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Background Major depressive disorder (MDD) is a serious mood disorder and leading cause of disability. Despite treatment advances, approximately 30% of individuals with MDD do not achieve adequate clinical response. Better understanding the biological mechanism(s) underlying clinical response to specific psychopharmacological interventions may help fine tune treatments in order to further modulate their underlying mechanisms of action. However, little is known regarding the effect of non-pharmacological treatments (NPTs) on candidate molecular biomarker levels in MDD. This review aims to identify molecular biomarkers that may elucidate NPT response for MDD. Methods We performed a systematic review and a multilevel linear mixed-effects meta-analyses, and a meta-regression. Searches were performed in PubMed, Scopus, and PsycINFO in October 2020 and July 2021. Results From 1387 retrieved articles, 17 and six studies were included in the systematic review and meta-analyses, respectively. Although there was little consensus associating molecular biomarker levels with symptomology and/or treatment response, brain metabolites accessed via molecular biomarker-focused neuroimaging techniques may provide promising information on whether an individual with MDD would respond positively to NPTs. Furthermore, non-invasive brain stimulation interventions significantly increased the expression of neurotrophic factors (NTFs) compared to sham/placebo, regardless of add-on pharmacological treatment. Conclusions NTFs are candidate biomarkers to fine-tune NIBS for MDD treatment. published

This study examined the effects of bihemispheric and unihemispheric transcranial Direct Current Stimulation (tDCS) over the inferior frontal gyrus (IFG) on proactive control. Sixteen participants were randomized to receive (i) bihemispheric tDCS, with a 35cm2 anodal electrode of the right IFG and a 35cm2 cathode electrode of left IFG or (ii) unihemispheric tDCS, with a 35cm2 anodal electrode of the right IFG and a 100cm2 electrode of the left IFG or (iii) sham tDCS, while performing a prepotent inhibition task. There were significant speed-accuracy tradeoff effects in terms of switch costs: unihemispheric tDCS significantly decreased the accuracy when compared to bihemispheric, and sham tDCS, while increased response time when comparing to bihemispheric and sham tDCS. The computational model showed a symmetrical field intensity for the bihemispheric tDCS montage, and an asymmetrical for the unihemispheric tDCS montage. This study confirms that unihemispheric tDCS over the rIFG has a significant impact on response inhibition. The lack of results of bihemispheric tDCS brings two important findings for this study: (i) left IFG seems to be also critically associated with inhibitory response control, and (ii) these results highlight the importance of considering the dual effects of tDCS when choosing the electrode montage., JL, SC, OFG are members of CIPSi, supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology and Higher Education through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653); and also through the Portuguese Foundation for Science and Technology PTDC/MHC-PCN/3950/2014. FF is funded by the following NIH grants: R21HD079048, R01HD082302, 1R44NS080632-01, 1R44AT008637, HD069776. SC is funded by the following Portuguese Fondation for Science and Technology (FCT) grant IF/00091/2015., info:eu-repo/semantics/publishedVersion

The ability to discriminate self- and non-self voice cues is a fundamental aspect of self-awareness and subserves self-monitoring during verbal communication. Nonetheless, the neurofunctional underpinnings of self-voice perception and recognition are still poorly understood. Moreover, how attention and stimulus complexity influence the processing and recognition of one's own voice remains to be clarified. Using an oddball task, the current study investigated how self-relevance and stimulus type interact during selective attention to voices, and how they affect the representation of regularity during voice perception. Event-related potentials (ERPs) were recorded from 18 right-handed males. Pre-recorded self-generated (SGV) and non-self (NSV) voices, consisting of a nonverbal vocalization (vocalization condition) or disyllabic word (word condition), were presented as either standard or target stimuli in different experimental blocks. The results showed increased N2 amplitude to SGV relative to NSV stimuli. Stimulus type modulated later processing stages only: P3 amplitude was increased for SGV relative to NSV words, whereas no differences between SGV and NSV were observed in the case of vocalizations. Moreover, SGV standards elicited reduced N1 and P2 amplitude relative to NSV standards. These findings revealed that the self-voice grabs more attention when listeners are exposed to words but not vocalizations. Further, they indicate that detection of regularity in an auditory stream is facilitated for one's own voice at early processing stages. Together, they demonstrate that self-relevance affects attention to voices differently as a function of stimulus type., This work was supported by Grants IF/00334/2012 and PTDC/ MHC-PCN/0101/2014 funded by Fundação para a Ciência e a Tecnologia (FCT, Portugal) and FEDER (Fundo Europeu de Desenvolvimento Regional) through the European programs QREN (Quadro de Referência Estratégico Nacional), and COMPETE (Programa Operacional Factores de Competitividade), awarded to A.P.P., and a by a FCT Postdoctoral Grant (SFRH/BPD/117187/2016) awarded to T.C. This work received additional support from Grant BIAL 238/16 funded by BIAL Foundation, awarded to A.P.P, info:eu-repo/semantics/publishedVersion

