Lost in Time: Temporal Monitoring Elicits Clinical Decrements in Sustained Attention Post-Stroke.

OBJECTIVES: Mental fatigue, 'brain fog', and difficulties maintaining engagement are commonly reported issues in a range of neurological and psychiatric conditions. Traditional sustained attention tasks commonly measure this capacity as the ability to detect target stimuli based on sensory features in the auditory or visual domains. However, with this approach, discrete target stimuli may exogenously capture attention to aid detection, thereby masking deficits in the ability to endogenously sustain attention over time. METHODS: To address this, we developed the Continuous Temporal Expectancy Task (CTET) where individuals continuously monitor a stream of patterned stimuli alternating at a fixed temporal interval (690 ms) and detect an infrequently occurring target stimulus defined by a prolonged temporal duration (1020 ms or longer). As such, sensory properties of target and non-target stimuli are perceptually identical and differ only in temporal duration. Using the CTET, we assessed stroke survivors with unilateral right hemisphere damage (N = 14), a cohort in which sustained attention deficits have been extensively reported. RESULTS: Stroke survivors had overall lower target detection accuracy compared with neurologically healthy age-matched older controls (N = 18). Critically, stroke survivors performance was characterised by significantly steeper within-block performance decrements, which occurred within short temporal windows (˜3 ½ min), and were restored by the break periods between blocks. CONCLUSIONS: These findings suggest that continuous temporal monitoring taxes sustained attention processes to capture clinical deficits in this capacity over time, and outline a precise measure of the endogenous processes hypothesised to underpin sustained attention deficits following right hemisphere stroke.

Effectiveness of a low support, remotely accessible, cognitive remediation training programme for chronic psychosis: cognitive, functional and cortical outcomes from a single blind randomised controlled trial.

BACKGROUND: Cognitive remediation (CR) training has emerged as a promising approach to improving cognitive deficits in schizophrenia and related psychosis. The limited availability of psychological services for psychosis is a major barrier to accessing this intervention however. This study investigated the effectiveness of a low support, remotely accessible, computerised working memory (WM) training programme in patients with psychosis. METHODS: Ninety patients were enrolled into a single blind randomised controlled trial of CR. Effectiveness of the intervention was assessed in terms of neuropsychological performance, social and occupational function, and functional MRI 2 weeks post-intervention, with neuropsychological and social function again assessed 3-6 months post-treatment. RESULTS: Patients who completed the intervention showed significant gains in both neuropsychological function (measured using both untrained WM and episodic task performance, and a measure of performance IQ), and social function at both 2-week follow-up and 3-6-month follow-up timepoints. Furthermore, patients who completed MRI scanning showed improved resting state functional connectivity relative to patients in the placebo condition. CONCLUSIONS: CR training has already been shown to improve cognitive and social function in patient with psychosis. This study demonstrates that, at least for some chronic but stable outpatients, a low support treatment was associated with gains that were comparable with those reported for CR delivered entirely on a 1:1 basis. We conclude that CR has potential to be delivered even in services in which psychological supports for patients with psychosis are limited.

Cognitive reserve and self-efficacy as moderators of the relationship between stress exposure and executive functioning among spousal dementia caregivers.

BACKGROUND: A substantial literature has reported that stress negatively impacts on cognitive processes. As dementia caregiving can be stressful, it has been hypothesized that the challenges of dementia care may increase caregivers' own vulnerability to cognitive decline. Prefrontal processes are thought to be most vulnerable to stress; however, few studies have examined whether greater caregiver stress predicts poorer executive dysfunction, and no previous research has considered potential moderators of this relationship. We examined (1) whether greater psychological stress mediated a relationship between caregiver stress exposure and executive functioning and (2) whether greater self-efficacy and cognitive reserve (CR) moderated this relationship. METHOD: Spousal dementia caregivers (n = 253) completed the Neuropsychiatric Inventory Questionnaire (stress exposure), the Perceived Stress Scale, the National Adult Reading Test (CR), the Fortinsky dementia-specific caregiver self-efficacy scale, and the Color Trails Test (executive functioning). Moderated mediation was tested using the PROCESS macro. Age, gender, and dementia risk factors were included as covariates. RESULTS: Greater stress exposure indirectly predicted executive functioning through psychological stress. Stronger relationships between greater psychological stress and poorer executive functioning were observed among caregivers with lower CR; there was no evidence that self-efficacy moderated the relationship between stress exposure and psychological stress. CONCLUSIONS: Our findings are in line with the idea that greater psychological stress in response to challenges associated with dementia care predicts poorer caregiver executive functioning, particularly among caregivers with low CR. However, these findings are cross sectional; it is also possible that poorer executive functioning contributes to greater caregiver stress.

