Impaired verbal memory in Parkinson disease: relationship to prefrontal dysfunction and somatosensory discrimination

OBJECTIVE: To study the neurocognitive profile and its relationship to prefrontal dysfunction in non-demented Parkinson's disease (PD) with deficient haptic perception. METHODS: Twelve right-handed patients with PD and 12 healthy control subjects underwent thorough neuropsychological testing including Rey complex figure, Rey auditory verbal and figural learning test, figural and verbal fluency, and Stroop test. Test scores reflecting significant differences between patients and healthy subjects were correlated with the individual expression coefficients of one principal component, obtained in a principal component analysis of an oxygen-15-labeled water PET study exploring somatosensory discrimination that differentiated between the two groups and involved prefrontal cortices. RESULTS: We found significantly decreased total scores for the verbal learning trials and verbal delayed free recall in PD patients compared with normal volunteers. Further analysis of these parameters using Spearman's ranking correlation showed a significantly negative correlation of deficient verbal recall with expression coefficients of the principal component whose image showed a subcortical-cortical network, including right dorsolateral-prefrontal cortex, in PD patients. CONCLUSION: PD patients with disrupted right dorsolateral prefrontal cortex function and associated diminished somatosensory discrimination are impaired also in verbal memory functions. A negative correlation between delayed verbal free recall and PET activation in a network including the prefrontal cortices suggests that verbal cues and accordingly declarative memory processes may be operative in PD during activities that demand sustained attention such as somatosensory discrimination. Verbal cues may be compensatory in nature and help to non-specifically enhance focused attention in the presence of a functionally disrupted prefrontal cortex.

fMRI of Emotion

Recent brain imaging work has expanded our understanding of the mechanisms of perceptual, cognitive, and motor functions in human subjects, but research into the cerebral control of emotional and motivational function is at a much earlier stage. Important concepts and theories of emotion are briefly introduced, as are research designs and multimodal approaches to answering the central questions in the field. We provide a detailed inspection of the methodological and technical challenges in assessing the cerebral correlates of emotional activation, perception, learning, memory, and emotional regulation behavior in healthy humans. fMRI is particularly challenging in structures such as the amygdala as it is affected by susceptibility-related signal loss, image distortion, physiological and motion artifacts and colocalized Resting State Networks (RSNs). We review how these problems can be mitigated by using optimized echo-planar imaging (EPI) parameters, alternative MR sequences, and correction schemes. High-quality data can be acquired rapidly in these problematic regions with gradient compensated multiecho EPI or high resolution EPI with parallel imaging and optimum gradient directions, combined with distortion correction. Although neuroimaging studies of emotion encounter many difficulties regarding the limitations of measurement precision, research design, and strategies of validating neuropsychological emotion constructs, considerable improvement in data quality and sensitivity to subtle effects can be achieved. The methods outlined offer the prospect for fMRI studies of emotion to provide more sensitive, reliable, and representative models of measurement that systematically relate the dynamics of emotional regulation behavior with topographically distinct patterns of activity in the brain. This will provide additional information as an aid to assessment, categorization, and treatment of patients with emotional and personality disorders.

Sleepiness and vigilance tests

Objective assessments of subjective complaints such as sleepiness, tiredness or fatigue using sleepiness and vigilance tests aim to identify its causes and to judge the fitness to drive or to work of the affected person. "Vigilance" comprises wakefulness, alertness and attention and is therefore not merely reciprocal to sleepiness. Since it is a complex phenomenon with several dimensions it is unlikely to be appropriately assessed by one single "vigilance test". One important dimension of vigilance discussed here is wakefulness with its counterpart of overt sleep and the whole spectrum of various levels in between. The transit zone between full wakefulness and overt sleep is mainly characterised by the subjective complaint of sleepiness, which cannot be measured directly. Only the consequences of reduced wakefulness such as a shortened sleep latency, slowed cognitive function and prolonged reaction time can be measured objectively. It is, therefore, more promising to combine a battery of subjective and objective tests to answer a specific question in order to achieve the most appropriate description for a given clinical or medicolegal situation. However even then we must keep in mind that many other important aspects of fitness to drive / fitness to work such as neurological, psychiatric and neuropsychological functions including risk taking behaviour are not covered by vigilance tests. A comprehensive, multidisciplinary approach is essential in such situations.

