Karl Wessel

Fractionating the Neural Mechanisms of Cognitive Control

Modifications of the Wisconsin Card Sorting Test were established. In these new task variants, participants were asked to exert sequential control over attentional sets or over intentional sets (task domain factor). Attentional set shifting requires changing the priorities by which sensory stimuli are selected, whereas intentional set shifting requires changing the priorities by which motor responses are selected. Auditory stimuli that signaled to maintain or shift set were presented immediately before (precuing) or after (postcuing) the selection of cards (cue timing factor). Twenty-four healthy young individuals participated. Performance data (response times, error percentages) indicated that intentional tasks were easier to perform than attentional tasks. The electroencephalogram was recorded during task performance, and the N1, medial frontal negativity (MFN), P3a, and sustained potential (SP) components of the cue event-related brain potentials (ERPs) were analyzed. Irrespective of the task domain, shift precues led to increased N1 amplitudes compared to shift postcues. When intentional sets had to be shifted, the MFNs in the postcuing condition were more pronounced than in the precuing condition. On the other hand, shifts of attentional sets resulted in a more prominent P3a in response to postcues compared to precues. Irrespective of the task domain, the shift effect that was evident in SPs was more pronounced in precue ERPs compared to postcue ERPs. We conclude that ERPs provide valid measures to empirically constrain theories about the neural mechanisms of cognitive control. The domain hypothesis of the fractionation of the neural mechanisms of cognitive control is introduced.

Effect of high‐dose methylprednisolone administration on immune functions in multiple sclerosis patients

Objectives – To investigate the in vivo effect of corticosteroid pulse therapy on immunocompetent cells in 18 patients given methylprednisolone to treat an acute episode of MS. Material and methods – Blood was sampled before and after 3 days of methylprednisolone administration at doses of 1 g/day. Lymphocyte subtyping was performed and whole blood cell cultures were used to measure the cytokine producing capacity for interleukin‐1 (IL‐1), interleukin‐2 (IL‐2), interferon‐γ (IFN‐γ), tumor necrosis factor‐a (TNF‐α) and interferon‐α (IFN‐α). In addition, serum levels of the immunoglobulin classes IgG, IgA and IgM were determined. Results – Before treatment, production of IL‐1 was significantly increased in MS patients as compared to healthy controls. After therapy, production of all cytokines was significantly decreased, whereas there were significant increases in the numbers of monocytes, neutrophils and T and B lymphocytes. Treatment had no effect on serum immunoglobulin levels. Conclusion – An important mechanism for the antiinflammatory effect of corticosteroids in MS results from a suppression of the activation of the peripheral immune compartment through inhibition of cytokine production and lymphocyte endothelial adhesiveness.

Long-latency reflexes, somatosensory evoked potentials and transcranial magnetic stimulation: relation of the three methods in multiple sclerosis

Afferent and efferent central pathways were tested by electrically elicited long-latency reflexes (LLRs), somatosensory evoked potentials (SEPs), and motor potentials (MEPs) evoked by transcranial magnetic stimulation (TMS) in 37 patients with multiple sclerosis. Of these 27 (72.9%) had abnormal results, with bilateral abnormalities in 17 (45.9%). MEPs were abnormal in 21 (56.8%), LLRs in 17 (45.9%) and SEPs in 16 (43.2%). Compared with TMS (MEPs) alone, additional testing of LLRs and SEPs revealed abnormalities in 6 additional patients (2 LLRs, 3 SEPs, 1 LLR and SEP). When the hands were analysed separately 32 (47.3%) showed abnormal results with TMS, 29 (39.2%) with LLRs and 22 (29.7%) with SEPs. All hands with absent or delayed N20 components of the SEP also had abnormal LLRs, supporting the hypothesis that LLRs and SEPs share the same afferent pathways. In contrast to this, 10 hands had normal LLRs but slightly delayed central motor conduction times. Calculating the sum of the latency of the N20 component of the SEP and the latency of the MEP, we found a mean cortical relay time for the LLR of 8.5 +/- 4.7 msec, which is compatible with a polysynaptic transcortical pathway. This is supported by our finding of a linear correlation between the LLR latency and the sum of N20 and MEP latencies.

