Neural Correlates of Semantic Interference and Phonological Facilitation in Picture Naming: A Systematic Review and Coordinate-Based Meta-analysis.

Semantic interference (SI) and phonological facilitation (PF) effects occur when multiple representations are co-activated simultaneously in complex naming paradigms, manipulating the context in which word production is set. Although the behavioral consequences of these psycholinguistic effects are well-known, the involved brain structures are still controversial. This paper aims to provide a systematic review and a coordinate-based meta-analysis of the available functional neuroimaging studies investigating SI and PF in picture naming paradigms. The included studies were fMRI experiments on healthy subjects, employing paradigms in which co-activations of representations were obtained by manipulating the naming context using semantically or phonologically related items. We examined the principal methodological aspects of the included studies, emphasizing the existing commonalities and discrepancies across single investigations. We then performed an exploratory coordinate-based meta-analysis of the reported activation peaks of neural response related to SI and PF. Our results consolidated previous findings regarding the involvement of the left inferior frontal gyrus and the left middle temporal gyrus in SI and brought out the role of bilateral inferior parietal regions in PF.

Neural alterations underlying executive dysfunction in Parkinson's disease: A systematic review and coordinate-based meta-analysis of functional neuroimaging studies.

Parkinson's Disease's (PD) neuropsychological profile is often characterized by altered performance in executive functions (EF) tasks, with a remarkable impact on patients' quality of life. To date, the available neuroimaging literature lacks conclusive evidence about neural patterns underlying EF deficits in PD. Here, we aimed to synthesize the results of PET/fMRI studies examining the differences in brain activation between PD patients and controls during EF tasks, focusing on the three main EF sub-components: cognitive flexibility, working memory, and response inhibition. We conducted a coordinate-based meta-analysis to assess the converging alterations in brain activity in PD patients compared to controls. We assessed the association between aberrant patterns of activity and the EF sub-domains. We found a significant association between hypoactivation patterns in PD converging at the level of the right inferior frontal gyrus in response inhibition tasks, whereas hypoactivation in the left inferior frontal gyrus was found in association with the cognitive flexibility domain. Our results confirm the existence of neural alterations in PD patients in relation to specific EF sub-domains.

Top-down reconfiguration of SMA cortical connectivity during action preparation.

The Bereitschaftspotential (BP), a scalp potential recorded in humans during action preparation, is characterized by a slow amplitude increase over fronto-central regions as action execution approaches. We recorded TMS evoked-potentials (TEP) stimulating the supplementary motor area (SMA) at different time-points during a Go/No-Go task to assess whether and how cortical excitability and connectivity of this region change as the BP increases. When approaching BP peak, left SMA reactivity resulted greater. Concurrently, its effective connectivity increased with the left occipital areas, while it decreased with the right inferior frontal gyrus, indicating a fast reconfiguration of cortical networks during the preparation of the forthcoming action. Functional connectivity patterns supported these findings, suggesting a critical role of frequency-specific inter-areal interactions in implementing top-down mechanisms in the sensorimotor system prior to action. These findings reveal that BP time-course reflects quantitative and qualitative changes in SMA communication patterns that shape mechanisms involved in motor readiness.

State-dependent effectiveness of cathodal transcranial direct current stimulation on cortical excitability.

The extensive use of transcranial direct current stimulation (tDCS) in experimental and clinical settings does not correspond to an in-depth understanding of its underlying neurophysiological mechanisms. In previous studies, we employed an integrated system of Transcranial Magnetic Stimulation and Electroencephalography (TMS-EEG) to track the effect of tDCS on cortical excitability. At rest, anodal tDCS (a-tDCS) over the right Posterior Parietal Cortex (rPPC) elicits a widespread increase in cortical excitability. In contrast, cathodal tDCS (c-tDCS) fails to modulate cortical excitability, being indistinguishable from sham stimulation. Here we investigated whether an endogenous task-induced activation during stimulation might change this pattern, improving c-tDCS effectiveness in modulating cortical excitability. In Experiment 1, we tested whether performance in a Visuospatial Working Memory Task (VWMT) and a modified Posner Cueing Task (mPCT), involving rPPC, could be modulated by c-tDCS. Thirty-eight participants were involved in a two-session experiment receiving either c-tDCS or sham during tasks execution. In Experiment 2, we recruited sixteen novel participants who performed the same paradigm but underwent TMS-EEG recordings pre- and 10 min post- sham stimulation and c-tDCS. Behavioral results showed that c-tDCS significantly modulated mPCT performance compared to sham. At a neurophysiological level, c-tDCS significantly reduced cortical excitability in a frontoparietal network likely involved in task execution. Taken together, our results provide evidence of the state dependence of c-tDCS in modulating cortical excitability effectively. The conceptual and applicative implications are discussed.

