A long-term neuropsychological evaluation in Fabry disease.

Fabry disease (FD) is a X-linked multi-systemic metabolic disorder with mainly renal, cardiac and neurological dysfunction. The neuropsychological impact is still unclear, with previous study results ranging from disturbance of speed of information processing and executive functions to a normal cognitive profile. The aim of our study was to gain further insight into the neuropsychological involvement of FD. Patients with genetically proven FD were enrolled at the Ghent University Hospital by their treating neurologist. We evaluated the cognitive status of each patient by a thorough neuropsychological test battery and these exact same neuropsychological assessments were repeated after a follow-up period of 2-4 years and at a second follow-up moment 1-4 years after the first follow-up. Thirteen patients with FD were included (8 female) with mean age of 41.5 years (SD ± 13.9) at baseline. All patients had normal neuropsychological test results on the subtests included in the cognitive battery at baseline, according to age-, gender- and education matched normative data. At the first follow-up moment (2-4 years after baseline), six patients were included (3 male), mean age 45.3 years. At the second follow-up (1-4 years after first follow-up), four patients (2 male) were included, with mean age 45 years. Both at the first and second follow-up moments, all patients obtained normal scores on the subtests. The cognitive functioning appeared to be in the normal range at baseline and did not decline over a follow-up period of 3-8 years, suggesting that cognition in FD patients may be well-preserved in time.

Multifocal intraparietal activation during discrimination of action intention in observed tool grasping.

The way we grasp an object varies depending on how we want to use that object, and this knowledge can be used to predict the object-related behavior of others. In this study, we assessed the neural correlates that determine the action intention of another person based on observed prehensile movements. Fourteen right-handed volunteers watched video clips of a person performing right-handed transitive grasping gestures that were either aimed at displacing or using a tool-object. Clips showing the grasping and displacement of neutral shapes served as a control condition. By discrimination of the actor's intention, three roughly symmetrical foci were activated in the anterior, middle, and caudal segments of the intraparietal sulci, and in the fusiform gyri and parts of the lateral occipital complex. Anterior intraparietal activation has been associated with the representation of object goals (object specific), and the present findings extend its involvement to functional goals (use-specific). Activation in the middle intraparietal region during intention discrimination was very similar to the activation elicited in a saccadic localizer task, suggesting a relation with spatial attention and eye movements. The caudal intraparietal region has been related with visuospatial guidance of reaching, and its activation during action intention discrimination indicates that the visuospatial properties of the observed reaching movement contribute to understanding of actions. As these parietal regions are strongly linked with motor behavior, our results appear to support the motor simulation hypothesis for action understanding with the preferential recruitment of the mirror-neuron system. This could at least be the case when no contextual information other than the visual properties of the movement is provided to discriminate the intention of an observed hand action.

Pre-existing cognitive impairment in candidates for cardiac surgery: an overview.

Until now, little attention has been paid to the preoperative status of the patient awaiting cardiac surgery when investigating the effects of cardiac surgery on cognition. However, there is growing evidence that pre-bypass patients show poorer cognitive function than healthy subjects. This article reviews existing published evidence of poor cognitive function in pre-bypass patients by describing patient characteristics, providing an inventory of affected neurocognitive domains, discussing adequate control groups and proposing potential aetiological mechanisms of neuropsychological dysfunctioning. It is concluded that there is a growing need for future research into this important topic on cognitive dysfunctioning in candidates for coronary artery bypass grafting surgery.

Conceptual and physical object qualities contribute differently to motor affordances.

