Benno Koch

Do Normal D-dimer Levels Reliably Exclude Cerebral Sinus Thrombosis?

Background and Purpose— Cerebral sinus thrombosis (CST) needs to be considered in the differential diagnosis of all patients with acute headache. Early diagnosis is essential because early treatment may prevent morbidity and may even be life-saving. Definite exclusion, however, needs advanced neuroradiologic diagnostics, which are not readily available in many hospitals. Because measurement of D-dimers has been demonstrated to be helpful in excluding thromboembolic disease, our aim was to investigate whether D-dimers would be also sensitive enough to exclude CST. Methods— We undertook a prospective multicenter study over a 2.5-year period including all patients who came to the emergency departments with symptoms suggestive of CST. All patients were diagnosed either by magnetic resonance venography, spiral computed tomography scan venography, or intra-arterial digital subtraction angiography. D-dimer levels were measured at admission and analyzed by the same method in all patients. Results— A total of 343 patients were included. CST was diagnosed in 35 patients, of whom 34 had D-dimers above the cutoff value (>500 &mgr;g/L). From the 308 patients not having CST, D-dimers were elevated in 27. Sensitivity of D-dimers was 97.1%, with a negative predictive value of 99.6%. Specificity was 91.2%, with a positive predictive value of 55.7%. D-dimers were positively correlated with the extent of the thrombosis and negatively correlated with the duration of symptoms (Spearman rank correlation coefficients 0.76, −0.58, respectively). Conclusions— D-dimer measurement is useful in patients with suspected CST. Normal D-dimers make the presence of CST very unlikely.

Focal basal ganglia lesions are associated with impairments in reward-based reversal learning

The basal ganglia (BG) are thought to play a key role in learning from feedback, with mesencephalic dopamine neurons coding errors in reward prediction, thereby mediating information processing in the BG and the prefrontal cortex. In the present study, reward-based learning was assessed in patients with focal BG lesions, by studying outcome-based acquisition and reversal of stimulus-stimulus associations with different reward magnitudes in two probabilistic learning tasks. Eleven patients with selective BG lesions (three females) and 18 healthy control subjects (six females) participated in this study. Two cognitive transfer tasks provided a measure of declarative learning strategy application. On the group level, BG patients showed deficits in reversal learning, with dorsal striatum lesion patients being most severely affected. While basic mechanisms of learning from feedback such as the processing of different reward magnitudes appeared to be intact, patients needed more trials than controls to learn a second reward-based task, suggesting reduced carry-over effects in learning. A patient with a bilateral BG lesion showed better performance than controls on most learning tasks, applying a compensatory declarative learning strategy. The results are discussed in terms of the implication of different BG subregions in different aspects of learning from feedback.

Involvement of the mediodorsal thalamic nucleus in mediating recollection and familiarity

The mediodorsal (MD) thalamic nucleus is thought to play an important role in memory processes. Distinct hippocampal-thalamic-prefrontal connections have been described as the potential neural substrate for both, recollection and familiarity. The aim of this study was to investigate whether the MD is part of the circuits underlying these two memory components. We assessed the effects of ischemic thalamic lesions with or without MD involvement on performance in a word list discrimination task and standard tests of memory and executive function. Estimates of recollection and familiarity were derived using the dual-process signal-detection model (DPSD). The results revealed impairments in both, recollection and familiarity, after unilateral thalamic damage, with recollection being more affected than familiarity. There were no significant differences in the memory performance of patients with MD lesions compared to patients with ventrolateral-thalamic lesions except for familiarity estimates, which were lower for the latter group. Lesions involving the MD led to recollection deficits, although inspection of individual cases suggested a decrease in both memory components after damage in the medial part of this nucleus. Executive dysfunction was associated with lateral MD lesions and also ventrolateral-thalamic damage. The findings suggest that MD contributes to recollection, with some preliminary evidence of a contribution of the medial MD to familiarity. The small sample size does, however, not yet allow any clear conclusions in this regard. Since damage in the ventrolateral thalamus leads to memory and executive dysfunction, further research is needed to elucidate the role of this thalamic region in cognition.

