patients, in contrast to controls, did not preplan the sequence by rearranging the ensemble of activity cues prior to execution of the action sequence. Patients performance was more comparable to controls tested in a random presentation in which preplanning was not possible. Our results further suggest that patients are less efficient in selecting activity cues from working memory, especially in more demanding situations when activity cues have to be completely reordered for guiding a sequence of actions. These results point to an executive dysfunction in CHI subjects that may contribute to the deficits known as inflexible and rigid behavior.

Inhibitory and facilitatory location priming in patients with left-sided visual hemi-neglect

In visual search for pop-out targets, reaction times are facilitated when the target on the current trial appears at a previous target location, and inhibited when it appears at a previous distractor location, relative to when it appears at a previously empty (neutral) location (Maljkovic and Nakayama, Perception and Psychophysics 58:977–991, 1996). However, while normal subjects are able to positively/negatively tag selected target/rejected distractor locations to guide search on the next trial, patients with visual hemi-neglect may have a (uni- or bilateral) deficit in these functions that may contribute to their disturbed visual scanning behavior. To examine this, using a pop-out search task, the present study assessed cross-trial facilitatory and inhibitory priming in 14 patients with left-sided visual hemi-neglect and in 14 age-, education-, and IQ-matched control subjects. The group of neglect patients did show significant facilitatory and inhibitory priming. However, while control subjects exhibited balanced effects of facilitation and inhibition, inhibition was relatively reduced in magnitude in neglect patients. In particular, inhibition was virtually absent in two patients with lesions affecting superior regions of the frontal cortex, putatively encroaching on the frontal eye field of the right hemisphere. These findings provide neuropsychological evidence that facilitatory and inhibitory priming effects are based on dissociable mechanisms, consistent with Geyer et al. (Journal of Experimental Psychology: Human Perception and Performance 33:788–797, 2007).

Therapie zerebraler visueller Wahrnehmungsstörungen

ZusammenfassungZerebrale Sehstörungen treten häufig (20–40%) nach einer Hirnschädigung auf. Hierzu zählen homonyme Gesichtsfeldausfälle und assoziierte Lese- und Explorationsdefizite, Einbußen im Visus, Kontrastsehen, der Hell-/Dunkeladaptation, der Fusion sowie visuell-räumliche Wahrnehmungsstörungen, der multimodale Neglekt sowie das Balint-Syndrom. Die Leitsymptome bei den Gesichtsfeldausfällen sind Anstoßen an/Übersehen von Hindernisse(n) und langsames, fehlerhaftes Lesen. Leitsymptom bei reduziertem Visus und Kontrastsehen ist Verschwommensehen. Patienten mit Helladaptationsstörungen sind blendempfindlich, solche mit Dunkeladaptationsstörung benötigen mehr Licht. Fusionsstörungen führen rasch zu Verschwommensehen und asthenopischen Beschwerden. Räumliche Defizite stehen im Vordergrund beim Neglektsyndrom. Massive räumliche und Aufmerksamkeitseinbußen finden sich beim Balint-Holmes-Syndrom. Die Behandlungsverfahren lassen sich dem Restitutions-, Kompensations- oder Substitutionsansatz zuordnen. Für den multimodalen Neglekt stehen inzwischen neue und wirksame Behandlungsverfahren zur Verfügung. Für das Balint-Holmes-Syndrom existieren derzeit nur Behandlungsansätze.AbstractCerebral visual disorders are frequent after brain damage (20–40%). Among them, homonymous field defects and associated reading and visual exploration disorders, reduced visual acuity, contrast sensitivity and light/dark adaptation, fusional disorders, visuospatial deficits, multimodal hemineglect, and Balint-Holmes syndrome are the most common. Prototypical symptoms are the omission of obstacles and hemianopic alexia in visual field disorders, blurred vision in reduced acuity and/or contrast sensitivity or impaired fusion, blinding in impaired light adaptation and dark vision in impaired dark adaptation, and impaired action and orientation in visuospatial deficits. Neglect is characterized by omissions of stimuli on the contralesional side in space or the body. Patients with Balint-Holmes syndrome show severe spatial and attentional deficits. Systematic treatments can be categorized as restitution, compensation, and substitution approaches. Hemineglect can be ameliorated by novel, more effective treatment approaches, whereas only initial stages of treatment are available for Balint-Holmes syndrome.

