Persistent cognitive slowing in post-COVID patients: longitudinal study over 6 months.

BACKGROUND: Fatigue is a frequent and one of the most debilitating symptoms in post-COVID syndrome (PCS). Recently, we proposed that fatigue is caused by hypoactivity of the brain's arousal network and reflected by a reduction of cognitive processing speed. However, it is unclear whether cognitive slowing is revealed by standard neuropsychological tests, represents a selective deficit, and how it develops over time. OBJECTIVES: This prospective study assesses whether PCS patients show deficits particularly in tests relying on processing speed and provides the first longitudinal assessment focusing on processing speed in PCS patients. METHODS: Eighty-eight PCS patients with cognitive complaints and 50 matched healthy controls underwent neuropsychological assessment. Seventy-seven patients were subsequently assessed at 6-month follow-up. The Test for Attentional Performance measured tonic alertness as primary study outcome and additional attentional functions. The Neuropsychological Assessment Battery evaluated all key cognitive domains. RESULTS: Patients showed cognitive slowing indicated by longer reaction times compared to control participants (r = 0.51, p < 0.001) in a simple-response tonic alertness task and in all more complex tasks requiring speeded performance. Reduced alertness correlated with higher fatigue (r = - 0.408, p < 0.001). Alertness dysfunction remained unchanged at 6-month follow-up (p = 0.240) and the same was true for most attention tasks and cognitive domains. CONCLUSION: Hypoarousal is a core deficit in PCS which becomes evident as a selective decrease of processing speed observed in standard neuropsychological tests. This core deficit persists without any signs of amelioration over a 6-month period of time.

The Relationship Between Cognitive Impairments and Sleep Quality Measures in Persistent Insomnia Disorder.

Study Objectives: Persistent insomnia disorder (pID) is linked to neurocognitive decline and increased risk of Alzheimer's Disease (AD) in later life. However, research in this field often utilizes self-reported sleep quality data - which may be biased by sleep misperception - or uses extensive neurocognitive test batteries - which are often not feasible in clinical settings. This study therefore aims to assess whether a simple screening tool could uncover a specific pattern of cognitive changes in pID patients, and whether these relate to objective aspect(s) of sleep quality. Methods: Neurocognitive performance (Montreal Cognitive Assessment; MoCA), anxiety/depression severity, and subjective sleep quality (Pittsburgh Sleep Quality Index: PSQI; Insomnia Severity Index: ISI) data were collected from 22 middle-aged pID patients and 22 good-sleepers. Patients underwent overnight polysomnography. Results: Compared to good-sleepers, patients had lower overall cognitive performance (average: 24.6 versus 26.3 points, Mann-Whitney U = 136.5, p = <0.006), with deficits in clock drawing and verbal abstraction. In patients, poorer overall cognitive performance correlated with reduced subjective sleep quality (PSQI: r(42) = -0.47, p = 0.001; and ISI: r(42) = -0.43, p = 0.004), reduced objective sleep quality (lower sleep efficiency: r(20) = 0.59, p = 0.004 and less REM-sleep: r(20) = 0.52, p = 0.013; and increased sleep latency: r(20) = -0.57, p = 0.005 and time awake: r(20) = -0.59, p = 0.004). Cognitive performance was not related to anxiety/depression scores. Conclusion: Using a simple neurocognitive screening tool, we found that pID patients showed cognitive deficiencies that related to both subjective/self-reported and objective/polysomnographic measures of sleep quality. Furthermore, these cognitive changes resembled those seen in preclinical non-amnestic AD, and thus could indicate incumbent neurodegenerative processes in pID. Interestingly, increased REM-sleep was correlated with better cognitive performance. However, whether REM-sleep is protective against neurodegeneration requires further investigation.

Neural distinctiveness of fatigue and low sleep quality in multiple sclerosis.