Inter-Individual Variability in tDCS Effects: A Narrative Review on the Contribution of Stable, Variable, and Contextual Factors.

Due to its safety, portability, and cheapness, transcranial direct current stimulation (tDCS) use largely increased in research and clinical settings. Despite tDCS's wide application, previous works pointed out inconsistent and low replicable results, sometimes leading to extreme conclusions about tDCS's ineffectiveness in modulating behavioral performance across cognitive domains. Traditionally, this variability has been linked to significant differences in the stimulation protocols across studies, including stimulation parameters, target regions, and electrodes montage. Here, we reviewed and discussed evidence of heterogeneity emerging at the intra-study level, namely inter-individual differences that may influence the response to tDCS within each study. This source of variability has been largely neglected by literature, being results mainly analyzed at the group level. Previous research, however, highlighted that only a half-or less-of studies' participants could be classified as responders, being affected by tDCS in the expected direction. Stable and variable inter-individual differences, such as morphological and genetic features vs. hormonal/exogenous substance consumption, partially account for this heterogeneity. Moreover, variability comes from experiments' contextual elements, such as participants' engagement/baseline capacity and individual task difficulty. We concluded that increasing knowledge on inter-dividual differences rather than undermining tDCS effectiveness could enhance protocols' efficiency and reproducibility.

Aftereffects to Prism Exposure without Adaptation: A Single Case Study.

Visuo-motor adaptation to optical prisms (Prism Adaptation, PA), displacing the visual scene laterally, is a behavioral method used for the experimental investigation of visuomotor plasticity, and, in clinical settings, for temporarily ameliorating and rehabilitating unilateral spatial neglect. This study investigated the building up of PA, and the presence of the typically occurring subsequent Aftereffects (AEs) in a brain-damaged patient (TMA), suffering from apperceptive agnosia and a right visual half-field defect, with bilateral atrophy of the parieto-occipital cortices, regions involved in PA and AEs. Base-Right prisms and control neutral lenses were used. PA was achieved by repeated pointing movements toward three types of stimuli: visual, auditory, and bimodal audio-visual. The presence and the magnitude of AEs were assessed by proprioceptive, visual, visuo-proprioceptive, and auditory-proprioceptive straight-ahead pointing tasks. The patient's brain connectivity was investigated by Diffusion Tensor Imaging (DTI). Unlike control participants, TMA did not show any adaptation to prism exposure, but her AEs were largely preserved. These findings indicate that AEs may occur even in the absence of PA, as indexed by the reduction of the pointing error, showing a dissociation between the classical measures of PA and AEs. In the PA process, error reduction, and its feedback, may be less central to the building up of AEs, than the sensorimotor pointing activity per se.

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.

Exploring the time-course and the reference frames of adaptation to optical prisms and its aftereffects.

Prism adaptation (PA) is used to investigate visuo-motor plasticity and to rehabilitate the syndrome of Unilateral Spatial Neglect (USN). After PA, participants show aftereffects (AEs), contralateral to the side of the optical displacement in several tasks. This study explored the features of these AEs, specifically the "egocentric" versus "allocentric, object-based", reference frames involved, and their time course. In three experiments, healthy participants adapted to prismatic lenses inducing a horizontal displacement of the visual field. In Experiment #1, participants adapted to rightward displacing prisms. Four tasks were used requiring repeated pointings towards the participant's subjective egocentric straight-ahead, with the availability of proprioceptive or visual-proprioceptive signals, and, in some conditions, of an external allocentric visual frame (i.e., a rectangular paper sheet). Experiment #2 explored the role of the position of the allocentric frame, with AEs being tested by straight-ahead and frame bisection tasks, requiring pointing toward the external visual frame, placed in different positions of the working space. An egocentric visual proprioceptive task was administered after prism removal and after the execution of the allocentric tasks, to assess the effectiveness of the PA, as indexed by the AEs, and their persistence up to the end of the administration of the allocentric tasks. Experiment #3 differed from #2 in that participants adapted to leftward displacing lenses. Consistent with evidence from USN patients, in Experiment #1, in the egocentric tasks, AEs lasting up to 30 min after PA were found. In Experiment #2, AEs in "allocentric" tasks did not occur, regardless of frame position. Experiment #3 showed AEs in both the "egocentric" and the "allocentric" tasks, with the latter being minor in size. These findings illustrate that the spatial reference systems modulated by PA in extra-personal space primarily operate in spatial "egocentric" reference frames, with a comparatively minor and direction-specific role of "allocentric" frames.

The role of the right posterior parietal cortex in prism adaptation and its aftereffects.

Adaptation to optical prisms (Prismatic Adaptation, PA) displacing the visual scene laterally, on one side of visual space, is both a procedure for investigating visuo-motor plasticity and a powerful tool for the rehabilitation of Unilateral Spatial Neglect (USN). Two processes are involved in PA: i) recalibration (the reduction of the error of manual pointings toward the direction of the prism-induced displacement of the visual scene); ii) the successive realignment after prisms' removal, indexed by the Aftereffects (AEs, in egocentric straight-ahead pointing tasks, the deviation in a direction opposite to the visual displacement previously induced by prisms). This study investigated the role of the posterior parietal cortex (PPC) of the right hemisphere in PA and AEs, by means of low frequency repetitive Transcranial Magnetic Stimulation (rTMS). Proprioceptive and Visuo-proprioceptive egocentric straight-ahead pointing tasks were used to assess the presence and magnitude of AEs. The primary right visual cortex (V1) was also stimulated, to assess the selectivity of the PPC effects on the two processes of PA (recalibration and realignment) in comparison with a cortical region involved in visual processing. Results showed a slower adaptation to prisms when rTMS was delivered before PA, regardless of target site (right PPC or V1). AEs were reduced only by PPC rTMS applied before or after PA, as compared to a sham stimulation. These findings suggest a functional and neural dissociation between realignment and recalibration. Indeed, PA interference was induced by rTMS to both the PPC and V1, indicating that recalibration is supported by a parieto-occipital network. Conversely, AEs were disrupted only by rTMS delivered to the PPC, thus unveiling a relevant role of this region in the development and maintenance of the realignment.

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.

The Role of the Left and Right Anterior Temporal Poles in People Naming and Recognition.

People's identity recognition and the neural correlates underlying this process are still a matter of debate. While neuropsychological reports on single cases show a crucial role of the left anterior temporal lobe (ATL) in proper naming, and of the right ATL in people's identification, reviews are less consistent. Moreover, it is still controversial whether familiarity and personal semantics access rely on amodal processes or follow modality-dependent paths. To disentangle these issues, we tested, in a parallel-group design, neurologically unimpaired subjects in two famous people recognition tasks after anodal tDCS over the left or right ATL or after a placebo stimulation condition. In the famous people recognition task, subjects were presented with visual (face recognition) or auditory (voice recognition) stimuli and subjects had to judge whether stimuli belonged to a famous or non-famous person (familiarity test); then, if the stimulus was recognized as famous, participants had to provide personal semantic information about the character; finally, to investigate proper naming, subjects were asked to name the famous person. While right ATL anodal tDCS increased accuracy in famous faces (but not voices) judgment and personal semantics retrieval, left ATL stimulation increased proper naming for both visual and auditory stimuli. Our data support a key role of the right ATL in famous people recognition and access to personal semantics from visual inputs, while the left ATL seems crucial for proper naming, which seems to occur at a later stage, when presentation modality no longer affects the process.

Pearls and pitfalls in brain functional analysis by event-related potentials: a narrative review by the Italian Psychophysiology and Cognitive Neuroscience Society on methodological limits and clinical reliability-part I.

Event-related potentials (ERPs) are obtained from the electroencephalogram (EEG) or the magnetoencephalogram (MEG, event-related fields (ERF)), extracting the activity that is time-locked to an event. Despite the potential utility of ERP/ERF in cognitive domain, the clinical standardization of their use is presently undefined for most of procedures. The aim of the present review is to establish limits and reliability of ERP medical application, summarize main methodological issues, and present evidence of clinical application and future improvement. The present section of the review focuses on well-standardized ERP methods, including P300, Contingent Negative Variation (CNV), Mismatch Negativity (MMN), and N400, with a chapter dedicated to laser-evoked potentials (LEPs). One section is dedicated to proactive preparatory brain activity as the Bereitschaftspotential and the prefrontal negativity (BP and pN). The P300 and the MMN potentials have a limited but recognized role in the diagnosis of cognitive impairment and consciousness disorders. LEPs have a well-documented usefulness in the diagnosis of neuropathic pain, with low application in clinical assessment of psychophysiological basis of pain. The other ERP components mentioned here, though largely applied in normal and pathological cases and well standardized, are still confined to the research field. CNV, BP, and pN deserve to be largely tested in movement disorders, just to explain possible functional changes in motor preparation circuits subtending different clinical pictures and responses to treatments.

The neural correlates of auditory-verbal short-term memory: a voxel-based lesion-symptom mapping study on 103 patients after glioma removal.

The relationship between verbal-auditory short-term memory (STM) and language is an open area of debate and contrasting hypotheses have been proposed, suggesting either that STM would strongly rely on language-related processes, or that it depends on a dedicated system related to language, but independent from it. In this study we examined 103 patients undergoing surgery for glioma resection in the left or right hemisphere, and we conducted a VLSM analysis on their behavioral performance on auditory-verbal STM, as well as on more general verbal and nonverbal tasks. The aim was to investigate whether the anatomical correlates of auditory-verbal STM were part of the language system or they were spatially segregated from it. VLSM results showed that digit span scores were linked to lesions in both the left supramarginal gyrus and superior-posterior temporal areas, as reported in the literature on patients with a selective deficit of auditory-verbal STM. Conversely, other verbal tasks involved areas only partly overlapping with those found for digit span, with repetition being affected by lesions in more anterior regions in the parietal, temporal, and frontal lobes, and word comprehension by lesions in a network including cortical and subcortical pathways in the temporal lobe. The present results, thus, show that auditory-verbal STM neural correlates are only partially overlapping with those supporting comprehension and production: while the left posterior-superior temporal cortex, involved in speech perception, takes part in both functions, the left supramarginal gyrus has a consistent and specific role only in STM, supporting the hypothesis of interacting but segregated networks.

Somatosensory cortical representation of the body size.

The knowledge of the size of our own body parts is essential for accurately moving in space and efficiently interact with objects. A distorted perceptual representation of the body size often represents a core diagnostic criterion for some psychopathological conditions. The metric representation of the body was shown to depend on somatosensory afferences: local deafferentation indeed causes a perceptual distortion of the size of the anesthetized body part. A specular effect can be induced by altering the cortical map of body parts in the primary somatosensory cortex. Indeed, the present study demonstrates, in healthy adult participants, that repetitive Transcranial Magnetic Stimulation to the somatosensory cortical map of the hand in both hemispheres causes a perceptual distortion (i.e., an overestimation) of the size of the participants' own hand (Experiments 1-3), which does not involve other body parts (i.e., the foot, Experiment 2). Instead, the stimulation of the inferior parietal lobule of both hemispheres does not affect the perception of the own body size (Experiment 4). These results highlight the role of the primary somatosensory cortex in the building up and updating of the metric of body parts: somatosensory cortical activity not only shapes our somatosensation, it also affects how we perceive the dimension of our body.

Keeping order in the brain: The supramarginal gyrus and serial order in short-term memory.

A wide range of human activities are performed sequentially in few seconds. We need to maintain a correct temporal order of words in language, movements in actions, directions in navigation, etc. Therefore, it is plausible, in a more economical perspective, that our brain is equipped with a dedicated mechanism for storing a temporal sequence for a short time. To investigate it, we run four TMS experiments, in which participants performed different short-term memory tasks, i.e., three (verbal, spatial, motor) requiring maintenance of an ordered sequence and one (visual) of a static pattern. We demonstrated, for the first time, that the left supramarginal gyrus is one of the key nodes of the STM network involved in retaining an abstract representation of serial order information, independently from the content information, namely the nature of the item to be remembered, which instead is stored separately.

TMS-EEG approach unveils brain mechanisms underlying conscious and unconscious face perception.

BACKGROUND: Conscious perception of external stimuli has been related to recurrent activity in distributed cortical networks, although brain mechanisms controlling unconscious processing and stimuli access to conscious report need to be clarified. OBJECTIVE: This study aims at investigating modulations in cortical excitability related to conscious perception and unconscious processing of face stimuli with different visibility levels. METHODS: We used TMS-EEG over the right occipital face area (rOFA), or the right premotor cortex (rPMC) as control site, to measure cortical excitability during a backward masking paradigm with individually defined stimuli visibility. RESULTS: Event related potentials showed significant differences for faces compared to houses, and detected faces compared to missed ones, 200 ms post target onset. TMS over rOFA, but not over rPMC, triggered a relative positivity starting 150 ms post target when faces with high visibility were consciously reported. Moreover, rOFA TMS evoked differential responses for high versus low visible faces in conscious and unconscious processing at 290-390 and 180-240 ms, respectively. CONCLUSION: Results unveiled a causal link between rOFA excitability and late responses related to access to conscious perception, suggesting a critical role of recurrent activity, but distinct components, for consciously perceived stimuli and unconscious face processing.

