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Significance: Convolutional neural networks (CNNs) show the potential for automated classification of different cancer lesions. However, their lack of interpretability and explainability makes CNNs less than understandable. Furthermore, CNNs may incorrectly concentrate on other areas surrounding the salient object, rather than the network’s attention focusing directly on the object to be recognized, as the network has no incentive to focus solely on the correct subjects to be detected. This inhibits the reliability of CNNs, especially for biomedical applications. Aim: Develop a deep learning training approach that could provide understandability to its predictions and directly guide the network to concentrate its attention and accurately delineate cancerous regions of the image. Approach: We utilized Selvaraju et al.’s gradient-weighted class activation mapping to inject interpretability and explainability into CNNs. We adopted a two-stage training process with data augmentation techniques and Li et al.’s guided attention inference network (GAIN) to train images captured using our customized mobile oral screening devices. The GAIN architecture consists of three streams of network training: classification stream, attention mining stream, and bounding box stream. By adopting the GAIN training architecture, we jointly optimized the classification and segmentation accuracy of our CNN by treating these attention maps as reliable priors to develop attention maps with more complete and accurate segmentation. Results: The network’s attention map will help us to actively understand what the network is focusing on and looking at during its decision-making process. The results also show that the proposed method could guide the trained neural network to highlight and focus its attention on the correct lesion areas in the images when making a decision, rather than focusing its attention on relevant yet incorrect regions. Conclusions: We demonstrate the effectiveness of our approach for more interpretable and reliable oral potentially malignant lesion and malignant lesion classification.

Almost two decades ago, the sticky mittens paradigm was demonstrated as a way to train reaching and grasping behaviors in pre‐reaching infants, and consequently improve visual attentional abilities. In that first study, Needham and colleagues fitted 3‐month‐old infants with Velcro loop‐covered mittens and allowed them to interact with Velcro hook‐covered toys over the course of 2 weeks. In this review, we scrutinize the 17 studies that have followed those first sticky mittens results in regards to the motor, social perception, and visual attentional domains. Furthermore, we discuss the proposed mechanisms of the sticky mittens training. Current evidence strongly suggests that sticky mittens training facilitates social perception, which is consistent with prior correlational work showing links between action production and action perception. However, studies targeting motor and visual attentional abilities have too diverse results to warrant firm conclusions. We conclude that future research should focus on uncovering if there is a connection between sticky mittens training and motor behavior., We evaluated the sticky mittens effect in different domains and found that sticky mittens training has the strongest effects in the social perception domain. We emphasize a need for more research in the core domain–the motor domain.

Connectivity impairment has frequently been associated with the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Although the connectivity of the resting state has mainly been studied, we expect the transition between baseline and task may also be impaired in ADHD children. Twenty-three typically developing (i.e., control) and 36 disordered (ADHD and autism-comorbid ADHD) children were subjected to connectivity analysis. Specifically, they performed an attention task, visual oddball, while their brains were measured by functional near-infrared spectroscopy. The results of the measurements revealed three key findings. First, the control group maintained attentive connectivity, even in the baseline interval. Meanwhile, the disordered group showed enhanced bilateral intra- and interhemispheric connectivities while performing the task. However, right intrahemispheric connectivity was found to be weaker than those for the control group. Second, connectivity and activation characteristics might not be positively correlated with each other. In our previous results, disordered children lacked activation in the right middle frontal gyrus. However, within region connectivity of the right middle frontal gyrus was relatively strong in the baseline interval and significantly increased in the task interval. Third, the connectivity-based biomarker performed better than the activation-based biomarker in terms of screening. Activation and connectivity features were independently optimized and cross validated to obtain the best performing threshold-based classifier. The effectiveness of connectivity features, which brought significantly higher training accuracy than the optimum activation features, was confirmed (88% versus 76%). The optimum screening features were characterized by two trends: (1) strong connectivities of right frontal, left frontal, and left parietal lobes and (2) weak connectivities of left frontal, left parietal, and right parietal lobes in the control group. We conclude that the attentive task-based connectivity effectively shows the difference between control and disordered children and may represent pathological characteristics to be feasibly implemented as a supporting tool for clinical screening.

Earlier evidence has revealed a bi‐directional causal relationship between anxiety and attention biases in adults and children. This study investigated the prospective and concurrent relations between anxiety and attentional bias in a sample of 89 families (mothers, fathers, and first‐born children). Parents’ and children's attentional bias was measured when children were 7.5 years old, using both a visual probe task and visual search task with angry versus happy facial expressions. Generalized and social anxiety symptoms in parents and children were measured when children were 4.5 and 7.5 years old. Anxiety in parents and children was prospectively (but not concurrently) related to their respective attentional biases to threat: All participants showed a larger attentional bias to threat in the visual search (but not in the visual probe) task if they were more anxious at the 4.5 (but not at the 7.5) year measurement. Moreover, parents’ anxiety levels were prospectively predictive of the visual search attentional bias of their children after controlling for child anxiety. More anxiety in mothers at 4.5 years was related to a faster detection of angry among happy faces, while more anxiety in fathers predicted a faster detection of happy among angry faces in chil‐dren at 7.5 years. We found no direct association between parental and child attentional biases. Our study contributes to the recently emerging literature on attentional biases as a potential mechanism in the intergenerational transmission of anxiety by showing that parents’ anxiety rather than parents’ attentional bias contributes to the intergenerational transmission of risk for child anxiety.