BACKGROUND AND PURPOSE: Fatigue and low sleep quality in multiple sclerosis (MS) are closely related symptoms. Here, the associations between the brain's functional connectivity (FC) and fatigue and low sleep quality were investigated to determine the degree of neural distinctiveness of these symptoms. METHOD: A hundred and four patients with relapsing-remitting MS (age 38.9 ± 10.2 years, 66 females) completed the Modified Fatigue Impact Scale and the Pittsburgh Sleep Quality Index and underwent resting-state functional magnetic resonance imaging. FC was analyzed using independent-component analysis in sensorimotor, default-mode, fronto-parietal and basal-ganglia networks. Multiple linear regression models allowed us to test the association between FC and fatigue and sleep quality whilst controlling for one another as well as for demographic, disease-related and imaging variables. RESULTS: Higher fatigue correlated with lower sleep quality (r = 0.54, p < 0.0001). Higher fatigue was associated with lower FC of the precentral gyrus in the sensorimotor network, the precuneus in the posterior default-mode network and the superior frontal gyrus in the left fronto-parietal network, independently of sleep quality. Lower sleep quality was associated with lower FC of the left intraparietal sulcus in the left fronto-parietal network, independently of fatigue. Specific associations were found between fatigue and the sensorimotor network's global FC and between low sleep quality and the left fronto-parietal network's global FC. CONCLUSION: Despite the high correlation between fatigue and low sleep quality in the clinical picture, our findings clearly indicate that, on the neural level, fatigue and low sleep quality in MS are associated with decreased FC in distinct functional brain networks.

Systematic quantitative assessment of motor function in clinically isolated REM sleep behaviour disorder: A diagnostic window into early alpha-synucleinopathies.

Mild motor abnormalities can herald the beginning of Parkinson´s disease but their diagnostic value is limited by multifactorial ageing-related influences on motor function. We characterized mild motor abnormalities in different motor domains by conducting a systematic motor assessment in 20 patients with clinically isolated REM sleep behaviour disorder (iRBD) without parkinsonian motor signs and 20 healthy controls. We addressed the influence of lifestyle factors and age on motor function, which needs to be distinguished from neurodegenerative motor features, and assessed the diagnostic value of innovative and established quantitative motor tests in iRBD. Patients with iRBD showed abnormalities in perceptual motor speed (falling stick test), trunk movement coordination (bend, twist and touch test) and dynamic balance (line walk test) without alterations in simple motor speed (alternate tap test), dexterity (grooved pegboard), static balance (force plate) and gait (timed up and go test). The falling stick test showed the highest diagnostic accuracy in identifying subjects with RBD (ROC-AUC 0.85, p ≤ 0.001). Multivariate analysis revealed physical activity and age as additional determinants of motor test performance. iRBD comprises a wide spectrum of mild motor abnormalities which cannot be verified by established tests for motor speed, gait and balance. The falling stick test, an innovative screening test for perceptual motor speed, provides high diagnostic potential in identifying subjects with subclinical neurodegenerative symptoms before parkinsonian motor signs become apparent. Normative data for physical activity and age need to be obtained to ensure correct interpretation of motor test results in prodromal Parkinson-related disease.

A smart peek: Processing of rapid visual displays is disturbed in newly diagnosed, cognitively intact MS patients and refers to cognitive performance and disease progression in late stages.

BACKGROUND: MS can reduce the speed of information processing (IPS) leading to a variable pattern of cognitive impairment. To better understand this deficit, a separate evaluation of the sensory, cognitive, and motor speed component is required. Tests using rapid visual displays allow for assessment of separate components of information uptake. We utilized such a test to compare deficit profiles at the earlier and later stage of MS and their relation to cognitive ability and disease progression. METHOD: Two groups were evaluated: "Early MS" comprised N = 24 patients with disease durations <2 years; "late MS" N = 45 with disease durations >12 years. Rapid visual displays of letters were utilized to derive individual profiles of visual information uptake according to the 'theory of visual attention' (TVA). The resulting data was then compared with measures of disability, fatigue, depression, IPS, visual-spatial ability, verbal and visual memory. RESULTS: In the EMS group, where cognitive impairment was the exception, three of the four main parameters of visual information uptake were already modified, i.e. processing rate C, storage capacity K, and iconic memory µ. In LMS an additional elevation of the fourth parameter, i.e., the perceptual threshold t0 was evident. Threshold values were related to most clinical and cognitive measures. CONCLUSIONS: An early deficit pattern of visual information uptake can be detected at a stage, when performance in tests of IPS is still well-preserved. At later disease stages, a single parameter reflecting the threshold of conscious visual perception may provide a valid estimate of cognitive performance and disease progression.

