Amyotrophic lateral sclerosis affects cortical and subcortical activity underlying motor inhibition and action monitoring.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by muscular atrophy, spasticity, and bulbar signs caused by loss of upper and lower motor neurons. Evidence suggests that ALS additionally affects other brain areas including premotor cortex and supplementary motor area. Here, we studied movement execution and inhibition in ALS patients using a stop-signal paradigm and functional magnetic resonance imaging. Seventeen ALS patients and 17 age-matched healthy controls performed a stop-signal task that required responding with a button press to a right- or left-pointing black arrow (go-stimuli). In stop-trials, a red arrow (stop-stimulus) was presented shortly after the black arrow indicating to withhold the prepared movement. Patients had by trend higher reaction times in go-trials but did not differ significantly in their inhibition performance. Patients showed stronger inhibition-related activity in inferior, superior, and middle frontal gyri as well as in putamen and pallidum. Error-related activity, conversely, was found to be stronger in healthy controls, particularly in the insula bilaterally. Patients also showed increased activity in the motor cortex during button presses. The results provide evidence for altered prefrontal and subcortical networks underlying motor execution, motor inhibition, and error monitoring in ALS.

The mental number line electrified: brain potentials in a numerical flanker task.

It has been suggested that the mental representation of numbers is spatial in nature such that numbers are ordered on a mental number line. In the present investigation we use a variant of the Eriksen flanker task requiring a magnitude decision (smaller or larger than 5) for a central target number by pressing a response button with the right or left hand. The target number is flanked by irrelevant distracters that are either identical to the target, different from the target but biasing the same response, or different from the target and biasing a different response. Response latencies and event-related brain potentials were obtained in a group of healthy adults. Besides the typical response congruency effects on response latency and the N2 component of the ERP, we observed several other effects. First, numerical distance of the target to the standard 5 influenced decision latencies and amplitude and latency of the P3 component with smaller distances leading to longer decision latencies, longer P3 latencies and smaller P3 amplitudes. Second, smaller numerical distance between target and distracters led to faster decisions for response congruent and to slower decisions for response-incongruent trials. For response-incongruent trials P3 amplitude was small/large and P3 latency was long/short for small/large distances. These findings underscore the spatial character of number representation and further show that the relation between targets and distracters, although task irrelevant, is assessed automatically with facilitatory and inhibitory effects driven by spatial distance on the mental number line.

Intertemporal choice in Parkinson's disease.

The administration of dopamine agonists in Parkinson's disease has been associated with impulse control disorders, in particular, pathological gambling. In the present investigation, 17 patients with Parkinson's disease without impulse control disorders and 17 matched control participants were offered choices between monetary rewards (ranging between 11 and 80 euros) available immediately and larger rewards (between 25 and 85 euros) available after delays ranging from 7 to 186 days. Participants had a 1-in-6 chance of winning a reward that they chose on 1 randomly selected trial. Assuming a hyperbolic discounting model, k values were estimated from the pattern of participants' choices. Patients were tested twice, once on dopamine agonist medication and once after 12 hours without medication. Patients showed a considerably steeper discounting function than healthy controls independent of medication status, with k values more than 3 times larger than those of controls. This study shows that patients with Parkinson's disease without clinically apparent impulse control disorders nevertheless tend to make impulsive decisions in intertemporal monetary choice. The lack of difference between sessions could be a result either of the persistent effects of dopaminergic therapy or hint at a genuine medication-independent change in intertemporal choice behavior in Parkinson's disease. This needs to be addressed in further studies. The paradigm used is easy to apply and should be used more extensively to describe decision behavior in Parkinson's disease.

Association of Locus Coeruleus and Substantia Nigra Pathology With Cognitive and Motor Functions in Patients With Parkinson Disease.

