Irene Daum

Cerebellar contributions to cognitive functions: A progress report after two decades of research

Accumulating evidence from both human lesion and functional neuroimaging studies appears to support the hypothesis that the cerebellum contributes to non-motor functions. Along similar lines, cognitive, affective and behavioural changes in psychiatric disorders, such as autism, schizophrenia and dyslexia, have been linked to structural cerebellar abnormalities. The aim of this special issue was to evaluate the current knowledge base after more than 20 years of controversial discussion. The contributions of the special issue cover the most important cognitive domains, i.e., attention, memory and learning, executive control, language and visuospatial function. The available empirical evidence suggests that cognitive changes in patients with cerebellar dysfunction are mild and clearly less severe than the impairments observed after lesions to neocortical areas to which the cerebellum is closely connected via different cerebro-cerebellar loops. Frequently cited early findings, e.g., with respect to a specific cerebellar involvement in attention, have not been replicated or might be confounded by motor or working memory demands of the respective attention task. On the other hand, there is now convincing evidence for a cerebellar involvement in the mediation of a range of cognitive domains, most notably verbal working memory. Verbal working memory problems may partly underlie the compromised performance of cerebellar lesion patients on at least some complex cognitive tasks. Although investigations have moved from anecdotical case reports to hypothesis-driven controlled clinical group studies based on sound methods which are complemented by state-of-the-art functional neuroimaging studies, the empirical evidence available so far does not yet allow a convincing theory of the mechanisms of a cerebellar involvement in cognitive function. Future studies are clearly needed to further elucidate the nature of the processes linked to cerebellar mediation of cognitive processes and their possible link to motor theories of cerebellar function, e.g., its role in prediction and/or timing.

Cerebellar involvement in executive control.

The cerebellum has long been considered to be mainly involved in motor function. In the last 20 years, evidence from neuroimaging studies and from investigations of patients with cerebellar lesions has shown that the cerebellum plays a role in a range of cognitive functions. While cerebellar contributions have been shown for learning and memory, the cerebellum has also been linked to higher order cognitive control processes frequently referred to as executive functions. Although it is widely accepted that the cerebellum contributes to cognitive processing, the nature of cerebellar involvement is not well understood. The present paper focuses on the role of the cerebellum in executive processing, reviewing findings derived from neuroimaging studies or from studies investigating deficits related to cerebellar dysfunction. As executive functions cannot be considered as a unitary concept, special emphasis is put on cerebellar contributions to different aspects of executive control such as working memory, multitasking or inhibition. Referring to models derived from motor control, possible mechanisms of cerebellar involvement in executive processing are discussed. Finally, methodological problems in assessing executive deficits in general and in assessing the cerebellar contribution to executive processing in particular are addressed.

Emotional processing following cortical and subcortical brain damage: contribution of the fronto-striatal circuitry

The present study examined the differential contribution of cortical and subcortical brain structures in emotional processing by comparing patients with focal cortical lesions (n = 32) to those with primarily subcortical dysregulation of the basal ganglia (Parkinsons disease n = 14). A standardized measure of emotional perception (Tübingen Affect Battery) was used. Only patients in the more advanced stages of Parkinsons disease and patients with focal damage to the (right) frontal lobe differed significantly from controls in both facial expression and affective prosody recognition. The findings imply involvement of the fronto-striatal circuitry in emotional processing.

Classical conditioning after temporal lobe lesions in man : impairment in conditional discrimination

Left and right temporal lobectomy patients, patients with frontal lobe lesions, and healthy control subjects participated in an eyelid conditioning study based on conditional discrimination learning. All groups acquired the first conditioned response at a similar time during learning, but both temporal lobectomy groups showed poorer discrimination than control subjects. The results support models that relate hippocampal function to operation of if-then rules.

Elevated impulsivity and impaired decision-making cognition in heavy users of MDMA (“Ecstasy”)

RationaleIn animal studies, the common club drug 3,4-methylendioxymethamphetamine (MDMA, “Ecstasy”) consistently caused a prolonged loss of presynaptic serotonergic neurons, and evidence suggests that MDMA consumption may also affect the human serotonergic system. Serotonin (5-HT) has been implicated in the regulation of impulsivity and such executive functions as decision-making cognition. In fact, MDMA users have shown elevated impulsivity in two studies, but little is known about decision making in drug-free MDMA consumers.ObjectiveThe aim of this study was to examine the cognitive neurotoxicity of MDMA with regard to behavioral impulsivity and decision-making cognition.MethodsNineteen male, abstinent, heavy MDMA users; 19 male, abstinent cannabis users; and 19 male, drug-naïve controls were examined with the Matching Familiar Figures Test (MFFT) as well as with a Go/No-Go Task (GNG) for impulsivity and with a Gambling Task (GT) for executive functioning.ResultsMDMA users showed significantly elevated impulsivity in the MFFT Impulsivity score (I-score), but not in commission errors of the GNG, compared with controls. Cannabis users did not yield altered impulsivity compared with controls. In the GT, MDMA users performed significantly worse than cannabis consumers and controls, whereas cannabis users exhibited the same decision-making capacity as controls. In addition, the I-score as well as the decision-making performance was correlated with measures of MDMA intake. The I-score and the decision-making performance were also correlated.ConclusionThese results suggest that heavy use of MDMA may elevate behavioral impulsivity and impair decision-making cognition possibly mediated by a selective impairment of the 5-HT system.