Neuroscientists have begun to investigate whether different political attitudes are associated with specificmind-brain markers. In this article, we build on political neuroscience research to briefly illustrate thestructure and function of a Threatening, Reactionary, Unforgiving, Machiavellian, and Partisan (T.R.U.M.P.)mindset. Additionally, we discussed, building on neuroscience and clinical evidence, how to counteractthe T.R.U.M.P. mindset., info:eu-repo/semantics/publishedVersion

Obsessive-compulsive personality (OCPD) disorder is characterized by a pattern of excessive self-control, perfectionism and behavioral and cognitive rigidity. Despite the fact that OCPD is the most common personality disorder in the general population, published studies looking at the brain correlates of this disorder are practically nonexistent. The main goal of this study was to analyze the presence of brain alterations in OCPD when compared to healthy controls, specifically at the level of the Default Mode Network (DMN). The DMN is a well-established resting state network which was found to be associated with psychological processes that may play a key role in OCPD (e.g., self-awareness, episodic future thinking and mental simulation). Ten individuals diagnosed with OCPD and ten healthy controls underwent a clinical assessment interview and a resting-state functional magnetic resonance imaging (fMRI) acquisition. The results show that OCPD patients presented an increased functional connectivity in the precuneus (i.e., a posterior node of the DMN), known to be involved in the retrieval manipulation of past events in order to solve current problems and develop plans for the future. These results suggest that this key node of the DMN may play an important role in the pathophysiology of OCPD., This study was conducted at Psychology Research Centre (UID/PSI/01662/2013), University of Minho, and supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Education and Science through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653).Joana Coutinho was funded by a FCT postdoctoral grant (number: SFRH/BPD/75014/2010) and Bial Foundation (grant number 87/12)., info:eu-repo/semantics/publishedVersion

It has been already shown that delivering tDCS that are spaced by an interval alters its impact on motor plasticity. These effects can be explained, based on metaplasticity in which a previous modification of activity in a neuronal network can change the effects of subsequent interventions in the same network. But to date there is limited data assessing metaplasticity effects in cognitive functioning., This work was supported by the Portuguese Foundation for Science and Technology (FCT) with two individual grants (SFRH/BPD/86041/2012 and SFRH/BPD/86027/2012).

[Letter to the editor], There are only a few treatments available for Tourette syndrome (TS). These treatments frequently do notwork in patients with moderate to severe TS [1]. Neuroimaging studies show a correlation between tics severity and increased activation over motor pathways, along with reduced activation over the control areas of the cortico-striato-thalamo-cortical circuits [2]. Moreover, the temporal pattern of tic generation suggests that cortical activation especially in the SMA precedes subcortical activation [3]. Following this assumption, here we explored the brain effects of 10-daily sessions of cathodal transcranial Direct Current Stimulation (tDCS) delivered over the pre-SMA in a patient with refractory and severe TS and also assessed whether those changes were long lasting (up to 6 months)., Study funding: This work was supported by the Portuguese Foundation for Science and Technology (FCT) with two individual grants (SFRH/BPD/86041/2012 and SFRH/BPD/86027/2012).Disclosure: The authors report no disclosures relevant to the manuscript.

Recent studies have demonstrated the positive effects of musical training on the perception of vocally expressed emotion. This study investigated the effects of musical training on event-related potential (ERP) correlates of emotional prosody processing. Fourteen musicians and fourteen control subjects listened to 228 sentences with neutral semantic content, differing in prosody (one third with neutral, one third with happy and one third with angry intonation), with intelligible semantic content (semantic content condition--SCC) and unintelligible semantic content (pure prosody condition--PPC). Reduced P50 amplitude was found in musicians. A difference between SCC and PPC conditions was found in P50 and N100 amplitude in non-musicians only, and in P200 amplitude in musicians only. Furthermore, musicians were more accurate in recognizing angry prosody in PPC sentences. These findings suggest that auditory expertise characterizing extensive musical training may impact different stages of vocal emotional processing., This work was supported by Grants IF/00334/2012, PTDC/PSIPCL/ 116626/2010 and PTDC/MHN-PCN/3606/2012 funded by Fundação para a Ciência e a Tecnologia (FCT, Portugal) and FEDER (Fundo Europeu de Desenvolvimento Regional) through the European programs QREN (Quadro de Referência Estratégico Nacional), and COMPETE (Programa Operacional Factores de Competitividade), awarded to A.P.P.