OBJECTIVE: To investigate the contribution of substantia nigra (SN) and locus coeruleus (LC) pathology to clinical signs and symptoms in Parkinson disease (PD) by applying neuromelanin-weighted imaging. METHODS: Forty-seven patients with PD and 53 matched controls underwent motor assessment, a neuropsychological test battery, and neuromelanin-weighted MRI. Patients with PD were enrolled after fulfilling the criteria for clinically established PD as defined by the Movement Disorders Society Clinical Diagnostic Criteria. Two independent raters identified SN and LC and calculated the contrast-to-noise ratio (CNR). RESULTS: The intrarater reliability demonstrated good reliability between raters with an intraclass correlation coefficient of 0.88 (p < 0.001) and an interrater reliability of 0.80 (p < 0.001). Both SN and LC CNRs were lower in patients with PD (p ≤ 0.001) compared to controls. The CNR of SN but not of LC was strongly correlated with disease duration (p ≤ 0.001). Neuromelanin pathology of the pars compacta-containing dorsolateral SN correlated with Movement Disorders Society-sponsored version of the Unified Parkinson's Disease Rating Scale I, II, and III but not cognitive function. In contrast, neuromelanin pathology of LC was associated with cognitive function in all tested domains but not with motor impairment or activities of daily living. No such associations were present in controls. CONCLUSIONS: Neuromelanin imaging of the SN and LC is well-suited to map neurodegeneration in PD. Neuromelanin pathology of the SN correlates with motor dysfunction whereas LC pathology is related to cognitive impairment. Neuromelanin-weighted imaging of the LC could thus serve as an imaging marker of executive and other cognitive dysfunction in PD. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that neuromelanin-weighted imaging was associated with the severity of various signs and symptoms in patients with PD.

Persistent cognitive impairment associated with cerebrospinal fluid anti-SARS-CoV-2 antibodies six months after mild COVID-19.

Neurological long-term sequelae are increasingly considered an important challenge in the recent COVID-19 pandemic. However, most evidence for neurological symptoms after SARS-CoV-2 infection and central nervous system invasion of the virus stems from individuals severely affected in the acute phase of the disease. Here, we report long-lasting cognitive impairment along with persistent cerebrospinal fluid anti-SARS-CoV-2 antibodies in a female patient with unremarkable standard examination 6 months after mild COVID-19, supporting the implementation of neuropsychological testing and specific cerebrospinal fluid investigation also in patients with a relatively mild acute disease phase.

Patients with primary biliary cholangitis and fatigue present with depressive symptoms and selected cognitive deficits, but with normal attention performance and brain structure.

BACKGROUND: In primary biliary cholangitis (PBC) fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI) study and correlated changes of white and grey brain matter with the cognitive and attention performance. METHODS: 20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM) and DTI analyses. Results were correlated to the cognitive and attention performance. RESULTS: Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance. CONCLUSIONS: Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain changes underlie fatigue in PBC.

Sex differences in left/right confusion.

In agreement with the literature, females (n=269) gave themselves significantly poorer ratings than males (n=164) in evaluating their ability to make fast and accurate left/right judgments. In order to evaluate the ecological validity of the self-ratings, subjects were tested on a task that required fast and accurate left/right judgments, on a mental rotation task, and on a task that required navigation of a virtual maze. The correlations between the performances and self-ratings were computed. Both males and females who gave themselves very poor LRC (left/right confusion) ratings had significantly lower accuracy scores on the left/right judgement task than males and females with average ratings, but there was no sex-specific relation between LRC ratings and left/right judgements that would explain why females give themselves lower LRC ratings. For females only, a weak correlation between LRC scores and the learning of the virtual maze was observed, but no significant correlations were observed between LRC scores and mental rotation performance. We conclude that self-ratings on left/right confusion questions, although they yield reliable sex differences, are poor predictors of actual performance on spatial tasks that involve left/right judgements. Thus, and in support of earlier speculations (Sholl and Egeth, 1981; Teng and Lee, 1982; Williams et al., 1993), the principal cause of the marked sex differences in LRC self-ratings likely lies in a greater willingness of females to rate themselves more poorly on questions of this type than is the case for men.