Cognitive trajectories after surgery: Guideline hints for assessment and treatment.

Elderly patients who undergo major surgery (not-neurosurgical) under general anaesthesia frequently complain about cognitive difficulties, especially during the first weeks after surgical "trauma". Although recovery usually occurs within a month, about one out of four patients develops full-blown postoperative Neurocognitive disorders (NCD) which compromise quality of life or daily autonomy. Mild/Major NCD affect approximately 10% of patients from three months to one year after major surgery. Neuroinflammation has emerged to have a critical role in the postoperative NCDs pathogenesis, through microglial activation and the release of pro-inflammatory cytokines which increase blood-brain-barrier permeability, enhance movement of leukocytes into the central nervous system (CNS) and favour the neuronal damage. Moreover, pre-existing Mild Cognitive Impairment, alcohol or drugs consumption, depression and other factors, together with several intraoperative and post-operative sequelae, can exacerbate the severity and duration of NCDs. In this context it is crucial rely on current progresses in serum and CSF biomarker analysis to frame neuroinflammation levels, along with establishing standard protocol for neuropsychological assessment (with specific set of tools) and to apply cognitive training or neuromodulation techniques to reduce the incidence of postoperative NCDs when required. It is recommended to identify those patients who would need such preventive intervention early, by including them in pre-operative and post-operative comprehensive evaluation and prevent the development of a full-blown dementia after surgery. This contribution reports all the recent progresses in the NCDs diagnostic classification, pathogenesis discoveries and possible treatments, with the aim to systematize current evidences and provide guidelines for multidisciplinary care.

Monopolar tDCS might affect brainstem reflexes: A computational and neurophysiological study.

OBJECTIVE: To assess whether monopolar multi-electrode transcranial direct current stimulation (tDCS) montages might selectively affect deep brain structures through computational predictions and neurophysiological assessment. METHODS: Electric field distribution in deep brain structures (i.e., thalamus and midbrain) were estimated through computational models simulating tDCS with two monopolar and two monopolar multi-electrode montages. Monopolar multi-electrode tDCS was then applied to healthy subject, and effects on pontine and medullary circuitries was evaluated studying changes in blink reflex (BR) and masseter inhibitory reflex (MIR). RESULTS: Computational results suggest that tDCS with monopolar multi-electrode montages might induce electric field intensities in deep brain structure comparable to those in grey matter, while neurophysiological results disclosed that BR and MIR were selectively modulated by tDCS only when cathode was placed over the right deltoid. CONCLUSIONS: Multi-electrode tDCS (anodes over motor cortices, cathode over right deltoid) could induce significant electric fields in the thalamus and midbrain, and selectively affect brainstem neural circuits. SIGNIFICANCE: Multi-electrode tDCS (anodes over motor cortices, cathode over right deltoid) might be further explored to affect brainstem activity, also in the context of non-invasive deep brain stimulation.

Modeling Electric Fields in Transcutaneous Spinal Direct Current Stimulation: A Clinical Perspective.

Clinical findings suggest that transcutaneous spinal direct current stimulation (tsDCS) can modulate ascending sensitive, descending corticospinal, and segmental pathways in the spinal cord (SC). However, several aspects of the stimulation have not been completely understood, and realistic computational models based on MRI are the gold standard to predict the interaction between tsDCS-induced electric fields and anatomy. Here, we review the electric fields distribution in the SC during tsDCS as predicted by MRI-based realistic models, compare such knowledge with clinical findings, and define the role of computational knowledge in optimizing tsDCS protocols. tsDCS-induced electric fields are predicted to be safe and induce both transient and neuroplastic changes. This could support the possibility to explore new clinical applications, such as spinal cord injury. For the most applied protocol (2-3 mA for 20-30 min, active electrode over T10-T12 and the reference on the right shoulder), similar electric field intensities are generated in both ventral and dorsal horns of the SC at the same height. This was confirmed by human studies, in which both motor and sensitive effects were found. Lastly, electric fields are strongly dependent on anatomy and electrodes' placement. Regardless of the montage, inter-individual hotspots of higher values of electric fields were predicted, which could change when the subjects move from a position to another (e.g., from the supine to the lateral position). These characteristics underlines the need for individualized and patient-tailored MRI-based computational models to optimize the stimulation protocol. A detailed modeling approach of the electric field distribution might contribute to optimizing stimulation protocols, tailoring electrodes' configuration, intensities, and duration to the clinical outcome.