Dual Task Effects on Visual Attention Capacity in Normal Aging.

Older adults show higher dual task performance decrements than younger adults. While this is assumed to be related to attentional capacity reductions, the precise affected functions are not specified. Such specification is, however, possible based on the "theory of visual attention" (TVA) which allows for modeling of distinct attentional capacity parameters. Furthermore, it is unclear whether older adults show qualitatively different attentional effects or whether they show the same effects as younger adults experience under more challenging conditions. By varying the complexity of the secondary task, it is possible to address this question. In our study, participants performed a verbal whole report of briefly presented letter arrays. TVA-based fitting of report performance delivered parameters of visual threshold t0, processing speed C, and visual short-term memory (VSTM) storage capacity K. Furthermore, participants performed a concurrent motor task consisting of continuous tapping of a (simple or complex) sequence. Both TVA and tapping tasks were performed under single and dual task conditions. Two groups of 30 younger adults each performed either the simple or complex tapping, and a group of 30 older adults performed the simple tapping condition. In older participants, VSTM storage capacity declined under dual task conditions. While no such effect was found in younger subjects performing the simple tapping sequence under dual task conditions, the younger group performing the complex tapping task under dual task conditions also showed a significant VSTM capacity reduction. Generally, no significant effect on other TVA parameters or on tapping accuracy was found. Comparable goodness-of-fit measures were obtained for the TVA modeling data in single and dual tasks, indicating that tasks were executed in a qualitatively similar, continuous manner, although quantitatively less efficiently under dual- compared to single-task conditions. Taken together, our results show that the age-specific effects of motor-cognitive dual task interference are reflected by a stronger decline of VSTM storage capacity. They support an interpretation of VSTM as central attentional capacity, which is shared across visual uptake and concurrent motor performance. Capacity limits are reached earlier, and already under lower motor task complexity, in older compared to younger adults.

Spatial remapping in visual search: Remapping cues are provided at attended and ignored locations.

We experience the world as stable and continuous, despite the fact that visual input is overwritten on the retina with each new ocular fixation. Spatial remapping is the process that integrates selected visual information into successive (continuous) representations of our spatial environment, thereby allowing us to keep track of objects, and experience the world as stable, despite frequent eye (re-)fixations. The present paper investigates spatial remapping in the context of visual pop-out search. Within standard instances of the pop-out paradigm, reactions to stimuli at previously attended locations are facilitated (faster and more accurate), and reactions to stimuli at previously ignored locations are inhibited (slower and less accurate). The mechanisms that support facilitation at previously attended locations, and inhibition at previously ignored locations, serve to enhance the efficiency of visual search. It is thus natural to expect that information about which locations were previously attended to or ignored is stored and remapped as a concomitant to successive representations of the spatial environment. Using variants of the pop-out paradigm, we corroborate this expectation, and show that information concerning the prior status of locations, as attended to or ignored, is remapped following attention shifts, with some degradation of information concerning ignored locations.

Automatic affective responses towards the bed in patients with primary insomnia: evidence for a negativity bias.

Ruminating about sleep problems and negatively valenced thinking play a key role in the maintenance of sleep complaints in patients with insomnia. Based on associative learning principles, we hypothesized that repeated co-occurrence of negative thoughts (unconditioned stimulus) and the bedroom environment (conditioned stimulus) results in automatic negative affective responses towards the bed (conditioned response). Twenty-two insomniacs and 22 good sleepers performed a Single-Target Implicit Association Test measuring the strength of automatically triggered affective responses towards the bed. Results revealed a significant group difference, indicating a stronger negative affective response towards the bed in patients with insomnia. No correlations were found between the strength of negative affective responses towards the bed and subjective measures of sleep quality. As it might increase the stress experience further during bedtime, automatic negative responses towards the bed are likely to represent an additional factor accounting for the development and maintenance of sleep disorders and represent a potential target for therapeutic interventions.

