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Hemispheric lateralization of the neural encoding of temporal speech features: a whole-head magnetencephalography study.

Using a passive oddball design (randomized series of standard [frequent] and deviant [rare] stimuli), the present study investigated the neural encoding of syllables differing in a duration parameter (/da/ = short-lag voice onset time [VOT], /ta/ = long-lag VOT) by means of whole-head magnetencephalography (MEG). Dipolar activities at the level of the supratemporal planes allowed to explain the evoked magnetic fields. The N1m/P2m-complex (magnetic equivalent to the N /P2-wave of the electroencephalogram) in response to standard stimuli showed bilateral symmetric distribution. Furthermore, the latency of P2m significantly depended on VOT. Finally, the mismatch response to the deviant /da/-syllables-which represent in German a very frequent word (English: 'here' or 'there')- evolved significantly earlier in the left hemisphere as compared to the right side. In conclusion, processing speed may be an important aspect of the hemispheric specialization of language.

Adult↗

Retrograde cerebral perfusion during thoracic aortic surgery and late neuropsychological dysfunction.

OBJECTIVE: Retrograde cerebral perfusion (RCP) is commonly used in thoracic aortic surgery, ostensibly to provide metabolic support, maintain cerebral hypothermia and/or wash out particulate emboli. We tested the hypothesis that RCP would affect neuropsychological outcome in a clinical cohort. METHODS: Ninety-four patients undergoing elective thoracic aortic repairs requiring deep hypothermic circulatory arrest consented to participate in this study. These patients underwent preoperative neuropsychological evaluation and comprise the reference group. Fifty-six of these patients also underwent neuropsychological evaluation several weeks postoperatively, 12 of whom (21%) had RCP. The neuropsychological domains tested were attention, processing speed, memory, executive function, and fine motor function. A global assessment of impairment, negative neuropsychological outcome (NNO), was defined as a postoperative decrease in function in two or more neuropsychological domains for patients with at least three domains tested both pre- and postoperatively (n=48). The relationship of three potential predictors (RCP, cerebral ischemia time and patient age) to negative outcomes was analyzed using Wilcoxon two-sample tests, chi(2) tests, Mantel-Haenszel tests and multiple logistic regression. P<0.05 was considered significant. RESULTS: Memory dysfunction and NNO had strong associations with RCP. This effect remained significant when controlling separately for age and cerebral ischemia time. CONCLUSIONS: The effects of RCP are difficult to distinguish from those of age and prolonged cerebral ischemia time, because complex thoracic aortic repairs are associated with advanced age, prolonged cerebral ischemia and use of RCP. Despite this limitation, these preliminary data indicated that RCP had no beneficial effect (and most likely a negative effect) upon cognitive outcome.

Adult↗

Comparison of endogenous event-related potentials in attend and non-attend conditions: latency changes with normal aging.

OBJECTIVE: Endogenous event-related potential (ERP) components have been observed under both attend and non-attend conditions, but it appears that at least some of the attend and non-attend components are functionally and topographically distinct. Also, under active task conditions, motivational and attentional variations may modulate the amplitude of the ERP. These various effects of attention on the ERP can complicate comparisons of the ERPs of normal subjects with the ERPs of clinical subjects, who may have reduced attentional capabilities. The experiment reported here sought to develop a non-task paradigm that reliably produces the same ERP components typically seen under task conditions. METHODS: Using rare auditory stimuli that were discrepant from the frequent stimuli both in frequency and intensity, stimuli were presented under non-attend instructions and under instruction to count the rare stimuli. The ERPs in these two conditions were compared with ERPs in a standard oddball paradigm which used stimulus parameters comparable to those of most previous experiments on ERPs in aging. Fifty subjects, ranging in age from 20 to 77, participated. RESULTS: The ERPs to the DISCREPANT oddball stimuli under non-task conditions were similar in scalp distribution to the ERPs to the same stimuli in the ATTEND condition and to the ERPs in the STANDARD/ATTEND condition. Furthermore, there were no significant differences in the age-related increase in ERP latencies among the DISCREPANT/IGNORE, the DISCREPANT/ATTEND, and the STANDARD/ATTEND conditions. CONCLUSION: The results indicate that increases in ERP latencies with aging can be assessed in the absence of task requirements, and that the paradigm described here may prove useful in investigating cognitive processing speed in clinical populations.

