Transcranial electrical stimulation modulates emotional experience and metabolites in the prefrontal cortex in a donation task.

Understanding the neural, metabolic, and psychological mechanisms underlying human altruism and decision-making is a complex and important topic both for science and society. Here, we investigated whether transcranial Direct Current Stimulation (tDCS) applied to two prefrontal cortex regions, the ventromedial prefrontal cortex (vmPFC, anode) and the right dorsolateral prefrontal cortex (DLPFC, cathode) can induce changes in self-reported emotions and to modulate local metabolite concentrations. We employed in vivo quantitative MR Spectroscopy in healthy adult participants and quantified changes in GABA and Glx (glutamate + glutamine) before and after five sessions of tDCS delivered at 2 mA for 20 min (active group) and 1 min (sham group) while participants were engaged in a charitable donation task. In the active group, we observed increased levels of GABA in vmPFC. Glx levels decreased in both prefrontal regions and self-reported happiness increased significantly over time in the active group. Self-reported guiltiness in both active and sham groups tended to decrease. The results indicate that self-reported happiness can be modulated, possibly due to changes in Glx concentrations following repeated stimulation. Therefore, local changes may induce remote changes in the reward network through interactions with other metabolites, previously thought to be unreachable with noninvasive stimulation techniques.

Bridging phenomenology and neural mechanisms of inner speech: ALE meta-analysis on egocentricity and spontaneity in a dual-mechanistic framework.

The neural mechanisms of inner speech remain unclear despite its importance in a variety of cognitive processes and its implication in aberrant perceptions such as auditory verbal hallucinations. Previous research has proposed a corollary discharge model in which inner speech is a truncated form of overt speech, relying on speech production-related regions (e.g. left inferior frontal gyrus). This model does not fully capture the diverse phenomenology of inner speech and recent research suggesting alternative perception-related mechanisms of generation. Therefore, we present and test a framework in which inner speech can be generated by two separate mechanisms, depending on its phenomenological qualities: a corollary discharge mechanism relying on speech production regions and a perceptual simulation mechanism within speech perceptual regions. The results of the activation likelihood estimation meta-analysis examining inner speech studies support the idea that varieties of inner speech recruit different neural mechanisms.

Aberrant oscillatory activity in neurofibromatosis type 1: an EEG study of resting state and working memory.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic neurodevelopmental disorder commonly associated with impaired cognitive function. Despite the well-explored functional roles of neural oscillations in neurotypical populations, only a limited number of studies have investigated oscillatory activity in the NF1 population. METHODS: We compared oscillatory spectral power and theta phase coherence in a paediatric sample with NF1 (N = 16; mean age: 13.03 years; female: n = 7) to an age/sex-matched typically developing control group (N = 16; mean age: 13.34 years; female: n = 7) using electroencephalography measured during rest and during working memory task performance. RESULTS: Relative to typically developing children, the NF1 group displayed higher resting state slow wave power and a lower peak alpha frequency. Moreover, higher theta power and frontoparietal theta phase coherence were observed in the NF1 group during working memory task performance, but these differences disappeared when controlling for baseline (resting state) activity. CONCLUSIONS: Overall, results suggest that NF1 is characterised by aberrant resting state oscillatory activity that may contribute towards the cognitive impairments experienced in this population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03310996 (first posted: October 16, 2017).

Experimental investigation of training schedule on home-based working memory training in healthy older adults.

Introduction: The efficacy of working memory training (WMT) for cognitive enhancement in healthy older adults has been extensively investigated. Typically, WMT results in improved performance on the training task, but limited or no transfer of improvement to other cognitive tasks. Accordingly, there is a need to identify optimal intervention parameters to maximize training and transfer task effects of WMT. The current study aimed to investigate the effect of training schedule on training and transfer task performance of WMT in healthy older adults. A secondary aim was to examine the feasibility of participants performing the intervention online at home, unsupervised, and using their personal devices. Methods: Participants (N = 71; mean age: 66 years) completed sixteen WMT or active-control sessions over eight (distributed) or four (intensive) weeks. Adaptive verbal and spatial n-back tasks were used as the WMT tasks. We tested near transfer effects to a digit-span task and far transfer effects to an abstract relational reasoning task. Results: Participants successfully performed the cognitively demanding intervention using their own devices, online at home, and with minimal contact with the researcher. We observed a significant improvement in WMT task performance in the WMT group relative to active-controls, but no evidence of near or far transfer. Similar training effects were observed irrespective of the intensity of the training schedule. Discussion: Our results suggest that comparable benefits could be observed when using less intensive schedules that may be more easily accommodated into everyday life.

