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PubMed2006

Effects of acute tryptophan depletion on cognition, memory and motor performance in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neuropsychiatric disease, which is not only characterized by motor symptoms, but also by cognitive and psychiatric symptoms. It is hypothesized that some of the non-motor symptoms are related to the serotonergic deficiency that is present in PD. AIM: To study the influence of serotonin on cognition, memory and motor performance in PD. METHODS: In a double blind, randomized, placebo-controlled, cross-over design, the effect of acute tryptophan depletion (ATD) on the Visual Verbal Learning Task (VVLT), the Concept Shifting Task (CST), Simple Reaction Time Task (SRT), Finger Precuing Task (FPT) and the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS, Section 3) was investigated in 15 PD patients in early stages of their disease and 15 healthy volunteers, matched for age, sex and educational status. RESULTS: With the exception of the absence of a differential effect for PD patients with the long interval of the SRT, ATD produced similar effects in PD patients and control subjects on all tasks. These included impairment of delayed recall and delayed recognition on the VVLT, and improved SRT and FPT for 'short intervals'. The UPDRS in patients remained unaffected after ATD. CONCLUSION: Serotonin does not appear to play a disease-specific role in cognition and reaction time in early stage PD patients, nor does acute reduction of cerebral serotonin levels affect motor symptoms in a clinically relevant way.

Aged↗
PubMed2005

Pretreatment with hyperbaric oxygen and its effect on neuropsychometric dysfunction and systemic inflammatory response after cardiopulmonary bypass: a prospective randomized double-blind trial.

OBJECTIVE: Animal studies have shown that pretreatment with hyperbaric oxygen can induce central nervous system ischemic tolerance and also modulate the inflammatory response. We evaluated this therapy in patients undergoing cardiopulmonary bypass. METHODS: Sixty-four patients were prospectively randomized to group A (n = 31; atmospheric air, 1.5 atmospheres absolute) or group B (n = 33; hyperbaric oxygen, 2.4 atmospheres absolute) before on-pump coronary artery bypass grafting. Age, sex, body mass index, diabetes, hypertension, smoking, coronary disease severity, left ventricular function, Parsonnet score, Euroscore, bypass time, myocardial ischemia time, and number of grafts were comparable in both groups. Canadian Cardiovascular Society angina, New York Heart Association dyspnea, and previous myocardial infarction were significantly higher in group B. Inflammatory markers were analyzed before surgery and 2 and 24 hours after bypass. Neuropsychometric testing was performed 48 hours before surgery and 4 months after surgery and included trail making A and B, the Rey auditory verbal learning test, grooved peg board, information processing table A, and digit span forward and backward. Neuropsychometric dysfunction was defined as more than 1 SD deterioration in more than 2 neuropsychometric tests. Chi-square tests, Fisher tests, t tests, and analysis of variance were used as appropriate for statistical analysis. RESULTS: Group A had a significant postoperative increase in the inflammatory markers soluble E-selectin, CD18, and heat shock protein 70. This was not observed in group B. Neuropsychometric dysfunction was also significantly higher in group A compared with group B. There was no difference in any other early postoperative clinical outcome. CONCLUSIONS: Our results seem to indicate that pretreatment with hyperbaric oxygen can reduce neuropsychometric dysfunction and also modulate the inflammatory response after cardiopulmonary bypass. However, further multicenter randomized trials are needed to clinically evaluate this form of therapy.

Aged↗
PubMed2006

Deficits in predictive smooth pursuit after mild traumatic brain injury.

