Multimodal approaches supporting the diagnosis, prognosis and investigation of neural correlates of disorders of consciousness: A systematic review.

The limits of the standard, behaviour-based clinical assessment of patients with disorders of consciousness (DoC) prompted the employment of functional neuroimaging, neurometabolic, neurophysiological and neurostimulation techniques, to detect brain-based covert markers of awareness. However, uni-modal approaches, consisting in employing just one of those techniques, are usually not sufficient to provide an exhaustive exploration of the neural underpinnings of residual awareness. This systematic review aimed at collecting the evidence from studies employing a multimodal approach, that is, combining more instruments to complement DoC diagnosis, prognosis and better investigating their neural correlates. Following the PRISMA guidelines, records from PubMed, EMBASE and Scopus were screened to select peer-review original articles in which a multi-modal approach was used for the assessment of adult patients with a diagnosis of DoC. Ninety-two observational studies and 32 case reports or case series met the inclusion criteria. Results highlighted a diagnostic and prognostic advantage of multi-modal approaches that involve electroencephalography-based (EEG-based) measurements together with neuroimaging or neurometabolic data or with neurostimulation. Multimodal assessment deepened the knowledge on the neural networks underlying consciousness, by showing correlations between the integrity of the default mode network and the different clinical diagnosis of DoC. However, except for studies using transcranial magnetic stimulation combined with electroencephalography, the integration of more than one technique in most of the cases occurs without an a priori-designed multi-modal diagnostic approach. Our review supports the feasibility and underlines the advantages of a multimodal approach for the diagnosis, prognosis and for the investigation of neural correlates of DoCs.

Technologies for frailty, comorbidity, and multimorbidity in older adults: a systematic review of research designs.

BACKGROUND: Frailty, neurodegeneration and geriatric syndromes cause a significant impact at the clinical, social, and economic level, mainly in the context of the aging world. Recently, Information and Communication Technologies (ICTs), virtual reality tools, and machine learning models have been increasingly applied to the care of older patients to improve diagnosis, prognosis, and interventions. However, so far, the methodological limitations of studies in this field have prevented to generalize data to real-word. This review systematically overviews the research designs used by studies applying technologies for the assessment and treatment of aging-related syndromes in older people. METHODS: Following the PRISMA guidelines, records from PubMed, EMBASE, and Web of Science were systematically screened to select original articles in which interventional or observational designs were used to study technologies' applications in samples of frail, comorbid, or multimorbid patients. RESULTS: Thirty-four articles met the inclusion criteria. Most of the studies used diagnostic accuracy designs to test assessment procedures or retrospective cohort designs to build predictive models. A minority were randomized or non-randomized interventional studies. Quality evaluation revealed a high risk of bias for observational studies, while a low risk of bias for interventional studies. CONCLUSIONS: The majority of the reviewed articles use an observational design mainly to study diagnostic procedures and suffer from a high risk of bias. The scarce presence of methodologically robust interventional studies may suggest that the field is in its infancy. Methodological considerations will be presented on how to standardize procedures and research quality in this field.

Betting on Non-Invasive Brain Stimulation to Treat Gambling Disorder: A Systematic Review and Meta-Analysis.

Gambling disorder (GD) is a behavioral addiction that severely impacts individuals' functioning, leading to high socioeconomic costs. Non-invasive brain stimulation (NiBS) has received attention for treating psychiatric and neurological conditions in recent decades, but there is no recommendation for its use for GD. Therefore, this study aimed to systematically review and analyze the available literature to determine the effectiveness of NiBS in treating GD. Following the PRISMA guidelines, we screened four electronic databases up to July 2022 and selected relevant English-written original articles. We included ten papers in the systematic review and seven in the meta-analysis. As only two studies employed a sham-controlled design, the pre-post standardized mean change (SMCC) was computed as effect size only for real stimulation. The results showed a significant effect of NiBS in reducing craving scores (SMCC = -0.69; 95% CI = [-1.2, -0.2], p = 0.010). Moreover, considering the GD's frequent comorbidity with mood disorders, we ran an exploratory analysis of the effects of NiBS on depressive symptoms, which showed significant decreases in post-treatment scores (SMCC = -0.71; 95% CI = [-1.1, -0.3], p < 0.001). These results provide initial evidence for developing NiBS as a feasible therapy for GD symptoms but further comprehensive research is needed to validate these findings. The limitations of the available literature are critically discussed.