Information processing deficits as a driving force for memory impairment in MS: A cross--sectional study of memory functions and MRI in early and late stage MS.

BACKGROUND: Memory impairment (MI) is a common symptom of MS. Previous studies were conflicting in respect to the possible existence of early MI and the role of hippocampal atrophy. The objective of this study was to investigate MI and structural MRI correlates in homogenous groups of early and late MS, controlling for a potential information-processing speed (IPS) deficit, and utilizing multiple memory test paradigms. METHODS: 152 individually matched subjects were recruited: early MS (EMS, N = 25, disease duration 1.0 ± 0.8 years), late MS (LMS, N = 52, 16.5 ± 5.2 years), and corresponding controls. Five memory tests were utilized to account for differences in learning material (verbal, visual), encoding (incidental, intentional), and retrieval (free recall, recognition, recurring recognition). Performance was related to IPS, memory-specific (hippocampal volumes), and unspecific MRI measures (T1/T2LL, brain volume, cortical thickness). RESULTS: Memory was impaired across all tests in LMS, but not in EMS. LMS-patients were also significantly impaired in IPS which was correlated with several memory scores. Regression analyses revealed IPS and cortical thickness as predictors for visual MI, and IPS, sex, and left hippocampal volume as predictors for verbal MI. CONCLUSION: Additionally to direct destructions in memory specific tracts such as the hippocampus, memory decline in MS may also be related to a general factor comprising slowed information-processing and global tissue loss.

Simultaneous object perception deficits are related to reduced visual processing speed in amnestic mild cognitive impairment.

Simultanagnosia, an impairment in simultaneous object perception, has been attributed to deficits in visual attention and, specifically, to processing speed. Increasing visual attention deficits manifest over the course of Alzheimer's disease (AD), where the first changes are present already in its symptomatic predementia phase: amnestic mild cognitive impairment (aMCI). In this study, we examined whether patients with aMCI due to AD show simultaneous object perception deficits and whether and how these deficits relate to visual attention. Sixteen AD patients with aMCI and 16 age-, gender-, and education-matched healthy controls were assessed with a simultaneous perception task, with shapes presented in an adjacent, embedded, or overlapping manner, under free viewing without temporal constraints. We used a parametric assessment of visual attention based on the Theory of Visual Attention. Results show that patients make significantly more errors than controls when identifying overlapping shapes, which correlate with reduced processing speed. Our findings suggest simultaneous object perception deficits in very early AD, and a visual processing speed reduction underlying these deficits.

Neuro-cognitive mechanisms of simultanagnosia in patients with posterior cortical atrophy.

Posterior cortical atrophy is dominated by progressive degradation of parieto-occipital grey and white matter, and represents in most cases a variant of Alzheimer's disease. Patients with posterior cortical atrophy are characterized by increasing higher visual and visuo-spatial impairments. In particular, a key symptom of posterior cortical atrophy is simultanagnosia i.e. the inability to perceive multiple visual objects at the same time. Two neuro-cognitive mechanisms have been suggested to underlie simultanagnosia, either reduced visual short-term memory capacity or decreased visual processing speed possibly resulting from white matter impairments over and above damage to cortical brain areas. To test these distinct hypotheses, we investigated a group of 12 patients suffering from posterior cortical atrophy with homogenous lesion sides in parieto-occipital cortices and varying severity of grey and white matter loss. More specifically, we (i) tested whether impaired short-term memory capacity or processing speed underlie symptoms of simultanagnosia; (ii) assessed the link to grey and white matter damage; and (iii) integrated those findings into a neuro-cognitive model of simultanagnosia in patients with posterior cortical atrophy. To this end, simultaneous perception of multiple visual objects was tested in patients with posterior cortical atrophy mostly with positive Alzheimer's disease biomarkers and healthy age-matched controls. Critical outcome measures were identification of overlapping relative to non-overlapping figures and visuo-spatial performance in tests sensitive to simultanagnosia. Using whole report of briefly presented letter arrays based on the mathematically formulated 'Theory of Visual Attention', we furthermore quantified parameters of visual short-term memory capacity and visual processing speed. Grey and white matter atrophy was assessed by voxel-based morphometry analyses of structural magnetic resonance data. All patients showed severe deficits of simultaneous perception. Compared to controls, we observed a specific slowing of visual processing speed, while visual short-term memory capacity was preserved. In a regression analysis, processing speed was identified as the only significant predictor of simultaneous perception deficits that explained a high degree of variance (70-82%) across simultanagnosia tasks. More severe slowing was also indicative for more severe impairments in reading and scene comprehension. Voxel-based morphometry yielded extensive reductions of grey and white matter in parieto-occipital and thalamic brain areas. Importantly, the degree of individual atrophy of white matter in left superior parietal lobe, but not of any grey matter region, was associated with processing speed. Based on these findings, we propose that atrophy of white matter commonly observed in posterior cortical atrophy leads to slowing of visual processing speed, which underlies the overt clinical symptoms of simultanagnosia.