Acoustic Stimulation↗

Neuropsychological functioning in children with early-treated phenylketonuria: impact of white matter abnormalities.

Impact of white matter abnormalities (WMAs) on neuropsychological functioning in children with early-treated phenylketonuria (ETPKU) was examined. Children with ETPKU (20 males, 12 females, mean age 11 years 2 months, SD 3 years 6 months) and controls (20 males, 14 females, mean age 10 years 4 months, SD 3 years 1 month) aged 7 to 18 years were assessed using tests of attention, processing speed, memory and learning, executive function, and academic achievement. Those with ETPKU, exhibiting WMAs extending into subcortical/frontal regions (n=14), displayed significant impairments in a number of domains. Children with ETPKU but no WMAs (n=6), or pathology restricted to the posterior periventricular region (n=12), displayed only mild deficits. Concurrent phenylalanine levels correlated weakly with cognitive parameters, whereas lifetime phenylalanine levels were associated with deficits in several cognitive domains. Impairments in children with extensive WMAs are consistent with compromised neural transmission, which is characterized by dysmyelination. However, children with no detectable, or mild WMAs, also displayed cognitive problems, indicating that neuropsychological functioning in children with ETPKU is determined by a complex interaction of biological and environmental factors.

Adolescent↗

Neurocognitive Manifestations of Human Immunodeficiency Virus.

Is human immunodeficiency virus still a terminal condition? Recent advances in treatment have significantly reduced both mortality and morbidity associated with HIV, but these treatments have not been successful in eradicating the virus itself. As such, HIV has evolved into a chronic condition that is complicated by neurocognitive factors. Cognitive difficulties associated with HIV are characterized by a subcortical pattern with primary deficits in information processing speed and psychomotor speed. These deficits interfere with the ability of patients to complete important instrumental activities of daily living even in the absence of dementia. Treatment of HIV improves neurocognitive functioning, but the regimens are complex and patient adherence is critical. Cognitive factors can negatively impact treatment adherence, which in turn results in poorer immunological, cognitive, and psychiatric outcome. This cycle emphasizes the important interrelationships between symptom expression and treatment outcome in patients with HIV. The nature of these relationships will change with further developments in treatment regimens such as once-daily dosing. Less complex treatment approaches should improve health outcome as well as provide additional opportunities to further understand the impact of HIV on brain function.

Journal Article↗

Neuropsychological functioning in a patient with paraneoplastic limbic encephalitis.

A 54-year-old woman with clinically diagnosed paraneoplastic limbic encephalitis secondary to adenocarcinoma of the lung is described. Neuropsychological evaluation revealed intact visual perception, visual construction, language, speeded processing, and verbal abstract reasoning in the presence of a severe anterograde amnesia for both verbal and visual information. A profound consolidation problem is discussed in view of other diseases of the mesial temporal lobes resulting in impaired consolidation of new material.

Adenocarcinoma↗

Verbal memory deficits associated with fornix atrophy in carbon monoxide poisoning.

Magnetic resonance (MR) images and neuropsychological testing data of 69 carbon monoxide (CO) poisoned patients were prospectively obtained within 1 day of CO poisoning, two weeks and six months. CO patients' Day 1 cross-sectional fornix surface area measurements, corrected for head size by using a fornix-to-brain ratio (FBR), were compared to normal age and gender-matched controls. Additionally, a within-subjects analysis was performed comparing the mean areas between CO patients' Day 1, 2 weeks and 6-month FBR. The FBR was correlated with patients' neuropsychological data. There were no significant differences between CO patients' Day 1 fornix measurements compared to normal control subjects. However, significant atrophic changes in the fornix of CO poisoned patients occurred at two weeks with no progressive atrophy at 6 months. By 6 months, CO patients showed significant decline on tests of verbal memory (when practice effects were taken into account), whereas visual memory, processing speed and attention/concentration did not decline. This study indicates that CO results in brain damage and cognitive impairments in the absence of lesions and other neuroanatomic markers.