Motor experiences and active exploration during early childhood may affect individual differences in a wide range of perceptual and cognitive abilities. In the current study, we suggest that active exploration of objects facilitates the ability to process object forms and magnitudes, which in turn impacts the development of numerosity perception. We tested our hypothesis by conducting a preregistered active exploration intervention with 59 8‐month‐old infants. The minimal intervention consisted of actively playing with and exploring blocks once a day for 8 weeks. In order to control for possible training effects on attention, we used book reading as a control condition. Pre‐ and post‐test assessments using eye‐tracking showed that block play improved visual form perception, where infants became better at detecting a deviant shape. Furthermore, using three control tasks, we showed that the intervention specifically improved infants' ability to process visual forms and the effect could not be explained by a domain general improvement in attention or visual perception. We found that the intervention did not improve numerosity perception and suggest that because of the sequential nature of our hypothesis, a longer time frame might be needed to see improvements in this ability. Our findings indicate that if infants are given more opportunities for play and exploration, it will have positive effects on their visual form perception, which in turn could help their understanding of geometrical concepts., Playing with blocks leads 8‐month‐old infants to develop better visual form perception, conceptualized here as detecting a deviant shape, compared to infants who were assigned to a reading control group.

Speech perception deficits are commonly reported in dyslexia but longitudinal evidence that poor speech perception compromises learning to read is scant. We assessed the hypothesis that phonological skills, specifically phoneme awareness and RAN, mediate the relationship between speech perception and reading. We assessed longitudinal predictive relationships between categorical speech perception, phoneme awareness, RAN, language, attention and reading at ages 5½ and 6½ years in 237 children many of whom were at high risk of reading difficulties. Speech perception at 5½ years correlated with language, attention, phoneme awareness and RAN concurrently and was a predictor of reading at 6½ years. There was no significant indirect effect of speech perception on reading via phoneme awareness, suggesting that its effects are separable from those of phoneme awareness. Children classified with dyslexia at 8 years had poorer speech perception than age‐controls at 5½ years and children with language disorders (with or without dyslexia) had more severe difficulties with both speech perception and attention control. Categorical speech perception tasks tap factors extraneous to perception, including decision‐making skills. Further longitudinal studies are needed to unravel the complex relationships between categorical speech perception tasks and measures of reading and language and attention. Funding Information: Wellcome Trust. Grant Number: WT082032MA

Recent studies with infants and adults demonstrate a facilitative role of labels in object categorization. A common interpretation is that labels highlight commonalities between objects. However, direct evidence for such a mechanism is lacking. Using a novel object category with spatially separate features that are either of low or high variability across the stimulus set, we tracked 12‐month‐olds’ attention to object features during learning and at test. Learning occurred in both conditions, but what was learned depended on whether or not labels were heard. A detailed analysis of eye movements revealed that infants in the two conditions employed different object processing strategies. In the silent condition, looking patterns were governed exclusively by the variability of object parts. In the label condition, infants’ categorization performance was linked to their relative attention to commonalities. Moreover, the commonality focus persisted after learning even in the absence of labels. These findings constitute the first experimental evidence that labels induce a persistent focus on commonalities.

Infants as young as 2 months can integrate audio and visual aspects of speech articulation. A shift of attention from the eyes towards the mouth of talking faces occurs around 6 months of age in monolingual infants. However, it is unknown whether this pattern of attention during audiovisual speech processing is influenced by speech and language experience in infancy. The present study investigated this question by analysing audiovisual speech processing in three groups of 4‐ to 8‐month‐old infants who differed in their language experience: monolinguals, unimodal bilinguals (infants exposed to two or more spoken languages) and bimodal bilinguals (hearing infants with Deaf mothers). Eye‐tracking was used to study patterns of face scanning while infants were viewing faces articulating syllables with congruent, incongruent and silent auditory tracks. Monolinguals and unimodal bilinguals increased their attention to the mouth of talking faces between 4 and 8 months, while bimodal bilinguals did not show any age difference in their scanning patterns. Moreover, older (6.6 to 8 months), but not younger, monolinguals (4 to 6.5 months) showed increased visual attention to the mouth of faces articulating audiovisually incongruent rather than congruent faces, indicating surprise or novelty. In contrast, no audiovisual congruency effect was found in unimodal or bimodal bilinguals. Results suggest that speech and language experience influences audiovisual integration in infancy. Specifically, reduced or more variable experience of audiovisual speech from the primary caregiver may lead to less sensitivity to the integration of audio and visual cues of speech articulation.

The paper and board industry (PBI) faces a series of challenges, ranging from shifts in the availability and quality of raw materials to the generation of large amounts of sidestreams whose disposal entails significant costs. The concept of the “Multiple Input-Multiple Output (MIMO) Paper Mill” is proposed here as an option for addressing these issues by introducing, on the one hand, flexibility regarding the types of fibre sources that can be used as raw materials and, on the other, a full utilisation of all fractions of the raw materials, including those that were so far considered to be sidestreams of papermaking. With regard to raw material flexibility, researchers have implemented various pretreatment and pulping methods on potential alternative, non-wood, fibre sources for the PBI, which can be found primarily in agro-industrial residues and plants specially cultivated for this purpose. Research on the conversion of various types of papermaking sidestreams into energy and material products has also been extensive, with the new products aimed at (re)use within both the PBI itself and other sectors. Given that technical aspects have gained the most attention so far, more focus should now be placed also on the economic and organisational sides of the concept. It is also crucial to start evaluating integrated MIMO cases, taking into account the interconnected effects that new raw materials have on the papermaking process and its sidestreams, instead of looking into isolated MI and MO examples.