It is less than you expected: The feedback-related negativity reflects violations of reward magnitude expectations

The anterior cingulate cortex (ACC) is involved in performance monitoring and in learning from performance feedback. Recent research suggests that the feedback-related negativity (FRN), an event-related potentials (ERP) component reflecting neural activity in the ACC, codes the size of a negative prediction error when reward probabilities are varied. There is as yet no clear evidence that the FRN is also sensitive to violations of reward magnitude expectations. In the present study, 20 healthy young subjects engaged in a learning task in which a coin had to be found on each trial. The value of the coin (the potential reward magnitude) was varied from trial to trial and amounted to 5 cent, 20 cent or 50 cent. Analysis of ERPs revealed that FRN amplitude differences between reward and non-reward were significantly modulated by (potential) reward magnitude. This effect was driven by the neural response to non-reward: the larger the potential reward, the larger was the FRN amplitude in response to non-reward. In contrast, the P300 was larger for positive outcomes and showed an effect of (potential) reward magnitude independent of valence. Together with evidence from previous studies, these results show that the FRN codes negative prediction errors in the context of varying reward probabilities and magnitudes. The findings are in line with recent results based on functional neuroimaging and lend further support to the idea of a key role of the ACC in the integration of information on different aspects of performance outcomes.

Structural encoding and recognition of biological motion: evidence from event-related potentials and source analysis.

In the present study, we investigated how different processing stages involved in the perceptual analysis of biological motion (BM) are reflected by modulations in event-related potentials (ERP) in order to elucidate the time course and location of neural processing of BM. Data analysis was carried out using conventional averaging techniques as well as source localization with low resolution brain electromagnetic tomography (LORETA). ERPs were recorded in response to point-light displays of a walking person, an inverted walking person and displays of scrambled motion. Analysis yielded a pronounced negativity with a peak at 180 ms after stimulus onset which was more pronounced for upright walkers than for inverted walkers and scrambled motion. A later negative component between 230 and 360 ms after stimulus onset had a larger amplitude for upright and inverted walkers as compared to scrambled walkers. In the later component, negativity was more pronounced in the right hemisphere revealing asymmetries in BM perception. LORETA analysis yielded evidence for sources specific to BM within the right fusiform gyrus and the right superior temporal gyrus for the second component, whereas sources for BM in the early component were located in areas associated with attentional aspects of visual processing. The early component might reflect the pop-out effect of a moving dot pattern representing the highly familiar form of a human figure, whereas the later component might be associated with the specific analysis of motion patterns providing biologically relevant information.

Executive function, mentalizing and humor in major depression

Major depression is associated with cognitive deficits including memory, executive functions, and affect perception, which have been linked to dysfunction of fronto-subcortical networks. However, little is known about social cognition on more complex socially relevant tasks, such as humor processing. In this investigation a computerized humor-processing task was administered to 27 patients with a diagnosis of major depression (Dep) and 27 healthy controls (HC). Theory of mind (mentalizing) and executive functions were also assessed. Both groups were similar in IQ, age, and gender. Depressed patients performed below the control group with respect to both affective and cognitive aspects of humor processing, and these were related to mentalizing and executive performance. Our findings suggest social cognition deficits in major depression. Ability to process humor and appreciate mentalistic perspectives may in turn influence social interactions and should be given consideration in therapeutic approaches to depression.

Brain correlates of risky decision-making.

Understanding the neurocognitive basis of risk-taking behavior is an important issue, especially in economic decision-making. Classical behavioral studies have shown that risk-attitude changes across different contexts, but little is so far known about the brain correlates of processing of outcomes across such context shifts. In this study, EEG was recorded while subjects performed a gambling task. Participants could choose between a risky and a safer option, within two different contexts: one in which options yielded gains and losses of the same magnitude (Zero Expected Value context) and another in which gains were larger than losses (Positive Expected Value context). Based on their risk-attitude, two groups were compared: subjects who are risk-seekers in the zero Expected Value context (Zero-Oriented group) and subjects who are risk-seekers in the positive Expected Value condition (Positive-Oriented group). The Feedback Related Negativity (FRN) reflects this distinction, with each group being insensitive to magnitude of outcomes in the condition in which they were risk-prone. P300 amplitude mirrored the behavioral results, with larger amplitudes in the condition in which each group showed a higher risk-tendency. Source analyses highlighted the involvement of posterior cingulate cortex in risky decision-making. Taken together, the findings make a contribution to the clarification of the neurocognitive substrates of risky decision-making.

Mentalizing in economic decision-making.

In the Ultimatum Game, participants typically reject monetary offers they consider unfair even if the alternative is to gain no money at all. In the present study, ERPs were recorded while subjects processed different offers of a proposer. In addition to clearly fair and unfair offers, mid-value offers which cannot be easily classified as fair or unfair and therefore involve more elaborate decision making were analyzed. A fast initial distinction between fair and other kinds of offers was reflected by amplitude of the feedback related negativity (FRN). Mid-value offers were associated with longer RTs, and a larger N350 amplitude. In addition, source analyses revealed a specific involvement of the superior temporal gyrus and the inferior parietal lobule during processing of mid-value offers compared to offers categorized clearly as fair or unfair, suggesting a contribution of mentalizing about the intention of the proposer to the decision making process. Taken together, the present findings support the idea that economic decisions are significantly affected by non-rational factors, trying to narrow the gap between formal theory and the real decisional behaviour.