Priming studies have demonstrated that an object's intrinsic and extrinsic qualities (size, orientation) influence subsequent motor behavior thus suggesting that these object qualities 'afford' actions that are congruent with the prime. We present four experiments that aim to evaluate the relative effect of conceptual and physical object qualities on action priming. In Experiment 1 equally graspable known and unknown tools are presented as primes. In Experiment 2 the primes depict high versus low graspable unfamiliar tools, and in Experiments 3 and 4 we present simple graspable shapes versus high graspable unfamiliar or familiar tools respectively. In all experiments the (unrelated) task consists of a timed motor response to the direction of a centrally placed arrow that is superimposed on the prime. Whereas tool familiarity reveals no significant difference on reaction time (Exp 1), responses to high graspable unfamiliar tools (Exp 2) and simple graspable shapes (Exps 3 and 4) are significantly faster. We conclude that motor affordances are most readily determined by object qualities that depend on the object's physical appearance provided by visual information. Conceptual information about the stimuli, such as semantic category or stored knowledge about its function and associated movements, does not appear to produce detectable effects of action priming in this paradigm.

Neurocognitive consequences of surgically corrected congenital heart defects: A review.

With advances in surgical procedures, neuropsychological assessment after congenital heart defects and pre, peri- and/or postoperative predictors of adverse outcome has become an important focus in research. We aim to summarize neuropsychological sequelae associated with different types of congenital heart defects, critically review the methodology used in more than 20 empirical studies that were retrieved from biomedical electronic search engines, and identify possible directions for future research. Despite the lack of adequate control groups and long-term studies, there seem to be some cognitive deficits. The largest group of children with isolated congenital heart defects present with normal intellectual capacities. However, they tend to show language deficits and motor dysfunction. Although performances on memory tasks are good, unambiguous conclusions concerning their attentional and executive functioning are still lacking. Serious behavioral problems are not an issue. In addition to a detailed description of the (neuro) psychological consequences of pediatric cardiac surgery, an overview of the predictors of the cognitive defects is provided.

Memory performance during the intracarotid amobarbital procedure and neuropsychological assessment in medial temporal lobe epilepsy: the limits of material specificity.

We investigated the relationship between material-specific memory performance elicited during the Wada test, or intracarotid amobarbital procedure (IAP), and classic neuropsychological assessment in 89 surgical candidates with refractory medial temporal lobe epilepsy (MTLE). The neuropsychological battery included measures of simple and complex verbal and visual memory, whereas the IAP material consisted of verbal and dually encodable stimuli. Neuropsychological testing revealed that reduced verbal memory performance was associated with left-sided MTLE, whereas visual memory tasks revealed no differences between patients with left-sided and right-sided MTLE. During IAP, memory performance was worse with the ipsilesional hemisphere, regardless of lesion side. Most importantly, performance on verbal memory tests was significantly, but moderately, correlated with left hemispheric IAP performance, indicating that memory tasks using verbal material are a valid marker of left hemispheric integrity in left language-dominant MTLE patients and significantly predict left hemispheric memory performance during IAP. In contrast, performance on classic visual memory tests is unrelated to right hemispheric IAP performance, suggesting that the currently used visual memory stimuli do not reflect right hemispheric sensitivity.

Clinical relevance of memory performance during Wada is stimulus type dependent.

OBJECTIVES: This study aimed to investigate whether different types of memory stimulus provide different information during the Wada or intracarotid amytal procedure (IAP) in patients with refractory medial temporal lobe epilepsy (MTLE). METHODS: Eighty nine surgical candidates with documented MTLE and selected for left hemispheric language dominance underwent memory assessment with verbal and dually encodable stimuli during a presurgical IAP. RESULTS: The overall IAP memory performance with the left hemisphere is significantly better than with the right hemisphere regardless of lesion side. This can be explained by the left hemispheric advantage of encoding all stimuli, whereas the right hemisphere has only limited resources to encode verbal stimuli. More importantly, it appeared that dually encodable items remain more readily recognised following injection ipsilateral to the lesion, whereas verbal items are always better recognised following right hemisphere injection regardless of lesion side. CONCLUSIONS: Verbal IAP stimuli show left hemispheric sensitivity in left language dominant MTLE patients. The dually encodable items of the IAP appear lesion sensitive.