The Effect of Spinal Tap Test on Different Sensory Modalities of Postural Stability in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND/AIMS: Postural instability in patients with normal pressure hydrocephalus (NPH) is a most crucial symptom leading to falls with secondary complications. The aim of the current study was to evaluate the therapeutic effect of spinal tap on postural stability in these patients. METHODS: Seventeen patients with clinical symptoms of NPH were examined using gait scale, computerized dynamic posturography (CDP), and neuropsychological assessment. Examinations were done before and after spinal tap test. RESULTS: The gait score showed a significant improvement 24 h after spinal tap test in all subtests and in the sum score (p < 0.003), while neuropsychological assessment did not reveal significant differences 72 h after spinal tap test. CDP showed significant improvements after spinal tap test in the Sensory Organization Tests 2 (p = 0.017), 4 (p = 0.001), and 5 (p = 0.009) and the composite score (p = 0.01). Patients showed best performance in somatosensory and worst performance in vestibular dominated tests. Vestibular dominated tests did not improve significantly after spinal tap test, while somatosensory and visual dominated tests did. CONCLUSION: Postural stability in NPH is predominantly affected by deficient vestibular functions, which did not improve after spinal tap test. Conditions which improved best were mainly independent from visual control and are based on proprioceptive functions.

What you get from what you see: Parametric assessment of visual processing capacity in multiple sclerosis and its relation to cognitive fatigue.

Multiple sclerosis (MS(1)) is a diffusely disseminated inflammatory disease affecting widespread cerebral networks. Major cognitive impairments are a reduction of processing capacity and mental fatigue, i.e., an "abnormal sense of tiredness or lack of energy". Here, the present study provides the first assessment of the distinct components of visual processing capacity based on a 'theory of visual attention' (TVA(2)) in MS patients and relates it to measures of subjective as well as (more) objective fatigue. The performance of 36 relapsing-remitting MS patients in a whole report task of brief letter arrays was compared to healthy control subjects matched for gender, age and education. Additionally, the sustained attention test PASAT-3(3) served as a measure of objective fatigue, and the self-report questionnaire MFIS(4) as a measure of subjective fatigue. Results indicate generally diminished processing speed as well as iconic memory buffers, and increased perceptual thresholds in MS patients compared to healthy controls. Block-wise analysis of attentional parameters shows that the processing speed performance of MS patients declines in the second half of the TVA-based test compared to healthy controls and in particular for patients with high versus low objective fatigue. These findings describe which aspects of processing capacity are impaired in MS, and show that fatigue mainly affects speed of processing. Thus, TVA-based assessment provides a novel approach in the determination of cognitive impairments and fatigue in MS. However, further research is required to elucidate the complex relations of processing capacity and cognitive functions in MS.

How reliable is the classification of cognitive impairment across different criteria in early and late stages of multiple sclerosis?