Relationship between inflammation and cognitive function in obstructive sleep apnea

OBJECTIVES: Obstructive sleep apnea (OSA) can have adverse effects on cognitive functioning, mood, and cardiovascular functioning. OSA brings with it disturbances in sleep architecture, oxygenation, sympathetic nervous system function, and inflammatory processes. It is not clear which of these mechanisms is linked to the decrease in cognitive functioning. This study examined the effect of inflammatory parameters on cognitive dysfunction. MATERIALS AND METHODS: Thirty-nine patients with untreated sleep apnea were evaluated by polysomnography and completed a battery of neuropsychological tests. After the first night of evaluation in the sleep laboratory, blood samples were taken for analysis of interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptor 1 (sTNF-R1). RESULTS: sTNF-R1 significantly correlated with cognitive dysfunction. In hierarchical linear regression analysis, measures of obstructive sleep apnea severity explained 5.5% of the variance in cognitive dysfunction (n.s.). After including sTNF-R1, percentage of variance explained by the full model increased more than threefold to 19.6% (F = 2.84, df = 3, 36, p = 0.05). Only sTNF-R1 had a significant individual relationship with cognitive dysfunction (beta = 0.376 t = 2.48, p = 0.02). CONCLUSIONS: sTNF-R1 as a marker of chronic inflammation may be associated with diminished neuropsychological functioning in patients with OSA.

Hemispheric lateralization patterns and psychotic experiences in healthy subjects

The hypothesis that psychotic experiences in healthy subjects are associated with a dysfunction of the right hemisphere is supported by some, but not all, available studies. Differences in gender composition of study samples may explain in part the divergent findings. The present study was carried out in 42 healthy, right-handed university students. Scores on the Schizophrenia and Paranoia scales of the Minnesota Multidimensional Personality Inventory-2 were used in correlation analyses and to define a High- and a Low-Psychotic group. Brain Electrical Microstates and Low Resolution Electromagnetic Tomography (LORETA) source analyses of the auditory P300 (P3a and P3b) components of the event-related potential, as well as a battery of neuropsychological tests, were used to assess hemispheric functioning. Scores on the Paranoia scale were positively associated with a leftward shift of the P3a topographic descriptors in females but not in males. When comparing High-Psychotic and Low-Psychotic females, a leftward shift of P3a descriptors and an increased cortical activation in left fronto-temporal areas were observed in the High-Psychotic group. Our results demonstrated gender-related differences in the pattern of hemispheric imbalance associated with psychotic experiences in healthy subjects.

Faces and emotions: brain electric field sources during covert emotional processing

Covert brain activity related to task-free, spontaneous (i.e. unrequested), emotional evaluation of human face images was analysed in 27-channel averaged event-related potential (ERP) map series recorded from 18 healthy subjects while observing random sequences of face images without further instructions. After recording, subjects self-rated each face image on a scale from “liked” to “disliked”. These ratings were used to dichotomize the face images into the affective evaluation categories of “liked” and “disliked” for each subject and the subjects into the affective attitudes of “philanthropists” and “misanthropists” (depending on their mean rating across images). Event-related map series were averaged for “liked” and “disliked” face images and for “philanthropists” and “misanthropists”. The spatial configuration (landscape) of the electric field maps was assessed numerically by the electric gravity center, a conservative estimate of the mean location of all intracerebral, active, electric sources. Differences in electric gravity center location indicate activity of different neuronal populations. The electric gravity center locations of all event-related maps were averaged over the entire stimulus-on time (450 ms). The mean electric gravity center for disliked faces was located (significant across subjects) more to the right and somewhat more posterior than for liked faces. Similar differences were found between the mean electric gravity centers of misanthropists (more right and posterior) and philanthropists. Our neurophysiological findings are in line with neuropsychological findings, revealing visual emotional processing to depend on affective evaluation category and affective attitude, and extending the conclusions to a paradigm without directed task.

