Decision Making and the Brain: Neurologists' View

The article reflects the fact, that concepts like decision making and free will have entered the field of cognitive neuroscience towards the end of 20th century. It gives an overview of brain structures involved in decision making and the concept of free will; and presenting the results of clinical observations and new methods (functional neuroimaging, electrophysiology) it postulates possible mechanisms of these processes. We give a review of the neuroanatomy, specially discussing those parts of the brain important to the present topic, because the process of decision making is dependent on deep subcortical as well as superficial cortical structures. Dopamine has a central role in the in process of reward related behaviour and hedonism. A list of brain structures, related to dopamine action, is also given. The article especially concentrates on the Single Photon Emission Computer Tomography studies in patients with Parkinson's disease (neuroimaging), as well as to the studies concerning the Readiness Potential and Endogeneous Potential P300 (electrophysiology). In the end, we discuss the volition, whose functional anatomy overlaps with the functional anatomy of free will and decision making processes.cognitive neuroscience, brain, decision making, free will, electrophysiology, functional imaging, dopamine

Emotional Intelligence and Perceived Stress in Pharmacists Completing Post-Graduate Specialization Programs: A Cross-Sectional Study

Background: Emotional Intelligence (EI) has been recognized by the International Pharmaceutical Federation as a required competency for a pharmacist. This study aimed to compare EI and Perceived Stress (PS) levels in pharmacists who completed the post-graduate specialization program (the Case), and pharmacists who started the program (the Control group). Materials and Methods: Validated instruments measuring EI and PS were distributed online to participating postgraduates or alumni. All complete responses were analyzed; data from participants who had undergone previous EI training were excluded. Comparing the groups, additional EI domains’ subanalysis and their correlations with PS were made. Results: The overall response rate was 67.8%. There was no expected difference between the groups either in EI or in the PS levels, and the overall population reached means of 119.30±12.92 and 17.25±6.46, respectively. The highest EI levels were found in sales and marketing professionals in the pharmaceutical industry and the lowest in clinical pharmacy practitioners. EI and PS were highly negatively correlated (r=-0,543), thus indicating that developing EI may have protective effects against stress. Subanalysis revealed the highest potential for stress-protective effects in the Emotional Self-Management and Emotional Self-Control subdomains (r=-0,528, r=-0,457, respectively). Conclusion: Given the expanded importance of EI development in pharmacy practice, the results of the study could be a basis for the specialization and continuing pharmacist education program creators to evaluate the curricula and propose changes in the methodologies, contents, and approaches in work to meet development needs of post-graduate pharmacists better. Further research should confirm the findings of the EI subanalysis

Central nervous system physiology

This is the second chapter of the series on the use of clinical neurophysiology for the study of movement disorders. It focusses on methods that can be used to probe neural circuits in brain and spinal cord. These include use of spinal and supraspinal reflexes to probe the integrity of transmission in specific pathways; transcranial methods of brain stimulation such as transcranial magnetic stimulation and transcranial direct current stimulation, which activate or modulate (respectively) the activity of populations of central neurones; EEG methods, both in conjunction with brain stimulation or with behavioural measures that record the activity of populations of central neurones; and pure behavioural measures that allow us to build conceptual models of motor control. The methods are discussed mainly in relation to work on healthy individuals. Later chapters will focus specifically on changes caused by pathology

Chronic Subthalamic Nucleus Stimulation in Parkinson's Disease: Optimal Frequency for Gait Depends on Stimulation Site and Axial Symptoms

Axial symptoms emerge in a significant proportion of patients with Parkinson's disease (PD) within 5 years of deep brain stimulation (STN-DBS). Lowering the stimulation frequency may reduce these symptoms. The objectives of the current study were to establish the relationship between gait performance and STN-DBS frequency in chronically stimulated patients with PD, and to identify factors underlying variability in this relationship. Twenty-four patients treated chronically with STN-DBS (>4 years) were studied off-medication. The effect of stimulation frequency (40–140 Hz, 20 Hz-steps, constant energy) on gait was assessed in 6 sessions spread over 1 day. Half of the trials/session involved walking through a narrow doorway. The influence of stimulation voltage was investigated separately in 10 patients. Gait was measured using 3D motion capture and axial symptoms severity was assessed clinically. A novel statistical method established the optimal frequency(ies) for each patient by operating on frequency-tuning curves for multiple gait parameters. Narrowly-tuned optimal frequencies (20 Hz bandwidth) were found in 79% of patients. Frequency change produced a larger effect on gait performance than voltage change. Optimal frequency varied between patients (between 60 and 140 Hz). Contact site in the right STN and severity of axial symptoms were independent predictors of optimal frequency (P = 0.009), with lower frequencies associated with more dorsal contacts and worse axial symptoms. We conclude that gait performance is sensitive to small changes in STN-DBS frequency. The optimal frequency varies considerably between patients and is associated with electrode contact site and severity of axial symptoms. Between-subject variability of optimal frequency may stem from variable pathology outside the basal ganglia