Dietary Tyrosine Intake (FFQ) Is Associated with Locus Coeruleus, Attention and Grey Matter Maintenance: An MRI Structural Study on 398 Healthy Individuals of the Berlin Aging Study-II.

BACKGROUND AND OBJECTIVE: It is documented that low protein and amino-acid dietary intake is related to poorer cognitive health and increased risk of dementia. Degradation of the neuromodulatory pathways, (comprising the cholinergic, dopaminergic, serotoninergic and noradrenergic systems) is observed in neurodegenerative diseases and impairs the proper biosynthesis of key neuromodulators from micro-nutrients and amino acids. How these micro-nutrients are linked to neuromodulatory pathways in healthy adults is less studied. The Locus Coeruleus-Noradrenergic System (LC-NA) is the earliest subcortical structure affected in Alzheimer's disease, showing marked neurodegeneration, but is also sensitive for age-related changes. The LC-NA system is critical for supporting attention and cognitive control, functions that are enhanced both by tyrosine administration and chronic tyrosine intake. The purpose of this study was to 1) investigate whether the dietary intake of tyrosine, the key precursor for noradrenaline (NA), is related to LC signal intensity 2) whether LC mediates the reported association between tyrosine intake and higher cognitive performance (measured with Trail Making Test - TMT), and 3) whether LC signal intensity relates to an objective measure of brain maintenance (BrainPAD). METHODS: The analyses included 398 3T MRIs of healthy participants from the Berlin Aging Study II to investigate the relationship between LC signal intensity and habitual dietary tyrosine intake-daily average (HD-Tyr-IDA - measured with Food Frequency Questionnaire - FFQ). As a control procedure, the same analyses were repeated on other main seeds of the neuromodulators' subcortical system (Dorsal and Medial Raphe, Ventral Tegmental Area and Nucleus Basalis of Meynert). In the same way, the relationships between the five nuclei and BrainPAD were tested. RESULTS: Results show that HD-Tyr-IDA is positively associated with LC signal intensity. Similarly, LC disproportionally relates to better brain maintenance (BrainPAD). Mediation analyses reveal that only LC, relative to the other nuclei tested, mediates the relationship between HD-Tyr-IDA I and performance in the TMT and between HD-Tyr-IDA and BrainPAD. CONCLUSIONS: These findings provide the first evidence linking tyrosine intake with LC-NA system signal intensity and its correlation with neuropsychological performance. This study strengthens the role of diet for maintaining brain and cognitive health and supports the noradrenergic theory of cognitive reserve. Within this framework, adequate tyrosine intake might increase the resilience of LC-NA system functioning, by preventing degeneration and supporting noradrenergic metabolism required for LC function and neuropsychological performance.

Verbal intelligence is a more robust cross-sectional measure of cognitive reserve than level of education in healthy older adults.