Children with Developmental Coordination Disorder (DCD) fail to acquire adequate motor skill, yet surprisingly little is known about the oculomotor system in DCD. Successful completion of motor tasks is supported by accurate visual feedback. The purpose of this study was to determine whether any oculomotor differences can distinguish between children with and without a motor impairment. Using eye tracking technology, visual fixation, smooth pursuit, and pro‐ and anti‐saccade performance were assessed in 77 children that formed three groups: children with DCD (aged 7–10), chronologically age (CA) matched peers, and a motor‐match (MM) group (aged 4–7). Pursuit gain and response preparation in the pro‐ and anti‐saccade tasks were comparable across groups. Compared to age controls, children with DCD had deficits in maintaining engagement in the fixation and pursuit tasks, and made more anti‐saccade errors. The two typically developing groups performed similarly, except on the fast speed smooth pursuit and antisaccade tasks, where the CA group outperformed the younger MM group. The findings suggest that children with DCD have problems with saccadic inhibition and maintaining attention on a visual target. Developmental patterns were evident in the typically developing groups, suggesting that the pursuit system and cognitive control develop with age. This study adds to the literature by being the first to systematically identify specific oculomotor differences between children with and without a motor impairment. Further examination of oculomotor control may help to identify underlying processes contributing to DCD. A video abstract of this article can be viewed at: https://youtu.be/NinXa2KlB4M. [Correction added on 27 January 2017, after first online publication: The video abstract link was added.]

Background: Attentional dysfunction is believed to be a prominent and distinguishing neuropsychological feature of dementia with Lewy bodies (DLB); yet, the specific nature of the attentional deficit and factors that can potentially influence attentional processing in DLB have not been fully defined. Aims: To clarify the nature of the attentional deficit in early-stage DLB relative to patients with early-stage dementia of the Alzheimer’s type (DAT) and elderly controls, and examine the effect of task complexity and type of cognitive load on attentional processing in DLB. Methods: Attentional impairment and fluctuating attention were investigated in three groups of subjects—patients with clinical features of early probable DLB (n = 20), a group with early probable DAT (n = 19) and healthy elderly controls (n = 20)—using an experimental computerised reaction time paradigm. Results: Patients with DLB showed greater attentional impairment and fluctuations in attention relative to patients with DAT and elderly controls. The attentional deficit was generalised in nature but increased in magnitude as greater demands were placed on attentional selectivity. Attentional deficits in DLB were most pronounced under task conditions that required more active recruitment of executive control and visuospatial cognitive processes. Conclusions: Attentional deficits in DLB are widespread and encompass all aspects of attentional function. Deficits in higher cortical function influence the degree of attentional impairment and fluctuating attention, suggesting that attentional processing in DLB is mediated by interacting cortical and subcortical mechanisms. These findings serve to clarify the nature of the attentional deficit in DLB and have potentially important ramifications for our understanding of the neurocognitive underpinnings of fluctuations.

Objective: To assess visual search and recognition of roadside targets and safety errors during a landmark and traffic sign identification task in drivers with Alzheimer's disease. Methods: 33 drivers with probable Alzheimer's disease of mild severity and 137 neurologically normal older adults underwent a battery of visual and cognitive tests and were asked to report detection of specific landmarks and traffic signs along a segment of an experimental drive. Results: The drivers with mild Alzheimer's disease identified significantly fewer landmarks and traffic signs and made more at-fault safety errors during the task than control subjects. Roadside target identification performance and safety errors were predicted by scores on standardised tests of visual and cognitive function. Conclusions: Drivers with Alzheimer's disease are impaired in a task of visual search and recognition of roadside targets; the demands of these targets on visual perception, attention, executive functions, and memory probably increase the cognitive load, worsening driving safety.

Objectives: The evolutionary pattern of spontaneous recovery from acute neglect was studied by assessing cognitive deficits and motor impairments. Detailed lesion reconstruction was also performed to correlate the presence of and recovery from neglect to neural substrates. Methods: A consecutive series of right brain-damaged (RBD) patients with and without neglect underwent weekly tests in the acute phase of the illness. The battery assessed neglect deficits, neglect-related deficits, and motor impairment. Age-matched normal subjects were also investigated to ascertain the presence of non lateralised attentional deficits. Some neglect patients were also available for later investigation during the chronic phase of their illness. Results: Partial recovery of neglect deficits was observed at the end of the acute period and during the chronic phase. Spatial attention was impaired in acute neglect patients, while non spatial attentional deficits were present in RBD patients with and without acute neglect. A strong association was found between acute neglect and fronto-parietal lesions. Similar lesions were associated with neglect persistence. In the chronic stage, neglect recovery was paralleled by improved motor control of the contralesional upper limb, thus emphasising that neglect is a negative prognostic factor in motor functional recovery. Conclusions: These findings show that spatial attention deficits partially improve during the acute phase of the disease in less than half the patients investigated. There was an improvement in left visuospatial neglect at a later, chronic stage of the disease, but this recovery was not complete.