Signs and symptoms method in neuropsychology: A standardized observational examination of cognitive functions can be effective in detecting mild cognitive impairment.

OBJECTIVE: The present study aimed at investigating the sensitivity and specificity of the NeuroPsychological Examination (NPE), a systematic collection of cognitive signs and symptoms based on the observation of the patient's behavior during a clinical interview, in detecting Mild Cognitive Impairment (MCI). METHOD: 475 participants, 208 suffering from MCI, 188 suffering from dementia and 79 subjective cognitive decline (SCD), have been assessed using NPE for the presence of signs and symptoms of cognitive impairment. Receiver operating characteristic (ROC) curve analysis and the Youden's test were used to determine the more appropriate cutoff points for the number of neuropsychological signs at the NPE that enabled to discriminate SCD from MCI, SCD from dementia and MCI from dementia. A sensitivity and specificity analysis and comparisons among the three groups were conducted. RESULTS: The mean number of signs at the NPE were 1.73 for SCD, 7.98 for MCI and 12.82 for dementia. Pairwise comparisons among the three group of participants showed significant differences (SCD vs. MCI, p < .001, r = -0.66; SCD vs. dementia, p < .001, r = -0.76; MCI vs. dementia, p < .001, r = -0.44). The criterion of 3 signs at the NPE showed a sensitivity of 0.95 (95% CI [0.91, 0.97]) and a specificity of 0.76 (95% CI [0.65, 0.84]) in discriminating SCD from MCI participants. CONCLUSIONS: A signs and symptoms approach could be a useful tool for clinical neuropsychologists working in the field of MCI and dementia assessment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Diencephalic versus Hippocampal Amnesia in Alzheimer's Disease: The Possible Confabulation-Misidentification Phenotype.

BACKGROUND: Alzheimer's disease (AD) is clinically heterogeneous, including the classical-amnesic (CA-) phenotype and some variants. OBJECTIVE: We aim to describe a further presentation we (re)named confabulation-misidentification (CM-) phenotype. METHODS: We performed a retrospective longitudinal case-series study of 17 AD outpatients with the possible CM-phenotype (CM-ADs). Then, in a cross-sectional study, we compared the CM-ADs to a sample of 30 AD patients with the CA-phenotype (CA-ADs). The primary outcome was the frequency of cognitive and behavioral features. Data were analyzed as differences in percentage by non-parametric Chi Square and mean differences by parametric T-test. RESULTS: Anterograde amnesia (100%) with early confabulation (88.2%), disorientation (88.2%) and non-infrequently retrograde amnesia (64.7%) associated with reduced insight (88.2%), moderate prefrontal executive impairment (94.1%) and attention deficits (82.3%) dominated the CM-phenotype. Neuropsychiatric features with striking misidentification (52.9%), other less-structured delusions (70.6%), and brief hallucinations (64.7%) were present. Marked behavioral disturbances were present early in some patients and very common at later stages. At the baseline, the CM-ADs showed more confabulation (p < 0.001), temporal disorientation (p < 0.02), misidentification (p = 0.013), other delusions (p = 0.002), and logorrhea (p = 0.004) than the CA-ADs. In addition, more social disinhibition (p = 0.018), reduction of insight (p = 0.029), and hallucination (p = 0.03) persisted at 12 months from baseline. Both the CA- and CM-ADs showed anterior and medial temporal atrophy. Compared to HCs, the CM-ADs showed more right fronto-insular atrophy, while the CA-ADs showed more dorsal parietal, precuneus, and right parietal atrophy. CONCLUSION: We described an AD phenotype resembling diencephalic rather than hippocampal amnesia and overlapping the past-century description of presbyophrenia.

Effectiveness of noninvasive brain stimulation in the treatment of anxiety disorders: a meta-analysis of sham or behaviour-controlled studies.