Adolescent↗

A meta-analysis of the neuropsychological sequelae of HIV infection.

This meta-analysis summarizes the broad spectrum of neuropsychological research on HIV disease across a sample of 41 primary studies and an aggregate of 8,616 participants for 10 major neuropsychological ability areas. Analyses of the course of cognitive decline within and across Centers for Disease Control classifications reveals statistically significant cognitive deficits from asymptomatic HIV to AIDS. Effect sizes (Cohen, 1988) were calculated to reflect between-group (asymptomatic, symptomatic, AIDS) differences in each neuropsychological domain. Relatively small effect sizes were obtained for the asymptomatic (0.05-0.21) patients, and generally small to moderate effect sizes were obtained for symptomatic (0.18-0.65) HIV+ patients, with motor functioning exhibiting the greatest effects in this later disease stage. The most notable deficits in cognitive functioning were found in the AIDS group with moderate (attention and concentration) to large (motor functioning) effect sizes with values ranging from 0.42-0.82. Comparison of cognitive functioning as a function of disease progression revealed that motor functioning, executive skills, and information processing speed were among the cognitive domains showing the greatest decline from early to later stages of HIV. These findings indicate that cognitive deficits in the early stages of HIV are small and increase in the later phases of the illness, and that specific patterns of cognitive deficits can be detected with disease progression. These results and their clinical utility are further discussed.

AIDS Dementia Complex↗

Neuropsychological deficits in patients with chronic fatigue syndrome.

The degree of neuropsychological dysfunction across multiple domains was examined in individuals suffering from chronic fatigue syndrome (CFS). In this descriptive study, a similar series of neuropsychological tests was administered to a group of CFS patients and healthy participants. More specifically, CFS patients (n = 141) who met the 1994 Case Definition criteria were compared to 76 healthy control participants on tests of memory, attention (concentration), speed of information processing, motor speed, and executive functioning. On the 18 measures administered, CFS patients scored 1 standard deviation below the healthy mean on nine measures and scored 2 standard deviations below the healthy mean on four of the measures. Moreover, results indicated that CFS patients were more likely than healthy controls to fail (1.6 SD below the healthy mean) at least one test in each of the following domains: attention, speed of information processing, and motor speed, but not on measures of memory and executive functioning. Finally, CFS patients demonstrated a greater total number of tests failed across domains.

Adult↗

Relation between subjective fogginess and neuropsychological testing following concussion.

The purpose of this study was to examine the relation between the subjective report of feeling foggy at one-week post concussion and acute neuropsychological outcome. The outcome variables were derived from a computerized neuropsychological screening battery, Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). Participants were 110 high school students who sustained a sports-related concussion and were evaluated 5-10 days post injury (M = 6.8 days). Athletes were divided into two groups on the basis of self-reported fogginess. The first group reported no fogginess (n = 91), whereas the second group reported experiencing some degree of fogginess (n = 19) on a 6-point scale. The athletes with persistent fogginess experienced a large number of other post-concussion symptoms, compared to the athletes with no reported fogginess. In addition, the athletes with persistent fogginess had significantly slower reaction times, reduced memory performance, and slower processing speed. Thus, athletes with any degree of self-reported fogginess at one-week post injury are likely to have adverse effects from their concussions in multiple domains.

Adolescent↗

Usability of a theory of visual attention (TVA) for parameter-based measurement of attention II: evidence from two patients with frontal or parietal damage.

Based on a 'Theory of Visual Attention' (TVA), whole and partial report of brief letter arrays is presented as a diagnostic tool to estimate four clinically significant attentional components: perceptual processing speed, visual working memory storage capacity, efficiency of top-down control, and spatial distribution of attention. The procedure used was short enough to be applicable within a standard clinical setting. Two brain-damaged patients, selected based on lesion location and neuropsychological test profile, were compared to a control group of 22 healthy subjects. One patient with a right inferior parietal lesion showed a pattern of non-spatially and spatially lateralized attention deficits that is typically found in neglect patients. Results from the second patient supported the decisive role of superior frontal brain structures for top-down control of visual attention. This double dissociation supports the hypothesis that, even with a short version of whole and partial report, valid and meaningful results can be obtained in the neuropsychological assessment of attention deficits. The potential and constraints of TVA-based parameter estimation for the clinical application are discussed.

Attention↗

Comparing attentional skills in children with acquired and developmental central nervous system disorders.

Attentional impairments in children occur in the context of both developmental and acquired disorders involving the central nervous system (CNS) and may have implications for ongoing development, potentially impeding cognitive, educational, and behavioral functions. Using a continuous performance paradigm (CPT), this study compared attentional profiles of children with developmental and acquired conditions impacting on the CNS: (i) attention deficit-hyperactivity disorder (ADHD: n=27); (ii) moderate traumatic brain injury (TBI: n=41); (iii) acute lymphoblastic leukemia (n=31); and (iv) insulin-dependent diabetes mellitus (n=39). A healthy control group (n=46) was also examined. Groups were compared on measures of sustained attention, selective attention, and response inhibition. In addition, measures of performance variability and deterioration and processing speed were examined. Results showed that children with ADHD exhibited global and severe attentional impairments in contrast to all other groups. Children with moderate TBI displayed mild attentional difficulties, restricted to selective and sustained attention domains. In conclusion, although CPT parameters differentiated the ADHD group from all others, a disorder-specific profile was not observed.

Adolescent↗

Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS).

Cognitive impairment occurs in roughly 50% of patients with multiple sclerosis (MS). It is well known that processing speed and episodic memory deficits are the most common neuropsychological (NP) sequelae in this illness. Consensus has emerged about the specific tests that prove most helpful for routine monitoring of MS associated cognitive impairment. The purpose of this study was to examine the validity of the Minimal Assessment of Cognitive Function in MS (MACFIMS), a recommended battery based on the findings of an international conference held in 2001. We tested 291 MS patients and 56 healthy controls. Frequencies of impairment paralleled those reported in previous work for both individual cognitive domains and general impairment. All tests were impaired in the MS group, and distinguished relapsing-remitting (RR) from secondary progressive (SP) course. Principle components analysis showed a distinct episodic memory component. Most of the MACFIMS tests discriminated disabled from employed patients. However, in regression models accounting for all NP tests, those emphasizing verbal memory and executive function were most predictive of vocational status. We conclude that the MACFIMS is a valid approach to routine NP assessment of MS patients. Future work is planned to determine its psychometric properties in a longitudinal study.

Cognition Disorders↗

Neuropsychological and neuroimaging changes in preclinical Alzheimer's disease.

Alzheimer's disease (AD) is a common, devastating form of dementia. With the advent of promising symptomatic treatment, the importance of recognizing AD at its very earliest stages has increased. We review the extant neuropsychological and neuroimaging literature on preclinical AD, focusing on longitudinal studies of initially nondemented individuals and cross-sectional investigations comparing at-risk with normal individuals. We systematically reviewed 91 studies of neuropsychological functioning, structural neuroimaging, or functional neuroimaging in preclinical AD. The neuropsychological studies indicated that preclinical AD might be characterized by subtle deficits in a broad range of neuropsychological domains, particularly in attention, learning and memory, executive functioning, processing speed, and language. Recent findings from neuroimaging research suggest that volume loss and cerebral blood flow or metabolic changes, particularly in the temporal lobe, may be detected before the onset of dementia. There exist several markers of a preclinical period of AD, in which specific cognitive and biochemical changes precede the clinical manifestations. The preclinical indicators of AD reflect early compromise of generalized brain integrity and temporal lobe functioning in particular.

Alzheimer Disease↗

When does Huntington's disease begin?