Background: “Normal” pressure hydrocephalus (NPH) is associated with injury to neurotransmitter and neuropeptide systems that recovers after surgery. This could be linked to changes in galanin, a neuropeptide with inhibitory effects on basal forebrain cognitive function. Objective: To examine changes in CSF galanin concentrations in patients with normal pressure hydrocephalus undergoing shunt surgery, and to investigate the relation between these changes and cognitive functioning. Methods: Eight patients underwent surgery for idiopathic normal pressure hydrocephalus. Lumbar CSF galanin determinations, cognitive status, and clinical status were quantified before operation and six months after. Cognition was assessed by an extensive battery of tests measuring attention, memory, speed of mental processing, visuospatial function, and frontal lobe function. Results: CSF galanin concentration decreased after surgery. This reduction correlated with improved clinical and cognitive functioning, specifically with attention and visuomotor speed, visuoconstructive and frontal functioning, and clinical status according to the NPH scale, including the sphincter and cognitive components. Conclusions: The cognitive and clinical improvement after shunt implantation correlated with CSF galanin levels, suggesting that the distribution or function of this agent involves cerebral structures that have some potential for recovery. In this study, galanin was related to several cognitive functions that may be associated with the fronto-subcortical deficits underlying cognitive dysfunction in normal pressure hydrocephalus.

Objectives: The lack of agreement regarding assessment methods is responsible for the variability in the reported rate of occurrence of spatial neglect after stroke. The aim of this study was to assess the sensitivity of different tests of neglect after right hemisphere stroke. Methods: Two hundred and six subacute right hemisphere stroke patients were given a test battery including a preliminary assessment of anosognosia and of visual extinction, a clinical assessment of gaze orientation and of personal neglect, and paper and pencil tests of spatial neglect in the peripersonal space. Patients were compared with a previously reported control group. A subgroup of patients (n=69) received a behavioural assessment of neglect in daily life situations. Results: The most sensitive paper and pencil measure was the starting point in the cancellation task. The whole battery was more sensitive than any single test alone. About 85% of patients Presented some degree of neglect on at least one measure. An important finding was that behavioural assessment of neglect in daily life was more sensitive than any other single measure of neglect. Behavioural neglect was considered as moderate to severe in 36% of cases. A factorial analysis revealed that paper and pencil tests were related to two underlying factors. Dissociations were found between extrapersonal neglect, personal neglect, anosognosia, and extinction. Anatomical analyses showed that neglect was more common and severe when the posterior association cortex was damaged. Conclusions: The automatic rightward orientation bias is the most sensitive clinical measure of neglect. Behavioural assessment is more sensitive than any single paper and pencil test. The results also support the assumption that neglect is a heterogeneous disorder.

Objective: Patients with left neglect on line bisection show normal implicit sensitivity to manipulations of both the stimulus and the visual background. Three experiments were designed to define this sensitivity more exactly. Methods: Normal controls and patients with left neglect performed a series of horizontal line bisection tasks. Independent variables were the configurations of the backgrounds for the line—rectangle, square, circle, left and right pointing isosceles triangles—and whether the background was the shape of the piece of paper or an outline drawn on a standard piece of paper. In a separate experiment different components of the triangle were outlined on a piece of paper. Deviation from true midpoint was calculated. Results: Simply placing the target lines in a symmetric background such as a square or circle did not reliably reduce neglect. A triangle asymmetric in the horizontal plane caused a shift in bisection away from the triangle9s vertex. With right pointing triangles the perceived midpoint shifted to the left of true centre (crossed over). The effects of the triangles were comparable in the patients and the controls when controlled for baseline bisection bias. The critical components of the triangles were the angular legs. This effect of background was not influenced by lesion site or by hemianopia. Conclusions: Patients with left visual neglect remain sensitive to covert manipulations of the visual background that implicitly shift the perceived midpoint of a horizontal line. This effect is strong enough to eliminate neglect on a bisection task. The mechanism of this effect is expressed through preattentive visual capacities.

Multisensory information has been shown to modulate attention in infants and facilitate learning in\ud adults, by enhancing the amodal properties of a stimulus. However, it remains unclear whether this\ud translates to learning in a multisensory environment across middle childhood, and particularly in the\ud case of incidental learning. One hundred and eighty-one children aged between 6 and 10 years\ud participated in this study using a novel Multisensory Attention Learning Task (MALT). Participants\ud were asked to respond to the presence of a target stimulus whilst ignoring distractors. Correct target\ud selection resulted in the movement of the target exemplar to either the upper left or right screen\ud quadrant, according to category membership. Category membership was defined either by visual-only,\ud auditory-only or multisensory information. As early as 6 years of age, children demonstrated greater\ud performance on the incidental categorization task following exposure to multisensory audiovisual\ud cues compared to unisensory information. These findings provide important insight into the use of\ud multisensory information in learning, and particularly on incidental category learning. Implications\ud for the deployment of multisensory learning tasks within education across development will be\ud discussed.

Background: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions. Objective: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH). Methods: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors. Results: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing—namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion. Conclusions: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.

