Effect of prefrontal transcranial direct current stimulation on sexual arousal: A proof of concept study.

There is preliminary evidence that high-frequency repetitive transcranial magnetic stimulation targeting the right dorsolateral prefrontal cortex (DLPFC) could reduce cue-induced sexual arousal. Here, we aimed to replicate this finding by using transcranial direct current stimulation (tDCS). In a randomized, double-blind, sham-controlled crossover study design, 24 healthy male participants received anodal tDCS over right DLPFC, anodal tDCS over left DLPFC, and sham tDCS with exposure to neutral and sexual video cues before and after each intervention. None of the interventions significantly reduced subjective sexual arousal. Stimulation parameters should be varied in further studies to identify factors relevant to the intended effect.

Disentangling dyskinesia from parkinsonism in motor structures of patients with schizophrenia.

Patients with schizophrenia frequently suffer from motor abnormalities, but underlying alterations in neuroarchitecture remain unclear. Here, we aimed to disentangle dyskinesia from parkinsonism in motor structures of patients with schizophrenia and to assess associated molecular architecture. We measured grey matter of motor regions and correlated volumetric estimates with dyskinesia and parkinsonism severity. Associations with molecular architecture were identified by cross-modal spatial correlations between ensuing maps of abnormality-related volume alterations and neurotransmitter maps from healthy populations. Both phenomena were linked to (specific) striatal and basal forebrain reductions as well as to D1 receptor density. Dyskinesia also manifested in cerebellar decrease, while parkinsonism was associated with less motor cortex volume. The parkinsonism-related brain pattern was additionally associated with 5-HT1A/2A and µ-opioid receptors distribution. Findings suggest the need to develop psychopharmacological compounds that display not only selectivity for receptor subtypes but also anatomical selectivity for alleviating dyskinesia without worsening parkinsonism and vice versa.

Preconditioning prefrontal connectivity using transcranial direct current stimulation and transcranial magnetic stimulation.

Transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) have been shown to modulate functional connectivity. Their specific effects seem to be dependent on the pre-existing neuronal state. We aimed to precondition frontal networks using tDCS and subsequently stimulate the left dorsolateral prefrontal cortex (lDLPFC) using TMS. Thirty healthy participants underwent excitatory, inhibitory, or sham tDCS for 10 min, as well as an excitatory intermittent theta-burst (iTBS) protocol (600 pulses, 190 s, 20 × 2-s trains), applied over the lDLPFC at 90% of the individual resting motor threshold. Functional connectivity was measured in three task-free resting state fMRI sessions, immediately before and after tDCS, as well as after iTBS. Testing the whole design did not yield any significant results. Analysis of the connectivity between the stimulation site and all other brain voxels, contrasting only the interaction effect between the experimental groups (excitatory vs. inhibitory) and the repeated measure (post-tDCS vs. post-TMS), revealed significantly affected voxels bilaterally in the anterior cingulate and paracingulate gyri, the caudate nuclei, the insula and operculum cortices, as well as the Heschl's gyrus. Post-hoc ROI-to-ROI analyses between the significant clusters and the striatum showed post-tDCS, temporo-parietal-to-striatal and temporo-parietal-to-fronto-cingulate differences between the anodal and cathodal tDCSgroup, as well as post-TMS, striatal-to-temporo-parietal differences between the anodal and cathodal groups and frontostriatal and interhemispheric temporo-parietal cathodal-sham group differences. Excitatory iTBS to a tDCS-inhibited lDLPFC thus yielded more robust functional connectivity to various areas as compared to excitatory iTBS to a tDCS-enhanced DLPFC. Even considering reduced statistical power due to low subject numbers, results demonstrate complex, whole-brain stimulation effects. They are possibly facilitated by cortical homeostatic control mechanisms and show the feasibility of using tDCS to modulate subsequent TMS effects. This proof-of-principle study might stimulate further research into the principle of preconditioning that might be useful in the development of protocols using DLPFC as a stimulation site for the treatment of depression.

Pattern learning reveals brain asymmetry to be linked to socioeconomic status.

Socioeconomic status (SES) anchors individuals in their social network layers. Our embedding in the societal fabric resonates with habitus, world view, opportunity, and health disparity. It remains obscure how distinct facets of SES are reflected in the architecture of the central nervous system. Here, we capitalized on multivariate multi-output learning algorithms to explore possible imprints of SES in gray and white matter structure in the wider population (n ≈ 10,000 UK Biobank participants). Individuals with higher SES, compared with those with lower SES, showed a pattern of increased region volumes in the left brain and decreased region volumes in the right brain. The analogous lateralization pattern emerged for the fiber structure of anatomical white matter tracts. Our multimodal findings suggest hemispheric asymmetry as an SES-related brain signature, which was consistent across six different indicators of SES: degree, education, income, job, neighborhood and vehicle count. Hence, hemispheric specialization may have evolved in human primates in a way that reveals crucial links to SES.

Evidence and expert consensus based German guidelines for the use of repetitive transcranial magnetic stimulation in depression.