Diminished production of type-I interferons and interleukin-2 in patients with multiple sclerosis

Abstract Several lines of evidence have supported the role of immunological mechanisms in the pathogenesis of multiple sclerosis (MS) and new immunomodulatory strategies for its treatment, e.g. subcutaneous application of interferon (IFN)-β, have emerged. We investigated the ability of peripheral blood mononuclear cells (PBMC) in 21 consecutive patients with clinically definite MS to produce interferons and lymphokines in response to viral or mitogenic stimulation. Ten patients showed clinical signs of disease activity (acute relapse) and 11 patients were in a stable condition. Additionally, white blood count, leukocyte differentiation and lymphocyte subtyping were performed. A group of age-related healthy blood donors served as control (n=20). There was no difference between patients and controls in the production of IFN-γ, tumor necrosis factor (TNF)-α and soluble interleukin (IL)-2 receptor. IFN-α and IFN-β responsiveness, however, was significantly lower in patients with stable disease than in patients with active disease and controls (p<0.001). Furthermore, secretion of IL-2 after stimulation was significantly diminished in both patient groups as compared to the control group (p<0.01). Analysis of T-cell subsets revealed a significantly lower amount of CD8+ T-cells in patients with stable disease, leading to a significantly higher CD4/CD8 ratio in this group as compared to patients with active disease. Our study depicted an IL-2 deficiency in MS patients which is shared with other autoimmune diseases. In addition, our findings suggest that the ability to produce type-I IFNs, IFN-α and IFN-β, is primarily impaired in MS patients and changes in correlation to the course of disease activity.

Thalamic stroke: correlation of clinical symptoms, somatosensory evoked potentials, and CT findings

We studied 18 patients with a single ischemic thalamic lesion, who had somatosensory disturbances and/or central pain in the opposite hemibody, by correlating their clinical symptoms, somatosensory evoked potentials (SEPs), and computed tomography (CT) findings. Patients were divided into three groups: (1) those with somatosensory deficits, central pain, and abnormal SEPs, which comprised two thirds of the patients (classic thalamic pain syndrome), (2) those with somatosensory deficits, no central pain, and abnormal SEPs (analgetic thalamic syndrome), and (3) those with almost normal sense perception, central pain, and normal SEPs (pure algetic thalamic syndrome). CT evidence of a paramedian or anterolateral thalamic lesion might be an indicator for the development of central pain, because these types of infarctions occurred only in patients with the classic thalamic syndrome or the pure algetic thalamic syndrome. The differentiation of the thalamic syndrome into three subtypes is of prognostic value, because patients with a loss of cortical SEPs and a posterolateral ischemic thalamic lesion on the CT scan probably will not exhibit central pain.

Acute exacerbation of multiple sclerosis increases plasma levels of S-100 protein.

Objectives ‐ To determine whether an increase in plasma concentration of S‐100 protein can serve as a marker for acute exacerbation of multiple sclerosis. Material and methods ‐ The plasma level of S‐100 protein was investigated in 28 patients suffering from multiple sclerosis. Of these, 17 patients were admitted for acute exacerbation and 11 patients had a stable disease with no clinical signs for acute exacerbation. S‐100 protein concentrations in plasma were determined with an immunofluorometric sandwich assay. Results ‐ Plasma concentrations were significantly elevated in patients who were examined within 7 days after the onset of acute exacerbation (n=6). S‐100 levels of patients 8 to 28 days after the onset of acute exacerbation (n=11) did not differ from healthy controls (n=120). Eleven patients with multiple sclerosis without acute exacerbation had moderately elevated plasma levels. Conclusion ‐ The plasma concentration of S‐100 protein is a sensitive although unspecific indicator of neuronal damage and may be of use as a marker of disease activity in multiple sclerosis.