Objective: To determine how cortical compensation occurs in higher cognitive systems during the recovery phase of diffuse axonal injury (DAI). Design: 12 right-handed patients with a magnetic resonance imaging (MRI) lesion pattern compatible with pure DAI were identified. Pure DAI was defined as finding of traumatic microbleeds on T2*-weighted gradient-echo images in the absence of otherwise traumatic or non-traumatic MRI abnormalities. 12 matched healthy controls were also enrolled. Functional magnetic resonance imaging (fMRI) was used to assess brain activation during a working memory test (Paced Visual Serial Attention Test (PVSAT)). Results: No significant group differences were observed in reaction times for the PVSAT. Although patients with pure DAI committed a few errors during the PVSAT, controls respond correctly to each probe. Controls showed activations in the left frontal gyrus, left parietal gyrus and right inferior parietal gyrus. Patients with pure DAI showed activations in the left inferior frontal gyrus, right inferior frontal gyrus and right middle frontal gyrus. Between-group analysis of the PVSAT task showed significantly greater activation of the right inferior frontal gyrus (BA 45) and right middle frontal gyrus (BA 9) in patient with pure DAI versus controls. Conclusions: Patients with pure DAI require compensatory activation of the contralateral (right) prefrontal region to carry out activities similar to healthy controls. These findings provide further evidence for the adaptive capacity of neuronal systems and brain plasticity during the recovery stages of DAI.

Background: Levodopa (L-dopa) is the gold standard treatment for Parkinson’s disease, but a lack of clear efficacy combined with a perceived liability to neuropsychiatric side effects has limited L-dopa use in patients with parkinsonism and dementia. Therefore, the effect of L-dopa on the cognitive profile of dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) is unclear. Aim: To ascertain the acute and long-term effects of L-dopa on aspects of attention and cognition in patients with DLB and PDD, and to compare these with the effects in Parkinson’s disease. Method: Baseline cognitive and motor function was assessed off L-dopa in patients with Parkinson’s disease (n = 22), PDD (n = 27) and DLB (n = 11) using standard “bedside” measures and a computerised programme detecting reaction times and accuracy. All patients then underwent an acute L-dopa challenge with subsequent subjective and objective analysis of alertness, verbal recall, reaction times and accuracy. The same parameters were measured after 3 months on L-dopa to assess the prolonged effect. Results: Acute L-dopa challenge considerably improved motor function and subjective alertness in all patients without compromising either reaction times or accuracy, but increased fluctuations were noted in both groups with dementia. Neuropsychiatric scores improved in patients with Parkinson’s disease both with and without dementia on L-dopa at 3 months. Although patients with Parkinson’s disease also had better mean global cognitive function at this time, mean verbal attention and memory deteriorated, and patients with PDD had slower reaction times in some tests. No patient had a marked deterioration over this time. Patients with DLB did not experience any adverse cognitive or neuropsychiatric effects after 3 months of L-dopa treatment. Conclusion: The use of L-dopa in patients with parkinsonism with dementia does not adversely affect cognitive function.

Objective: To investigate the effects of attentional deficits on activities of daily living (ADL) in patients with dementia associated with Parkinson’s disease (PDD). Method: 461 patients were assessed neuropsychologically. Factor analyses were used to differentiate attention from other cognitive functions and to differentiate different aspects of ADL functions. The effects of the attentional measure on ADL were examined using sequential multiple regression, controlling for age, sex, education, severity of motor symptoms and other cognitive functions. Results: Three cognitive factors were identified, with one factor emerging as a measure of vigilance and focused attention. This factor predicted different aspects of ADL status even after controlling for motor functions and other cognitive factors. The attention factor was the single strongest cognitive predictor of ADL status, matching the strength of the effects of motor functions on ADL status. Conclusion: Impaired attention is an important determinant of ADL functions in patients with PDD.

Background: There is some evidence that patients with Parkinson's disease may impaired in prospective memory performance (planning and self initiated realisation of delayed intentions). Little is known about the effect of the disease on distinct phases of prospective memory and the potential mechanisms underlying these effects. Objective: To investigate intention formation, intention retention, intention initiation, and intention execution of patients with Parkinson's disease and test for the mediating influence of working memory, inhibition, short term retrospective memory, and divided attention. Methods: 16 patients with Parkinson's disease and 16 age and education matched normal controls were given a complex event based prospective memory task which differentiates four phases of prospective remembering. In addition, participants completed tasks assessing potential cognitive mediators. Results: On the prospective remembering task, Parkinson patients were impaired in the intention formation phase and showed a trend towards impairment in the intention initiation. In contrast, there were no impairments of retrospective intention retention or the fidelity with which the patients executed their previously developed plan. The group effects were related to interindividual differences in working memory span. Conclusions: The results suggest that the planning phase of prospective remembering is specifically impaired in Parkinson's disease, and that the impairment is related to working memory deficit. In contrast, even when complex intentions have to be remembered, the retrospective storage of intentions to be performed is not impaired.

Background: Cerebral small vessel disease is a common cause of cognitive impairment and vascular dementia. The cognitive deficit differs from that in Alzheimer’s disease, with greater executive/attentional dysfunction and relatively intact episodic memory. Objective: To develop brief assessment tools that are better adapted to the neuropsychological profile of cerebral small vessel disease. Methods: 32 subjects with ischaemic leukoaraiosis (history of lacunar stroke and leukoaraiosis on MRI), aged 50 to 84 years, and 17 age and education matched controls had a brief executive assessment, which took 20 minutes to administer, and a wide range of additional tests. The ability of the brief executive assessment to discriminate between groups—both individually and in combination—was evaluated and compared with that of the whole battery. Results: The brief executive assessment provided good sensitivity and specificity for identifying subjects with ischaemic leukoaraiosis (sensitivity 88%, specificity 88%, using the optimal combination of scores). The best individual tests were trail making and digit symbol, which were both far more sensitive than the mini-mental state examination (MMSE). The ability to discriminate between groups was maintained in subjects with MMSE >27 and across the whole age range. The brief executive assessment performed well compared with the whole battery, with additional tests accounting for only a further 12% of between-group variance. Conclusions: The brief executive assessment was sensitive to deficits found in ischaemic leukoaraiosis and discriminated them from the cognitive effects of healthy aging. The assessment has potential for bedside use and as a cognitive end point for clinical trials.