Given that even mild traumatic brain injury (TBI) may produce extensive diffuse axonal injury (DAI), we hypothesized that mild TBI patients would show deficits in predictive smooth pursuit eye movements (SPEM), associated with impaired cognitive functions, as these processes are dependent on common white matter connectivity between multiple cerebral and cerebellar regions. The ability to predict target trajectories during SPEM was investigated in 21 mild TBI patients using a periodic sinusoidal paradigm. Compared to 26 control subjects, TBI patients demonstrated decreased target prediction. TBI patients also showed increased eye position error and variability of eye position, which correlated with decreased target prediction. In all subjects, average target prediction, eye position error and eye position variability correlated with scores related to attention and executive function on the California Verbal Learning Test (CVLT-II). However, there were no differences between TBI and control groups in average eye gain or intra-individual eye gain variability, or in performance on the Wechsler Abbreviated Scale of Intelligence (WASI), suggesting that the observed deficits did not result from general oculomotor impairment or reduced IQ. The correlation between SPEM performance and CVLT-II scores suggests that predictive SPEM may be a sensitive assay of cognitive functioning, including attention and executive function. This is the first report to our knowledge that TBI patients show impaired predictive SPEM and eye position variability, and that these impairments correlate with cognitive deficits.

Adolescent↗
PubMed2006

Increased oculomotor deficits during target blanking as an indicator of mild traumatic brain injury.

Given the susceptibility of cerebellar-cortical tracts to shearing injury from traumatic brain injury (TBI), we investigated impairment in the generation of predictive eye movements and its relationship to cognitive deficits in mild TBI patients using a smooth pursuit target-blanking paradigm. Compared to a target-tracking paradigm without blanking, this paradigm more greatly necessitates the generation of predictive eye movements, which are subserved by brain regions involved in cognitive processing. Mild TBI patients showed impaired prediction of target trajectories during target blanking, demonstrated by generation of saccades at earlier and more variable time points, as well as greater and more variable oculomotor error compared to controls. In addition, California Verbal Learning Test (CVLT-II) scores related to working memory, learning, and executive function were more highly correlated with oculomotor variability during target blanking than during target tracking. Our results suggest that a disruption of cerebellar-cortical connections in TBI may account for both oculomotor and cognitive impairment, and that measures of predictive eye movements during target blanking may be a sensitive metric of cognitive deficits after mild TBI.

Adolescent↗
PubMed2006

Sequelae of fume exposure in confined space welding: a neurological and neuropsychological case series.

Welding fume contains manganese (Mn) which is known to be bio-available to and neurotoxic for the central nervous system. Although an essential metal, Mn overexposure may cause manganism, a parkinsonian syndrome. The present welder study sought to improve the clinical portrait of manganism and to determine dose-effect relationships. The welders were employed in the construction of the new Bay Bridge (San Francisco) and welded in confined spaces for up to 2 years with minimal protection and poor ventilation. Neurological, neuropsychological, neurophysiological, and pulmonary examinations were given to 49 welders. Clinical cases were selected on the basis of apriori defined criteria pertaining to welding history and neurological/neuropsychological features. Among the 43 eligible welders, 11 cases of manganism were identified presenting with the following symptoms: sleep disturbance, mood changes, bradykinesia, headaches, sexual dysfunction, olfaction loss, muscular rigidity, tremors, hallucinations, slurred speech, postural instability, monotonous voice, and facial masking. Significant associations between outcome variables and cumulative exposure index (CEI) or blood Mn (MnB) were obtained with CEI for variables implicating attention and concentration, working and immediate memory, cognitive flexibility, and verbal learning; and with MnB for executive function, cognitive flexibility, visuo-spatial construction ability, and visual contrast sensitivity. This study strongly suggests that neuropsychological features contribute in a dose-effect related way to the portrait of manganism usually characterized by tremor, loss in balance, diminished cognitive performance, and signs and symptoms of parkinsonism.

Adult↗
PubMed2006

Predicting memory decline in normal elderly: genetics, MRI, and cognitive reserve.