Subclinical thyroid dysfunction and cognitive decline in old age

BACKGROUND Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). METHODS Prospective longitudinal study of men and women aged 70-82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests. RESULTS Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up. CONCLUSION We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.

Ecological validity of virtual reality daily living activities screening for early dementia: longitudinal study

Background: Dementia is a multifaceted disorder that impairs cognitive functions, such as memory, language, and executive functions necessary to plan, organize, and prioritize tasks required for goal-directed behaviors. In most cases, individuals with dementia experience difficulties interacting with physical and social environments. The purpose of this study was to establish ecological validity and initial construct validity of a fire evacuation Virtual Reality Day-Out Task (VR-DOT) environment based on performance profiles as a screening tool for early dementia. Objective: The objectives were (1) to examine the relationships among the performances of 3 groups of participants in the VR-DOT and traditional neuropsychological tests employed to assess executive functions, and (2) to compare the performance of participants with mild Alzheimer’s-type dementia (AD) to those with amnestic single-domain mild cognitive impairment (MCI) and healthy controls in the VR-DOT and traditional neuropsychological tests used to assess executive functions. We hypothesized that the 2 cognitively impaired groups would have distinct performance profiles and show significantly impaired independent functioning in ADL compared to the healthy controls. Methods: The study population included 3 groups: 72 healthy control elderly participants, 65 amnestic MCI participants, and 68 mild AD participants. A natural user interface framework based on a fire evacuation VR-DOT environment was used for assessing physical and cognitive abilities of seniors over 3 years. VR-DOT focuses on the subtle errors and patterns in performing everyday activities and has the advantage of not depending on a subjective rating of an individual person. We further assessed functional capacity by both neuropsychological tests (including measures of attention, memory, working memory, executive functions, language, and depression). We also evaluated performance in finger tapping, grip strength, stride length, gait speed, and chair stands separately and while performing VR-DOTs in order to correlate performance in these measures with VR-DOTs because performance while navigating a virtual environment is a valid and reliable indicator of cognitive decline in elderly persons. Results: The mild AD group was more impaired than the amnestic MCI group, and both were more impaired than healthy controls. The novel VR-DOT functional index correlated strongly with standard cognitive and functional measurements, such as mini-mental state examination (MMSE; rho=0.26, P=.01) and Bristol Activities of Daily Living (ADL) scale scores (rho=0.32, P=.001). Conclusions: Functional impairment is a defining characteristic of predementia and is partly dependent on the degree of cognitive impairment. The novel virtual reality measures of functional ability seem more sensitive to functional impairment than qualitative measures in predementia, thus accurately differentiating from healthy controls. We conclude that VR-DOT is an effective tool for discriminating predementia and mild AD from controls by detecting differences in terms of errors, omissions, and perseverations while measuring ADL functional ability.

Orthostatic hypotension in Parkinson's disease: association with cognitive decline?

BACKGROUND Orthostatic hypotension is common in Lewy body disorders and may be related to disease progression and the spread of Lewy body pathology. We therefore hypothesize that PD patients with orthostatic hypotension (OH) have a different cognitive profile compared to PD patients without OH. METHODS This cross-sectional study included 175 PD patients. Blood pressure (BP) was measured with a validated digital blood pressure monitor and patients with a systolic BP drop of > or =20 mmHg or a systolic pressure of <90 mm Hg after standing were considered to have OH. Cognition was assessed using MMSE extended by a selection of computerized cognitive tests focusing on reaction time, sustained attention, working memory and episodic verbal and visual memory. RESULTS Eighty-seven (49.7%) of the PD patients had OH. These patients were significantly more impaired in sustained attention and visual episodic memory compared to PD patients without OH. CONCLUSION We conclude that there are differences in the neuropsychological performance of patients with PD and OH, supporting the hypothesis that OH might be a marker for disease progression and cognitive decline in PD.