Language activation distributions revealed by fMRI in post-operative epilepsy patients: differences between left- and right-sided resections.

OBJECTIVE: To reveal differences of cerebral activation related to language functions in post-operative temporal lobe epilepsy (TLE) patients. METHODS: Right (RTL) and left temporal lobe (LTL) resected patients, and healthy controls were studied using functional magnetic resonance imaging (fMRI). Only patients with complete left-hemispheric language dominance according to the intracarotid amytal procedure (IAP) were included. Language-related activations were evoked by performing word generation and text reading language tasks. Activation lateralization and temporo-frontal distribution effects were analysed. RESULTS: For word generation, only LTL patients showed reduced left lateralized activation compared to controls, due to a decrease in activation in the left prefrontal cortex and an increase in the right prefrontal cortex. For reading, the left-hemispheric lateralization in RTL patients increased because of enhanced activity in the left prefrontal cortex, whereas for LTL patients the activation became bilaterally distributed over the temporal lobes. Lateralization results between pre-operative IAP and post-operative fMRI were highly discordant. Significant temporo-frontal distribution changes manifested from the reading but not from the word generation task. CONCLUSION: The cerebral language representation in post-operative LTL epilepsy patients is more bi-hemispherically lateralized than in controls and RTL patients. Post-operative temporo-frontal and interhemispheric redistribution effects, involving contralateral homologous brain areas, are suggested to contribute to the cerebral reorganisation of language function.

Does egocentric mental rotation elicit sex differences?

Mental rotation tests traditionally show a male performance advantage. Some neuroimaging studies have reported sex-specific cortical activation patterns during mental rotation. However, these experiments used abstract stimuli and some studies did not systematically exclude performance as a confounding variable. The mental rotation of hands and hand-related objects, compared to abstract objects, is known to evoke an egocentric motor strategy. In this study, we used fMRI to explore potential gender-specific cortical activation patterns for the mental rotation of hands and tools in a sample with an adequate and equal performance for men and women. We found a common neural substrate for men and women comprising superior parietal lobe, dorsolateral premotor cortex, and extrastriate occipital areas, compatible with an egocentric motor strategy for the mental rotation of hands and tools. Sex differences were modest and limited to the mental rotation of hands. Women recruited more left ventral premotor cortex, which could imply that women rely more on imitation or use more perceptual comparisons. Men, on the other hand, drafted more the lingual gyrus, possibly referring to more extensive semantic or early visual processing. We conclude that men and women use a very similar motor strategy during egocentric mental rotation with a potential gender-specific accent.

Effect of cardiovascular disease on hemodynamic response to cognitive activation: a functional transcranial Doppler study.

We compared the cerebrovascular response to various cognitive tasks of cardiovascular patients and healthy controls by using transcranial Doppler ultrasonography (TCD). Cognitive task-induced cerebral blood flow velocity (BFV) changes in 66 candidates for coronary artery bypass graft surgery (mean age 59.4 +/- 7.5) were compared with the functional BFV measurement of 60 healthy controls (mean age 58 +/- 7). Absolute BFV values during baseline and activation were monitored with TCD. Relative increase of the BFV was calculated from the immediately preceding rest period to the following activation. A manova with group (patients versus controls) as between-subjects factor showed no differences in absolute BFV during the rest period. For absolute BFV during activation, a significant difference between the two groups was found. Although for each test the percentage change was smaller in the cardiac group, the difference just failed to reach significance. An explorative multivariate linear regression analysis with the absolute activation and percentage change as dependent variables and coronary risk factors as independent variables revealed no significant predictors. Using functional TCD we found that BFV values during activation were significantly lower in cardiac patients compared with healthy controls. Future research should focus on the possible explanations of this phenomenon.

MRI language dominance assessment in epilepsy patients at 1.0 T: region of interest analysis and comparison with intracarotid amytal testing.