Consequences of altered cerebellar input for the cortical regulation of motor coordination, as reflected in EEG potentials

Abstract The cerebellum is certainly involved in fine coordination of movements, but has no efferences of its own to the muscles. Thus, it can exert its influence only via other cerebral areas that have those efferences. This study investigated in patients with cerebellar atrophy how cortical motor areas are affected by dysfunction of the cerebellum. The main question was whether the patients’ slow cortical electroencephalogram (EEG) potentials during key-press preparation and execution would be generally altered or would be specifically altered when fine coordination was needed. In the coordination task, right- and left-hand keys had to be pressed simultaneously with different forces, under visual feedback. Control tasks were to press with both hands equally or with one hand only. The patients indeed had a performance deficit in the coordination task. Their cortical EEG potentials were already drastically reduced in the simple tasks, but were enhanced by the same amount as in healthy subjects when more coordination was needed. These results suggest that the cerebellum is not exclusively active in fine coordination, but is generally involved in any kind of preparatory and executive activity, whereas the motor cortex becomes more active with fine coordination. The role of the cerebellum might be to provide the motor cortex with information needed for coordinating movements. In cerebellar atrophy, this altered input may be sufficient for the motor cortex in controlling simple tasks, but not for complex ones.

Basilar branch disease presenting with progressive pure motor stroke.

Objectives ‐ Isolated infarcts of the pons cause well definable neurological syndromes with distinct pathomechanism, clinical course and prognosis. Patients and results ‐ We report 8 cases suffering from a pure motor hemiparesis that was severely progressive within the 1st 3 days and unresponsive to aspirin. A relatively good recovery was observed in all patients, however, stroke recurrence occurred in 2 cases within 3 months and resulted in pseudobulbar paralysis and tetraparesis. MRI displayed unilateral (n=6) and bilateral (n=2) ventromedial pontine infarctions (VPI). Angiographic evaluation (n=4) or color Duplex examination (n=4) revealed atherosclerotic lesions but no basilar artery occlusion. Conclusion ‐ Although VPI due to basilar branch disease may clinically mimic a classical lacunar syndrome, it is related to a particular pathogenetic mechanism different from microangiopathy or embolism. In contrast to the MRI feature of lacunes, VPI typically extend to the basal surface of the pons. The progressive pattern, ending up in a relative uniform clinical picture, is probably caused by propagating thrombosis.

Temporal dynamics of selective attention and conflict resolution during cross-dimensional go-nogo decisions

BackgroundDecision-making is a fundamental capacity which is crucial to many higher-order psychological functions. We recorded event-related potentials (ERPs) during a visual target-identification task that required go-nogo choices. Targets were identified on the basis of cross-dimensional conjunctions of particular colors and forms. Color discriminability was manipulated in three conditions to determine the effects of color distinctiveness on component processes of decision-making.ResultsTarget identification was accompanied by the emergence of prefrontal P2a and P3b. Selection negativity (SN) revealed that target-compatible features captured attention more than target-incompatible features, suggesting that intra-dimensional attentional capture was goal-contingent. No changes of cross-dimensional selection priorities were measurable when color discriminability was altered. Peak latencies of the color-related SN provided a chronometric measure of the duration of attention-related neural processing. ERPs recorded over the frontocentral scalp (N2c, P3a) revealed that color-overlap distractors, more than form-overlap distractors, required additional late selection. The need for additional response selection induced by color-overlap distractors was severely reduced when color discriminability decreased.ConclusionWe propose a simple model of cross-dimensional perceptual decision-making. The temporal synchrony of separate color-related and form-related choices determines whether or not distractor processing includes post-perceptual stages. ERP measures contribute to a comprehensive explanation of the temporal dynamics of component processes of perceptual decision-making.

Voluntary palatal tremor is associated with hyperactivation of the inferior olive: a functional magnetic resonance imaging study.

Voluntary palatal tremor in a patient with essential palatal tremor induced activation predominantly within regions corresponding to the inferior olive, adjacent brainstem, and dentate nuclei. Finger movements elicited only ipsilateral lobular cerebellar activation, suggesting a dysfunctional nuclear activation by palatal tremor.