INTRODUCTION: Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) offer a promising alternative to psychotherapeutic and pharmacological treatments for depression. This paper aims to present a practical guide for its clinical implementation based on evidence from the literature as well as on the experience of a group of leading German experts in the field. METHODS: The current evidence base for the use of rTMS in depression was examined via review of the literature. From the evidence and from clinical experience, recommendations for the use of rTMS in clinical practice were derived. All members of the of the German Society for Brain Stimulation in Psychiatry and all members of the sections Clinical Brain Stimulation and Experimental Brain Stimulation of the German Society for Psychiatry, Psychotherapy, Psychosomatics and Mental Health were invited to participate in a poll on whether they consent with the recommendations. FINDINGS: Among rTMS experts, a high consensus rate could be identified for clinical practice concerning the setting and the technical parameters of rTMS treatment in depression, indications and contra-indications, the relation of rTMS to other antidepressive treatment modalities and the frequency and management of side effects.

Prediction of response to repetitive transcranial magnetic stimulation in phantom sounds based on individual brain anatomy.

Non-invasive brain stimulation can reduce the severity of tinnitus phantom sounds beyond the time of stimulation by inducing regional neuroplastic changes. However, there are no good clinical predictors for treatment outcome. We used machine learning to investigate whether brain anatomy can predict therapeutic outcome. Sixty-one chronic tinnitus patients received repetitive transcranial magnetic stimulation of left dorsolateral prefrontal and temporal cortex. Before repetitive transcranial magnetic stimulation, a structural magnetic resonance image was obtained from all patients. To predict individual treatment response in new subjects, we employed a support vector machine ensemble for individual out-of-sample prediction. In the cross-validation, the support vector machine ensemble based on stratified sub-sampling and feature selection yielded an area under the curve of 0.87 for prediction of therapy success in new, previously unseen subjects. This corresponded to a balanced accuracy of 83.5%, sensitivity of 77.2% and specificity of 87.2%. Investigating the most selected features showed the involvement of the auditory cortex but also revealed a network of non-auditory brain areas. These findings suggest that idiosyncratic brain patterns accurately predict individual responses to repetitive transcranial magnetic stimulation treatment for tinnitus. Our findings may hence pave the way for future investigations into the precision treatment of tinnitus, involving automatic identification of the appropriate treatment method for the individual patient.

Adaptation of a semantic picture-word interference paradigm for future language mapping with transcranial magnetic stimulation: A behavioural study.

Neuro-navigated transcranial magnetic stimulation (TMS) helps to identify language-related cortical regions prior to brain tumour surgery. We adapted a semantic picture-word interference (PWI) paradigm from psycholinguistics to high-resolution TMS language mapping which prospectively can be used to specifically address the level of semantic processing. In PWI, pictures are presented along with distractor words which facilitate or inhibit the lexical access to the picture name. These modulatory effects of distractors can be annihilated in language-sensitive areas by the inhibitory effects of TMS on language processing. The rationale here is to observe the distractor effect without active stimulation and then to observe presumably its elimination by interference of the TMS stimulation. The special requirements to use PWI in this setting are (1) identifying word material for accelerating reliably naming latencies, choosing (2) the ideal presentation modality, and (3) the appropriate timing of distractor presentation. These are then controlled in real TMS language mapping. To adapt a semantic PWI naming paradigm for TMS application we employed 30 object-pictures in spoken German language. Part-whole associative semantic related or unrelated distractors were presented in two experiments including 15 healthy volunteers each, once auditorily and once visually. Data analysis across the entire stimulus set revealed a trend for facilitation in the visual condition, whereas no effects were observed for auditory distractors. In a sub-set, we found a significant facilitation effect for visual semantic distractors. Thus, with this study we provide a well-controlled item set for future studies implementing effective TMS language mapping applying visual semantic PWI.

Repetitive Transcranial Magnetic Stimulation as a Potential Tool to Reduce Sexual Arousal: A Proof of Concept Study.

BACKGROUND: Hypersexuality and hyposexuality occur frequently, often in a variety of psychiatric disorders, and are difficult to treat. While there is meta-analytic evidence for the significant effect of non-invasive brain stimulation on drug and food craving, no study has investigated the potential of this technique to modulate sexual behavior. AIM: Here, we tested the hypothesis that a single session of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) would reduce sexual arousal. METHODS: We employed a randomized, double-blind, sham-controlled crossover study design. 19 healthy male participants received high-frequency rTMS over the left DLPFC, high-frequency rTMS over the right DLPFC, and sham rTMS (each 10 Hz; 110% resting motor threshold; 60 trains with 50 pulses) in randomized and counterbalanced order with a 1-week interval between stimulation sessions to avoid carryover effects. Participants were exposed to neutral and sexual cues before and after each intervention and rated their sexual arousal after each block of cue presentation. MAIN OUTCOME MEASURE: Efficacy of the respective intervention was operationalized by the change of subjective sexual arousal according to a rating scale. RESULTS: rTMS of the right DLPFC significantly reduced subjective sexual arousal (t18 = 2.282, P = .035). In contrast, neither sham rTMS nor rTMS of the left DLPFC affected sexual arousal (P > .389). Greater rTMS-induced reduction of subjective sexual arousal was observed in participants with higher trait-based dyadic sexual desire within the last 12 months (r = -0.417, P = .038). CLINICAL IMPLICATION: Non-invasive brain stimulation might hold potential for influencing hypersexual behavior. STRENGTH & LIMITATION: This was a randomized, double-blind, sham-controlled crossover study with subjective but no physiological measures of sexual arousal. CONCLUSION: The results indicate that 1 session of high-frequency rTMS (10 Hz) of the right DLPFC could significantly reduce subjective sexual arousal induced by visual stimuli in healthy subjects. On this basis, future studies with larger sample sizes and more stimulation sessions are needed to explore the therapeutic potential of rTMS in hypersexual behavior. Schecklmann M, Sakreida K, Oblinger B, et al. Repetitive Transcranial Magnetic Stimulation as a Potential Tool to Reduce Sexual Arousal: A Roof of Concept Study. J Sex Med 2020;17:1553-1559.

