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.

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.

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.

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.

Gray matter increase induced by practice correlates with task-specific activation: a combined functional and morphometric magnetic resonance imaging study.

The neurophysiological basis of practice-induced gray matter increase is unclear. To study the relationship of practice-induced gray matter changes and neural activation, we conducted a combined longitudinal functional and morphometric (voxel-based morphometry) magnetic resonance imaging (MRI) study on mirror reading. Compared with normal reading, mirror reading resulted in an activation of the dorsolateral occipital cortex, medial occipital cortex, superior parietal cortex, medial and dorsolateral prefrontal cortex, as well as anterior insula and cerebellum. Daily practice of 15 min for 2 weeks resulted in an increased performance of mirror reading. After correction for pure performance effects, we found a practice-related decrease of activation at the right superior parietal cortex and increase of activation at the right dorsal occipital cortex. The longitudinal voxel-based morphometry analysis yielded an increase of gray matter in the right dorsolateral occipital cortex that corresponded to the peak of mirror-reading-specific activation. This confirms that short-term gray matter signal increase corresponds to task-specific processing. We speculate that practice-related gray matter signal changes in MRI are primarily related to synaptic remodeling within specific processing areas.

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.

Persistent cognitive impairment in depression: the role of psychopathology and altered hypothalamic-pituitary-adrenocortical (HPA) system regulation.

BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system and cognitive impairment are consistent findings in depression. This study examines the associations between HPA system regulation, cognitive functioning, and psychopathology in depressed inpatients on admission and at discharge. METHODS: The HPA system dysregulation was evaluated with the dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test. Cognitive assessment included speed of information processing, divided and selective attention, as well as short-term and working memory. Psychopathology was evaluated with the Hamilton Rating Scale for Depression (HAMD). Data from 75 depressed inpatients are reported, 51 (68%) of them achieved remission. RESULTS: Despite a significant reduction of depressive symptoms between admission and discharge, a high rate of patients remained cognitively impaired. Selective attention improved significantly in remitters and nonremitters, while speed of information processing increased only in remitters. The cortisol response to the DEX/CRH test decreased significantly only in remitters, which was uncorrelated with cognitive performance. In nonremitters, severity of depression was significantly correlated with information processing time while improvement in short-term memory was negatively associated with the cortisol response at discharge. CONCLUSIONS: Our data support the assumption that psychopathological symptoms and the HPA system dysregulation can be dissociated in their impact on cognitive functioning in depressed patients.

Overweight and obesity affect treatment response in major depression.

BACKGROUND: Epidemiologic and clinical studies suggest comorbidity between major depressive disorder (MDD) and obesity. To elucidate the impact of weight on the course of depression beyond comorbidity, we investigated psychopathology, attention, neuroendocrinology, weight change, and treatment response in MDD patients, depending on their weight. METHODS: Four hundred eight inpatients with MDD participated in the Munich Antidepressant Response Signature Study, designed to discover biomarkers and genotypes that are predictive for clinical outcome. Psychopathology and anthropometric parameters were monitored weekly in 230 patients. In subsamples, combined dexamethasone-corticotropin-releasing hormone and attention tests were conducted at admission and discharge. One thousand twenty-nine diagnosed matched controls served for morphometric comparisons. RESULTS: Patients with MDD had a significantly higher body mass index (BMI) compared with healthy controls. Patients with high BMI (> or =25) showed a significantly slower clinical response, less improvement in neuroendocrinology and attention, and less weight gain than did patients with normal BMI (18.5 < or = BMI < 25) during antidepressant treatment. CONCLUSIONS: Our findings suggest that overweight and obesity characterize a subgroup of MDD patients with unfavorable treatment outcome.

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.

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 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.

Effect of repeated gaboxadol administration on night sleep and next-day performance in healthy elderly subjects.

Aging is associated with dramatic reductions in sleep continuity and sleep intensity. Since gaboxadol, a selective GABA(A) receptor agonist, has been demonstrated to improve sleep consolidation and promote deep sleep, it may be an effective hypnotic, particularly for elderly patients with insomnia. In the present study, we investigated the effects of subchronic gaboxadol administration on nocturnal sleep and its residual effects during the next days in elderly subjects. This was a randomized, double-blind, placebo-controlled, balanced crossover study in 10 healthy elderly subjects without sleep complaints. The subjects were administered either placebo or 15 mg gaboxadol hydrochloride at bedtime on three consecutive nights. Sleep was recorded during each night from 2300 to 0700 h and tests assessing attention (target detection, stroop test) and memory function (visual form recognition, immediate word recall, digit span) were applied at 0900, 1400, and 1700 h during the following days. Compared with placebo, gaboxadol significantly shortened subjective sleep onset latency and increased self-rated sleep intensity and quality. Polysomnographic recordings showed that it significantly decreased the number of awakenings, the amount of intermittent wakefulness, and stage 1, and increased slow wave sleep and stage 2. These effects were stable over the three nights. None of the subjects reported side effects. Next-day cognitive performance was not affected by gaboxadol. Gaboxadol persistently improved subjective and objective sleep quality and was devoid of residual effects. Thus, at the employed dose, it seems an effective hypnotic in elderly subjects.

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.

The time course of selective visual attention: theory and experiments.

Historically, the psychophysical evidence for "selective attention" originated mainly from visual search experiments. A first important distinction in the processing of information in visual search tasks is its separation in two stages. The first, early "preattentive" stage operates in parallel across the entire visual field extracting single "primitive features" without integrating them. The second "attentive" stage corresponds to the specialized integration of information from a limited part of the field at any one time, i.e. serially. So far, models based on the above mentioned two-stage processes have been able to distinguish features from conjunction search conditions based on the observed slopes of the linear relation between reaction time (i.e., search time) and the number of items in the stimulus array. We propose a neuroscience based model for visual attention that works across the visual field in parallel, but due to its intrinsic dynamics can show the two experimentally observed modes of visual attention, namely: the serial focal attention and the parallel spread of attention over space. The model demonstrates that neither explicit serial focal search nor saliency maps need to be assumed. In the present model the focus of attention is not included in the system but only emerges after convergence of the dynamical behaviour of the neural networks. Furthermore, existing models have not been able to explain the variation of slopes observed in different kinds of conjunction search modes. We hypothesize that the different slopes can be explained by assuming that selective attention is guided by an independent mechanism which corresponds to the independent search for each feature. The model consistently integrates the different neuroscience levels by considering the microscopic neurodynamical mechanism that underlies visual attention, the different brain areas of the dorsal or "where" and ventral or "what" paths of the visual cortex, and behavioural data.

A biased competition based neurodynamical model of visual neglect.

On the computational basis of a neurodynamical cortical model, we investigate a specific top-down visual cognitive impairment in brain-damaged patients known as visual spatial neglect. The computational cortical model accounts the neurodynamics underlying selective visual attention, is based on the "biased competition hypothesis" and structured in several network modules which can be related with the different areas of the dorsal and ventral path of the visual cortex. Spatial and object attention are accomplished by a multiplicative gain control that emerges dynamically through intercortical mutual biased coupling. By damaging the model in different ways, a variety of dysfunctions associated with visual neglect can be simulated and explained as disruption of specific subsystems. Essentially, the damage destabilizes the underlying intra- and intermodular mutually biased neurodynamical competition that macroscopically yields the functional deficits observed in visual neglect patients. In particular, we are able to explain the asymmetrical effect of spatial cueing on neglect, and the phenomenon of extinction in the framework of visual search.

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.