Objectives: To establish the frequency of cognitive impairment in a population based sample of patients with recently diagnosed relapsing-remitting multiple sclerosis (RRMS), and to determine the relation between cognitive abnormalities and the extent of macroscopic and microscopic tissue damage revealed by magnetic resonance imaging (MRI) and magnetisation transfer (MT) imaging. Methods: 58 patients with RRMS consecutively diagnosed in the previous six months in Aquitaine and 70 healthy controls underwent a battery of neuropsychological tests. Lesion load and atrophy indices (brain parenchymal fraction and ventricular fraction) were measured on brain MRI. MT ratio (MTR) histograms were obtained from lesions, normal appearing white matter (NAWM), and normal appearing grey matter (NAGM). Gadolinium enhanced lesions were counted. Results: 44 RRMS patients could be individually matched with healthy controls for age, sex, and education. Patients performed worse in tests of verbal and spatial memory, attention, information processing speed, inhibition, and conceptualisation. Measures of attention and information processing speed were correlated with lesion load, mean NAWM MTR, and the peak location of the NAGM MTR histogram in the patients. Multivariate regression analysis showed that lesion load and mean NAWM MTR were among the MR indices that were most significantly associated with impairment of attention and information processing speed in these early RRMS cases. Conclusions: Cognitive impairment appears to be common in the early stages of RRMS, mainly affecting attention, information processing speed, memory, inhibition, and conceptualisation. The severity of these deficits reflects the extent of the lesions and the severity of tissue disorganisation outside lesions.

To determine in vivo cortical acetylcholinesterase (AChE) activity and cognitive effects in subjects with mild Alzheimer's disease (AD, n = 14) prior to and after 12 weeks of donepezil therapy.Cognitive and N-[(11)C]methyl-piperidin-4-yl propionate ([(11)C]PMP) AChE positron emission tomography (PET) assessments before and after donepezil therapy.Analysis of the PET data revealed mean (temporal, parietal, and frontal) cortical donepezil induced AChE inhibition of 19.1% (SD 9.4%) (t = -7.9; p0.0001). Enzyme inhibition was most robust in the anterior cingulate cortex (24.2% (6.9%), t = -14.1; p0.0001). Donepezil induced cortical inhibition of AChE activity correlated with changes in the Stroop Color Word interference scores (R(2) = 0.59, p0.01), but not with primary memory test scores. Analysis of the Stroop test data indicated that subjects with AChE inhibition greater than the median value (22.2%) had improved scores on the Stroop Color Word Test compared with subjects with less inhibition who had stable to worsening scores (t = -2.7; p0.05).Donepezil induced inhibition of cortical AChE enzyme activity is modest in patients with mild AD. The degree of cortical enzyme inhibition correlates with changes in executive and attentional functions.

Aims: To investigate the dynamic time course of transient global amnesia (TGA)—that is, the process of recovery and the interindividual variability—by testing four patients during the day of TGA itself (on three occasions) and at follow up (on two occasions). Methods: A specially designed protocol focusing on semantic (both conceptual and autobiographical knowledge) and episodic (both anterograde and retrograde components) memory. Results: Every patient showed marked impairment of both anterograde and retrograde episodic memory during the acute phase, with a relative preservation of personal and conceptual semantic knowledge. During the following phase, the authors observed similarities and differences among the patients' patterns of recovery. In general, retrograde amnesia recovered before the anterograde amnesia and anterograde episodic memory was recovered gradually in every case. In contrast, shrinkage of retrograde amnesia was more heterogeneous. In two of the patients, this shrinkage followed a chronological gradient and the most remote events were recovered first. In the two other patients, it depended more on the strength of the trace, and there was no temporal gradient. For the latter, an executive deficit could account for difficulties in accessing both conceptual knowledge and autobiographical memories. Conclusions: This profile of recovery suggests a "neocortical to medial temporal" process in every case, and the possibility of an additional frontal dysfunction in some cases. Hence, the acute phase seems to be characterised by a common episodic impairment. This variability between subjects appears in the recovery phase with two different patterns of impairment.

Objectives: Anatomical evidence and lesion studies, as well as functional magnetic resonance imaging (fMRI) studies, indicate that the cerebellum contributes to higher cognitive functions. Cerebellar posterior lateral regions seem to be relevant for cognition, while vermal lesions seem to be associated with changes in affect. However, the results remain controversial. Deficits of patients are sometimes still attributed to motor impairment. Methods: We present data from a detailed neuropsychological examination of 21 patients with cerebellar lesions due to tumour or haematoma, and 21 controls matched for age, sex, and years of education. Results: Patients showed deficits in executive function, and in attentional processes such as working memory and divided attention. Further analysis revealed that patients with right-sided lesions were in general more impaired than those with left-sided lesions. Conclusions: Those hypotheses that suggest that lesions of the right cerebellar hemisphere lead to verbal deficits, while those of the left lead to non-verbal deficits, have in part been confirmed. The generally greater impairment of those patients with a right-sided lesion has been interpreted as resulting from the connection of the right cerebellum to the left cerebral hemisphere, which is dominant for language functions and crucial for right hand movements. Motor impairment was correlated with less than half of the cognitive measures, with no stronger tendency for correlation with cognitive tests that require motor responses discernible. The results are discussed on the basis of an assumption that the cerebellum has a predicting and preparing function, indicating that cerebellar lesions lead to a "dysmetria of thought."