The primary goal of this study was to test the reliability of presurgical language lateralization in epilepsy patients with functional magnetic resonance imaging (fMRI) with a 1.0-T MR scanner using a simple word generation paradigm and conventional equipment. In addition, hemispherical fMRI language lateralization analysis and region of interest (ROI) analysis in the frontal and temporo-parietal regions were compared with the intracarotid amytal test (IAT). Twenty epilepsy patients under presurgical evaluation were prospectively examined by both fMRI and IAT. The fMRI experiment consisted of a word chain task (WCT) using the conventional headphone set and a sparse sequence. In 17 of the 20 patients, data were available for comparison between the two procedures. Fifteen of these 17 patients were categorized as left hemispheric dominant, and 2 patients demonstrated bilateral language representation by both fMRI and IAT. The highest reliability for lateralization was obtained using frontal ROI analysis. Hemispherical analysis was less powerful and reliable in all cases but one, while temporo-parietal ROI analysis was unreliable as a stand-alone analysis when compared with IAT. The effect of statistical threshold on language lateralization prompted for the use of t-value-dependent lateralization index plots. This study illustrates that fMRI-determined language lateralization can be performed reliably in a clinical MR setting operating at a low field strength of 1 T without expensive stimulus presentation systems.

Predictors of cognitive impairment in advanced Parkinson's disease.

OBJECTIVE: To investigate the cognitive profile of patients with idiopathic Parkinson's disease and to determine the demographic and medical variables that contribute to the cognitive outcome. DESIGN: Retrospective cohort analysis. METHODS: 100 patients with idiopathic Parkinson's disease were given a neuropsychological test battery investigating attention, memory, and visuospatial and executive functions. Test performance was compared against normative data, and linear regression determined significant predictors of cognitive impairment from a set of demographic and disease course variables. RESULTS: Frontal-type cognitive dysfunction was widespread in patients with advanced Parkinson's disease. Attention and memory were mildly to moderately impaired, whereas visuospatial function showed only subtle impairment. Older age and tremor at onset were significant predictors of poor cognitive performance. CONCLUSIONS: The observed cognitive impairment in patients with advanced Parkinson's disease is more than expected for normal aging. Although in apparent contrast with most previous research, reporting a greater risk of cognitive dysfunction in Parkinson's disease patients with predominant akinesia/rigidity, tremor at onset may be a marker for more widespread brain pathology that contributes to an increased risk of cognitive impairment.

Regional cerebral blood flow and episodic memory in Parkinson's disease: a single photon emission tomography study.

In this paper we examined 46 nondemented Parkinson's disease (PD) patients by means of perfusion single photon emission computed tomography (SPECT) and neuropsychological testing. The aim was to detect correlations of regional cerebral blood flow with episodic memory performance, using an operator-independent technique for the analysis of SPECT data. A significant positive correlation was found between prefrontal blood flow and episodic memory performances. However, age was the most important determinant of memory scores. Age also correlated significantly negatively with prefrontal perfusion. Our methodology also allowed detection of an inverse correlation of left medial temporal lobe perfusion with the memory score. This had not been found in previous studies and might indicate compensatory mechanisms in the brain of PD patients. It is concluded that episodic memory in nondemented PD patients is most dependent on the effects of aging and that the aging effects on cerebral perfusion in the PD brain parallel to a large extent the findings in normal controls.

Cerebral blood flow velocity changes during dichotic listening with directed or divided attention: a transcranial Doppler ultrasonography study.

Simultaneous bilateral transcranial Doppler ultrasonography (TCD) monitoring of blood flow velocity (BFV) in the middle cerebral arteries was performed in 28 normal right-handed volunteers during linguistic dichotic listening tasks to investigate the effect of hemispheric specialisation and allocation of attention. A control task that required the repetition of monaurally presented words was followed by three randomised dichotic listening tasks in which the subjects were instructed to direct their attention to the word stimuli of the right ear, the left ear, or to divide their attention between both ears. Behavioural data indicated that the subjects used the required attentional strategies. A significant right ear advantage was not obtained in the divided attention condition due to a ceiling effect. Each task resulted in a significant bilateral increase in BFV. We found no significant lateralisation of BFV change for any of the tasks. We noted marked differences in BFV change between the different conditions that were significant in the right hemisphere, showed a borderline significance in the left hemisphere and appeared to be related with the difficulty of the task. We conclude that the hemodynamic changes caused by attentional strategies or hemispheric specialisation in processing dichotic stimuli over and above the effect of bilateral auditory stimulation, are too subtle to be detected as lateralised changes in BFV. Functional TCD could be used for the evaluation of a task's workload relative to other tasks, and may contribute to elucidate the role of the right hemisphere in attention and arousal.

Test-retest reliability of functional transcranial Doppler ultrasonography.

The present study evaluates the reproducibility of lateralised blood flow velocity (BFV) changes measured with transcranial Doppler (TCD) ultrasonography during various cognitive paradigms. A total of 20 right-handed volunteers were confronted twice with 13 verbal and visuospatial tasks, with a time interval of 23 to 71 days. No statistically significant differences were found between the lateralisation indices (left BFV change minus right BFV change) on the first and second examinations. Lateralisation indices of eight tasks showed a significant test-retest reliability (r = 0.61 to 0.83). The reproducibility of cognitively induced lateralised BFV changes appears to be task-dependent. The possible influence from technical, physiological, and psychological factors is discussed. We conclude that functional neuroimaging studies based on blood flow data should preferably select cognitive paradigms that demonstrated sufficient test-retest reliability.

Regional brain activity during different paradigms of mental rotation in healthy volunteers: a positron emission tomography study.

Positron emission tomography (PET) was used to observe changes in regional cerebral blood flow (rCBF) in 10 right-handed healthy volunteers performing two paradigms of mental rotation. In one paradigm, subjects mentally rotated a single alphanumeric stimulus to determine whether it was shown in a normal or mirror-image position. In a second paradigm, subjects mentally rotated and compared pairs of figurative stimuli to determine whether the stimuli were identical or mirror-images. In both paradigms, rCBF was compared with a control task that used identical stimuli, but required no mental rotation. Mental rotation of single alphanumeric stimuli engendered activation in the primary somatomotor area in the left precentral gyrus. Mental rotation of paired figures engendered activation in the left superior parietal lobule and the right frontal medial gyrus. A deactivated area was located in the medial part of the left superior frontal gyrus. Comparison of both paradigms revealed that the left gyrus precentralis was activated significantly during the alphanumeric condition and that the left gyrus lingualis was significantly activated during the paired figures condition. Motor processes may be an inherent part of every mental rotation but the type of motor involvement appears strongly dependent on the specific task or the specific stimuli. Similar paradigms, designed to isolate the same cognitive function, in the same subjects, using the same imaging technology and methodology, but differing only in stimulus material, lead to different areas of neural activation. Task specificity determines the most significant changes in cerebral blood flow in different mental rotation paradigms.

Transcranial Doppler ultrasonography monitoring of cerebral hemodynamics during performance of cognitive tasks: a review.

The examination of blood flow velocity (BFV) changes during the performance of mental tasks is one of the applications of transcranial Doppler (TCD) ultrasonography. The purpose of this review is to summarize the results of the functional TCD literature, to investigate the effects of methodological differences between studies, and to provide guidelines for future research. It is concluded that larger series of more homogeneous groups concerning age and handedness, and stricter criteria for subject selection and laboratory setting are required. The implication of quantitative and qualitative performance measures and psychological parameters (motivation, anxiety, and task anticipation) could also yield important information. We recommend future agreement upon a more standardized methodology. TCD promises to be a useful tool to provide further insight into the cerebral organization and temporal reactivity of the human brain.