BACKGROUND: The possibility of using noninvasive brain stimulation to treat mental disorders has received considerable attention recently. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are considered to be effective treatments for depressive symptoms. However, no treatment recommendation is currently available for anxiety disorders, suggesting that evidence is still limited. We conducted a systematic review of the literature and a quantitative analysis of the effectiveness of rTMS and tDCS in the treatment of anxiety disorders. METHODS: Following PRISMA guidelines, we screened 3 electronic databases up to the end of February 2020 for English-language, peer-reviewed articles that included the following: a clinical sample of patients with an anxiety disorder, the use of a noninvasive brain stimulation technique, the inclusion of a control condition, and pre/post scores on a validated questionnaire that measured symptoms of anxiety. RESULTS: Eleven papers met the inclusion criteria, comprising 154 participants assigned to a stimulation condition and 164 to a sham or control group. We calculated Hedge's g for scores on disorder-specific and general anxiety questionnaires before and after treatment to determine effect size, and we conducted 2 independent random-effects meta-analyses. Considering the well-known comorbidity between anxiety and depression, we ran a third meta-analysis analyzing outcomes for depression scores. Results showed a significant effect of noninvasive brain stimulation in reducing scores on disorder-specific and general anxiety questionnaires, as well as depressive symptoms, in the real stimulation compared to the control condition. LIMITATIONS: Few studies met the inclusion criteria; more evidence is needed to strengthen conclusions about the effectiveness of noninvasive brain stimulation in the treatment of anxiety disorders. CONCLUSION: Our findings showed that noninvasive brain stimulation reduced anxiety and depression scores compared to control conditions, suggesting that it can alleviate clinical symptoms in patients with anxiety disorders.

ICT technologies as new promising tools for the managing of frailty: a systematic review.

OBJECTIVES: Frailty is a major health issue as it encompasses functional decline, physical dependence, and increased mortality risk. Recent studies explored Information and Communication Technology (ICT) interventions as alternatives to manage frailty in older persons. The aim of the present systematic review was to synthesize current evidence on ICT application within the complex models of frailty care in older people. METHODS: Data sources included PubMed, PsycINFO, EMBASE and Web of Science, considering eligible those reviews on ICT application in samples of older persons formally assessed as frail. Records were screened by two independent researchers, who extracted data and appraised methodological quality of reviews and studies. RESULTS: Among the 764 retrieved papers, two systematic reviews were included. Most of the studies analyzed defined frailty considering only few components of the phenotype and used ICT to stratify different levels of frailty or to support traditional screening strategies. Assessment of frailty was the context in which ICT has been mostly tested as compared to intervention. Cost effectiveness evaluations of the ICT technologies were not reported. CONCLUSIONS: The research investigating the use of ICT in the context of frailty is still at the very beginning. Few studies strictly focused on the assessment of frailty, while intervention on frailty using ICT was rarely reported. The lack of a proper characterization of the frail condition along with the methodological limitations prevented the investigation of ICT within complex care models. Future studies are needed to effectively integrate ICT in the care of frailty in orders.

A Systematic Review Of Implicit Attitudes And Their Neural Correlates In Eating Behaviour.

An increasing number of studies suggests that implicit attitudes toward food and body shape predict eating behaviour and characterize patients with eating disorders (EDs). However, literature has not been previously analysed, thus differences between patients with EDs and healthy controls and the level of automaticity of the processes involved in implicit attitudes are still matters of debate. The present systematic review aimed to synthetize current evidence from papers investigating implicit attitudes towards food and body in healthy and EDs populations. PubMed, EMBASE (Ovid), PsycINFO, Web of Science and Scopus were systematically screened and 183 studies using different indirect paradigms were included in the qualitative analysis. The majority of studies reported negative attitudes towards overweight/obese body images in healthy and EDs samples and weight bias as a diffuse stereotypical evaluation. Implicit food attitudes are consistently reported as valid predictors of eating behaviour. Few studies on the neurobiological correlates showed neurostimulation effects on implicit attitudes, but the automaticity at brain level of implicit evaluations remains an open area of research. In conclusion, implicit attitudes are relevant measures of eating behaviour in healthy and clinical settings, although evidence about their neural correlates is limited.

Usability Issues of Clinical and Research Applications of Virtual Reality in Older People: A Systematic Review.

Aging is a condition that may be characterized by a decline in physical, sensory, and mental capacities, while increased morbidity and multimorbidity may be associated with disability. A wide range of clinical conditions (e.g., frailty, mild cognitive impairment, metabolic syndrome) and age-related diseases (e.g., Alzheimer's and Parkinson's disease, cancer, sarcopenia, cardiovascular and respiratory diseases) affect older people. Virtual reality (VR) is a novel and promising tool for assessment and rehabilitation in older people. Usability is a crucial factor that must be considered when designing virtual systems for medicine. We conducted a systematic review with Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines concerning the usability of VR clinical systems in aging and provided suggestions to structure usability piloting. Findings show that different populations of older people have been recruited to mainly assess usability of non-immersive VR, with particular attention paid to motor/physical rehabilitation. Mixed approach (qualitative and quantitative tools together) is the preferred methodology; technology acceptance models are the most applied theoretical frameworks, however senior adapted models are the best within this context. Despite minor interaction issues and bugs, virtual systems are rated as usable and feasible. We encourage usability and user experience pilot studies to ameliorate interaction and improve acceptance and use of VR clinical applications in older people with the aid of suggestions (VR-USOP) provided by our analysis.