Effects of deep brain stimulation frequency on eye movements and cognitive control

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). Varying the frequency DBS has differential effects on axial and distal limb functions, suggesting differing modulation of relevant pathways. The STN is also a critical node in oculomotor and associative networks, but the effect of stimulation frequency on these networks remains unknown. This study aimed to investigate the effects of 80 hz vs. 130 Hz frequency STN-DBS on eye movements and executive control. Twenty-one STN-DBS PD patients receiving 130 Hz vs. 80 Hz stimulation were compared to a healthy control group (n = 16). All participants were tested twice in a double-blind manner. We examined prosaccades (latency and gain) and antisaccades (latency of correct and incorrect antisaccades, error rate and gain of the correct antisaccades). Executive function was tested with the Stroop task. The motor condition was assessed using Unified Parkinson's Disease Rating Scale part III. The antisaccadic error rate was higher in patients (p = 0.0113), more so in patients on 80 Hz compared to 130 Hz (p = 0.001) stimulation. The differences between patients and controls and between frequencies for all other eye-movements or cognitive measures were not statistically significant. We show that 80 Hz STN-DBS in PD reduces the ability to maintain stable fixation but does not alter inhibition, resulting in a higher antisaccade error rate presumably due to less efficient fixation, without altering the motor state. This provides a wider range of stimulation parameters that can reduce specific DBS-related effects without affecting motor outcomes

Subthalamic deep brain stimulation sweet spots and hyperdirect cortical connectivity in Parkinson’s disease

Objectives Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy. Methods High angular resolution diffusion imaging in twenty patients with advanced Parkinson’s disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy. Results All patients responded well to treatment (46% mean improvement off medication UPDRS-III [p<0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X=-10(-9.5), Y=-13(-1) and Z=-7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity. Interpretation These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia

Dopaminergic Pathway Genes Influence Adverse Events Related to Dopaminergic Treatment in Parkinson's Disease

Dopaminergic pathway is the most disrupted pathway in the pathogenesis of Parkinson's disease. Several studies reported associations of dopaminergic genes with the occurrence of adverse events of dopaminergic treatment. However, none of these studies adopted a pathway based approach. The aim of this study was to comprehensively evaluate the influence of selected single nucleotide polymorphisms of key dopaminergic pathway genes on the occurrence of motor and non-motor adverse events of dopaminergic treatment in Parkinson's disease. In total, 231 Parkinson's disease patients were enrolled. Demographic and clinical data were collected. Genotyping was performed for 16 single nucleotide polymorphisms from key dopaminergic pathway genes. Logistic and Cox regression analyses were used for evaluation. Results were adjusted for significant clinical data. We observed that carriers of at least one COMT rs165815 C allele had lower odds for developing visual hallucinations (OR = 0.34; 95% CI = 0.16–0.72; p = 0.004), while carriers of at least one DRD3 rs6280 C allele and CC homozygotes had higher odds for this adverse event (OR = 1.88; 95% CI = 1.00–3.54; p = 0.049 and OR = 3.31; 95% CI = 1.37–8.03; p = 0.008, respectively). Carriers of at least one DDC rs921451 C allele and CT heterozygotes had higher odds for orthostatic hypotension (OR = 1.86; 95% CI = 1.07–3.23; p = 0.028 and OR = 2.30; 95% CI = 1.26–4.20; p = 0.007, respectively). Heterozygotes for DDC rs3837091 and SLC22A1 rs628031 AA carriers also had higher odds for orthostatic hypotension (OR = 1.94; 95% CI = 1.07–3.51; p = 0.028 and OR = 2.57; 95% CI = 1.11–5.95; p = 0.028, respectively). Carriers of the SLC22A1 rs628031 AA genotype had higher odds for peripheral edema and impulse control disorders (OR = 4.00; 95% CI = 1.62–9.88; p = 0.003 and OR = 3.16; 95% CI = 1.03–9.72; p = 0.045, respectively). Finally, heterozygotes for SLC22A1 rs628031 and carriers of at least one SLC22A1 rs628031 A allele had lower odds for dyskinesia (OR = 0.48; 95% CI = 0.24–0.98, p = 0.043 and OR = 0.48; 95% CI = 0.25–0.92; p = 0.027, respectively). Gene-gene interactions, more specifically DDC-COMT, SLC18A2-SV2C, and SLC18A2-SLC6A3, also significantly influenced the occurrence of some adverse events. Additionally, haplotypes of COMT and SLC6A3 were associated with the occurrence of visual hallucinations (AT vs. GC: OR = 0.34; 95% CI = 0.16–0.72; p = 0.005) and orthostatic hypotension (ATG vs. ACG: OR = 2.48; 95% CI: 1.01–6.07; p = 0.047), respectively. Pathway based approach allowed us to identify new potential candidates for predictive biomarkers of adverse events of dopaminergic treatment in Parkinson's disease, which could contribute to treatment personalization