Recent studies have detected basal ganglia atrophy in clinically asymptomatic persons with the genetic mutation that causes Huntington's disease (HD). Whether reductions in caudate and putamen volume on MRI scans are associated with changes in cognitive and neurologic functioning was examined in 13 healthy adults with the IT-15 mutation. Reduced striatal volume was found to correlate with greater neurologic (largely motor) impairment, slower mental processing speed, and poorer verbal learning, although none of the participants met even liberal criteria for clinical diagnosis of HD. These correlations are strikingly similar to those observed in symptomatic HD patients, possibly reflecting the earliest manifestations of disease.

Adult↗

A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia.

Cognitive impairment is a core feature of schizophrenia and a major impediment to social and vocational rehabilitation. A number of studies have claimed cognitive benefits from treatment with various atypical antipsychotic drugs (APDs). The currently available evidence supporting cognitive improvement with atypical APDs was evaluated in two meta-analyses. Studies that (1) prospectively examined cognitive change to the atypical APDs clozapine, olanzapine, quetiapine, and risperidone, (2) included a commonly used neuropsychological test, and (3) provided data from which relevant effect sizes could be calculated, were included. Forty-one studies met these criteria. Neuropsychological test data from each study were combined into a Global Cognitive Index and nine cognitive domain scores. Two meta-analyses were carried out. The first included 14 controlled, random assignment trials that assigned subjects to an atypical APD and a typical APD control arm. The second analysis included all prospective investigations of atypical treatment and the within-group change score divided by its standard deviation served as an estimate of effect size (ES). The first analysis revealed that atypicals are superior to typicals at improving overall cognitive function (ES=0.24). Specific improvements were observed in the learning and processing speed domains. The second analysis extended the improvements to a broader range of cognitive domains (ES range=0.17-0.46) and identified significant differences between treatments in attention and verbal fluency. Moderator variables such as study blind and random assignment influence results of cognitive change to atypical APDs. Atypical antipsychotics produce a mild remediation of cognitive deficits in schizophrenia, and specific atypicals have differential effects within certain cognitive domains.

Antipsychotic Agents↗

Effects of risperidone on auditory event-related potentials in schizophrenia.

Schizophrenia is associated with cognitive deficits for which treatments remain elusive. The effects of risperidone (an antipsychotic differing in some of its pharmacological properties from typical agents) on cognitive deficits have not been extensively investigated. Mismatch negativity (MMN), N2 and P3 are cognitive event-related potentials that index preattentive (MMN) and attention-dependent information processing (N2, P3) and provide a measure of cognitive deficits in schizophrenia. The effects of risperidone treatment on MMN, N2 and P3 generation in chronic schizophrenic patients were investigated in an open- label, uncontrolled study. Risperidone treatment significantly reduced psychotic symptoms. It was associated with a decrease of peak latencies, particularly pronounced for P3. However, it did not significantly affect abnormal MMNor P3 amplitudes. The results suggest an effect of risperidone on processing speed, particularly in attention-dependent tasks. These results are in agreement with findings in recent studies on the cognitive effects of risperidone.

Journal Article↗

Metallic photonic crystals based on solution-processible gold nanoparticles.

We demonstrate the fabrication of metallic photonic crystals, in the form of a periodic array of gold nanowires on a waveguide, by spin-coating a colloidal gold suspension onto a photoresist mask and subsequent annealing. The photoresist mask with a period below 500 nm is manufactured by interference lithography on an indium tin oxide (ITO) glass substrate, where the ITO layer has a thickness around 210 nm and acts as the waveguide. The width of the nanowires can be controlled from 100 to 300 nm by changing the duty cycle of the mask. During evaporation of solvent, the gold nanoparticles are drawn to the grooves of the grating with apparently complete dewetting off the photoresist for channels less than 2 microm in width, which therefore form nanowires after the annealing process. Strong coupling between the waveguide mode and the plasmon resonance of the nanowires, which is dependent on the polarization and incidence angle of the light wave, is demonstrated by optical extinction measurements. Continuity of the nanowires is confirmed by conductivity properties. Simplicity, high processing speed, and low cost are the main advantages of this method, which may have a plethora of applications in telecommunication, all-optical switching, sensors, and semiconductor devices.

Crystallization↗