Stimulating the ventrolateral prefrontal cortex (VLPFC) modulates frustration-induced aggression: A tDCS experiment.

BACKGROUND: The prefrontal cortex is crucial for top-down regulation of aggression, but the neural underpinnings of aggression are still poorly understood. Past research showed the transcranial direct current stimulation (tDCS) over the ventrolateral prefrontal cortex (VLPFC) modulates aggression following exposure to risk factors for aggression (e.g., social exclusion, violent media). Although frustration is a key risk factor for aggression, no study to date has examined the modulatory role of tDCS on frustration-induced aggression. OBJECTIVES: By exploring the VLPFC involvement in frustration-aggression link, we tested the hypothesis that the anodal tDCS over right and left VLPFC modulates frustration-induced aggression. We also explored whether tDCS interacts with gender to influence frustration-induced aggression. METHODS: 90 healthy participants (45 men) were randomly assigned to receive anodal or sham tDCS over the right or left VLPFC before being frustrated by an accomplice. To increase reliability, several tasks were used to measure aggression. RESULTS: We found that anodal tDCS over the left VLPFC, compared to sham stimulation, increased aggression. Unexpectedly, no main effect was found following tDCS of right VLPFC. However, we also found a significant interaction between gender and tDCS, showing that males were more aggressive than females following sham stimulation, but females became as aggressive as males following active tDCS. CONCLUSION: Overall, these results shed light on the neural basis of frustration-induced aggression, providing further evidence for the involvement of VLPFC in modulating aggressive responses, and on gender differences in aggression. Future research should further investigate the role of stimulating the VLPFC on frustration-induced aggression.

The role of ventromedial prefrontal cortex and temporo-parietal junction in third-party punishment behavior.

Third parties punish, sacrificing personal interests, offenders who violate either fairness or cooperation norms. This behavior is defined altruistic punishment and the degree of punishment typically increases with the severity of the norm violation. An opposite and apparently paradoxical behavior, namely anti-social punishment, is the tendency to spend own money to punish cooperative or fair behaviors. Previous fMRI studies correlated punishment behavior with increased activation of brain areas belonging to the reward system (e.g. the ventromedial prefrontal cortex, VMPFC), the mentalizing (e.g. the temporoparietal junction, TPJ) and central-executive networks. In the present study, we aimed at investigating the causal role of VMPFC and TPJ in punishment behaviors through the application of anodal transcranial direct current stimulation (tDCS). Sixty healthy participants were randomly assigned to three tDCS conditions: (1) anodal tDCS over VMPFC, (2) anodal tDCS over right TPJ (rTPJ), (3) sham stimulation. At the end of the stimulation, participants played a third-party punishment game, consisting in viewing a series of fair or unfair monetary allocations between unknown proposers and recipients. Participants were asked whether and how much they would punish the proposers using their own monetary endowment. To test membership effects, proposers and recipients could be either Italian or Chinese. Anodal tDCS over VMPFC increased altruistic punishment behavior whereas anodal tDCS over rTPJ increased anti-social punishment choices compared with sham condition, while membership did not influence participant's choices. Our results support the idea that the two types of punishment behaviors rely upon different brain regions, suggesting that reward and mentalizing systems underlie, respectively, altruistic and anti-social punishment behaviors.

Transcranial direct current stimulation modulates implicit attitudes towards food in eating disorders.

OBJECTIVE: Neuromodulation of regions involved in food processing is increasingly used in studies on eating behaviors, but results are controversial. We assessed the effects of anodal transcranial direct current stimulation (a-tDCS) on food and body implicit preferences in patients with eating disorders (EDs). METHOD: Thirty-six ED patients and 36 healthy females completed three sessions with a-tDCS applied to the medial-prefrontal cortex (mPFC), the right extrastriate body area (rEBA) or in sham mode. Each participant then completed three Implicit Association Tests (IATs) on tasty/tasteless food, underweight/overweight body images, flowers versus insects as control. Differences in latency between incongruent and congruent blocks were calculated (D score). RESULTS: The tDCS by group interaction was significant for the IAT-food D score, with patients showing weaker preference for tasty food than controls in sham, but not a-tDCS sessions. In particular, rEBA stimulation significantly increased patients' D score compared to sham. Moreover, a-tDCS over mPFC and rEBA selectively increased patients' reaction times in the incongruent blocks of the IAT-food. DISCUSSION: A-tDCS on frontal and occipito-temporal cortices modulated food preferences in ED patients. The effect was specific for food images and selective in patients, but not in healthy participants. These findings suggest that neuromodulation of these regions could affect implicit food attitudes.

Transcranial direct current stimulation to prevent and treat surgery-induced opioid dependence: a systematic review.

Opioid misuse leading to dependence is a major health issue. Recent studies explored valid alternatives to treat pain in postsurgical settings. This systematic review aims to discuss the role of transcranial direct current stimulation (tDCS) in preventing and treating postoperative pain and opioid dependence. PubMed and Embase databases were screened, considering studies testing tDCS effects on pain and opioid consumption in surgical settings and opioid addiction. Eight studies met our inclusion criteria. Results showed a reduction of postoperative pain, opioid consumption and cue-induced craving following cortical stimulation. Despite the limited number of studies, this review shows preliminary encouraging evidence regarding the analgesic role of tDCS. However, future studies are needed to further investigate the application of tDCS in postsurgical settings.

Tracking the Effect of Cathodal Transcranial Direct Current Stimulation on Cortical Excitability and Connectivity by Means of TMS-EEG.

Transcranial direct current stimulation (tDCS) is increasingly used in both research and therapeutic settings, but its precise mechanisms remain largely unknown. At a neuronal level, tDCS modulates cortical excitability by shifting the resting membrane potential in a polarity-dependent way: anodal stimulation increases the spontaneous firing rate, while cathodal decreases it. However, the neurophysiological underpinnings of anodal/cathodal tDCS seem to be different, as well as their behavioral effect, in particular when high order areas are involved, compared to when motor or sensory brain areas are targeted. Previously, we investigated the effect of anodal tDCS on cortical excitability, by means of a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Results showed a diffuse rise of cortical excitability in a bilateral fronto-parietal network. In the present study, we tested, with the same paradigm, the effect of cathodal tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 10 min of cathodal or sham tDCS over the right PPC, while recording HD-EEG. Indexes of global and local cortical excitability were obtained both at sensors and cortical sources level. At sensors, global and local mean field power (GMFP and LMFP) were computed for three temporal windows (0-50, 50-100, and 100-150 ms), on all channels (GMFP), and in four different clusters of electrodes (LMFP, left and right, in frontal and parietal regions). After source reconstruction, Significant Current Density was computed at the global level, and for four Broadmann's areas (left/right BA 6 and 7). Both sensors and cortical sources results converge in showing no differences during and after cathodal tDCS compared to pre-stimulation sessions, both at global and local level. The same holds for sham tDCS. These data highlight an asymmetric impact of anodal and cathodal stimulation on cortical excitability, with a diffuse effect of anodal and no effect of cathodal tDCS over the parietal cortex. These results are consistent with the current literature: while anodal-excitatory and cathodal-inhibitory effects are well-established in the sensory and motor domains, both at physiological and behavioral levels, results for cathodal stimulation are more controversial for modulation of exitability of higher order areas.

Stimulating Self-Regulation: A Review of Non-invasive Brain Stimulation Studies of Goal-Directed Behavior.

Self-regulation enables individuals to guide their thoughts, feelings, and behaviors in a purposeful manner. Self-regulation is thus crucial for goal-directed behavior and contributes to many consequential outcomes in life including physical health, psychological well-being, ethical decision making, and strong interpersonal relationships. Neuroscientific research has revealed that the prefrontal cortex plays a central role in self-regulation, specifically by exerting top-down control over subcortical regions involved in reward (e.g., striatum) and emotion (e.g., amygdala). To orient readers, we first offer a methodological overview of tDCS and then review experiments using non-invasive brain stimulation techniques (especially transcranial direct current stimulation) to target prefrontal brain regions implicated in self-regulation. We focus on brain stimulation studies of self-regulatory behavior across three broad domains of response: persistence, delay behavior, and impulse control. We suggest that stimulating the prefrontal cortex promotes successful self-regulation by altering the balance in activity between the prefrontal cortex and subcortical regions involved in emotion and reward processing.