The dorsolateral prefrontal cortex (DLPFC) is involved in the cognitive appraisal and modulation of the pain experience. In this sham-controlled study, with healthy volunteers, we used bi-hemispheric transcranial direct current stimulation (tDCS) over the DLPFC to assess emotional reactions elicited by pain observation. Left-cathodal/right-anodal tDCS decreased valence and arousal evaluations compared to other tDCS conditions. Compared to sham condition, both left-cathodal/right-anodal and left-anodal/right-cathodal tDCS decreased hostility, sadness and self-pain perception. These decreased sensations after both active tDCS suggest a common role for left and right DLPFC in personal distress modulation. However, the differences in arousal and valence evaluations point to distinct roles of lateralized DLPFC in cognitive empathy, probably through distinct emotion regulation mechanisms., This experiment was supported by the National Council for Scientific and Technological Development (CNPq-480891/2012-5). LMM is supported by a scientific initiation grant (CNPq – 160553/2013-0). OML is supported by a FAPESP PhD grant (FAPESP – 2012/24696-1). PSB is a CNPq research fellow (304164/2012-7).

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, primarily characterized by motor symptoms such as tremor, rigidity, bradykinesia, stiffness, slowness and impaired equilibrium. Although the motor symptoms have been the focus in PD, slight cognitive deficits are commonly found in non-demented and non-depressed PD patients, even in early stages of the disease, which have been linked to the subsequent development of pathological dementia. Thus, strongly reducing the quality of life (QoL). Both levodopa therapy and deep brain stimulation (DBS) have yield controversial results concerning the cognitive symptoms amelioration in PD patients. That does not seems to be the case with transcranial direct current stimulation (tDCS), although better stimulation parameters are needed. Therefore we hypothesize that simultaneously delivering cathodal tDCS (or ctDCS), over the right prefrontal cortex delivered with anodal tDCS (or atDCS) to left prefrontal cortex could be potentially beneficial for PD patients, either by mechanisms of homeostatic plasticity and by increases in the extracellular dopamine levels over the striatum., This work was supported by the Portuguese Foundation for Science and Technology with individual Grants (SFRH/BPD/86027/ 2012) and (SFRH/BPD/86041/2012). The sponsors had no role in the establishment of the present hypothesis

Individuals with Williams syndrome display indiscriminate approach towards strangers. Neuroimaging studies conducted so far have linked this social profile to structural and/or functional abnormalities in WS amygdala and prefrontal cortex. In this study, the neuropsychological hypotheses of amygdala and prefrontal cortex involvement in WS hypersociability was explored using three behavioral tasks – facial emotional recognition task, a social approach task and a go no/go task. Thus, a group 15 individuals with Williams syndrome was compared to two groups of normal developing individuals – a group of 15 individuals matched for chronological age (CA) and 15 individualsmatched for mental age (MA), and sex. Individuals with WS present a specific impairment in recognizing negative facial expressions and do not display impairments in response inhibition when compared with typically developing groups. Although these findings partially support the amygdala contribution to WS hypersociability, we found that general cognitive functioning predicted this performance. Additionally, individuals with WS did not differ from both CA and MA groups in the recognition of angry facial expressions, a finding suggesting that they are actually able to identify stimuli associated with social threat. Overall, the results seem to indicate that this social profile must be understood within a developmental framework., Fundação para a Ciência e a Tecnologia (FCT) - bolsa PIC/IC/83290/2007

Obsessive Compulsive Disorder (OCD) involves failures in two main inhibitory processes, namely cognitive (obsessions) and behavioral (compulsions). Recent research has supported two cortical-subcortical pathways on OCD pathogenesis: (a) the frontostriatal loop (dorsolateral-caudate-striatum-thalamus) responsible for impairments of behavioral inhibition; (b) the orbitofrontal loop (orbitofrontal, medial prefrontal and cingulate) responsible for impairments with cognitive inhibitory processes. These failures in both cognitive and motor inhibitory systems may mediate several neuropsychological deficits in these patients, namely memory, attention, planning and decision making. But are those deficits related to specific hemispheric effects, namely functional imbalance between hemispheres? In this article we hypothesize that: (1) OCD patients have an inter-hemispheric functional imbalance, probably due to inadequate filtering at the thalamic level; (2) the restoration of inter-hemispheric balance, will be correlative to symptomatic improvement.

Williams syndrome (WS) is a neurodevelopmental genetic disorder often described as being characterized by a dissociative cognitive architecture, in which profound impairments of visuo-spatial cognition contrast with relative preservation of linguistic, face recognition and auditory short-memory abilities. This asymmetric and dissociative cognition has been also proposed to characterize WS memory ability, with sparing of auditory short-term memory and impairment of spatial and long-term memory abilities. In this study, we explored the possibility of a double memory dissociation in WS (short- versus long-term memory; verbal versus visual memory). Thus, verbal memory abilities were assessed using California Verbal Learning Test and Digit Span and Rey-Osterrieth Complex Figure and Corsi Blocks was used to assess visual–spatial memory abilities. Overall, WS subjects were found to present a generalized significant impairment in verbal and visuo-spatial components either in short- or long-term memory. In sum, data from this study brings support for a developmental delay hypothesis, rather than a double dissociation within memory systems in WS., Fundação para a Ciência e Tecnologia (FCT) - POCTI/PSI/58364/2004 and SFRH/BD/16091/2004