Non-invasive brain stimulation modulates GABAergic activity in neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as autism. GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigates whether application of anodal transcranial direct current stimulation (atDCS) can modulate GABA and working memory in NF1. Thirty-one NF1 adolescents 11-18 years, were recruited to this single-blind sham-controlled cross-over randomized trial. AtDCS or sham stimulation was applied to the left Dorsolateral Prefrontal Cortex (DLPFC) and MR Spectroscopy was collected before and after intervention in the left DLPFC and occipital cortex. Task-related functional MRI was collected before, during, and after stimulation. Higher baseline GABA+ in the left DLPFC was associated with faster response times on baseline working memory measures. AtDCS was seen to significantly reduced GABA+ and increase brain activation in the left DLPFC as compared to sham stimulation. Task performance was worse in the aTDCS group during stimulation but no group differences in behavioural outcomes were observed at the end of stimulation. Although our study suggests aTDCS modulates inhibitory activity in the DLPFC, further work is needed to determine whether repeated sessions of atDCS and strategies such as alternating current stimulation offer a better therapeutic approach.

Neuroanatomical correlates of working memory performance in Neurofibromatosis 1.

Introduction: Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive impairments, particularly with deficits in working memory. Prior research indicates that brain structure is affected in NF1, but it is unclear how these changes relate to aspects of cognition. Methods: 29 adolescents aged 11-17 years were compared to age and sex-matched controls. NF1 subjects were assessed using detailed multimodal measurements of working memory at baseline followed by a 3T MR scan. A voxel-based morphometry approach was used to estimate the total and regional gray matter(GM) volumetric differences between the NF1 and control groups. The working memory metrics were subjected to a principal component analysis (PCA) approach. Results: The NF1 groups showed increased gray matter volumes in the thalamus, corpus striatum, dorsal midbrain and cerebellum bilaterally in the NF1 group as compared to controls. Principal component analysis on the working memory metrics in the NF1 group yielded three independent factors reflecting high memory load, low memory load and auditory working memory. Correlation analyses revealed that increased volume of posterior cingulate cortex, a key component of the default mode network (DMN) was significantly associated with poorer performance on low working memory load tasks. Conclusion: These results are consistent with prior work showing larger subcortical brain volumes in the NF1 cohort. The strong association between posterior cingulate cortex volume and performance on low memory load conditions supports hypotheses of deficient DMN structural development, which in turn may contribute to the cognitive impairments in NF1.

The Neural Representations of Emotional Experiences Are More Similar Than Those of Neutral Experiences.