Objectives: To determine the relative impact of hydrocephalus and spinal dysraphism in young adults on intellectual and cognitive functioning. Sub-groups of patients with congenital hydrocephalus and/or spina bifida were assessed between 1995 and 2003. The entry criteria were that individuals should have (i) intact global function, (ii) average verbal intelligence (or above), and (iii) should not have clinical depression. There were three sub-groups: patients with hydrocephalus and spina bifida, patients with hydrocephalus without spina bifida, and patients with spina bifida without hydrocephalus. Methods: Patients were neuropsychologically assessed as part of their normal clinical assessment during their annual medical review. Each individual completed a screening battery assessing global functioning, verbal intelligence, and mood. In addition they completed additional tests including measures of emotional intelligence, memory, attention, and executive function. Results were analysed to compare the performance of the patient sub-groups and to compare them to a healthy control group. Results: Patients with hydrocephalus (with or without spina bifida) were significantly impaired on the vast majority of all test scores as compared to patients with spina bifida and healthy controls. They were particularly poor on measures assessing executive function. By contrast for patients with spina bifida with no associated hydrocephalus, the significant majority of all test scores fell within the average range or above. Conclusions: The neuropsychological profile of patients with hydrocephalus is one of relative impairment and this is so whether or not spina bifida is present. In spina bifida alone, in the absence of hydrocephalus, cognitive function is relatively spared.

Previous research on patients with left tactile extinction has shown that crossing of hands, so that each hand is on the opposite side of the body midline relative to the other, improves detection of stimuli given to the left hand.To study the influence of the spatial position of limbs on left tactile extinction, and its relations with left visual neglect.Normal participants and patients with right cerebral hemisphere damage and left tactile extinction were asked to detect single or double light touch stimuli applied to their cheeks, hands, or knees with their arm and legs either in anatomical or in crossed position, increasing the attentional load of the task.In patients with left extinction, limb crossing caused a deterioration in performance for stimuli applied to right body parts, with only a tendency to an improvement in detection for left body parts (only two of 24 patients showed substantial (20%) improvement in left extinction after limb crossing). After crossing, left limb detections of double stimuli decreased with increasing degrees of visual neglect.In conditions of high attentional load, limb crossing may impair tactile detection in most patients with left extinction, and particularly in those showing signs of left visual neglect. These results underline the importance of general attentional capacity in determining tactile extinction. Attentional and somatotopic mechanisms of extinction may assume different weights in different patients.

Objective: (1) To assess cognitive function and cerebral magnetic resonance imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to monitor disease evolution, cognitive dysfunction, and cerebral lesion burden over time (mean 8.5 year follow up period); (3) to study the relation between clinical, neuropsychological, and MRI data. On follow up assessment, visual and auditory oddball event related potentials (ERPs) were recorded as psychophysiological evaluation of cognitive status. Correlations between neuropsychological, MRI, and ERP data were also analysed. Methods: Neuropsychological study assessed verbal and non-verbal IQ, deterioration index (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial short-term and long term memory. MRI assessment detected presence of demyelinating lesions by using a semiquantitative method as well as cortical and subcortical atrophy over time. Results: Attention, short-term and long term visuospatial memory were mildly impaired at baseline and remained unaltered longitudinally. At retesting a significant worsening of verbal long term memory (p=0.023), DI presence (p=0.041) and the increase of supratentorial and subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions as well as cortical atrophy correlated significantly with attention and memory tests at baseline. Follow up assessment revealed significant correlation between cortical atrophy and attention as well as visuospatial short-term memory; spatial long term memory correlated significantly with lesions in body of lateral ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more visual P300 (58.4 % of cases) than auditory wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI and auditory P300 latency with frontal horn and brain stem lesions. Conclusions: These findings revealed mild cognitive impairment in MS patients particularly consistent with slowing information processing over time. Increased MRI lesions do not correlate with the clinical course of the disease and cognitive deficit evolution. Thus, cognitive dysfunction could be related to disease peculiarity and not to the time course. Correlations between P300, neuropsychological, and MRI findings provide further information about ERP application to examine cognitive impairment in MS and probably to investigate their neural origin.

Background: Rivastigmine enhances cholinergic activity and has been shown in clinical trials to decrease the rate of deterioration in Alzheimer's disease. It remains unclear where in the brain it exerts its effect. Functional magnetic resonance imaging (fMRI) can be used to measure changes in brain function and relate these to cognition. Objectives: To use fMRI to study brain activation with rivastigmine treatment. Methods: The effect on brain activation of a single dose of rivastigmine was tested in seven patients with mild Alzheimer's disease using fMRI during face encoding, and in five patients during a parametric working memory task. Results: During face encoding, rivastigmine increased bilateral activation in the fusiform gyrus. Brain activation was also enhanced in the prefrontal cortex in a simple working memory task. When working memory load was further increased, not only was increased activation seen, but in certain areas there was also decreased activation. Conclusions: These findings link the previously observed increase in cognitive performance in Alzheimer's disease after treatment with a cholinesterase inhibitor to altered brain activation. Although the results cannot be generalised to the Alzheimer's disease population at large, they provide evidence that in mild Alzheimer's disease, rivastigmine enhances brain activation in the fusiform and frontal cortices. This is compatible with the concept of cholinergic circuitry.