BACKGROUND: Prevalence rates of cognitive impairment (CI) in multiple sclerosis (MS) vary between 40% and 80%. Differences in classification criteria for CI may explain this variance. OBJECTIVE: This study reviewed and compared classification criteria for CI in patients with early and late MS. METHODS: The paper consists of two parts: a systematic review of published classification criteria and the presentation of new data. Criteria were reviewed in respect to percentage of abnormal parameters and cut-offs concerning standard deviations. Thereafter, criteria were applied to cognitive data of 25 patients with early MS (duration ≤ 2 y), 52 matched patients with late MS (≥ 12 y), and 75 matched controls. The test battery assessed alertness, divided attention, mental flexibility, verbal and visual learning, memory, and visuospatial abilities. RESULTS: Seventy classification criteria were revealed and grouped into 20 distinct approaches that can be subdivided into three basic classification strategies. Most commonly, CI was defined as performing 1.5 SD or 2 SD below the normative mean in 18-30% of test parameters (n=42). Other criteria utilized cognitive domains (n=6), composite indices (n=8), or combinations of cut-offs and strategies. The stringency of the criteria was correlated with the prevalence rate of CI (r=-.43) and disease duration (r=.48). In the new data, a substantial effect of classification criteria was found with a prevalence rate ranging from 0 to 68% in early and 4 to 81% in late MS. Increased rates of CI in patients vs. controls were found following 18 out of 20 criteria in the sample of late MS. In early MS, an increased rate of CI was only found following a liberal 1.5 SD cut-off criterion. Inter-rater reliability between all criteria was moderate. However, between criteria of comparable stringency the inter-rater reliability was found to be strong. CONCLUSION: Classification based on different published criteria is not fully comparable and criteria need to be better homogenized.

A biased competition account of attention and memory in Alzheimer's disease.

The common view of Alzheimer's disease (AD) is that of an age-related memory disorder, i.e. declarative memory deficits are the first signs of the disease and associated with progressive brain changes in the medial temporal lobes and the default mode network. However, two findings challenge this view. First, new model-based tools of attention research have revealed that impaired selective attention accompanies memory deficits from early pre-dementia AD stages on. Second, very early distributed lesions of lateral parietal networks may cause these attention deficits by disrupting brain mechanisms underlying attentional biased competition. We suggest that memory and attention impairments might indicate disturbances of a common underlying neurocognitive mechanism. We propose a unifying account of impaired neural interactions within and across brain networks involved in attention and memory inspired by the biased competition principle. We specify this account at two levels of analysis: at the computational level, the selective competition of representations during both perception and memory is biased by AD-induced lesions; at the large-scale brain level, integration within and across intrinsic brain networks, which overlap in parietal and temporal lobes, is disrupted. This account integrates a large amount of previously unrelated findings of changed behaviour and brain networks and favours a brain mechanism-centred view on AD.

How does phasic alerting improve performance in patients with unilateral neglect? A systematic analysis of attentional processing capacity and spatial weighting mechanisms.

In visual hemi-neglect, non-spatial deficits such as reduced intrinsic alertness can significantly modulate the degree of left visual field inattention. However, to date, the precise mechanisms mediating this effect are hardly understood. In the present study, we assessed the influence of increased alertness on both general attentional capacity (perceptual processing speed) and spatial attentional selection processes (spatial distribution of attentional weighting). For this purpose, a whole-report paradigm based on Bundesen's 'theory of visual attention' (TVA) was combined with a non-spatial, visual alerting cue. Three different cue-target stimulus onset asynchronies (SOAs; of 80, 200, and 650 ms), allowed us to observe the time course of the alerting-cue effects. A group of six patients with visual hemi-neglect was examined and their performance compared with six healthy control subjects matched for age, gender, and education. In neglect patients, the alerting cue evoked a phasic increase of perceptual processing speed. However, this effect was mainly found in the ipsilateral, i.e. in the "preserved" hemifield. Importantly, however, patients displayed a fast-evolving and short-lasting, phasic modulation of spatial attentional weighting, with a re-distribution of attentional weights from the pathological rightward bias to a normal, more balanced distribution of visual attention. In control participants, the cueing effects on perceptual processing speed and spatial weighting were generally less pronounced than in neglect patients. Replicating results of a prior study, cueing induced a stable, slightly leftward, distribution of attentional weights, whilst in the no-cue condition, a temporary rightward shift of attentional weights was found. This pattern of effects suggests a close interaction between alertness and spatial-attentional weighting in the syndrome of visual hemi-neglect. It supports the hypothesis that the manifestation of spatial neglect involves at least in part intrinsic alertness deficits. It also provides clues to a more detailed account of the mechanisms responsible for alleviating neglect in patients following manipulations of the alertness level, both in the short (cueing) and in the long term (alertness training).