Relationship between Reaction Times and Post-COVID-19 Symptoms Assessed by a Web-Based Visual Detection Task.

Long-COVID is a clinical condition in which patients affected by SARS-CoV-2 usually report a wide range of physical and cognitive symptoms from 3 to 6 months after the infection recovery. The aim of the current study was to assess the link between self-reported long-COVID symptoms and reaction times (RTs) in a self-administered Visual Detection Task (VDT) in order to identify the predictor symptoms of the slowing in reaction times to determine attention impairment. In total, 362 participants (age (mean ± S.D.: 38.56 ± 13.14); sex (female-male: 73.76-26.24%)) responded to a web-based self-report questionnaire consisting of four sections: demographics, disease-related characteristics, and medical history questions. The final section consisted of a 23 item 5-point Likert-scale questionnaire related to long-term COVID-19 symptoms. After completing the questionnaire, subjects performed a VDT on a tablet screen to assess reaction times (RTs). An exploratory factorial analysis (EFA) was performed on the 23 long-COVID symptom questions, identifying 4 factors (cognition, behavior, physical condition, presence of anosmia and/or ageusia). The most important predictors of RTs were cognition and physical factors. By dissecting the cognitive and physical factors, learning, visual impairment, and headache were the top predictors of subjects' performance in the VDT. Long-COVID subjects showed higher RTs in the VDT after a considerable time post-disease, suggesting the presence of an attention deficit disorder. Attention impairment due to COVID-19 can be due to the presence of headaches, visual impairments, and the presence of cognitive problems related to the difficulty in learning new activities. The link between the slowing of reaction times and physical and cognitive symptoms post-COVID-19 suggests that attention deficit disorder is caused by a complex interaction between physical and cognitive symptoms. In addition, the study provides evidence that RTs in a VDT represent a reliable measure to detect the presence of long-COVID neurological sequelae.

The Effects of a New Integrated and Multidisciplinary Cognitive Rehabilitation Program Based on Mindfulness and Reminiscence Therapy in Patients with Parkinson's Disease and Mild Cognitive Impairment: A Pilot Study.

Background: Mindfulness trainings have shown promising results as treatment for behavioural symptoms in several pathologies. In addition, mindfulness protocols induced an improvement in memory and attention. Therefore, mindfulness could be an effective intervention for patients affected by Parkinson's disease (PD) and mild cognitive impairment (MCI), who are characterized by both behavioural and cognitive dysfunctions. Methods: We assessed differences in Montreal Cognitive Assessment (MoCA) scores and in Beck Depression Inventory II (BDI-II) scores in patients affected by PD and MCI enrolled in two different rehabilitation programs (an experimental vs. an usual structured program for cognitive rehabilitation). Participants in the experimental group (MILC-tr) underwent innovative rehabilitation program involving mindfulness and reminiscence activities. Assessments were performed before (T0) and at the end of the rehabilitation program (T1). Results: Friedman test showed a significant improvement between timepoints in MoCA global score (x2 = 4.000, p = 0.046), MoCA memory sub-scale score (x2 = 4.571, p = 0.033), and BDI-II cognitive and affective factors (x2 = 4.000, p = 0.046) only for patients in MILC-tr group. Mann-Whitney test showed a significant difference between group comparing differences in Δ scores between T0 and T1 in the MoCA memory sub-scale score (U = 190.50, p = 0.035). Conclusions: Mindfulness-based rehabilitation programs could be effective in patients affected by PD and MCI.

Brain positron emission tomography (PET) and cognitive abnormalities one year after COVID-19.

Emerging evidence indicates that the etiologic agent responsible for coronavirus disease 2019 (COVID-19), can cause neurological complications. COVID-19 may induce cognitive impairment through multiple mechanisms. The aim of the present study was to describe the possible neuropsychological and metabolic neuroimaging consequences of COVID-19 12 months after patients' hospital discharge. We retrospectively recruited 7 patients (age [mean ± SD] = 56 years ± 12.39, 4 men) who had been hospitalized for COVID-19 with persistent neuropsychological deficits 12 months after hospital discharge. All patients underwent cognitive assessment and brain (18F-FDG) PET/CT, and one also underwent 18F-amyloid PET/CT. Of the seven patients studied, four had normal glucose metabolism in the brain. Three patients showed various brain hypometabolism patterns: (1) unilateral left temporal mesial area hypometabolism; (2) pontine involvement; and (3) bilateral prefrontal area abnormalities with asymmetric parietal impairment. The patient who showed the most widespread glucose hypometabolism in the brain underwent an 18F-amyloid PET/CT to assess the presence of Aß plaques. This examination showed significant Aß deposition in the superior and middle frontal cortex, and in the posterior cingulate cortex extending mildly in the rostral and caudal anterior cingulate areas. Although some other reports have already suggested that brain hypometabolism may be associated with cognitive impairment at shorter intervals from SarsCov-2 infection, our study is the first to assess cognitive functions, brain metabolic activity and in a patient also amyloid PET one year after COVID-19, demonstrating that cerebral effects of COVID-19 can largely outlast the acute phase of the disease and even be followed by amyloid deposition.

Energy Delivered by Subthalamic Deep Brain Stimulation for Parkinson Disease Correlates With Depressive Personality Trait Shift.

OBJECTIVES: Despite the large amount of literature examining the potential influence of subthalamic nucleus deep brain stimulation (STN-DBS) on psychiatric symptoms and cognitive disorders, only a few studies have focused on its effect on personality. We investigated the correlation between total electrical energy delivered (TEED) and the occurrence of depressive traits in patients with Parkinson disease (PD) after one year of DBS. MATERIALS AND METHODS: Our study involved 20 patients with PD (12 women, mean [±SD] age 57.60 ± 7.63 years) who underwent bilateral STN-DBS, whose personality characteristics were assessed using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), according to the core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD) procedure. RESULTS: We found that despite a marked improvement in motor functions and quality of life after 12 months, patients showed a significant increase in MMPI-2 subscales for depression (D scale and Depression scale) and in other content component scales (low self-esteem, work interference, and negative treatment indicators). Interestingly, only the TEED on the right side was inversely correlated with the changes in scale D (rs = -0.681, p = 0.007), whereas depressive traits did not correlate with disease duration, levodopa equivalent daily dose (LEDD) reduction, patient's age, or severity of motor symptoms. CONCLUSIONS: Our preliminary observations indicate that despite the excellent motor outcome and general improvement in quality of life, DBS treatment can result in patients poorly adjusting to their personal, familiar, and socio-professional life. Different influences and multiple factors (such as TEED, intra/postsurgical procedure, coping mechanisms, and outcome expectations) may affect depressive traits. Further advances are expected to improve stimulation methods.

Emotional and autonomic response to visual erotic stimulation in patients with functional hypothalamic amenorrhea.

