Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients

The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies

Neuro-cognitive architecture of executive functions: A latent variable analysis

Executive functions refer to high-level cognitive processes that, by operating on lower-level mental processes, flexibly regulate and control our thoughts and goal-directed behavior. Despite their crucial role, the study of the nature and organization of executive functions still faces inherent difficulties. Moreover, most executive function models put under test until now are brain-free models: they are defined and discussed without assumptions regarding the neural bases of executive functions. By using a latent variable approach, here we tested a brain-centered model of executive function organization proposing that two distinct domain-general executive functions, namely, criterion setting and monitoring, may be dissociable both functionally and anatomically, with a left vs. right hemispheric preference of prefrontal cortex and related neural networks, respectively. To this end, we tested a sample of healthy participants on a battery of computerized tasks assessing criterion setting and monitoring processes and involving diverse task domains, including the verbal and visuospatial ones, which are well-known to be lateralized. By doing this, we were able to specifically assess the influence of these task domains on the organization of executive functions and to directly contrast a process-based model of EF organization versus both a purely domain-based model and a process-based, but domain-dependent one. The results of confirmatory factor analyses showed that a purely process-based model reliably provided a better fit to the observed data as compared to alternative models, supporting the specific theoretical model that fractionates a subset of executive functions into criterion setting and monitoring with hemispheric specializations emerging regardless of the task domain

Temporal judgments of actions following unilateral brain damage

Sense of time is a complex construct, and its neural correlates remain to date in most part unknown. To complicate the frame, physical attributes of the stimulus, such as its intensity or movement, influence temporal perception. Although previous studies have shown that time perception can be compromised after a brain lesion, the evidence on the role of the left and right hemispheres are meager. In two experiments, the study explores the ability of temporal estimation of multi-second actions and non-biological movements in 33 patients suffering from unilateral brain lesion. Furthermore, the modulatory role of induced embodiment processes is investigated. The results reveal a joint contribution of the two hemispheres depending not only on different durations but also on the presence of actions. Indeed, the left hemisphere damaged patients find it difficult to estimate 4500 ms or longer durations, while the right hemisphere damaged patients fail in 3000 ms durations. Furthermore, the former fail when a biological action is shown, while the latter fail in non-biological movement. Embodiment processes have a modulatory effect only after right hemisphere lesions. Among neuropsychological variables, only spatial neglect influences estimation of non-biological movement

Differential activity and clinical utility of latanoprost in glaucoma and ocular hypertension

Background: The purpose of this study was to demonstrate the hypotensive efficacy and tolerability of latanoprost when used as monotherapy and as polytherapy associated with antiglaucomatous medication proven to be ineffective in keeping intraocular pressure under control. Methods: Three hundred and thirty-seven patients (672 eyes) affected by primary open-angle glaucoma and intraocular hypertension were recruited over a period of 10 years from the Glaucoma Centre, Department of Ophthalmological Sciences, University of Rome "Sapienza", and treated, subject to informed consent, with latanoprost 0.005% alone or in combination with other ocular hypotensive drugs. The patients were followed during this period at regular intervals, with determination of visual field, fundus oculi, visual acuity, and eventual onset of local and systemic side effects. Results: Latanoprost used as monotherapy and as polytherapy renders possible optimal and durable control of intraocular pressure in the form of one antiglaucomatous drug because it can substitute for one or more drugs and obtain the same hypotensive effect. Conclusion: Latanoprost can be described as the ideal hypotensive drug, not only because of its ideal compliance profile (only one daily dose in the evening), excellent hypotensive effect, and, above all, few systemic side effects. © 2012 Pacella et al, publisher and licensee Dove Medical Press Ltd

Disconnections in personal neglect

Personal neglect is a disorder in the perception and representation of the body that causes the patients to behave as if the contralesional side of their body does not exist. This clinical condition has not been adequately investigated in the past as it has been considered a symptom of unilateral spatial neglect, which has mainly been studied with reference to extrapersonal space. Only a few studies with small samples have investigated the neuroanatomical correlates of personal neglect, and these have mainly focused on discrete cortical lesions and modular accounts, as well as being based on the hypothesis that this disorder is associated with somatosensory and spatial deficits. In the present study, we tested the novel hypothesis that personal neglect may be associated not only with discrete cortical and subcortical lesions, but also with disconnections of white matter tracts. We performed an advanced lesion analyses in a large sample of 104 right hemisphere damaged patients, 72 of whom were suffering from personal neglect. Results from the analyses of the grey and white matter were controlled for co-occurrent clinical variables such as extrapersonal neglect, anosognosia for hemiplegia and motor deficits, along with other lesion-related variables such as lesion size and the interval from the lesion onset to neuroimaging recordings. Our results reveal that personal neglect is associated with lesions in a medial network which involves the temporal cortex (Heschl's gyrus), the ventro-lateral nuclei of the thalamus and the fornix. This suggests that personal neglect involves a convergence between sensorimotor processes, spatial representation and the processing of self-referred information (episodic memory)