The Cerebellum Is Involved in Reward-based Reversal Learning

The cerebellum has recently been discussed in terms of a possible involvement in reward-based associative learning. To clarify the cerebellar contribution, eight patients with focal vascular lesions of the cerebellum and a group of 24 healthy subjects matched for age and IQ were compared on a range of different probabilistic outcome-based associative learning tasks, assessing acquisition, reversal, cognitive transfer, and generalization as well as the effect of reward magnitude. Cerebellar patients showed intact acquisition of stimulus contingencies, while reward-based reversal learning was significantly impaired. In addition, the patients showed slower acquisition of new stimulus contingencies in a second reward-based learning task, which might reflect reduced carry-over effects. Reward magnitude affected learning only during initial acquisition, with better learning on trials with high rewards in patients and control subjects. Overall, the findings suggest that the cerebellum is implicated in reversal learning as a dissociable component of reward-based learning.

Differential involvement of the cerebellum in biological and coherent motion perception

Perception of biological motion (BM) is a fundamental property of the human visual system. It is as yet unclear which role the cerebellum plays with respect to the perceptual analysis of BM represented as point‐light displays. Imaging studies investigating BM perception revealed inconsistent results concerning cerebellar contribution. The present study aimed to explore the role of the cerebellum in the perception of BM by testing the performance of BM perception in patients suffering from circumscribed cerebellar lesions and comparing their performance with an age‐matched control group. Perceptual performance was investigated in an experimental task testing the threshold to detect BM masked by scrambled motion and a control task testing the detection of motion direction of coherent motion masked by random noise. Results show clear evidence for a differential contribution of the cerebellum to the perceptual analysis of coherent motion compared with BM. Whereas the ability to detect BM masked by scrambled motion was unaffected in the patient group, their ability to discriminate the direction of coherent motion in random noise was substantially affected. We conclude that intact cerebellar function is not a prerequisite for a preserved ability to detect BM. Because the dorsal motion pathway as well as the ventral form pathway contribute to the visual perception of BM, the question of whether cerebellar dysfunction affecting the dorsal pathway is compensated for by the unaffected ventral pathway or whether perceptual analysis of BM is performed completely without cerebellar contribution remains to be determined.

Altered Error Processing following Vascular Thalamic Damage: Evidence from an Antisaccade Task

Event-related potentials (ERP) research has identified a negative deflection within about 100 to 150 ms after an erroneous response – the error-related negativity (ERN) - as a correlate of awareness-independent error processing. The short latency suggests an internal error monitoring system acting rapidly based on central information such as an efference copy signal. Studies on monkeys and humans have identified the thalamus as an important relay station for efference copy signals of ongoing saccades. The present study investigated error processing on an antisaccade task with ERPs in six patients with focal vascular damage to the thalamus and 28 control subjects. ERN amplitudes were significantly reduced in the patients, with the strongest ERN attenuation being observed in two patients with right mediodorsal and ventrolateral and bilateral ventrolateral damage, respectively. Although the number of errors was significantly higher in the thalamic lesion patients, the degree of ERN attenuation did not correlate with the error rate in the patients. The present data underline the role of the thalamus for the online monitoring of saccadic eye movements, albeit not providing unequivocal evidence in favour of an exclusive role of a particular thalamic site being involved in performance monitoring. By relaying saccade-related efference copy signals, the thalamus appears to enable fast error processing. Furthermore early error processing based on internal information may contribute to error awareness which was reduced in the patients.