More than smell - COVID-19 is associated with severe impairment of smell, taste, and chemesthesis

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, generally lacked quantitative measurements, were mostly restricted to data from single countries. Here, we report the development, implementation and initial results of a multi-lingual, international questionnaire to assess self-reported quantity and quality of perception in three distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, 8 other, ages 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change+/-100) revealed a mean reduction of smell (-79.7+/- 28.7, mean+/- SD), taste (-69.0+/- 32.6), and chemesthetic (-37.3+/- 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell, but also affects taste and chemesthesis. The multimodal impact of COVID-19 and lack of perceived nasal obstruction suggest that SARS-CoV-2 infection may disrupt sensory-neural mechanisms.Additional co-authors: Veronica Pereda-Loth, Shannon B Olsson, Richard C Gerkin, Paloma Rohlfs Domínguez, Javier Albayay, Michael C. Farruggia, Surabhi Bhutani, Alexander W Fjaeldstad, Ritesh Kumar, Anna Menini, Moustafa Bensafi, Mari Sandell, Iordanis Konstantinidis, Antonella Di Pizio, Federica Genovese, Lina Öztürk, Thierry Thomas-Danguin, Johannes Frasnelli, Sanne Boesveldt, Özlem Saatci, Luis R. Saraiva, Cailu Lin, Jérôme Golebiowski, Liang-Dar Hwang, Mehmet Hakan Ozdener, Maria Dolors Guàrdia, Christophe Laudamiel, Marina Ritchie, Jan Havlícek, Denis Pierron, Eugeni Roura, Marta Navarro, Alissa A. Nolden, Juyun Lim, KL Whitcroft, Lauren R. Colquitt, Camille Ferdenzi, Evelyn V. Brindha, Aytug Altundag, Alberto Macchi, Alexia Nunez-Parra, Zara M. Patel, Sébastien Fiorucci, Carl M. Philpott, Barry C. Smith, Johan N Lundström, Carla Mucignat, Jane K. Parker, Mirjam van den Brink, Michael Schmuker, Florian Ph.S Fischmeister, Thomas Heinbockel, Vonnie D.C. Shields, Farhoud Faraji, Enrique Enrique Santamaría, William E.A. Fredborg, Gabriella Morini, Jonas K. Olofsson, Maryam Jalessi, Noam Karni, Anna D'Errico, Rafieh Alizadeh, Robert Pellegrino, Pablo Meyer, Caroline Huart, Ben Chen, Graciela M. Soler, Mohammed K. Alwashahi, Olagunju Abdulrahman, Antje Welge-Lüssen, Pamela Dalton, Jessica Freiherr, Carol H. Yan, Jasper H. B. de Groot, Vera V. Voznessenskaya, Hadar Klein, Jingguo Chen, Masako Okamoto, Elizabeth A. Sell, Preet Bano Singh, Julie Walsh-Messinger, Nicholas S. Archer, Sachiko Koyama, Vincent Deary, Hüseyin Yanik, Samet Albayrak, Lenka Martinec Novákov, Ilja Croijmans, Patricia Portillo Mazal, Shima T. Moein, Eitan Margulis, Coralie Mignot, Sajidxa Mariño, Dejan Georgiev, Pavan K. Kaushik, Bettina Malnic, Hong Wang, Shima Seyed-Allaei, Nur Yoluk, Sara Razzaghi, Jeb M. Justice, Diego Restrepo, Julien W Hsieh, Danielle R. Reed, Thomas Hummel, Steven D Munger, John E Haye

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake