The aging mind: A complex challenge for research and practice.

Cognitive decline as part of mental ageing is typically assessed with standardized tests; below-average performance in such tests is used as an indicator for pathological cognitive aging. In addition, morphological and functional changes in the brain are used as parameters for age-related pathological decline in cognitive abilities. However, there is no simple link between the trajectories of changes in cognition and morphological or functional changes in the brain. Furthermore, below-average test performance does not necessarily mean a significant impairment in everyday activities. It therefore appears crucial to record individual everyday tasks and their cognitive (and other) requirements in functional terms. This would also allow reliable assessment of the ecological validity of existing and insufficient cognitive skills. Understanding and dealing with the phenomena and consequences of mental aging does of course not only depend on cognition. Motivation and emotions as well personal meaning of life and life satisfaction play an equally important role. This means, however, that cognition represents only one, albeit important, aspect of mental aging. Furthermore, creating and development of proper assessment tools for functional cognition is important. In this contribution we would like to discuss some aspects that we consider relevant for a holistic view of the aging mind and promote a strengthening of a multidisciplinary approach with close cooperation between all basic and applied sciences involved in aging research, a quick translation of the research results into practice, and a close cooperation between all disciplines and professions who advise and support older people.

Use of NeuroEyeCoach™ to Improve Eye Movement Efficacy in Patients with Homonymous Visual Field Loss.

Visual field deficits are common in patients with damaged retinogeniculostriate pathways. The patient's eye movements are often affected leading to inefficient visual search. Systematic eye movement training also called compensatory therapy is needed to allow patients to develop effective coping strategies. There is a lack of evidence-based, clinical gold-standard registered medical device accessible to patients at home or in clinical settings and NeuroEyeCoach (NEC) is developed to address this need. In three experiments, we report on performance of patients on NEC compared to the data obtained previously on the earlier versions of the search task (n = 32); we assessed whether the self-administered computerised tasks can be used to monitor the progress (n = 24) and compared the findings in a subgroup of patients to a healthy control group. Performance on cancellation tasks, simple visual search, and self-reported responses on activities of daily living was compared, before and after training. Patients performed similarly well on NEC as on previous versions of the therapy; the inbuilt functionality for pre- and postevaluation functions was sensitive to allowing assessment of improvements; and improvements in patients were significantly greater than those in a group of healthy adults. In conclusion, NeuroEyeCoach can be used as an effective rehabilitation tool to develop compensatory strategies in patients with visual field deficits after brain injury.

The functional connectome of cognitive reserve.

Cognitive Reserve (CR) designates the brain's capacity to actively cope with insults through a more efficient use of its resources/networks. It was proposed in order to explain the discrepancies between the observed cognitive ability and the expected capacity for an individual. Typical proxies of CR include education and Intelligence Quotient but none totally account for the variability of CR and no study has shown if the brain's greater efficiency associated with CR can be measured. We used a validated model to estimate CR from the residual variance in memory and general executive functioning, accounting for both brain anatomical (i.e., gray matter and white matter signal abnormalities volume) and demographic variables (i.e., years of formal education and sex). Functional connectivity (FC) networks and topological properties were explored for associations with CR. Demographic characteristics, mainly accounted by years of formal education, were associated with higher FC, clustering, local efficiency and strength in parietal and occipital regions and greater network transitivity. Higher CR was associated with a greater FC, local efficiency and clustering of occipital regions, strength and centrality of the inferior temporal gyrus and higher global efficiency. Altogether, these findings suggest that education may facilitate the brain's ability to form segregated functional groups, reinforcing the view that higher education level triggers more specialized use of neural processing. Additionally, this study demonstrated for the first time that CR is associated with more efficient processing of information in the human brain and reinforces the existence of a fine balance between segregation and integration. Hum Brain Mapp 37:3310-3322, 2016.. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

The contribution of single case studies to the neuroscience of vision.

Visual neuroscience is concerned with the neurobiological foundations of visual perception, that is, the morphological, physiological, and functional organization of the visual brain and its co-operative partners. One important approach for understanding the functional organization of the visual brain is the study of visual perception from the pathological perspective. The study of patients with focal injury to the visual brain allows conclusions about the representation of visual perceptual functions in the framework of association and dissociation of functions. Selective disorders have been reported for more "elementary" visual capabilities, for example, color and movement vision, but also for visuo-cognitive capacities, such as visual agnosia or the visual field of attention. Because these visual disorders occur rather seldom as selective and specific dysfunctions, single cases have always played, and still play, a significant role in gaining insights into the functional organization of the visual brain.

Neuropsychology of Neuroendocrine Dysregulation after Traumatic Brain Injury.

Endocrine dysfunction is a common effect of traumatic brain injury (TBI). In addition to affecting the regulation of important body functions, the disruption of endocrine physiology can significantly impair mental functions, such as attention, memory, executive function, and mood. This mini-review focuses on alterations in mental functioning that are associated with neuroendocrine disturbances in adults who suffered TBI. It summarizes the contribution of hormones to the regulation of mental functions, the consequences of TBI on mental health and neuroendocrine homeostasis, and the effects of hormone substitution on mental dysfunction caused by TBI. The available empirical evidence suggests that comprehensive assessment of mental functions should be standard in TBI subjects presenting with hormone deficiency and that hormone replacement therapy should be accompanied by pre- and post-assessments.

The contribution of LM to the neuroscience of movement vision.

The significance of early and sporadic reports in the 19th century of impairments of motion vision following brain damage was largely unrecognized. In the absence of satisfactory post-mortem evidence, impairments were interpreted as the consequence of a more general disturbance resulting from brain damage, the location and extent of which was unknown. Moreover, evidence that movement constituted a special visual perception and may be selectively spared was similarly dismissed. Such skepticism derived from a reluctance to acknowledge that the neural substrates of visual perception may not be confined to primary visual cortex. This view did not persist. First, it was realized that visual movement perception does not depend simply on the analysis of spatial displacements and temporal intervals, but represents a specific visual movement sensation. Second persuasive evidence for functional specialization in extrastriate cortex, and notably the discovery of cortical area V5/MT, suggested a separate region specialized for motion processing. Shortly thereafter the remarkable case of patient LM was published, providing compelling evidence for a selective and specific loss of movement vision. The case is reviewed here, along with an assessment of its contribution to visual neuroscience.

Cognitive reserve in young and old healthy subjects: differences and similarities in a testing-the-limits paradigm with DSST.

Cognitive reserve (CR) is understood as capacity to cope with challenging conditions, e.g. after brain injury or in states of brain dysfunction, or age-related cognitive decline. CR in elderly subjects has attracted much research interest, but differences between healthy older and younger subjects have not been addressed in detail hitherto. Usually, one-time standard individual assessments are used to characterise CR. Here we observe CR as individual improvement in cognitive performance (gain) in a complex testing-the-limits paradigm, the digit symbol substitution test (DSST), with 10 repeated measurements, in 140 younger (20-30 yrs) and 140 older (57-74 yrs) healthy subjects. In addition, we assessed attention, memory and executive function, and mood and personality traits as potential influence factors for CR. We found that both, younger and older subjects showed significant gains, which were significantly correlated with speed of information processing, verbal short-term memory and visual problem solving in the older group only. Gender, personality traits and mood did not significantly influence gains in either group. Surprisingly about half of the older subjects performed at the level of the younger group, suggesting that interindividual differences in CR are possibly age-independent. We propose that these findings may also be understood as indication that one-time standard individual measurements do not allow assessment of CR, and that the use of DSST in a testing-the-limits paradigm is a valuable assessment method for CR in young and elderly subjects.

Does age matter? Age and rehabilitation of visual field disorders after brain injury.

Homonymous visual field disorders (HVFD) are frequent and disabling consequences of acquired brain injury, particularly in older age. Their rehabilitation is therefore of great importance. Compensatory oculomotor therapy has been found to be effective in improving the associated functional impairments in reading and visual exploration. But older age is commonly considered to adversely affect practice-dependent functional plasticity and, thus, functional and rehabilitation outcome after acquired brain injury. The effect of age in the compensatory treatment of HVFD, however, has never been investigated hitherto. It remains unknown whether age determines not only patients' functional impairments but also the rehabilitation outcome and the required amount of treatment. We therefore present the first study to determine the effect of age in 38 patients with HVFD receiving compensatory oculomotor treatment for their reading and visual exploration impairments. We investigated whether older patients with HVFD (1) show more pronounced impairments and less spontaneous adaptation, (2) show lesser compensatory treatment-related improvement in reading and visual exploration, and (3) require a higher amount of treatment than younger patients. Our main finding is that older patients achieve the same treatment-induced improvements in reading and visual exploration with the same amount of treatment as younger patients; severity of functional impairment also did not differ between older and younger patients, at least in reading. Age does not seem to be a critical factor determining the functional and rehabilitation outcome in the compensatory treatment of HVFD. Older age per se is not necessarily associated with a decline in practice-dependent functional plasticity and adaptation. To the contrary, the effectiveness of compensatory treatment to reduce the functional impairments to a similar extent in younger and older patients with HVFD adds to the growing evidence for a life-long potential for adaptation to the adverse effects of brain injury.

Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels.

Leptin, a peptide hormone from adipose tissue and key player in weight regulation, has been suggested to be involved in sleep and cognition and to exert antidepressant-like effects, presumably via its action on the HPA-axis and hippocampal function. This led us to investigate whether genetic variants in the leptin gene, the level of leptin mRNA-expression and leptin serum concentrations are associated with response to antidepressant treatment. Our sample consisted of inpatients from the Munich Antidepressant Response Signature (MARS) project with weekly Hamilton Depression ratings, divided into two subsamples. In the exploratory sample (n=251) 17 single nucleotide polymorphisms (SNPs) covering the leptin gene region were genotyped. We found significant associations of several SNPs with impaired antidepressant treatment outcome and impaired cognitive performance after correction for multiple testing. The SNP (rs10487506) showing the highest association with treatment response (p=3.9×10(-5)) was analyzed in the replication sample (n=358) and the association could be verified (p=0.021) with response to tricyclic antidepressants. In an additional meta-analysis combining results from the MARS study with data from the Genome-based Therapeutic Drugs for Depression (GENDEP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR(⁎)D) studies, nominal associations of several polymorphisms in the upstream vicinity of rs10487506 with treatment outcome were detected (p=0.001). In addition, we determined leptin mRNA expression in lymphocytes and leptin serum levels in subsamples of the MARS study. Unfavorable treatment outcome was accompanied with decreased leptin mRNA and leptin serum levels. Our results suggest an involvement of leptin in antidepressant action and cognitive function in depression with genetic polymorphisms in the leptin gene, decreased leptin gene expression and leptin deficiency in serum being risk factors for resistance to antidepressant therapy in depressed patients.

Rehabilitation of reading and visual exploration in visual field disorders: transfer or specificity?

Reading and visual exploration impairments in unilateral homonymous visual field disorders are frequent and disabling consequences of acquired brain injury. Compensatory therapies have been developed, which allow patients to regain sufficient reading and visual exploration performance through systematic oculomotor training. However, it is still unclear whether the reading and visual exploration impairments require specific compensatory training for their improvement. We present the first cross-over rehabilitation study to determine whether the training-related performance improvements are task-specific, or whether there is a transfer of training-related improvements between reading and visual exploration. We compared the therapeutic effects of compensatory oculomotor reading and visual exploration training in 36 patients with unilateral homonymous visual field loss in a cross-over design. In addition, we explored whether the training sequence determines the overall treatment outcome. Our findings demonstrate that the training-related improvements in reading and visual exploration are highly specific and task-dependent, and there was no effect of training sequence.

Line bisection in unilateral homonymous visual field defects.

The contralesional line bisection error in unilateral homonymous hemianopia is a frequent but neglected clinical phenomenon. Our knowledge about this bisection error is based on small samples of hemianopic patients. Moreover, horizontal line bisection has never been investigated in other unilateral visual field defects. The present study is the first to examine line bisection in a large, representative sample of patients with unilateral homonymous visual field defects. We investigated horizontal line bisection in 129 patients with left- or right-sided homonymous hemianopia (60.5%), upper and lower quadranopia (24.8%), and paracentral scotoma (14.7%), and determined the magnitude and direction of line bisection error. The contralesional horizontal line bisection error was present not only in patients with hemianopia but also in those with upper or lower quadranopia or paracentral scotoma. Neither the type nor the severity of the visual field defect was found to determine the bisection error. Only the side of the field defect seemed to determine the horizontal direction of the bisection error (left-/rightward). The contralesional bisection error is not a specifically "hemianopic" phenomenon. It is frequently associated with any unilateral homonymous visual field defect, i.e., hemianopia, upper/lower quadranopia, paracentral scotoma. Moreover, our results further support the recent finding that the contralesional bisection error is not a direct consequence of the visual field defect. Yet, they also suggest that, although the visual field defect does not seem to be the primary cause of the contralesional bisection error, it may nevertheless contribute to it.