Recall deficits in stroke patients with thalamic lesions covary with damage to the parvocellular mediodorsal nucleus of the thalamus

The functional role of the mediodorsal thalamic nucleus (MD) and its cortical network in memory processes is discussed controversially. While Aggleton and Brown (1999) suggested a role for recognition and not recall, Van der Werf et al. (2003) suggested that this nucleus is functionally related to executive function and strategic retrieval, based on its connections to the prefrontal cortices (PFC). The present study used a lesion approach including patients with focal thalamic lesions to examine the functions of the MD, the intralaminar nuclei and the midline nuclei in memory processing. A newly designed pair association task was used, which allowed the assessment of recognition and cued recall performance. Volume loss in thalamic nuclei was estimated as a predictor for alterations in memory performance. Patients performed poorer than healthy controls on recognition accuracy and cued recall. Furthermore, patients responded slower than controls specifically on recognition trials followed by successful cued recall of the paired associate. Reduced recall of picture pairs and increased response times during recognition followed by cued recall covaried with the volume loss in the parvocellular MD. This pattern suggests a role of this thalamic region in recall and thus recollection, which does not fit the framework proposed by Aggleton and Brown (1999). The functional specialization of the parvocellular MD accords with its connectivity to the dorsolateral PFC, highlighting the role of this thalamocortical network in explicit memory (Van der Werf et al., 2003).

Working memory and verbal fluency deficits following cerebellar lesions: relation to interindividual differences in patient variables.

Findings concerning cognitive impairment in patients with focal cerebellar lesions tend to be inconsistent and usually reflect a mild deficit. Patient variables such as lesion age and the age at lesion onset might affect functional reorganization and contribute to the variability of the findings. To assess this issue, 14 patients with focal vascular cerebellar lesions and 14 matched healthy control subjects performed a verbal working memory and a verbal long-term memory task as well as verbal fluency tasks. Patients showed deficits in working memory and verbal fluency, while recall of complex narrative material was intact. Verbal fluency performance correlated significantly with age in the patient group, with more severe impairments in older patients, suggesting that age at lesion onset is a critical variable for cognitive outcome. In controls, no significant correlations with age were observed. Taken together, our findings support the idea of cerebellar involvement in nonmotor functions and indicate the relevance of interindividual differences in regard to clinical parameters after focal cerebellar damage.

Subcortical contributions to multitasking and response inhibition.

The involvement of the prefrontal cortex in executive control has been well established. It is, however, as yet unclear whether the basal ganglia and the cerebellum as components of frontostriatal/frontocerebellar networks also contribute to the executive domains multitasking and response inhibition. To investigate this issue, groups of patients with selective vascular lesions of the basal ganglia (n=13) or the cerebellum (n=14) were compared with matched healthy control groups. Several paradigms assessing the ability to process concurrent visual and auditory input and to simultaneously perform verbal and manual responses as well as the inhibition of habitual or newly acquired response tendencies were administered. Basal ganglia patients showed marked response slowing during coordination of sensory input from different modalities and high error rates during the inhibition of overlearned responses. There was no clear evidence of a cerebellar involvement in multitasking or response suppression. Taken together, the findings provided evidence for a striatal involvement in both multitasking and response inhibition, emphasizing the functional implication of subcortical components in frontostriatal circuits.

Impairment of verbal recollection following ischemic damage to the right anterior hippocampus

Damage to the left medial temporal lobe (MTL) leads to an impairment of verbal recognition memory, affecting both the process of conscious recollection and familiarity-based recognition. Neuroimaging evidence, on the other hand, suggests a bilateral MTL contribution to verbal recollection. We investigated verbal recognition memory in three patients with focal ischemic lesions to the right MTL. The dual-process signal detection model and the process-dissociation procedure were applied to assess the contributions of recollection and familiarity to recognition memory. Compared to a group of 27 healthy age-matched controls, patients were impaired at recollection while familiarity was intact, and this effect was found for both estimation procedures. Detailed single-case analyses confirmed this pattern in two of the three right MTL patients. The findings suggest that, when task demands are high, as during recollective recognition, the right anterior hippocampus may also contribute to verbal recollection, thereby confirming neuroimaging evidence of a joint involvement of the left and the right MTL in verbal recollection.