Stimuli that evoke the same feelings can nevertheless look different and have different semantic meanings. Although we know much about the neural representation of emotion, the neural underpinnings of emotional similarity are unknown. One possibility is that the same brain regions represent similarity between emotional and neutral stimuli, perhaps with different strengths. Alternatively, emotional similarity could be coded in separate regions, possibly those sensitive to emotional valence and arousal. In behavior, the extent to which people consider similarity along emotional dimensions when they evaluate the overall similarity between stimuli has never been investigated. Although the emotional features of stimuli may dominate explicit ratings of similarity, it is also possible that people neglect emotional dimensions as irrelevant to that judgment. We contrasted these hypotheses in (male and female) healthy controls using two measures of similarity and two picture databases of complex negative and neutral scenes, the second of which provided exquisite control over semantic and visual attributes. The similarity between emotional stimuli was greater than between neutral stimuli in the inferior temporal cortex, the fusiform face area, and the precuneus. Additionally, only the similarity between emotional stimuli was significantly represented in early visual cortex, anterior insula and dorsal anterior cingulate cortex. Intriguingly, despite the stronger neural similarity between emotional stimuli, the same participants did not rate them as more similar to each other than neutral stimuli. These results contribute to our understanding of how emotion is represented within a general conceptual workspace and of the overgeneralization bias in anxiety disorders.SIGNIFICANCE STATEMENT We tested differences in similarity between emotional and neutral scenes. Arousal and negative valence did not increase similarity ratings. When conditions were equated on semantic similarity, participants rated emotional stimuli as similar to each other as neutral ones. Despite this equivalence, the similarity among the neural representations of emotional compared with neutral stimuli was higher in regions, which also expressed similarity between neutral stimuli and in unique regions. We report a striking difference between behavioral and neural similarity; strong neural similarity between emotional pictures did not influence similarity judgements in the same participants in the behavioral rating task after the scan. These findings may have an impact on research about the neural representations of emotional categories and the overgeneralization bias in anxiety disorders.

The effects of transcranial alternating current stimulation on memory performance in healthy adults: A systematic review.

The recent introduction of Transcranial Alternating Current stimulation (tACS) in research on memory modulation has yielded some exciting findings. Whilst evidence suggests small but significant modulatory effects of tACS on perception and cognition, it is unclear how effective tACS is at modulating memory, and the neural oscillations underlying memory. The aim of this systematic review was to determine the efficacy with which tACS, compared to sham stimulation, can modify working memory (WM) and long-term memory (LTM) performance in healthy adults. We examined how these effects may be moderated by specific tACS parameters and study/participant characteristics. Our secondary goal was to investigate the neural correlates of tACS' effects on memory performance in healthy adults. A systematic search of eight databases yielded 11,413 records, resulting in 34 papers that included 104 eligible studies. The results were synthesised by memory type (WM/LTM) and according to the specific parameters of frequency band, stimulation montage, individual variability, cognitive demand, and phase. A second synthesis examined the correspondence between tACS' effects on memory performance and the oscillatory features of electroencephalography (EEG) and magnetencephalography (MEG) recordings in a subset of 26 studies. The results showed a small-to-medium effect of tACS on WM and LTM performance overall. There was strong evidence to suggest that posterior theta-tACS modulates WM performance, whilst the modulation of LTM is achieved by anterior gamma-tACS. Moreover, there was a correspondence between tACS effects on memory performance and oscillatory outcomes at the stimulation frequency. We discuss limitations in the field and suggest ways to improve our understanding of tACS efficacy to ensure a transition of tACS from an investigative method to a therapeutic tool.

Cognitive and Electrophysiological Correlates of Working Memory Impairments in Neurofibromatosis Type 1.

Neurofibromatosis 1 (NF1) is a single gene disorder associated with working Memory (WM) impairments. The aim of this study was to investigate P300 event-related potential (ERP) associated with WM in NF1. Sixteen adolescents with NF1 were compared with controls on measures of WM and EEG was recorded during a WM nback task. The NF1 group showed poorer performance on measures of WM as compared to the control group. No group differences were observed in P300 amplitude at Pz, but P300 latency was shorter in the NF1 group. Topographic analyses of P300 amplitude showed group differences indicating neural processing differences in the NF1 group relative to controls, which possibly contribute to the cognitive deficits seen in this population.

The Left Angular Gyrus Is Causally Involved in Context-dependent Integration and Associative Encoding during Narrative Reading.

The role of the left angular gyrus (AG) in language processing remains unclear. In this study, we used TMS to test the hypothesis that the left AG causally supports the processes necessary for context-dependent integration and encoding of information during language processing. We applied on-line TMS over the left AG to disrupt the on-line context-dependent integration during a language reading task, specifically while human participants integrated information between two sequentially presented paragraphs of text ("context" and "target" paragraphs). We assessed the effect of TMS on the left AG by asking participants to retrieve integrated contextual information when given the target condition as cue in a successive memory task. Results from the memory task showed that TMS applied over the left AG during reading impaired the formation of integrated context-target representation. These results provide the first evidence of a causal link between the left AG function, on-line information integration, and associative encoding during language processing.

Non-pharmacological interventions for spatial neglect or inattention following stroke and other non-progressive brain injury.

BACKGROUND: People with spatial neglect after stroke or other brain injury have difficulty attending to one side of space. Various rehabilitation interventions have been used, but evidence of their benefit is unclear. OBJECTIVES: The main objective was to determine the effects of non-pharmacological interventions for people with spatial neglect after stroke and other adult-acquired non-progressive brain injury. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched October 2020), the Cochrane Central Register of Controlled Trials (CENTRAL; last searched October 2020), MEDLINE (1966 to October 2020), Embase (1980 to October 2020), the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1983 to October 2020), and PsycINFO (1974 to October 2020). We also searched ongoing trials registers and screened reference lists. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of any non-pharmacological intervention specifically aimed at spatial neglect. We excluded studies of general rehabilitation and studies with mixed participant groups, unless separate neglect data were available. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Review authors categorised the interventions into eight broad types deemed to be applicable to clinical practice through iterative discussion: visual interventions, prism adaptation, body awareness interventions, mental function interventions, movement interventions, non-invasive brain stimulation, electrical stimulation, and acupuncture. We assessed the quality of evidence for each outcome using the GRADE approach. MAIN RESULTS: We included 65 RCTs with 1951 participants, all of which included people with spatial neglect following stroke. Most studies measured outcomes using standardised neglect assessments. Fifty-one studies measured effects on ADL immediately after completion of the intervention period; only 16 reported persisting effects on ADL (our primary outcome). One study (30 participants) reported discharge destination, and one (24 participants) reported depression. No studies reported falls, balance, or quality of life. Only two studies were judged to be entirely at low risk of bias, and all were small, with fewer than 50 participants per group. We found no definitive (phase 3) clinical trials. None of the studies reported any patient or public involvement. Visual interventions versus any control: evidence is very uncertain about the effects of visual interventions for spatial neglect based on measures of persisting functional ability in ADL (2 studies, 55 participants) (standardised mean difference (SMD) -0.04, 95% confidence interval (CI) -0.57 to 0.49); measures of immediate functional ability in ADL; persisting standardised neglect assessments; and immediate neglect assessments. Prism adaptation versus any control: evidence is very uncertain about the effects of prism adaptation for spatial neglect based on measures of persisting functional ability in ADL (2 studies, 39 participants) (SMD -0.29, 95% CI -0.93 to 0.35); measures of immediate functional ability in ADL; persisting standardised neglect assessments; and immediate neglect assessments. Body awareness interventions versus any control: evidence is very uncertain about the effects of body awareness interventions for spatial neglect based on measures of persisting functional ability in ADL (5 studies, 125 participants) (SMD 0.61, 95% CI 0.24 to 0.97); measures of immediate functional ability in ADL; persisting standardised neglect assessments; immediate neglect assessments; and adverse events. Mental function interventions versus any control: we found no trials of mental function interventions for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of mental function interventions on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments. Movement interventions versus any control: we found no trials of movement interventions for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of body awareness interventions on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments. Non-invasive brain stimulation (NIBS) versus any control: evidence is very uncertain about the effects of NIBS on spatial neglect based on measures of persisting functional ability in ADL (3 studies, 92 participants) (SMD 0.35, 95% CI -0.08 to 0.77); measures of immediate functional ability in ADL; persisting standardised neglect assessments; immediate neglect assessments; and adverse events. Electrical stimulation versus any control: we found no trials of electrical stimulation for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of electrical stimulation on spatial neglect based on immediate neglect assessments. Acupuncture versus any control: we found no trials of acupuncture for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of acupuncture on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments. AUTHORS' CONCLUSIONS: The effectiveness of non-pharmacological interventions for spatial neglect in improving functional ability in ADL and increasing independence remains unproven. Many strategies have been proposed to aid rehabilitation of spatial neglect, but none has yet been sufficiently researched through high-quality fully powered randomised trials to establish potential or adverse effects. As a consequence, no rehabilitation approach can be supported or refuted based on current evidence from RCTs. As recommended by a number of national clinical guidelines, clinicians should continue to provide rehabilitation for neglect that enables people to meet their rehabilitation goals. Clinicians and stroke survivors should have the opportunity, and are strongly encouraged, to participate in research. Future studies need to have appropriate high-quality methodological design, delivery, and reporting to enable appraisal and interpretation of results. Future studies also must evaluate outcomes of importance to patients, such as persisting functional ability in ADL. One way to improve the quality of research is to involve people with experience with the condition in designing and running trials.

Targeted memory reactivation in REM but not SWS selectively reduces arousal responses.

A growing body of evidence suggests that sleep can help to decouple the memory of emotional experiences from their associated affective charge. This process is thought to rely on the spontaneous reactivation of emotional memories during sleep, though it is still unclear which sleep stage is optimal for such reactivation. We examined this question by explicitly manipulating memory reactivation in both rapid-eye movement sleep (REM) and slow-wave sleep (SWS) using targeted memory reactivation (TMR) and testing the impact of this manipulation on habituation of subjective arousal responses across a night. Our results show that TMR during REM, but not SWS significantly decreased subjective arousal, and this effect is driven by the more negative stimuli. These results support one aspect of the sleep to forget, sleep to remember (SFSR) hypothesis which proposes that emotional memory reactivation during REM sleep underlies sleep-dependent habituation.

Graded, multidimensional intra- and intergroup variations in primary progressive aphasia and post-stroke aphasia.

Language impairments caused by stroke (post-stroke aphasia, PSA) and neurodegeneration (primary progressive aphasia, PPA) have overlapping symptomatology, nomenclature and are classically divided into categorical subtypes. Surprisingly, PPA and PSA have rarely been directly compared in detail. Rather, previous studies have compared certain subtypes (e.g. semantic variants) or have focused on a specific cognitive/linguistic task (e.g. reading). This study assessed a large range of linguistic and cognitive tasks across the full spectra of PSA and PPA. We applied varimax-rotated principal component analysis to explore the underlying structure of the variance in the assessment scores. Similar phonological, semantic and fluency-related components were found for PSA and PPA. A combined principal component analysis across the two aetiologies revealed graded intra- and intergroup variations on all four extracted components. Classification analysis was used to test, formally, whether there were any categorical boundaries for any subtypes of PPA or PSA. Semantic dementia formed a true diagnostic category (i.e. within group homogeneity and distinct between-group differences), whereas there was considerable overlap and graded variations within and between other subtypes of PPA and PSA. These results suggest that (i) a multidimensional rather than categorical classification system may be a better conceptualization of aphasia from both causes; and (ii) despite the very different types of pathology, these broad classes of aphasia have considerable features in common.

The Emotional Facet of Subjective and Neural Indices of Similarity.

Emotional similarity refers to the tendency to group stimuli together because they evoke the same feelings in us. The majority of research on similarity perception that has been conducted to date has focused on non-emotional stimuli. Different models have been proposed to explain how we represent semantic concepts, and judge the similarity among them. They are supported from behavioural and neural evidence, often combined by using Multivariate Pattern Analyses. By contrast, less is known about the cognitive and neural mechanisms underlying the judgement of similarity between real-life emotional experiences. This review summarizes the major findings, debates and limitations in the semantic similarity literature. They will serve as background to the emotional facet of similarity that will be the focus of this review. A multi-modal and overarching approach, which relates different levels of neuroscientific explanation (i.e., computational, algorithmic and implementation), would be the key to further unveil what makes emotional experiences similar to each other.

Seeing the World as it is: Mimicking Veridical Motion Perception in Schizophrenia Using Non-invasive Brain Stimulation in Healthy Participants.

Schizophrenia (Sz) is a mental health disorder characterized by severe cognitive, emotional, social, and perceptual deficits. Visual deficits are found in tasks relying on the magnocellular/dorsal stream. In our first experiment we established deficits in global motion processing in Sz patients compared to healthy controls. We used a novel task in which background optic flow produces a distortion of the apparent trajectory of a moving stimulus, leading control participants to provide biased estimates of the true motion trajectory under conditions of global stimulation. Sz patients were significantly less affected by the global background motion, and reported trajectories that were more veridically accurate than those of controls. In order to study the mechanism of this effect, we performed a second experiment where we applied transcranial electrical stimulation over area MT+ to selectively modify global motion processing of optic flow displays in healthy participants. Cathodal and high frequency random noise stimulation had opposite effects on trajectory perception in optic flow. The brain stimulation over a control site and in a control task revealed that the effect of stimulation was specific for global motion processing in area MT+. These findings both support prior studies of impaired early visual processing in Sz and provide novel approaches for measurement and manipulation of the underlying circuits.

Laterality of anterior temporal lobe repetitive transcranial magnetic stimulation determines the degree of disruption in picture naming.

The bilateral anterior temporal lobes play a key role in semantic representation. This is clearly demonstrated by the performance of patients with semantic dementia, a disorder characterised by a progressive and selective decline in semantic memory over all modalities as a result of anterior temporal atrophy. Although all patients exhibit a progressive decline in both single-word production and comprehension, those with greater atrophy to the left anterior temporal lobe show a stronger decline in word production than comprehension. This asymmetry has been attributed to the greater connectivity of the left anterior temporal lobe with left-lateralised speech production mechanisms. Virtual lesioning of the left ATL using offline repetitive transcranial magnetic stimulation (rTMS) has been shown to disrupt picture naming, but, the impact of right ATL rTMS is yet to be explored. We tested the prediction that disruption of picture naming in normal participants by rTMS should be greater for the left than the right ATL. We found a significant increase in picture naming latencies specifically for stimulation of the left ATL only. Neither left nor right ATL TMS slowed performance in a number naming control task. These results support the hypothesis that although both temporal lobes are part of a widespread semantic network in the human brain, the left anterior temporal lobe possesses a stronger connection to left-lateralised speech production areas than the right temporal lobe.

Facilitation of Function and Manipulation Knowledge of Tools Using Transcranial Direct Current Stimulation (tDCS).

Using a variety of tools is a common and essential component of modern human life. Patients with brain damage or neurological disorders frequently have cognitive deficits in their recognition and manipulation of tools. In this study, we focused on improving tool-related cognition using transcranial direct current stimulation (tDCS). Converging evidence from neuropsychology, neuroimaging and non- invasive brain stimulation has identified the anterior temporal lobe (ATL) and inferior parietal lobule (IPL) as brain regions supporting action semantics. We observed enhanced performance in tool cognition with anodal tDCS over ATL and IPL in two cognitive tasks that require rapid access to semantic knowledge about the function or manipulation of common tools. ATL stimulation improved access to both function and manipulation knowledge of tools. The effect of IPL stimulation showed a trend toward better manipulation judgments. Our findings support previous studies of tool semantics and provide a novel approach for manipulation of underlying circuits.

The neural network for tool-related cognition: An activation likelihood estimation meta-analysis of 70 neuroimaging contrasts.

The ability to recognize and use a variety of tools is an intriguing human cognitive function. Multiple neuroimaging studies have investigated neural activations with various types of tool-related tasks. In the present paper, we reviewed tool-related neural activations reported in 70 contrasts from 56 neuroimaging studies and performed a series of activation likelihood estimation (ALE) meta-analyses to identify tool-related cortical circuits dedicated either to general tool knowledge or to task-specific processes. The results indicate the following: (a) Common, task-general processing regions for tools are located in the left inferior parietal lobule (IPL) and ventral premotor cortex; and (b) task-specific regions are located in superior parietal lobule (SPL) and dorsal premotor area for imagining/executing actions with tools and in bilateral occipito-temporal cortex for recognizing/naming tools. The roles of these regions in task-general and task-specific activities are discussed with reference to evidence from neuropsychology, experimental psychology and other neuroimaging studies.