Therapy for cerebral visual perception disturbances

ZusammenfassungZerebrale Sehstörungen treten häufig (20–40%) nach einer Hirnschädigung auf. Hierzu zählen homonyme Gesichtsfeldausfälle und assoziierte Lese- und Explorationsdefizite, Einbußen im Visus, Kontrastsehen, der Hell-/Dunkeladaptation, der Fusion sowie visuell-räumliche Wahrnehmungsstörungen, der multimodale Neglekt sowie das Balint-Syndrom. Die Leitsymptome bei den Gesichtsfeldausfällen sind Anstoßen an/Übersehen von Hindernisse(n) und langsames, fehlerhaftes Lesen. Leitsymptom bei reduziertem Visus und Kontrastsehen ist Verschwommensehen. Patienten mit Helladaptationsstörungen sind blendempfindlich, solche mit Dunkeladaptationsstörung benötigen mehr Licht. Fusionsstörungen führen rasch zu Verschwommensehen und asthenopischen Beschwerden. Räumliche Defizite stehen im Vordergrund beim Neglektsyndrom. Massive räumliche und Aufmerksamkeitseinbußen finden sich beim Balint-Holmes-Syndrom. Die Behandlungsverfahren lassen sich dem Restitutions-, Kompensations- oder Substitutionsansatz zuordnen. Für den multimodalen Neglekt stehen inzwischen neue und wirksame Behandlungsverfahren zur Verfügung. Für das Balint-Holmes-Syndrom existieren derzeit nur Behandlungsansätze.AbstractCerebral visual disorders are frequent after brain damage (20–40%). Among them, homonymous field defects and associated reading and visual exploration disorders, reduced visual acuity, contrast sensitivity and light/dark adaptation, fusional disorders, visuospatial deficits, multimodal hemineglect, and Balint-Holmes syndrome are the most common. Prototypical symptoms are the omission of obstacles and hemianopic alexia in visual field disorders, blurred vision in reduced acuity and/or contrast sensitivity or impaired fusion, blinding in impaired light adaptation and dark vision in impaired dark adaptation, and impaired action and orientation in visuospatial deficits. Neglect is characterized by omissions of stimuli on the contralesional side in space or the body. Patients with Balint-Holmes syndrome show severe spatial and attentional deficits. Systematic treatments can be categorized as restitution, compensation, and substitution approaches. Hemineglect can be ameliorated by novel, more effective treatment approaches, whereas only initial stages of treatment are available for Balint-Holmes syndrome.

Therapie zerebraler visueller Wahrnehmungsstörungen@@@Therapy for cerebral visual perception disturbances

ZusammenfassungZerebrale Sehstörungen treten häufig (20–40%) nach einer Hirnschädigung auf. Hierzu zählen homonyme Gesichtsfeldausfälle und assoziierte Lese- und Explorationsdefizite, Einbußen im Visus, Kontrastsehen, der Hell-/Dunkeladaptation, der Fusion sowie visuell-räumliche Wahrnehmungsstörungen, der multimodale Neglekt sowie das Balint-Syndrom. Die Leitsymptome bei den Gesichtsfeldausfällen sind Anstoßen an/Übersehen von Hindernisse(n) und langsames, fehlerhaftes Lesen. Leitsymptom bei reduziertem Visus und Kontrastsehen ist Verschwommensehen. Patienten mit Helladaptationsstörungen sind blendempfindlich, solche mit Dunkeladaptationsstörung benötigen mehr Licht. Fusionsstörungen führen rasch zu Verschwommensehen und asthenopischen Beschwerden. Räumliche Defizite stehen im Vordergrund beim Neglektsyndrom. Massive räumliche und Aufmerksamkeitseinbußen finden sich beim Balint-Holmes-Syndrom. Die Behandlungsverfahren lassen sich dem Restitutions-, Kompensations- oder Substitutionsansatz zuordnen. Für den multimodalen Neglekt stehen inzwischen neue und wirksame Behandlungsverfahren zur Verfügung. Für das Balint-Holmes-Syndrom existieren derzeit nur Behandlungsansätze.AbstractCerebral visual disorders are frequent after brain damage (20–40%). Among them, homonymous field defects and associated reading and visual exploration disorders, reduced visual acuity, contrast sensitivity and light/dark adaptation, fusional disorders, visuospatial deficits, multimodal hemineglect, and Balint-Holmes syndrome are the most common. Prototypical symptoms are the omission of obstacles and hemianopic alexia in visual field disorders, blurred vision in reduced acuity and/or contrast sensitivity or impaired fusion, blinding in impaired light adaptation and dark vision in impaired dark adaptation, and impaired action and orientation in visuospatial deficits. Neglect is characterized by omissions of stimuli on the contralesional side in space or the body. Patients with Balint-Holmes syndrome show severe spatial and attentional deficits. Systematic treatments can be categorized as restitution, compensation, and substitution approaches. Hemineglect can be ameliorated by novel, more effective treatment approaches, whereas only initial stages of treatment are available for Balint-Holmes syndrome.