Congenital portosystemic shunt: characterization of a multisystem disease

OBJECTIVES Congenital portosystemic shunts (CPSSs) are rare but increasingly recognized as a cause of important multisystem morbidity. We present new cases and a systematic literature review and propose an algorithm for the identification and care of affected patients. METHODS We reviewed the charts of consecutive patients seen in our pediatric liver clinic between 2003 and 2010 and systematically reviewed the literature of cases with CPSS. RESULTS We identified 316 published cases and 12 patients in our own clinic. Of the published cases (177 male), 185 had an extrahepatic and 131 an intrahepatic portosystemic shunt. Diagnosis was made at any age, from prenatal to late adulthood. Cardiac anomalies were found in 22% of patients. The main complications were hyperammonemia/neurological abnormalities (35%), liver tumors (26%), and pulmonary hypertension or hepatopulmonary syndrome (18%). The spectrum of neurological involvement ranged from changes in brain imaging, subtle abnormalities on neuropsychological testing, through learning disabilities to overt encephalopathy. Spontaneous shunt closure occurred mainly in infants with intrahepatic shunts. Therapeutic interventions included shunt closure by surgery or interventional radiology techniques (35%) and liver transplantation (10%) leading to an improvement of symptoms in the majority. These findings mirror the observations in our own patients. CONCLUSIONS In this largest review of the reported clinical experience, we identify that children with CPSS may present with otherwise unexplained developmental delay, encephalopathy, pulmonary hypertension, hypoxemia, or liver tumors. When CPSS is diagnosed, children should be screened for all of these complications. Spontaneous closure of intrahepatic shunts may occur in infancy. Closure of the shunt is indicated in symptomatic patients and is associated with a favorable outcome.

Can a novel computerized cognitive screening test provide additional information for early detection of Alzheimer's disease?

BACKGROUND: Virtual reality testing of everyday activities is a novel type of computerized assessment that measures cognitive, executive, and motor performance as a screening tool for early dementia. This study used a virtual reality day-out task (VR-DOT) environment to evaluate its predictive value in patients with mild cognitive impairment (MCI). METHODS: One hundred thirty-four patients with MCI were selected and compared with 75 healthy control subjects. Participants received an initial assessment that included VR-DOT, a neuropsychological evaluation, magnetic resonance imaging (MRI) scan, and event-related potentials (ERPs). After 12 months, participants were assessed again with MRI, ERP, VR-DOT, and neuropsychological tests. RESULTS: At the end of the study, we differentiated two subgroups of patients with MCI according to their clinical evolution from baseline to follow-up: 56 MCI progressors and 78 MCI nonprogressors. VR-DOT performance profiles correlated strongly with existing predictive biomarkers, especially the ERP and MRI biomarkers of cortical thickness. CONCLUSIONS: Compared with ERP, MRI, or neuropsychological tests alone, the VR-DOT could provide additional predictive information in a low-cost, computerized, and noninvasive way.

Visuospatial working memory in very preterm and term born children - Impact of age and performance

Working memory is crucial for meeting the challenges of daily life and performing academic tasks, such as reading or arithmetic. Very preterm born children are at risk of low working memory capacity. The aim of this study was to examine the visuospatial working memory network of school-aged preterm children and to determine the effect of age and performance on the neural working memory network. Working memory was assessed in 41 very preterm born children and 36 term born controls (aged 7–12 years) using functional magnetic resonance imaging (fMRI) and neuropsychological assessment. While preterm children and controls showed equal working memory performance, preterm children showed less involvement of the right middle frontal gyrus, but higher fMRI activation in superior frontal regions than controls. The younger and low-performing preterm children presented an atypical working memory network whereas the older high-performing preterm children recruited a working memory network similar to the controls. Results suggest that younger and low-performing preterm children show signs of less neural efficiency in frontal brain areas. With increasing age and performance, compensational mechanisms seem to occur, so that in preterm children, the typical visuospatial working memory network is established by the age of 12 years.