Disconnections in personal neglect

: Personal neglect is a disorder in the perception and representation of the body that causes the patients to behave as if the contralesional side of their body does not exist. This clinical condition has not been adequately investigated in the past as it has been considered a symptom of unilateral spatial neglect, which has mainly been studied with reference to extrapersonal space. Only a few studies with small samples have investigated the neuroanatomical correlates of personal neglect, and these have mainly focused on discrete cortical lesions and modular accounts, as well as being based on the hypothesis that this disorder is associated with somatosensory and spatial deficits. In the present study, we tested the novel hypothesis that personal neglect may be associated not only with discrete cortical and subcortical lesions, but also with disconnections of white matter tracts. We performed an advanced lesion analyses in a large sample of 104 right hemisphere damaged patients, 72 of whom were suffering from personal neglect. Results from the analyses of the grey and white matter were controlled for co-occurrent clinical variables such as extrapersonal neglect, anosognosia for hemiplegia and motor deficits, along with other lesion-related variables such as lesion size and the interval from the lesion onset to neuroimaging recordings. Our results reveal that personal neglect is associated with lesions in a medial network which involves the temporal cortex (Heschl's gyrus), the ventro-lateral nuclei of the thalamus and the fornix. This suggests that personal neglect involves a convergence between sensorimotor processes, spatial representation and the processing of self-referred information (episodic memory)

Latent disconnectome prediction of long-term cognitive-behavioural symptoms in stroke

Stroke significantly impacts the quality of life. However, the long-term cognitive evolution in stroke is poorly predictable at the individual level. There is an urgent need to better predict long-term symptoms based on acute clinical neuroimaging data. Previous works have demonstrated a strong relationship between the location of white matter disconnections and clinical symptoms. However, rendering the entire space of possible disconnection-deficit associations optimally surveyable will allow for a systematic association between brain disconnections and cognitive-behavioural measures at the individual level. Here we present the most comprehensive framework, a composite morphospace of white matter disconnections (disconnectome) to predict neuropsychological scores 1 year after stroke. Linking the latent disconnectome morphospace to neuropsychological outcomes yields biological insights that are available as the first comprehensive atlas of disconnectome-deficit relations across 86 scores-a Neuropsychological White Matter Atlas. Our novel predictive framework, the Disconnectome Symptoms Discoverer, achieved better predictivity performances than six other models, including functional disconnection, lesion topology and volume modelling. Out-of-sample prediction derived from this atlas presented a mean absolute error below 20% and allowed personalize neuropsychological predictions. Prediction on an external cohort achieved an R2 = 0.201 for semantic fluency. In addition, training and testing were replicated on two external cohorts achieving an R2 = 0.18 for visuospatial performance. This framework is available as an interactive web application (http://disconnectomestudio.bcblab.com) to provide the foundations for a new and practical approach to modelling cognition in stroke. We hope our atlas and web application will help to reduce the burden of cognitive deficits on patients, their families and wider society while also helping to tailor future personalized treatment programmes and discover new targets for treatments. We expect our framework's range of assessments and predictive power to increase even further through future crowdsourcing

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Motor awareness: a model based on neurological syndromes

Motor awareness is a complex, multifaceted construct involving the awareness of both (i) one's motor state while executing a movement or remaining still and (ii) one's motor abilities. The analysis of neurological syndromes associated with motor disorders suggests the existence of various different components which are, however, integrated into a model of motor awareness. These components are: (i) motor intention, namely, a conscious desire to perform an action; (ii) motor monitoring and error recognition, that is, the capacity to check the execution of the action and identify motor errors; and (iii) a general awareness of one's own motor abilities and deficits, that is, the capacity to recognize the general state of one's motor abilities about the performance of specific actions and the potential consequences of motor impairment. Neuroanatomical correlates involving the parietal and insular cortices, the medial and lateral frontal regions, and subcortical structures (basal ganglia and limbic system) support this multi-component model. Specific damage (or disconnections) to these structures results in a number of different disorders in motor awareness, such as anosognosia for hemiplegia and apraxia, and a number of symptoms which are specific to motor intention disorders (e.g., the Anarchic Hand Syndrome and Tourette's Syndrome) or motor monitoring (e.g., Parkinson's and Huntington's diseases). All of these clinical conditions are discussed in the light of a motor awareness model