BACKGROUND: Cognitive reserve is most commonly measured using socio-behavioural proxy variables. These variables are easy to collect, have a straightforward interpretation, and are widely associated with reduced risk of dementia and cognitive decline in epidemiological studies. However, the specific proxies vary across studies and have rarely been assessed in complete models of cognitive reserve (i.e. alongside both a measure of cognitive outcome and a measure of brain structure). Complete models can test independent associations between proxies and cognitive function in addition to the moderation effect of proxies on the brain-cognition relationship. Consequently, there is insufficient empirical evidence guiding the choice of proxy measures of cognitive reserve and poor comparability across studies. METHOD: In a cross-sectional study, we assessed the validity of 5 common proxies (education, occupational complexity, verbal intelligence, leisure activities, and exercise) and all possible combinations of these proxies in 2 separate community-dwelling older adult cohorts: The Irish Longitudinal Study on Ageing (TILDA; N = 313, mean age = 68.9 years, range = 54-88) and the Cognitive Reserve/Reference Ability Neural Network Study (CR/RANN; N = 234, mean age = 64.49 years, range = 50-80). Fifteen models were created with 3 brain structure variables (grey matter volume, hippocampal volume, and mean cortical thickness) and 5 cognitive variables (verbal fluency, processing speed, executive function, episodic memory, and global cognition). RESULTS: No moderation effects were observed. There were robust positive associations with cognitive function, independent of brain structure, for 2 individual proxies (verbal intelligence and education) and 16 composites (i.e. combinations of proxies). Verbal intelligence was statistically significant in all models. Education was significant only in models with executive function as the cognitive outcome variable. Three robust composites were observed in more than two-thirds of brain-cognition models: the composites of (1) occupational complexity and verbal intelligence, (2) education and verbal intelligence, and (3) education, occupational complexity, and verbal intelligence. However, no composite had larger average effects nor was more robust than verbal intelligence alone. CONCLUSION: These results support the use of verbal intelligence as a proxy measure of CR in cross-sectional studies of cognitively healthy older adults.

Cognitive rehabilitation for early stage Alzheimer's disease: a pilot study with an Irish population.

OBJECTIVES: Research shows that cognitive rehabilitation (CR) has the potential to improve goal performance and enhance well-being for people with early stage Alzheimer's disease (AD). This single subject, multiple baseline design (MBD) research investigated the clinical efficacy of an 8-week individualised CR intervention for individuals with early stage AD. METHODS: Three participants with early stage AD were recruited to take part in the study. The intervention consisted of eight sessions of 60-90 minutes of CR. Outcomes included goal performance and satisfaction, quality of life, cognitive and everyday functioning, mood, and memory self-efficacy for participants with AD; and carer burden, general mental health, quality of life, and mood of carers. RESULTS: Visual analysis of MBD data demonstrated a functional relationship between CR and improvements in participants' goal performance. Subjective ratings of goal performance and satisfaction increased from baseline to post-test for three participants and were maintained at follow-up for two. Baseline to post-test quality of life scores improved for three participants, whereas cognitive function and memory self-efficacy scores improved for two. CONCLUSIONS: Our findings demonstrate that CR can improve goal performance, and is a socially acceptable intervention that can be implemented by practitioners with assistance from carers between sessions. This study represents one of the promising first step towards filling a practice gap in this area. Further research and randomised-controlled trials are required.

Loss of insight in frontotemporal dementia, corticobasal degeneration and progressive supranuclear palsy.

Loss of insight is one of the core features of frontal/behavioural variant frontotemporal dementia (FTD). FTD shares many clinical and pathological features with corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). The aim of this study was to investigate awareness of cognitive deficits in FTD, CBD and PSP using a multidimensional approach to assessment, which examines metacognitive knowledge of the disorders, online monitoring of errors (emergent awareness) and ability to accurately predict performance on future tasks (anticipatory awareness). Thirty-five patients (14 FTD, 11 CBD and 10 PSP) and 20 controls were recruited. Results indicated that loss of insight was a feature of each of the three patient groups. FTD patients were most impaired on online monitoring of errors compared to the other two patient groups. Linear regression analysis demonstrated that different patterns of neuropsychological performance and behavioural rating scores predicted insight deficits across the three putative awareness categories. Furthermore, higher levels of depression were associated with poor anticipatory awareness, reduced empathy was related to impaired metacognitive awareness and impaired recognition of emotional expression in faces was associated with both metacognitive and anticipatory awareness deficits. The results are discussed in terms of neurocognitive models of awareness and different patterns of neurobiological decline in the separate patient groups.

Change in perceived stress and 2-year change in cognitive function among older adults: The Irish Longitudinal Study on Ageing.

Prolonged or severe stress can adversely affect older adults' cognitive function, but population-based studies investigating this relationship over time are rare. Previous studies have largely focused on stress either evaluated at a single time point or linked to specific life events. This study aimed to investigate whether a change in perceived stress over 2 years predicts a change in cognitive performance over the same time period in a population-based sample of older adults. Data from the first 2 waves of The Irish Longitudinal Study on Ageing were analyzed. Five thousand and seventy adults aged 50 and older completed the 4-item Perceived Stress Scale and measures of verbal fluency, immediate and delayed word recall 2 years apart. A first differences regression model revealed that the change in stress over 2 years was inversely associated with a change in immediate word recall performance, even after adjustment for change in possible confounders (B = -0.030, 95% CI [-.056, -.004], p < .05). No association was observed for delayed recall or verbal fluency performance. Change in perceived stress is inversely correlated with change in immediate recall, even over a short period. Stress modifying interventions could potentially reduce the risk of cognitive decline associated with ageing.

Visual attention: controlling what we see and do.

Controlling what we see and do in complex environments depends upon the interaction of top-down control mechanisms located in the prefrontal cortex, on the one hand, and bottom-up competition between objects for limited perceptual resources in posterior cortical areas, on the other.

Computerised working-memory focused cognitive remediation therapy for psychosis--A preliminary study.

BACKGROUND: Cognitive deficits are a core feature of schizophrenia and related psychotic disorders and are associated with decreased levels of functioning. Behavioural interventions have shown success in remediating these deficits; determining how best to maximise this benefit while minimising the cost is an important next step in optimising this intervention for clinical use. AIMS: To examine the effects of a novel working-memory focused cognitive remediation (CR) training on cognitive difficulties based on internet delivery of training and weekly telephone support. METHOD: Participants with a diagnosis of psychosis (n=56) underwent either 8 weeks of CR (approximately 20 h) or 8 weeks of treatment as usual (TAU). General cognitive ability, working memory and episodic memory were measured both pre and post intervention for all participants. RESULTS: In addition to improvements on trained working memory tasks, CR training was associated with significant improvements in two tests of verbal episodic memory. No association between CR and changes in general cognitive ability was observed. Effect sizes for statistically significant changes in memory were comparable to those reported in the literature based primarily on 1:1 training. CONCLUSIONS: The cognitive benefits observed in this non-randomised preliminary study indicate that internet-based working memory training can be an effective cognitive remediation therapy. The successes and challenges of an internet-based treatment are discussed.

Digit span and visual neglect: a puzzling relationship.

Weinberg et al. found a relationship between the presence of extinction and the discrepancy between backward and forward digit span among left hemiplegic patients. The present study replicates this finding in a group of 37 patients suffering from unilateral left visual neglect, demonstrating a strong relationship between degree of neglect and digit span discrepancy. A principal components analysis of a neurospychological examination revealed three main independent components--Neglect, Verbal Memory and Non-verbal Memory respectively. Digit Span Discrepancy had one of the highest loadings on the neglect factor, and loaded significantly on no other factor. Multiple regression analysis showed that the relationship of Digit Span Discrepancy with Degree of Neglect exists independently of visuo-spatial ability, and this is also true for paced auditory serial addition (PASAT) scores for one of the two main indices of neglect. The implications of this for understanding neglect are discussed.

Spatio-motor cueing in unilateral left neglect: the role of hemispace, hand and motor activation.

Reported beneficial effects of left arm activation on neglect are experimentally examined. The present study of a subject with left visual neglect compared left hand finger movement with an instruction to visually anchor perception on the left arm during letter cancellation. Only the finger movements significantly reduced neglect. Another comparison was between "out of sight" finger movements of the left hand in left and right hemispace, respectively. Only left hemispace "blind" finger movements significantly reduced neglect compared to the standard condition. Thirdly, blind left finger movements in left hemispace were compared with passive visual cueing (reading a changing number) and again it was found that only the finger movements reduced neglect. Finally, right finger movements in left hemispace were compared with left finger movements in left hemispace: only the latter reduced neglect. The implications of these findings for theory and therapy of neglect are discussed.

One hand is better than two: motor extinction of left hand advantage in unilateral neglect.

Severe left visual neglect has previously been shown to reduce when left hand movements in left hemispace were performed simultaneously to a series of cancellation tasks (Robertson and North, Neuropsychologia 30, 553-563, 1992). The present study demonstrates in two separate cases that this advantage associated with left hand activation was eliminated by simultaneous right hand activation, whether carried out in left or right hemispace. This suggests the existence of an extinction phenomenon for motor output which affects perceptual functioning, and a possible theoretical basis for this is discussed.

Active and passive activation of left limbs: influence on visual and sensory neglect.