What and where in mirror reading.

In a combined voxel-based morphometry and functional magnetic resonance imaging study on the practice of mirror reading, we recently found a shift of activation from right superior parietal to right dorsal occipital cortex and a corresponding increase of gray matter. We interpreted this shift of activation and the corresponding structural changes as a shift from effortful visuospatial transformation to a more direct processing of mirrored words (Ilg et al., 2008). To test this hypothesis, we now analyzed brain activation patterns associated with different aspects of mirror reading. Activation at the dorsal occipital cortex and bilateral parietal cortex (dorsal visual stream) was related to inverse text processing, whereas activation of areas at the inferior and ventral occipitotemporal cortex (ventral visual stream) was associated with decoding of mirrored words. This indicates that the dichotomy of content-related ("what") and process-related ("where") higher visual functions also applies to mirror reading.

The relationship between adult neuropsychological profiles and diabetic patients' glycemic control.

The purpose of this study was to assess, in relation to metabolic control, the cognitive, depressive, and anxiety symptoms among 40 adult patients (age: 18-60 years) with either type 1 (n = 28) or type 2 (n = 12) diabetes mellitus (DM1, DM2). Nineteen healthy subjects matched for age, gender, and education served as the control group. For most cognitive domains, no significant performance differences were found between subjects from the diabetic groups and control subjects. However, diabetes patients demonstrated reduced information processing accuracy along with impaired visual and verbal working memory performance. In addition, psychopathology scores were significantly elevated but did not reach the clinical criteria for depression or anxiety. Overall, there were no significant differences between diabetic subgroups, and no significant correlation was found between cognitive performance, psychopathology scores, and HbA1c values for either subgroup. Thus, patients with DM1 or DM2 may show mild-to-moderate cognitive impairment as well as subtle psychopathological symptoms. While cognitive impairments may be understood in terms of diabetes-associated cognitive dysfunction, psychopathological symptoms may also result from unsuccessful coping with high task demands in everyday life activities. The outcome of the current study underscores the importance of early clinical neuropsychological standardized assessment as well as the diagnosis of cognitive and psychopathological symptoms in adult patients with diabetes.

Neuropsychological profiles in MCI and in depression: Differential cognitive dysfunction patterns or similar final common pathway disorder?

The concept of "mild cognitive impairment" (MCI) refers to alterations in cognition in the transition between normal aging and dementia. However, from a neuropsychological point of view the conventional diagnostic criteria appear not sufficiently valid. In particular, it is still difficult to differentiate between subjects with MCI and subjects with depression plus cognitive deficits on the basis of their neuropsychological profiles. The aim of this study is to compare cognitive deficit patterns of subjects with MCI and with depression. 24 subjects with MCI, 50 subjects with depression (DEP) and 20 healthy control subjects were included (age: 55-74years). The neuropsychological assessment consisted of standardized tests to assess attention, memory, and executive functions. Compared to healthy controls both subject groups showed significantly lower performance in all cognitive domains. However, we did not find significant differences in cognitive performance between MCI and DEP subjects, neither at baseline nor at follow-up. In addition, preliminary results of follow-up assessments after 2 (DEP) and 6months (MCI), respectively, revealed no significant changes in cognition in subjects with depression, regardless of whether depressive symptoms had improved. Subjects with MCI also showed no changes in cognition at follow-up. The comparable neuropsychological patterns identified in the two subject groups may be understood as a consequence of similar alterations in cognitive systems, supporting the idea of a final common pathway disorder. Thus, the cognitive deficits present in a subgroup of subjects with depression may possibly better be understood in the context of MCI.

On the origin of line bisection error in hemianopia.

The contralesional line bisection error in hemianopia is a well-known clinical phenomenon. Its origin, however, is still unclear. We therefore investigated the causes of the hemianopic bisection error in 84 patients with unilateral homonymous hemianopia without visuospatial neglect. Our results suggest that the contralesional bisection error is neither a consequence of the visual field defect itself nor a manifestation of strategic adaptation of attention and eye movements into contralesional hemispace. Additional extrastriate brain injury, presumably to occipito-temporal areas including the occipital white matter, seems to be critical for the emergence of the contralesional bisection error that is frequently associated with but separable from homonymous hemianopia.