Consequences of brain tumour resection on emotion recognition.

Emotion processing impairments are common in patients undergoing brain surgery for fronto-temporal tumour resection, with potential consequences on social interactions. However, evidence is controversial concerning side and site of lesions causing such deficits. This study investigates visual and auditory emotion recognition in brain tumour patients with the aim of clarifying which lesion sites are related to impairments in emotion processing from different modalities. Thirty-four patients were evaluated, before and after surgery, on facial expression and emotional prosody recognition; voxel-based lesion-symptom mapping (VLSM) analyses were performed on patients' post-surgery MRI images. Results showed that patients' performance decreased after surgery in both visual and auditory modalities, but, in general, recovered 3 months after surgery. In facial expression recognition, left brain-damaged patients showed greater post-surgery deterioration than right brain-damaged ones, whose performance specifically decreased for sadness and fear. VLSM analysis revealed two segregated areas in the left hemisphere accounting for post-surgery scores for happy (fronto-temporo-insular region) and surprised (middle frontal gyrus and inferior fronto-occipital fasciculus) facial expressions. Our findings demonstrate that surgical removal of tumours in the fronto-temporal region produces impairment in facial emotion recognition with an overall recovery at 3 months, suggesting a partially different representation of positive and negative emotions in the left and right hemispheres for visually - but not auditory - presented emotions; moreover, we show that deficits in specific expression recognition are associated with discrete lesion locations.

Selective changes in moral judgment by noninvasive brain stimulation of the medial prefrontal cortex.

Multiple cortical networks intervene in moral judgment, among which the dorsolateral prefrontal cortex (DLPFC) and the medial prefrontal structures (medial PFC) emerged as two major territories, which have been traditionally attributed, respectively, to cognitive control and affective reactions. However, some recent theoretical and empirical accounts disputed this dualistic approach to moral evaluation. In the present study, to further assess the functional contribution of the medial PFC in moral judgment, we modulated its cortical excitability by means of transcranial direct current stimulation (tDCS) and tracked the change in response to different types of moral dilemmas, including switch-like and footbridge-like moral dilemmas, with and without personal involvement. One hundred participants (50 males) completed a questionnaire to assess the baseline levels of deontology. Next, participants were randomly assigned to receive anodal, sham, or cathodal tDCS over the medial prefrontal structures and then were asked to address a series of dilemmas. The results showed that participants who received anodal stimulation over the medial PFC provided more utilitarian responses to switch-like (but not footbridge-like) dilemmas than those who received cathodal tDCS. We also found that neurostimulation modulated the influence that deontology has on moral choices. Specifically, in the anodal tDCS group, participants' decisions were less likely to be influenced by their baseline levels of deontology compared with the sham or cathodal groups. Overall, our results seem to refute a functional role of the medial prefrontal structures purely restricted to affective reactions for moral dilemmas, providing new insights on the functional contribution of the medial PFC in moral judgment.

Modulation of negative emotions through anodal tDCS over the right ventrolateral prefrontal cortex.

Increasing evidence suggests that the right ventrolateral prefrontal cortex (rVLPFC) plays a critical role in emotion regulation, in particular concerning negative feelings. In the present research, we applied anodal transcranial direct current stimulation (tDCS) over the rVLPFC with a twofold purpose. First, we aimed at exploring the feasibility of modulating the subjective experience of emotions through tDCS in healthy participants. Second, we wanted to assess which specific emotion can be regulated (and which cannot) with this brain stimulation approach. We designed a double-blind, between-subjects, sham-controlled study in which 96 participants watched short video clips eliciting different emotions during anodal or sham tDCS over the rVLPFC. Emotional reactions to each video clip were assessed with self-report scales measuring eight basic emotions. Results showed that, in contrast to the sham condition, tDCS over the rVLPFC reduced the perceived extent of specific negative emotions, namely, fear, anxiety, and sadness, compared to other negative or positive feelings. Overall, these results support the role of rVLPFC in regulating negative emotions, mostly associated with the prevention of dangerous situations (i.e., fear, anxiety, and sadness).