A case of severe left visual neglect who had previously shown reductions in visual neglect with left hand movements in left hemispace showed the same phenomenon when the experiment was repeated, but failed to show it when the left hand was moved passively. However, neglect did reduce when he moved his left leg. Sensory extinction was not affected by left hand movements. Finally, hand movements in left hemispace also reduced neglect for stimuli in far as well as in peripersonal space. These results confirm the close link between visual attention and motor function and provide further support for the idea that contralesional limb movements may reduce visual neglect, possibly by activating a poorly attended body schema which in turn activates corresponding areas of extrapersonal space in at least two spatial systems (reaching and far space, respectively).

The automatic updating of egocentric spatial relationships and its impairment due to right posterior cortical lesions.

The non-visual updating of body-centred spatial relationships was investigated in an experiment in which blindfolded patients had to point to previously seen targets after a body rotation in the absence of vision. Patients with lesions to the right dorsal (RD) area were impaired at updating their positions relative to non-RD patients and normal subjects: they tended to underestimate systematically the angle through which they had turned. The results are interpreted in terms of impoverished locomotor input and/or systematically biased processing or locomotor proprioception in the RD patients, which prevented accurate tracking of changes in egocentric spatial relationships.

Divided attention impairments after traumatic brain injury.

This research investigated whether people with severe traumatic brain injury (TBI) are impaired on divided attention tasks requiring working memory. In experiment 1, a severe TBI and control group performed two tasks requiring working memory separately and concurrently. Results showed that the TBI group had impaired divided attention when performing the two tasks concurrently, although the two groups did not differ in performance when these tasks were performed separately. Experiment 2 showed that performance on the paced auditory serial addition task improved with increases in the intertrial interval for both TBI and control groups. A meta-analysis showed that TBIs are impaired on divided attention when the tasks require controlled processing, but not when the tasks can be carried out relatively automatically.

Attentional competition between modalities: extinction between touch and vision after right hemisphere damage.

The phenomenon of extinction, which occurs frequently after unilateral brain damage, involves a failure to detect the more contralesional of two simultaneously presented stimuli, but with preserved detection of single ipsilesional or contralesional stimuli. Current accounts suggest that the disorder reflects a bias of selective attention, in which ipsilesional stimuli have a competitive advantage. Extinction may be manifested within any one of the major sensory modalities (vision, audition, touch), or it may occur within several modalities in a given individual. Given recent evidence in normals for attentional links between separate sensory modalities, we examined whether extinction can also occur cross-modally, i.e. for double-simultaneous stimuli in separate sensory modalities. We tested whether an ipsilesional event sufficient to extinguish a contralesional stimulus within the same modality may also extinguish a contralesional stimulus in a different modality. Our three patients had right hemisphere damage, and reliable within-modality extinction for visual and tactile stimuli. They also showed significant cross-modal extinction, such that an ipsilesional tactile (or visual) event extinguished awareness of a simultaneous visual (or tactile) event on the contralesional side. These results, which provide the first quantitative evidence for cross-modal extinction, were replicated in a second experiment in which visual and tactile stimuli in the cross-modal conditions were presented at non-homologous elevations within each hemispace. We conclude that after unilateral damage, ipsilesional stimuli have a competitive advantage over contralesional stimuli, and that this affects competition between stimuli from different modalities as well as stimuli within the same modality. These findings are consistent with recent evidence for competitive interactions between tactile and visual events in the control of spatial attention in normals.

The absent mind: further investigations of sustained attention to response.

We have previously demonstrated that performance on a brief and conceptually simple laboratory task (the Sustained Attention to Response Test: SART) was predictive of everyday attentional failures and action slips in brain injured patients and normal control participants. The SART is a go-no-go paradigm in which the no-go target appears rarely and unpredictably. Performance on this measure was previously interpreted as requiring sustained attention to response rather than a putative 'response inhibition' capacity. Three further studies are presented which support this claim. They demonstrate that performance is crucially determined by the duration of time over which attention must be maintained on one's own actions that this demand underpins the task's relationship to everyday attentional lapses. In keeping with a number of recent studies it suggests that inefficiencies in the maintenance of attentional control may be apparent over much briefer periods than is traditionally considered using vigilance measures and analysis.