Is the origin of the hemianopic line bisection error purely visual? Evidence from eye movements in simulated hemianopia.

It is still unclear whether the contralateral line bisection error in unilateral homonymous hemianopia is caused by the visual field defect, strategic oculomotor adaptation or by additional extrastriate brain injury. We therefore simulated hemianopia in healthy participants using a gaze-contingent display paradigm and investigated its effects on manual and ocular line bisection performance and eye-movements. Although simulated hemianopia impaired line bisection and induced the adaptive oculomotor eye-movement pattern of hemianopic patients, it did not induce the contralateral bisection error, suggesting that neither the visual field defect nor oculomotor adaptation to it are the primary causes of the hemianopic bisection error.

Adaptation of eye-movements to simulated hemianopia in reading and visual exploration: Transfer or specificity?

Reading and visual exploration impairments in unilateral homonymous hemianopia are well-established clinical phenomena. Spontaneous adaptation of eye-movements to the visual field defect leads to improved reading and visual exploration performance. Yet, it is still unclear whether oculomotor adaptation to visual field loss is task-specific or whether there is a transfer of adaptation-related improvements between reading and visual exploration. We therefore simulated unilateral homonymous hemianopia in healthy participants and explored the specificity with which oculomotor adaptation to this pure visual-sensory dysfunction during uninstructed reading or visual exploration practice leads to improvements in both abilities. Our findings demonstrate that there is no transfer of adaptation-related changes of eye-movements and performance improvements between reading and visual exploration. Efficient oculomotor adaptation to visual field loss is highly specific and task-dependent.

Are hemianopic reading and visual exploration impairments visually elicited? New insights from eye movements in simulated hemianopia.

Hemianopic reading and visual exploration impairments are well-known clinical phenomena. Yet, it is unclear whether they are primarily caused by the hemianopic visual field defect itself or by additional brain injury preventing efficient spontaneous oculomotor adaptation. To establish the extent to which these impairments are visually elicited we simulated unilateral homonymous hemianopia in healthy participants, using a gaze-contingent display paradigm, and investigated its effect on reading and visual exploration. We demonstrate that simulated hemianopia induces the reading and visual exploration impairments of hemianopic patients. Over time, however, all participants showed efficient spontaneous oculomotor adaptation to the visual-sensory loss which improved their reading and visual exploration performance. Our results suggest that the hemianopic visual field defect is a major component of the chronic impairments of reading and visual and exploration found in hemianopic patients although it may not be their sole cause.

Rehabilitation of hemianopic dyslexia: are words necessary for re-learning oculomotor control?

Unilateral homonymous visual field disorders after brain damage are frequently associated with a severe impairment of reading, called hemianopic dyslexia. A specific treatment method has been developed which allows patients to regain sufficient reading performance by re-learning eye-movement control in reading through systematic oculomotor practice. However, it is still unclear whether the treatment effect associated with this training procedure critically depends on using text material. We therefore evaluated the effectiveness of systematic oculomotor training with non-text material (Arabic digits) in comparison with conventional oculomotor training using text material (words) in 40 patients with unilateral homonymous visual field disorders and hemianopic dyslexia. Non-text training was found to be as effective as conventional text training in improving reading performance and associated eye-movements in these patients. Our results suggest that using words is not critical to the treatment effect of this training procedure. Thus, lexical-semantic processes seem not to be necessary for re-learning eye-movement control in hemianopic dyslexia.

The significance of visual information processing in reading: Insights from hemianopic dyslexia.

We present the first comprehensive review of research into hemianopic dyslexia since Mauthner's original description of 1881. We offer an explanation of the reading impairment in patients with unilateral homonymous visual field disorders and clarify its functional and anatomical bases. The major focus of our review is on visual information processing, visuospatial attention and eye-movement control during reading. An advanced understanding of the basis of hemianopic dyslexia and its rehabilitation also increases our knowledge about normal reading and its underlying neural mechanisms. By drawing together various sources of evidence we illustrate the significance of bottom-up and attentional top-down control of visual information processing and saccadic eye-movements in reading. Reading depends critically on the cortical-subcortical network subserving the integration of visual, attentional and oculomotor processes involved in text processing.