In vivo biomarkers of structural and functional brain development and aging in humans.

Brain aging is a major determinant of aging. Along with the aging population, prevalence of neurodegenerative diseases is increasing, therewith placing economic and social burden on individuals and society. Individual rates of brain aging are shaped by genetics, epigenetics, and prenatal environmental. Biomarkers of biological brain aging are needed to predict individual trajectories of aging and the risk for age-associated neurological impairments for developing early preventive and interventional measures. We review current advances of in vivo biomarkers predicting individual brain age. Telomere length and epigenetic clock, two important biomarkers that are closely related to the mechanistic aging process, have only poor deterministic and predictive accuracy regarding individual brain aging due to their high intra- and interindividual variability. Phenotype-related biomarkers of global cognitive function and brain structure provide a much closer correlation to age at the individual level. During fetal and perinatal life, autonomic activity is a unique functional marker of brain development. The cognitive and structural biomarkers also boast high diagnostic specificity for determining individual risks for neurodegenerative diseases.

Motor-cognitive dual-task performance: effects of a concurrent motor task on distinct components of visual processing capacity.

Dual tasking, or the simultaneous execution of two continuous tasks, is frequently associated with a performance decline that can be explained within a capacity sharing framework. In this study, we assessed the effects of a concurrent motor task on the efficiency of visual information uptake based on the 'theory of visual attention' (TVA). TVA provides parameter estimates reflecting distinct components of visual processing capacity: perceptual threshold, visual processing speed, and visual short-term memory (VSTM) storage capacity. Moreover, goodness-of-fit values and bootstrapping estimates were derived to test whether the TVA-model is validly applicable also under dual task conditions, and whether the robustness of parameter estimates is comparable in single- and dual-task conditions. 24 subjects of middle to higher age performed a continuous tapping task, and a visual processing task (whole report of briefly presented letter arrays) under both single- and dual-task conditions. Results suggest a decline of both visual processing capacity and VSTM storage capacity under dual-task conditions, while the perceptual threshold remained unaffected by a concurrent motor task. In addition, goodness-of-fit values and bootstrapping estimates support the notion that participants processed the visual task in a qualitatively comparable, although quantitatively less efficient way under dual-task conditions. The results support a capacity sharing account of motor-cognitive dual tasking and suggest that even performing a relatively simple motor task relies on central attentional capacity that is necessary for efficient visual information uptake.

Contralesional spatial bias in chronic hemianopia: the role of (ec)centric fixation, spatial cueing and visual search.

Patients with homonymous hemianopia often show a contralesional shift towards their blind field when bisecting horizontal lines ('hemianopic line bisection error', HLBE). The reasons for this spatial bias are not well understood and debated. Eccentric fixation and adaptive orienting of eye movements towards the blind field have been suggested as hypothetical explanations but were not tested experimentally yet. Moreover, the role of spatial attention and visual search in the blind field are unsettled issues. Here, we tested in 20 stroke patients with chronic homonymous hemianopia (10 left-sided, 10 right-sided) without visual neglect, 10 healthy control subjects and 10 neurological control patients without hemianopia whether the HLBE is related to (a) eccentric fixation and (b) is influenced by spatial-attentional cueing (left, right) and (c) related to the degree of oculomotor compensation in the blind field. Perimetric mapping of the blind spot in the ipsilesional eye was performed in 39/40 subjects. Both hemianopic patient groups showed the typical HLBE towards their blind field, while the two control samples showed only a small but significant leftward shift known as pseudoneglect. The horizontal and vertical position of the blind spot in the ipsilesional eye was within normal limits in 38 out of 40 subjects, and did not differ significantly between the four samples. Moreover, the HLBE was not significantly correlated to the horizontal or vertical position of the centre of the blind spot, thus excluding eccentric fixation as an explanation for this spatial error. Furthermore, spatial cueing by manipulating the starting position of the bisection cue (left, right) did not affect the HLBE, arguing against attentional cueing effects well known from the line bisection error in patients with spatial neglect. Finally, the size of the saccadic search field in the scotoma was not significantly correlated to the HLBE in hemianopia. We conclude that eccentric fixation, contralesional hyperattention or ipsilesional hypoattention, or good or poor oculomotor compensation of the field loss itself are not likely causes of the HLBE in chronic homonymous hemianopia. Implications of these findings and alternative explanations are discussed.

Does spatial cueing affect line bisection in chronic hemianopia?

Patients with homonymous hemianopia often show a contralesional shift towards their blind field when bisecting horizontal lines ("hemianopic line bisection error", HLBE). The reasons for this spatial bias are not well understood and debated. Cueing of spatial attention modulates line bisection significantly in patients with visuospatial neglect. Moreover, recent evidence showed that attention training significantly improves deficits of visual search in hemianopia. Here, we tested in 20 patients with chronic homonymous hemianopia (10 left-sided, 10 right-sided) without visual neglect, 10 healthy control subjects, 10 neurological control patients, and 3 patients with left visuospatial neglect and leftsided hemianopia whether spatial cueing influences the HLBE. Subjects indicated verbally the midpoint of horizontal lines in a computerized line bisection task under four experimental cue positions (cue far left, mid-left, mid-right or far-right within the horizontal line). All 20 hemianopic patients showed the typical HLBE towards their blind field, while the two control samples showed only a small but significant leftward shift (pseudoneglect). None of the 4 cueing manipulations had a significant effect on the HLBE in the hemianopic patients. Moreover, no differential effects of cueing on line bisection results were obtained when analyzed in lesion subgroups of hemianopic patients with circumscribed occipital lesions (N=8) as contrasted with patients having more extended (occipito-temporal or temporal) lesions (N=12). This null-effect contrasts with marked cueing effects observed in 3 neglect patients with left hemianopia in the same tasks, showing the principal efficacy of our cueing manipulation. These results argue against attentional explanations of the HLBE.

Deficits of spatial and task-related attentional selection in mild cognitive impairment and Alzheimer's disease.

Visual selective attention was assessed with a partial-report task in patients with probable Alzheimer's disease (AD), amnestic mild cognitive impairment (MCI), and healthy elderly controls. Based on Bundesen's "theory of visual attention" (TVA), two parameters were derived: top-down control of attentional selection, representing task-related attentional weighting for prioritizing relevant visual objects, and spatial distribution of attentional weights across the left and the right hemifield. Compared with controls, MCI patients showed significantly reduced top-down controlled selection, which was further deteriorated in AD subjects. Moreover, attentional weighting was significantly unbalanced across hemifields in MCI and tended to be more lateralized in AD. Across MCI and AD patients, carriers of the apolipoprotein E ε4 allele (ApoE4) displayed a leftward spatial bias, which was the more pronounced the younger the ApoE4-positive patients and the earlier disease onset. These results indicate that impaired top-down control may be linked to early dysfunction of fronto-parietal networks. An early temporo-parietal interhemispheric asymmetry might cause a pathological spatial bias which is associated with ApoE4 genotype and may therefore function as early cognitive marker of upcoming AD.

[Therapy for cerebral visual perception disturbances]. / Therapie zerebraler visueller Wahrnehmungsstörungen.

Cerebral 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.

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 Parkinson's 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.

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.

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.