Introduction: Functional hypothalamic amenorrhea (FHA) is a clinical condition associated with high levels of physiological and psychological stress ranging from weight loss to maladaptive behavior and coping skills. A reliable measure of the psychophysiological response to stress and the ability to cope with stimuli is heart rate variability (HRV). Through the sympathetic (SNS) and parasympathetic nervous system (PNS), the autonomic nervous system (ANS) promotes various changes in HRV that reflect the individual's psychophysiological response to stress. FHA patients are characterized by high levels of PNS activation during psychological load, suggesting that parasympathetic hyperactivation could be a pathology marker. Methods: In the present study, we examine changes in HRV during observation of erotic, neutral, and disgusting images in 10 patients with FHA [(mean ± S.D.) age: 26.8 ± 5.9] and in 9 controls (age: 25.4 ± 6.4; BMI: 22.47 ± 2.97) to assess the differential activation of PNS and SNS between FHA patients and controls matched for age and without other clinical conditions. Results: Our results showed that FHA patients had significantly higher HRV activation while observing high emotional value images and not during the observation of neutral images confirming a parasympathetic hyperactivation. Discussion: HRV and cognitive and psychological testing, could provide new insights into understanding such a clinically understudied condition and provide further tools for clinical diagnosis and treatment.

Simultaneous Bilateral Frontal and Bilateral Cerebellar Transcranial Direct Current Stimulation in Treatment-Resistant Depression-Clinical Effects and Electrical Field Modelling of a Novel Electrodes Montage.

Depressive disorders are one of the leading causes of disability worldwide. Transcranial direct current stimulation (tDCS) is a safe, simple, non-invasive brain stimulation technique showing considerable effectiveness in improving depressive symptoms. Most studies to date have applied anodal tDCS to the left dorsolateral prefrontal cortex (DLPFC), in line with the hypothesis that depressed patients exhibit relative hypoactivity in the left DLPFC compared to the right. Considering the emerging role of the cerebellum in emotional processes, we aimed to study the effect of combining bilateral cerebellar tDCS with the commonly used bifrontal stimulation in patients with severe depression. This open-label pilot study entailed the simultaneous administration of bilateral cerebellar (anode over the left cerebellum, cathode over the right cerebellum) and bilateral frontal (anode over the left DLPFC, cathode over the right DLPFC) tDCS to patients (N = 12) with treatment-resistant depression. The 21-item Hamilton Depression Rating Scale (HDRS) and Beck's Depression Inventory-II (BDI-II) were selected as outcome measures. Electric fields distribution originating from this novel electrode montage was obtained by a computational method applied to a realistic human head model. We observed a 30% reduction of both clinician-rated and self-reported severity of depressive symptoms after only five days (10 sessions) of treatment. Younger age was associated with greater clinical improvement. Adverse events were similar to those of the conventional electrodes montage. The modelling studies demonstrated that the electric fields generated by each pair of electrodes are primarily distributed in the cortical areas under the electrodes. In conclusion, the cerebellum could represent a promising adjunctive target for tDCS interventions in patients with TRD, particularly for younger patients.

The Effect of Surgical Masks on the Featural and Configural Processing of Emotions.

From the start of the COVID-19 pandemic, the use of surgical masks became widespread. However, they occlude an important part of the face and make it difficult to decode and interpret other people's emotions. To clarify the effect of surgical masks on configural and featural processing, participants completed a facial emotion recognition task to discriminate between happy, sad, angry, and neutral faces. Stimuli included fully visible faces, masked faces, and a cropped photo of the eyes or mouth region. Occlusion due to the surgical mask affects emotion recognition for sadness, anger, and neutral faces, although no significative differences were found in happiness recognition. Our findings suggest that happiness is recognized predominantly via featural processing.

Cerebellar tDCS as Therapy for Cerebellar Ataxias.

In recent years, a growing body of literature has investigated the use of non-invasive brain stimulation (NIBS) techniques to influence cerebellar activity and the effects of cerebellar stimulation on other brain regions through its multiple complex projections. From the early 1990s, with the discovery of the so-called cerebellar inhibition (CBI), several studies have focused their attention on the use of cerebellar NIBS as treatment for different motor disorders. Cerebellar ataxias (CAs) represent the prototypical clinical manifestation of cerebellar alterations, but other movement disorders, such as Parkinson's disease, essential tremor, and dystonia have also been associated with alterations of networks which include the cerebellum, or of the cerebellum itself. Cerebellar transcranial direct current stimulation (ctDCS) could indeed represent an economical, non-invasive therapeutic tool with minimal side effects, thus improving the clinical management of patients and their quality of life. Studies show that ctDCS is effective as a therapeutic option for motor symptoms in patients with CAs, and especially in those with less severe forms, suggesting that ctDCS efficacy could result from augmented neuronal compensation, which itself relies on preserved cerebellar volume. Evidence for the efficacy of ctDCS is less conclusive for the other aforementioned motor disorders, although preliminary results are promising. Future studies should adopt more rigorous methods (e.g., larger sample sizes, double blinding, better characterization of the sample, reliable biomarkers), in order to allow the scientific community to derive higher-quality evidence on the efficacy of ctDCS as a therapeutic option for motor disorders.

Adaptive deep brain stimulation (aDBS).

Deep brain stimulation is an established technique for the treatment of movement disorders related to neurodegenerative diseases such as Parkinson's disease (PD) and essential tremor (ET). Its application seems also feasible for the treatment of neuropsychiatric disorders such as treatment resistant depression (TRD) and Tourette's syndrome (TS). In a typical deep brain stimulation system, the amount of current delivered to the patients is constant and regulated by the physician. Conversely, an adaptive deep brain stimulation system (aDBS) is a closed loop system that adjusts the stimulation parameters according to biomarkers which reflect the patient's clinical state. In this chapter, we examined the main issues related to aDBS systems, which are both clinical and technological in nature. From a clinical point of view, we have reported the major findings related to symptoms management using aDBS and principal findings in animal models, showing that the implementation of closed loop adaptive deep brain stimulation can ameliorate symptom management in neurodegenerative disorders. From the technological point of view, we reported the major advances related to aDBS system design and implementation, such as noise filtering methods, biomarkers recording and processing to adjust pulse delivery. To date, aDBS systems represent a major evolution in brain stimulation, further developments are needed to maximize the efficacy of this technique and to expand its use in a wide range of neuropsychiatric disorders.

Correspondence effect driven by salient visual asymmetries in integral object stimuli.

The handle-to-hand correspondence effect consists of faster and more accurate responses when the responding hand is aligned with the handle side of an object tool, compared to when they lay on opposite sides. This effect has been attributed to the activation of affordances. Recent studies, however, claimed that it may depend on the spatial coding of the object on the basis of its visual asymmetry (location-coding account). Affordances are namely direct and meaningful relations between recognized objects and the observers' action system. Therefore, any manipulation that disrupts the body structure of object tools could potentially affect their identification and prevent the activation of affordances. The present study investigated the nature of the handle-to-hand correspondence effects by manipulating structural asymmetry and visual salience of object tools, while preserving their integrity that is, leaving unaltered the original possibilities to activate grasping affordances. Three experiments were run. Results were consistent with the location-coding account and claim for accurate control of visual asymmetries in object stimuli during investigation of affordance effects.

Do already grasped objects activate motor affordances?

This study investigated whether in a stimulus-response compatibility (SRC) task affordance effects in response to picture of graspable objects emerge when these objects appear as already grasped. It also assessed whether the observed effects could be explained as due to spatial compatibility between the most salient part in the object/display and the hand of response rather than to action potentiation. To this aim, we conducted three behavioural experiments in which participants were required to discriminate the vertical orientation (upright vs. inverted) of an object presented in the centre of the screen, while ignoring the right-left orientation of its handle. The object could be presented alone, as already grasped, as partially masked (Experiment 1) or with a human hand close to its graspable side (Experiment 2). In addition, to assess the role of perceptual salience, the object could be presented with a human hand or a non-biological (a geometrical shape) distractor located opposite to the object's graspable side. Results showed faster responses when the object's handle was located on the same side of the responding hand with a larger effect when upright objects were shown as already grasped (Experiment 1) or when a hand was displayed close to its handle (Experiment 2), and a smaller reversed effect when the hand or the geometrical shape was located opposite to the handled side (Experiment 3). We interpreted these findings as indicating that handle orientation effects emerging in SRC tasks may result from the interplay between motor affordance and spatial compatibility mechanisms.