Major predictors of Alzheimer's disease (AD) include apolipoprotein E (APOE)-epsilon4, hippocampal atrophy on magnetic resonance imaging (MRI), and memory dysfunction prior to diagnosis. We examined 159 normal elderly subjects with MRI and the California Verbal Learning Test (CVLT); 84 returned for longitudinal follow-up 5 years later. Analyses at baseline revealed significant variance in hippocampal volume accounted for by cerebral volume and age but not by APOE isoform. However, interactions involving APOE isoform and laterality were observed. As hypothesized, an APOE x time interaction was revealed for CVLT long-delay free recall: APOE-epsilon3/4 subjects had significantly poorer performance than APOE-epsilon3/3 subjects at follow-up. Forward stepwise multiple regression analysis predicting follow-up long-delay free recall selected baseline recall, followed by number of APOE-epsilon4 alleles, followed by left-hippocampal volume. Age and sex did not enter into the model. We conclude that APOE-epsilon4 predicts longitudinal memory decline in healthy controls and that MRI morphometry of hippocampus adds slightly to predictive value.

Aged↗
PubMed2006

Neural mechanisms for response selection: comparing selection of responses and items from working memory.

Recent functional imaging studies of working memory (WM) have suggested a relationship between the requirement for response selection and activity in dorsolateral prefrontal (DLPFC) and parietal regions. Although a number of WM operations are likely to occur during response selection, the current study was particularly interested in the contribution of this neural network to WM-based response selection when compared to the selection of an item from a list being maintained in memory, during a verbal learning task. The design manipulated stimulus-response mappings so that selecting an item from memory was not always accompanied with selecting a motor response. Functional activation during selection supported previous findings of fronto-parietal involvement, although in contrast to previous findings left, rather than right, DLPFC activity was significantly more active for selecting a memory-guided motor response, when compared to selecting an item currently maintained in memory or executing a memory-guided response. Our results contribute to the debate over the role of fronto-parietal activity during WM tasks, suggesting that this activity appears particularly related to response selection, potentially supporting the hypothesized role of prefrontal activity in biasing attention toward task-relevant material in more posterior regions.

Cerebral Cortex↗
PubMed2004

Sequences assessed by declarative and procedural tests of memory in amnesic patients with hippocampal damage.

Previous research indicates that amnesic subjects tested on sequential learning or serial reaction time tasks can learn a repeated procedural sequence but are unable to explicitly recall the correct sequence when asked to generate the sequence. Rats with hippocampal lesions are also able to learn and remember procedural or implicit sequences but were impaired for declarative sequences. We used analogous procedures used in rats to assess the role of the hippocampus in the acquisition of declarative and procedural sequences in amnesic and control participants. Amnesic participants with damage restricted to the hippocampus and control participants were administered analogous tasks of declarative and procedural sequential learning using a computer version of the radial arm maze. The amnesic participants had slower response times during the acquisition of procedural sequences, but were not impaired compared to controls when switched to a random sequence, suggesting that both groups learned the sequence. Alternatively, the amnesic but not control participants were significantly impaired in the declarative sequence task. Our findings provide support for evolutionary continuity in cognitive function of the hippocampus in rats and humans and the dissociation between the declarative and procedural sequential learning. The performance differences on the two sequence learning tasks are likely due to the use of different strategies associated with learning sequences based on procedural versus declarative knowledge.

Adult↗
PubMed2005

Mnemonic anosognosia in Alzheimer's disease: a test of Agnew and Morris (1998).

Agnew and Morris [Agnew, S. K. & Morris, R. G. (1998). The heterogeneity of anosognosia for memory impairment in Alzheimer's disease: A review of the literature and a proposed model. Aging and Mental Health, 2, 9-15] model of awareness for memory functioning has attempted to account for the variance of anosognosia exhibited within the Alzheimer's disease (AD) population. There has been tentative evidence to suggest that the mnemonic anosognosia sub-type, proposed by this model, is common within the early stages of AD. However, this study is the first directly to test the model. Eighteen older adults with early AD and 18 healthy older adults were recruited. Awareness of memory functioning was monitored using patient-performance measures of "task specific" awareness; a measure of global memory awareness; and a patient-informant measure. The stability of participants' awareness was measured across three word recall lists and after a 20-min delay. Results suggested that, whilst the participants with early AD were less aware of their memory ability than the healthy older adults, they were able to improve their awareness following exposure to a memory task. Furthermore, the improvements in awareness were largely retained after the delay period. These findings are discussed in relation to Agnew and Morris [Agnew, S. K. & Morris, R. G. (1998). The heterogeneity of anosognosia for memory impairment in Alzheimer's disease: A review of the literature and a proposed model. Aging and Mental Health, 2, 9-15] model of mnemonic anosognosia and to current thinking about autobiographical memory.

Aged↗
PubMed2006

Effect of two prednisone exposures on mood and declarative memory.

Corticosteroids are essential for life and an integral part of the stress response. However, in excess, corticosteroids can be associated with a variety of effects on the brain including hippocampal atrophy and even neuronal death, mood changes, and declarative memory impairment. The magnitude of mood change in patients receiving prednisone is reportedly associated with previous lifetime corticosteroid exposure, consistent with a sensitization or kindling process whereby greater effects are observed with repeated exposure. To our knowledge, the effect of multiple corticosteroid exposures on mood and memory has not been previously examined prospectively in animals or humans. In this study, 30 human volunteers, with no history of systemic prescription corticosteroid therapy, were given (in random order using a crossover design) two 3-day exposures of prednisone (60 mg/day) and one of identical placebo, with 11-day washouts between each medication exposure. Before and after each 3-day prednisone/placebo exposure, declarative memory was assessed using different versions of the Rey Auditory Verbal Learning Test (RAVLT) to minimize practice or learning effects, while mood was assessed with the 21-item Hamilton Rating Scale for Depression, Young Mania Rating Scale and Internal State Scale. No significant mood changes were found. However, a significant decrease in aspects of RAVLT performance was observed after the first prednisone exposure consistent with a decline in declarative memory performance. The decline in RAVLT performance was significantly smaller after the second prednisone exposure as compared to the initial prednisone exposure. Thus, a second prednisone exposure was associated with an attenuated prednisone-effect on declarative memory. These data suggest tolerance or habituation, rather than sensitization, to prednisone effects on declarative memory during a second exposure. Implications and possible explanations for the findings are discussed.

Adult↗
PubMed2005

School performance in early and continuously treated phenylketonuria.

This study investigated the relationship between school performance, cognitive functions, and dietary control in a group of 26 early and continuously treated phenylketonuric patients, in comparison with 21 sex- and age-matched control subjects. The cognitive functions study included intelligence measurement, visual and auditory memory and auditory verbal learning abilities, attention, visuospatial, fine motor, language, and executive functions. Participants were asked about school performance. The indexes of dietary control for the first 6 years of life and for the 6 months before the study were calculated. The intelligence score was significantly lower in phenylketonuric patients (P < 0.0001). The percentage of patients with attention problems (P = 0.02), fine motor (P = 0.001) and executive dysfunctions (P = 0.013) was significantly higher than that for control subjects. Patients had more school problems than controls (P = 0.028). Intelligence score was also significantly lower in these patients (P = 0.046). The index of dietary control for the last 6 months was significantly higher than the index for the first 6 years of life, but only in the patients with school problems (P = 0.033). In conclusion, phenylketonuric patients presented more school problems than control subjects, probably related to the disturbed cognitive functions observed. The index of dietary control for the last 6 months yielded a close relationship with school performance.

Achievement↗
PubMed2004

Reduction of cingulate gray matter density in poor outcome bipolar illness.

Structural brain abnormalities are associated with poor outcome unipolar depressive disorder. Gray matter density can be assessed with an automated, operator independent analysis (SPM99). We thus compared 11 poor outcome bipolar patients with 15 age-, sex- and IQ-matched healthy volunteers with a standard neuropsychological examination and an Elscint 2.0 Tesla MRI scanner. At the time of examination, patients were neither hypomanic nor significantly depressed, but were significantly impaired on the McGlashan scale. Their memory function was characterized by reduced performance in the California verbal learning and digit-symbol substitution tests. Statistical parametric mapping revealed abnormal gray matter density, mainly in fronto-limbic cortex, but particularly widespread in cingulate cortex. Although causality of these changes is difficult to resolve, the results offer useful insights into the neural correlates of severe bipolar disorder.

Adolescent↗
PubMed2003

Cognitive deficits are associated with functional impairment in severely depressed patients.

Cognitive deficits have been associated with poorer function and quality of life (QOL) in schizophrenia, but no similar findings have been confirmed in persons with major depressive episode (MDE). We investigated whether cognitive deficits were associated with detrimental effects on the QOL of persons with primary MDE. Seventy-seven non-demented adults with MDE underwent evaluations of mood, cognition and QOL. Cognition was assessed with the Mini-Mental State Exam, and delayed recall on the Rey Auditory Verbal Learning Task and the Rey Figure. QOL assessments included instrumental activities of daily living (IADL), activities of daily living (ADL), and satisfaction in role functioning and relationships. Univariate correlation and regression models were used to find those mood and cognitive variables most closely related to each QOL dimension. ADL function and satisfaction with role functioning and relationships were most closely related to depression severity and age. IADL functioning, however, was most closely associated with global cognition. This study did not take into account the physical health of the participants, and all the participants were seriously ill with depression. Thus, the results may not apply to persons with less severe MDE. Antidepressant treatments that preserve or enhance global cognition in addition to relieving core depressive symptoms may lead to the best functional outcomes.

Activities of Daily Living↗
PubMed2005

Assessing cognitive deficits in bipolar disorder: are self-reports valid?

Patients with affective disorders frequently report problems with attention, concentration and memory, although little research has investigated subjective cognitive complaints relative to objective neuropsychological deficits. We compared subjective (self-rated) cognition and objective (clinician-rated) neuropsychological functioning in 37 DSM-IV bipolar outpatients. Subjects completed three standardized self-report inventories: the Cognitive Difficulties Scale (CDS), Cognitive Failures Questionnaire (CFQ), and Patient's Assessment of Own Functioning (PAOF). These were followed by a systematic neuropsychological test battery. More than 75% of our sample of bipolar patients displayed some cognitive deficits, most notably in the domains of verbal learning and memory. In general, patients' self-reports of impairment failed to reliably predict objective neuropsychological deficits. Mood ratings for mania and depression were not significantly correlated with any of the self-report inventories or the objective neuropsychological variables. The findings suggest that most bipolar patients demonstrate objective signs of cognitive impairment, but they are unable to report them accurately, at least using available self-report inventories. Such discrepancies could relate to impaired insight, efforts to conceal deficits, or to subthreshold affective symptoms.

Bipolar Disorder↗
PubMed2004

Symptoms and interference from memory in schizophrenia: evaluation of Frith's model of willed action.

The present study was undertaken to test Frith's [The Cognitive Neuropsychology of Schizophrenia, 1992. Erlbaum (UK) Taylor and Francis, East Sussex] model which states that certain symptoms of schizophrenia arise from diminished capacity to regulate willed (goal-directed) and stimulus-driven action systems. A total of 107 patients were administered the Rey Auditory Verbal Learning Test (RAVLT), a task that on interference trials requires individuals to recall target material while suppressing non-target distracting stimuli from memory. Symptom ratings were obtained using the SANS/SAPS [Andreasen, N.C., 1984. Scale for the Assessment of Negative Symptoms/Scale for the Assessment of Positive Symptoms [Manual] University of Iowa Press, Iowa City]. It was predicted that (1) negative symptoms would result in diminished recall, reflecting compromised activation of the willed action system, and (2) disorganized symptoms would be associated with heightened interference susceptibility resulting from diminished ability to suppress the stimulus-driven action system. Results revealed that diminished recall was related to negative, but not disorganized or positive symptoms. Symptom ratings were also evaluated in a subset of patients with intrusion error data (n=38). In this subset, it was found that patients who committed intrusion errors on the interference trials evidenced more disorganized, but not negative or positive symptoms, than individuals failing to commit such errors. These findings provide some support for Frith's hypothesis that impaired regulation of action systems may underlie some of the specific symptoms and cognitive impairments of this illness.

Adult↗
PubMed2006

Neurocognitive profile in 22q11 deletion syndrome and schizophrenia.

OBJECTIVE: Schizophrenia is associated with neurocognitive deficits, but its etiologic heterogeneity may complicate the delineation of a neurocognitive profile. Schizophrenia associated with 22q11 Deletion Syndrome (22qDS) represents a more genetically homogeneous subtype for study. We hypothesized that in adults with 22qDS the neurocognitive profiles would differ between those with and without schizophrenia. METHOD: Using a comprehensive battery of tests, we compared the neurocognitive performance profiles in those with schizophrenia (n=27; 14 M, 13 F; mean age=30.6 years, SD=7.7 years) and those with no history of psychosis (n=29; 16 M, 13 F; mean age=25.0 years, SD=9.0 years). RESULTS: The 22qDS groups with and without schizophrenia had similar mean estimated IQ (71.6, SD=8.2 and 74.8, SD=6.1, respectively) and academic achievement, however the neurocognitive profiles of the two groups differed significantly on multivariate analysis (F(24,31)=2.25, p=0.017). The group with schizophrenia performed significantly more poorly on tests of motor skills, verbal learning, and social cognition (effect sizes>or=0.8) after correction for multiple comparisons. Other tests, but not the attentional measures used, showed nominally significant differences. CONCLUSIONS: In adults with 22qDS, the pattern of neurocognitive differences between those with and without schizophrenia appears similar to that between patients with schizophrenia and controls. Attentional dysfunction may be a more general feature of 22qDS. The findings support 22qDS-schizophrenia as a genetic model for neurodevelopmental investigations of schizophrenia.

Adult↗
PubMed2005

Tiagabine enhances slow wave sleep and sleep maintenance in primary insomnia.

BACKGROUND AND PURPOSE: To evaluate the effect of tiagabine on sleep and next-morning alertness and performance in adult patients with primary insomnia. PATIENTS AND METHODS: Patients with primary insomnia, as defined by Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV), received tiagabine 4, 8, 12, 16 mg, and placebo in a randomized, double-blind, five-period, Latin square, crossover study. Efficacy was assessed using polysomnographic and self-report techniques; residual effects were evaluated using the Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT). RESULTS: Fifty-eight patients (40f, 18m; mean age 46.6+/-8.0 years) were randomized. Results showed a significant dose-dependent increase in slow wave sleep percentage with all tiagabine doses, a trend toward a dose-dependent increase in total sleep time, and no effect on latency to persistent sleep. Wake after sleep onset also decreased in a dose-dependent manner, with the 16-mg dose differing significantly from placebo. The tolerability profiles of tiagabine 4 and 8 mg were similar to placebo. The most common adverse events reported following tiagabine 12 and 16 mg were dizziness and nausea. Residual effects were only apparent at 12- and 16-mg doses. CONCLUSIONS: Tiagabine increased slow wave sleep and reduced wake after sleep onset in a dose-dependent manner. Tiagabine dosages up to 8 mg did not compromise next-morning alertness and psychomotor performance in adult patients with primary insomnia. Further investigation of tiagabine doses up to 8 mg is warranted.

Adult↗
PubMed2004

Word learning in dogs?

In a recent paper, Kaminski, Call and Fischer report pioneering research on word-learning in a dog. In this commentary we suggest ways of distinguishing referential word use from mere association. We question whether the dog is reasoning by exclusion and, if so, compare three explanations - learned heuristics, default assumptions, and pragmatic reasoning - as they apply to children and might apply to dogs. Kaminski et al.'s work clearly raises important questions about the origins and basis of word learning and social cognition.

Animals↗