Objectives: Advances in neuroimaging studies have recently improved the understanding of the functional anatomy of the calculation processes, having in particular underlined the central role of the angular gyrus (AG). In this study, the authors applied this knowledge to the surgical resection of a glioma invading the left AG, by localising and sparing the cortical areas involved in two different components of calculation (multiplication and subtraction), using direct electrical stimulations. Methods: A calculation mapping was performed in a patient without deficit except a slightly impaired performance for serial arithmetic subtraction, during the resection under local anaesthesia of a left parieto-occipital glioma invading the dominant AG. After somatosensory and language mappings, cortical areas involved in single digit multiplications and subtractions of seven were mapped using the method of electrostimulation, before glioma removal. Results: Distinct sites specifically involved in multiplication or subtraction were detected within the left AG, with a precise spatial distribution and overlapping. All the eloquent (somatosensory, language, and calculation) areas were surgically spared. Postoperatively, the patient had a transient complete deficit for arithmetic subtraction, without either multiplication or language disturbance. The tumour removal was complete. Conclusions: These findings suggest: firstly, the usefulness of an intraoperative calculation mapping during the removal of a lesion involving the left dominant AG, to avoid permanent postoperative deficit of arithmetic processes while optimising the quality of tumour resection; secondly, the possible existence of a well ordered and dynamic anatomo-functional organisation for different components of calculation within the left AG.

Objective: To assess the effects of left parietal injury on covert visual attention during a detection task and a pointing task. Methods: The Posner's paradigm was given to a patient who was found at the age of 74 to have spent all his life without the left parietal lobe as a result of a congenital perinatal insult and to a control subject. In one session subjects were required to provide an arbitrary response at stimulus appearance (key press). In another session subjects were required to point to the stimulus. Results: The patient was able to disengage covert attention from a cued position when the task was to provide an arbitrary key press response in a similar fashion to a control subject with no neurological deficits. By contrast, he was impaired in disengaging attention from a cued position when the task was to reprogramme an overt pointing action. Conclusions: Response to cued information is differentially available depending on task. It is suggested that mechanisms concerned with the attention for action systems are located within the left parietal lobe.

E-readers are fast rivaling print as a dominant method for reading. Because they offer accessibility options that are impossible in print, they are potentially beneficial for those with impairments, such as dyslexia. Yet, little is known about how the use of these devices influences reading in those who struggle. Here, we observe reading comprehension and speed in 103 high school students with dyslexia. Reading on paper was compared with reading on a small handheld e-reader device, formatted to display few words per line. We found that use of the device significantly improved speed and comprehension, when compared with traditional presentations on paper for specific subsets of these individuals: Those who struggled most with phoneme decoding or efficient sight word reading read more rapidly using the device, and those with limited VA Spans gained in comprehension. Prior eye tracking studies demonstrated that short lines facilitate reading in dyslexia, suggesting that it is the use of short lines (and not the device per se) that leads to the observed benefits. We propose that these findings may be understood as a consequence of visual attention deficits, in some with dyslexia, that make it difficult to allocate attention to uncrowded text near fixation, as the gaze advances during reading. Short lines ameliorate this by guiding attention to the uncrowded span.

Horizontal and vertical EOG recordings of eye movements were analyzed to determine the spatial and temporal distribution of blinks and the patterns of eye movements (saccades and fixation pauses) exhibited by six subjects during the reading of stories presented in two formats (on paper and on a VDT). The frequency and placement of blinks was not affected by the presentation condition. Blinks were determined to be non-randomly distributed during reading. Significantly more blinks (36%) occurred in conjunction with saccades than the proportion of time consumed by saccades (12%) would predict. Significantly more blinks (36%) occurred in the vicinity of line change saccades, which accounts for 15% of reading time, and with fixation pauses associated with regressions (42%), which accounts for 26% of reading time, than with fixation pauses during normal reading (22%), which accounts for 60% of reading time. The results of the study suggest that blink behavior during reading is under perceptual and cognitive control.

An hygienic survey for hydrogen sulfide, methyl mercaptan and its derivatives and sulfur dioxide in kraft mills and in sulfite mills revealed concentrations varying from 0 to 20 ppm hydrogen sulfide, 0 to 15 ppm methyl mercaptan and comparable amounts of dimethyl sulfide with dimethyl disulfide up to 1.5 ppm. The greatest emissions were detected at chip chutes and evaporation vacuum pumps. Batch operations yielded clearly higher sulfur dioxide concentrations (up to 20 ppm) as compared to a continuous ammonia-base digester. Furthermore, there was a strong correlation with the season in the sulfite mills where higher concentrations were found in the winter when natural ventilation was poorer. As to the health effects, the exposed workers complained of headaches and a decrease in concentration capacity more often than matched controls. The number of sick leaves was greater in the exposed workers than among the controls.