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.

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.

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.

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.

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.

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).

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.

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.

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.

The capacity of attention and simultaneous perception of objects: a group study of Huntington's disease patients.

Using a whole report-paradigm based on [Bundesen, C. (1990). A theory of visual attention. Psychological Review, 97, 523-547; Bundesen, C. (1998). A computational theory of visual attention. Philosophical Transactions of the Royal Society of London B, Biological Sciences, 353, 1271-1281] theory of visual attention (TVA), [Finke, K., Bublak, P., Dose, M., Müller, H. J., & Schneider, W. X. (2006). Parameter-based assessment of spatial and non-spatial attentional deficits in Huntington's disease. Brain, 129, 1137-1151] demonstrated profound reductions in perceptual processing speed and visual working memory (WM) storage capacity in Huntington's disease (HD) patients. A comparably severe impairment of visual processing capacity has previously been reported for two simultanagnosia patients [Duncan, J., Bundesen, C., Olson, A., Humphreys, G., Ward, R., Kyllingsbaek, S., van Raamsdonk, M., Rorden, C., & Chavda, S. (2003). Attentional functions in dorsal and ventral simultanagnosia. Cognitive Neuropsychology, 20, 675-702]. To investigate whether such a deficit does also prevail in HD, the simultaneous perception of visual objects was tested in 10 HD patients under free viewing conditions and without time constraints. Objects were presented under four different conditions: (i) single, (ii) multiple adjacent, (iii) multiple embedded, and (iv) multiple overlapping. The dependent measure was the percentage of identification failures. Performance was compared to that of 15 healthy subjects matched for age, education, gender and general mental ability. For HD patients, the percentage of errors in the various testing conditions was examined for correlations with the TVA parameters of visuo-perceptual processing speed and WM storage capacity. These parameters were estimated using verbal whole report of briefly presented letters. TVA permits the two parameters to be estimated mathematically independently and relatively unaffected by any motor deficits present in HD. The identification error rate was substantially increased in HD patients, compared to control subjects, in the overlapping-figures subtest. This deficit was significantly and negatively correlated with processing speed, whereas there was no correlation with WM storage capacity. These results demonstrate the presence of deficits in simultaneous perception in HD, related to a severe reduction in perceptual processing speed. The results are discussed with respect to a dopamine mediated decline of cortical cholinergic activation, diminishing the number of visual objects that can be simultaneously represented within the visual processing system.

Parameter-based assessment of spatial and non-spatial attentional deficits in Huntington's disease.

A major challenge for neuropsychological research on Huntington's disease is the identification of biomarkers for the disease at the level of cognitive functions. Given that cortical-striatal-thalamic circuits are particularly vulnerable, possible markers loading functionally on these brain regions should be particularly significant. We investigated whether parametric values derived from a 'theory of visual attention' (TVA) can serve that purpose. They are derived as mathematically independent, quantitative measures of attentional components, and the tasks require only non-speeded vocal responses. As such, the methodology seems well suited for testing patients with motor problems and general cognitive decline. Accumulating neuroanatomical evidence suggests that striatal atrophy in Huntington's disease is asymmetrical with a more pronounced left-sided degeneration. We applied a partial-report paradigm to analyse whether this results in a pathological (leftward) bias of the spatial distribution of attention. In partial report, red target letters are presented either alone or accompanied by either a second target or a green distractor letter presented in the same or in the opposite hemi-field. Since basal ganglia lesions have also been shown to cause spatially non-lateralized impairments, that is, reduced perceptual processing speed and visual working memory (WM) storage capacity within both hemi-fields, we tested possible reductions in these parameters with a whole-report paradigm. Here, columns of five red or green letters are briefly presented and the subject has to report as many as possible. Eighteen patients and 18 matched control subjects performed a partial- and a whole-report task with briefly presented letter displays. In partial report, Huntington's disease patients demonstrated a pathological bias, indicating increased attentional weighting to the left hemi-field. The extent of lateralization was strongly related to age at onset and to the number of cytosine-adenine-guanine (CAG) triplet repeats on gene IT15. In contrast, the extent of lateralization was not related to disease progression as reflected by the duration of the disease since onset of the first symptoms. In whole report, the non-lateralized attentional parameters processing speed and visual WM storage capacity were reduced bilaterally in both hemi-fields. The extent of the reduction was related to the disease duration since onset, whereas no significant correlation with CAG repeats or age at onset was found. Laterality of attentional weighting may, therefore, represent a possible trait marker reflecting the intensity of the pathogenic mechanisms, while the reduction of visual processing speed and storage capacity may be state markers for the stage of disease progression.