Deep brain stimulation of the globus pallidus pars interna in advanced Parkinson's disease.

Pallidotomy is now widely performed for the treatment of advanced Parkinson's disease (PD). Preliminary reports of the effect of globus pallidus pars interna deep brain stimulation (GPi DBS) have also been promising. We have analyzed a cohort of 22 consecutive patients enrolled in a multicenter study. Surgery was bilateral in 17 and unilateral in five patients. At 6-month follow-up, the bilaterally GPi-implanted patients demonstrated a marked improvement when examined after drug withdrawal ("off") and under optimal medication ("on") using the Unified Parkinson's Disease Rating Scale (UPDRS). The benefit induced by the stimulation in the "off" medication condition in the total motor score was 31% and in the activities of daily living (ADL) scores was 39%. During the "on" medication period, the reduction in the total "on" dyskinesias score was 66% and in the ADL score was 32%. A similar pattern of improvement was seen in the group of patients with unilateral GPi stimulation, although a second cohort of 12 patients not included in the multicenter study showed greater improvements in "on" motor functioning. Although the effect of DBS is predominantly reversible, electrode insertion alone resulted in measurable clinical effects in the absence of stimulation. Thus, at 6-month follow-up, the benefit observed without stimulation was up to 44% in the "on" dyskinesias score and 29% in timed tapping scores undertaken in the "off" medication state. Complications among 34 patients from all centers included perioperative infection (n=3), hardware fracture (n=2), and premature battery failure (n=3). These results show a positive antiparkinsonian effect of pallidal DBS. No specific complications were observed with bilateral procedures.

Between-task habituation in functional transcranial Doppler ultrasonography.

We investigated the variability of absolute blood flow velocity (BFV) and task-induced BFV change over consecutive cognitive tasks and compared two methods of baseline determination that are used to calculate relative BFV changes. Bilateral transcranial Doppler ultrasonography recordings of BFV in the middle cerebral arteries was performed in 90 right-handed volunteers during 13 cognitive tasks and their preceding rest periods. Both absolute BFV and elicited BFV changes between rest and activation significantly decreased over successive tasks. Instead of calculating an averaged baseline value, our results suggest that the rest phase immediately preceding the activation phase should be selected for baseline measurement. The between-task habituation effect could be due to a fading of attentional resources during the sustained and demanding performance.

Lateralization of cerebral blood flow velocity changes during cognitive tasks. A simultaneous bilateral transcranial Doppler study.

BACKGROUND AND PURPOSE: Transcranial Doppler ultrasonography (TCD) permits the assessment of cognitively induced cerebral blood flow velocity (BFV) changes. We sought to investigate the lateralization of BFV acceleration induced by a variety of cognitive tasks and to determine the influence of age, gender, IQ, and quality of the performance on the relative BFV changes. METHODS: Simultaneous bilateral TCD monitoring of BFV in the middle cerebral arteries (MCAs) was performed in 90 normal right-handed volunteers during 13 verbal and visuospatial tasks and their preceding rest periods. RESULTS: All tasks induced a significant bilateral BFV increase in the MCAs compared with the preceding rest periods. Five verbal tasks showed a significant left-hemispheric BFV acceleration. Linguistic tasks that required active or creative processing of the verbal stimuli, such as sentence construction or word fluency, elicited the most asymmetric response. Five visuospatial tasks revealed a significant right-hemispheric BFV shift. Paradigms that combined visuospatial attention and visuomotor manipulation showed the most lateralized acceleration. Older volunteers (aged >50 years) showed higher relative BFV changes, but lateralization was not influenced by age. Gender, IQ, and performance quality did not reveal significant effects on BFV change. CONCLUSIONS: Bilateral TCD is a noninvasive technique that has the potential to connect the particular change in flow pattern of the MCA distribution with selective cognitive activity and thus offers specific functional information of scientific and clinical value.