The potential of a mindfulness-enhanced, integrative neuropsychotherapy program for treating fatigue following stroke: A preliminary Study

Fatigue is a frequently reported symptom after a stroke. Although the phenomenology of poststroke fatigue is well known, clear definitions as well as diagnostic and therapeutic guidelines are missing. Poststroke fatigue can be regarded as a multidimensional phenomenon that might be influenced by neurological, physical, psychological, and cognitive factors. It can range from mild to severe and can affect every area of the activities of daily life. The objective of our preliminary study was to outline aspects of a specific treatment program for the management of poststroke fatigue. Eight patients were recruited for a mindfulness-enhanced, integrative neuropsychotherapy program. The treatment was a combination of neuropsychological interventions, psychoeducation, cognitive-behavioral therapy, and mindfulness techniques. The main treatment foci were (a) to facilitate an increased awareness of fatigue symptoms, (b) to help the patient detect and manage triggers of fatigue, and (c) to equip the patient with multiple self-help tools. Measures were assessed at the beginning, during, and at the end of treatment using self-assessment questionnaire for mental fatigue and related symptoms after neurological disorders and injuries. Significant pre- to post-assessment differences were observed. These findings suggest that patients may benefit from a specific treatment program in order to better adapt to poststroke fatigue. These findings encourage further investigation of this integrative treatment in larger samples that include adequate control treatments.

Neurocognitive deficits in children with brain tumors at diagnosis

Survivors of brain tumors are faced with a high risk for a wide range of cognitive problems and learning difficulties. These problems are caused by the lesion itself and its surgical removal as well as by the treatments to follow (chemo- and/or radiation therapy). A few recent studies have indicated that children with brain tumors (BT) might exhibit cognitive problems already at diagnosis, i.e. before the start of any medical treatment. The aim of the present study was to investigate the "baseline" neuropsychological profile in children with BT in comparison to children with an oncological diagnosis not involving the central nervous system (CNS). 20 children with BT and 27 children with an oncological disease without involvement of the CNS (age range: 6.1 to 16.9 years) were evaluated with an extensive battery of neuropsychological tests tailored to the patient's age. Furthermore, the child and its parents completed self-report questionnaires about emotional functioning and quality of life. In both groups, tests were administered before any therapeutic intervention such as surgery, chemotherapy or irradiation. Groups were comparable regarding age, gender and social economic status. Compared to the CG, patients with BTs performed significantly worse in tests of working memory, verbal memory and attention. In contrast the areas of perceptual reasoning, processing speed and verbal comprehension were preserved at this time. Younger children with BT were especially disadvantaged. Compared to aged matched children with malignancies not involving the CNS and older BT patients the young BT patients showed deficits in attention, working memory and verbal memory measures. Our results highlight the need for cognitive assessments and interventions early in the treatment process in order to minimize or even prevent academic difficulties as patients return to school.

Impacts of a word-picture training on literacy skills in elementary school children and youths with intellectual disabilities

Objective: There is convincing evidence that phonological, orthographic and semantic processes influence children’s ability to learn to read and spell words. So far only a few studies investigated the influence of implicit learning in literacy skills. Children are sensitive to the statistics of their learning environment. By frequent reading they acquire implicit knowledge about the frequency of letter patterns in written words, and they use this knowledge during reading and spelling. Additionally, semantic connections facilitate to storing of words in memory. Thus, the aim of the intervention study was to implement a word-picture training which is based on statistical and semantic learning. Furthermore, we aimed at examining the training effects in reading and spelling in comparison to an auditory-visual matching training and a working memory training program. Participants and Methods: One hundred and thirty-two children aged between 8 and 11 years participated in training in three weekly session of 12 minutes over 8 weeks, and completed other assessments of reading, spelling, working memory and intelligence before and after training. Results: Results revealed in general that the word-picture training and the auditory-visual matching training led to substantial gains in reading and spelling performance in comparison to the working-memory training. Although both children with and without learning difficulties profited in their reading and spelling after the word-picture training, the training program led to differential effects for the two groups. After the word-picture training on the one hand, children with learning difficulties profited more in spelling as children without learning difficulties, on the other hand, children without learning difficulties benefit more in word comprehension. Conclusions: These findings highlight the need for frequent reading trainings with semantic connections in order to support the acquisition of literacy skills.