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.

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.

Visual spatial and visual pattern working memory: neuropsychological evidence for a differential role of left and right dorsal visual brain.

According to neurophysiological, neuroimaging, and behavioural evidence, visual working memory (WM) can be separated into a "what" and a "where" component, reflecting the duality of visual processing. Whereas a wealth of empirical data suggests a right-sided fronto-parietal network critical for the maintenance of spatial information, the cortical structures underlying maintenance of object information have remained controversial. Although visual object processing depends on ventral, inferior temporal areas, recent neuroimaging results suggest that maintenance of visual object information involves a left-sided or bilateral fronto-parietal network. The aim of the present study is to further clarify the role of the left and right parietal lobes for pattern and spatial visual WM. Seven patients with left-sided, seven with right-sided parietal brain injury, and two age-matched healthy control groups performed a delayed-matching-to-sample task using either pattern (shape) or spatial (location) information or both. In addition, eight patients with left-sided injury sparing parietal areas were tested to further examine the specific role of the left parietal cortex in pattern WM. Left parietal injury resulted in pattern WM impairment, only, while right parietal injury was associated with pattern and spatial WM deficits. Non-parietal injury was not associated with comparable deficits. These results suggest that visual spatial WM depends critically on right parietal areas; in contrast, pattern WM depends on both, left and right parietal areas.

Rotation or translation of auditory space in neglect? A case study of chronic right-sided neglect.

Egocentric models of neglect explain the lateralised omission of stimuli in neglect patients by an ipsilesional shift of a subjective reference frame. However, they differ in the direction of shift (rotation around the midsagittal plane versus translation in front/back space). We tested this hypothesis in a patient (AJ) with persistent right-sided neglect following a left temporo-parieto-occipital and hypoxic lesion and in six age-matched healthy subjects. AJ showed visual neglect in line bisection, size matching, reading and visual search. Auditory localization was tested by using two different psychophysical techniques based on binaurally simulated stimuli for the horizontal plane in front and back space. Eye position was continuously monitored during stimulus presentation in all subjects. AJ revealed a significant ipsilesional, leftward shift of his auditory subjective median plane (ASMP) in front space (mean: -22.6 degrees), and a rightward shift of the ASMP in back space (+14.5 degrees). This pattern of results was replicated with a different psychophysical technique in a retest 10 months later. The rotational shift of AJ's ASMP contrasted with normal performance in the healthy subjects. Monaural hearing deficits can not account for these differential findings as all subjects (including AJ) performed normally. In conclusion, a rotation of the egocentric spatial reference frame may occur in the auditory modality for right-sided neglect.

Spatial and non-spatial attention deficits in neurodegenerative diseases: assessment based on Bundesen's theory of visual attention (TVA).

PURPOSE: The aim was to present evidence that, similarly as in neglect, a combined pattern of spatial and non-spatial deficits of visual attention can also be typically observed in patients suffering from neurodegenerative disorders. METHOD: Whole and partial report of brief letter arrays, based on Bundesen's 'theory of visual attention' (TVA), was applied in patients suffering from Huntington's disease (HD), mild cognitive impairment (MCI), or Alzheimer's disease (AD). TVA-based parameter estimates were derived reflecting (a) perceptual processing speed and visual working memory storage capacity as non-spatial aspects of visual attention (determined by whole report performance), and (b) spatial attentional weighting (determined by partial report performance). RESULTS: Processing speed was severely slowed in HD, and also reduced, although to a lesser degree, in MCI and AD patients. In HD and AD patients, but not in MCI patients, a strong leftward bias of spatial attention was observed. CONCLUSION: Neglect and neurodegenerative diseases both involve a similar constellation of non-spatial and spatial deficits of visual attention. Therefore, by using TVA-based measurement, results from both fields of research may fruitfully inform each other in future studies, thus improving our understanding of the interaction of spatial and non-spatial attention deficits and its behavioral consequences.

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.

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.

Noradrenergic blockade and numeric working memory in humans.

To investigate the noradrenergic modulation of working memory in humans single doses of two beta-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 beta-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.