Asymmetric loss of parietal activity causes spatial bias in prodromal and mild Alzheimer's disease.

BACKGROUND: In Alzheimer's disease (AD), loss of effective neuronal activity is reflected by cortical glucose hypometabolism. Hypometabolism in the posterior parietal cortex (PPC) is among the first in vivo signs of AD; however, its functional impact on large-scale brain mechanisms and behavior is poorly understood. The lateral PPC contributes to spatial attention constituting a basic function of the human brain. We hypothesized 1) that lateral PPC hypometabolism is associated with impaired spatial attention in very early AD and 2) that impaired competition of effective neuronal activity across hemispheres might underlie this deficit in terms of brain mechanisms. METHODS: A model-based imaging approach was applied to assess patients with prodromal (n = 28) and mild (n = 7) AD. Quantitative attention parameters, derived from performance on simple psychophysical tasks and analyzed by Bundesen's computational theory of visual attention, were related to brain metabolism, measured by (18)F-fluorodeoxyglucose positron emission tomography. RESULTS: Patients' left and right lateral PPC metabolism was reduced. Nine patients had significant spatial attentional bias on the left side and two patients on the right. Direction and degree of spatial bias was correlated with direction and degree of an interhemispheric metabolism bias in the inferior parietal lobe and temporoparietal junction. CONCLUSIONS: Our data provide evidence that in very early AD, asymmetric hypometabolism of the lateral PPC causes spatial attentional bias. Results are broadly consistent with the model that asymmetrically impaired effective neuronal PPC activity in AD biases the competition of visual objects for cortical representation and access to awareness to one side.

Staged decline of visual processing capacity in mild cognitive impairment and Alzheimer's disease.

Visual information intake was assessed with a whole-report task in patients with probable Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy elderly control subjects. Based on a theory of visual attention (TVA), four parameters were derived characterising different aspects of visual processing capacity: perceptual threshold, iconic memory, processing speed, and visual short-term memory (VSTM) storage capacity. Results indicated increased perceptual thresholds in MCI, and an additional decline in processing speed and VSTM storage capacity in AD. Cholinomimetic medication had beneficial effects on processing speed in AD patients. Perceptual thresholds were associated with disease duration, but not with cognitive measures, while the reverse was true for speed and VSTM measures. These results reveal a staged pattern of deficits affecting pre-attentive visual processing in MCI, and attentive processing in AD. It is compatible with the amyloid cascade hypothesis and suggests that impaired visual processing is a pathological feature present already at the MCI stage and might represent a distinct marker of upcoming AD independently from memory deficits.

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

INTRODUCTION: Theory 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 METHODS: Eighteen healthy volunteers (aged 20-35 years) received single oral doses of either 40 mg methylphenidate, 400 mg modafinil or placebo in a counterbalanced, double-blind crossover design. A whole report of visually presented letter arrays was performed 2.5-3.5 h after drug administration, and blood samples for plasma level analysis were taken. RESULTS: Methylphenidate 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. CONCLUSIONS: This 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).

The influence of alertness on spatial and nonspatial components of visual attention.

Three experiments investigated whether spatial and nonspatial components of visual attention would be influenced by changes in (healthy, young) subjects' level of alertness and whether such effects on separable components would occur independently of each other. The experiments used a no-cue/alerting-cue design with varying cue-target stimulus onset asynchronies in two different whole-report paradigms based on Bundesen's (1990) theory of visual attention, which permits spatial and nonspatial components of selective attention to be assessed independently. The results revealed the level of alertness to affect both the spatial distribution of attentional weighting and processing speed, but not visual short-term memory capacity, with the effect on processing speed preceding that on the spatial distribution of attentional weighting. This pattern indicates that the level of alertness influences both spatial and nonspatial component mechanisms of visual attention and that these two effects develop independently of each other; moreover, it suggests that intrinsic and phasic alertness effects involve the same processing route, on which spatial and nonspatial mechanisms are mediated by independent processing systems that are activated, due to increased alertness, in temporal succession.