Hemispheric Dominance for Language and Side Effects in Mapping the Inferior Frontal Junction Area with Transcranial Magnetic Stimulation.

BACKGROUND AND STUDY AIMS: Language mapping by navigated transcranial magnetic stimulation (TMS) is commonly applied over the left language-dominant hemisphere to indicate the language-related cortex. Detailed language mapping of Broca's region including stimulation targets in the immediate vicinity to the premotor cortex may raise concern about confounding unspecific motor effects. We performed interhemispheric comparisons to delineate such possible unspecific effects from true TMS-induced language inhibition. MATERIAL AND METHODS: Fifteen healthy German speakers named object pictures during navigated TMS over a left- and right-hemispheric target array covering the left inferior frontal junction area. Six mapping repetitions were conducted per hemisphere. Order of stimulation side was randomized between participants. Self-rating of discomfort was assessed after each stimulation; language errors and motor side effects were evaluated offline. RESULTS: Naming errors were observed significantly more frequently during left- than right-hemispheric stimulation. The same pattern was found for the most frequent error category of performance errors. Hierarchical cluster analyses of normalized ratings of error severity revealed a clear focus of TMS susceptibility for language inhibition in object naming at the dorsoposterior target sites only in the left hemisphere. We found no statistical difference in discomfort ratings between both hemispheres and also no interhemispheric difference in motor side effects, but we observed significantly stronger muscle contractions of the eyes as compared with the mouth. CONCLUSION: Our results of (1) unspecific pre-/motor effects similarly induced in both hemispheres, and (2) a specific focus of TMS susceptibility in the language-dominant hemisphere render any substantial contribution of nonlanguage-specific effects in TMS language mapping of the inferior frontal junction area highly unlikely.

Modulation of Fronto-Striatal Functional Connectivity Using Transcranial Magnetic Stimulation.

Background: The fronto-striatal network is involved in various motor, cognitive, and emotional processes, such as spatial attention, working memory, decision-making, and emotion regulation. Intermittent theta burst transcranial magnetic stimulation (iTBS) has been shown to modulate functional connectivity of brain networks. Long stimulation intervals, as well as high stimulation intensities are typically applied in transcranial magnetic stimulation (TMS) therapy for mood disorders. The role of stimulation intensity on network function and homeostasis has not been explored systematically yet. Objective: In this pilot study, we aimed to modulate fronto-striatal connectivity by applying iTBS at different intensities to the left dorso-lateral prefrontal cortex (DLPFC). We measured individual and group changes by comparing resting state functional magnetic resonance imaging (rsfMRI) both pre-iTBS and post-iTBS. Differential effects of individual sub- vs. supra-resting motor-threshold stimulation intensities were assessed. Methods: Sixteen healthy subjects underwent excitatory iTBS at two intensities [90% and 120% of individual resting motor threshold (rMT)] on separate days. Six-hundred pulses (2 s trains, 8 s pauses, duration of 3 min, 20 s) were applied over the left DLPFC. Directly before and 7 min after stimulation, task-free rsfMRI sessions, lasting 10 min each, were conducted. Individual seed-to-seed functional connectivity changes were calculated for 10 fronto-striatal and amygdala regions of interest with the SPM toolbox DPABI. Results: Sub-threshold-iTBS increased functional connectivity directly between the left DLPFC and the left and right caudate, respectively. Supra-threshold stimulation did not change fronto-striatal functional connectivity but increased functional connectivity between the right amygdala and the right caudate. Conclusion: A short iTBS protocol applied at sub-threshold intensities was not only sufficient, but favorable, in order to increase bilateral fronto-striatal functional connectivity, while minimizing side effects. The absence of an increase in functional connectivity after supra-threshold stimulation was possibly caused by network homeostatic effects.

Phonological picture-word interference in language mapping with transcranial magnetic stimulation: an objective approach for functional parcellation of Broca's region.

Functional imaging data suggest different regions for semantic, syntactic, and phonological processing in an anterior-to-posterior direction along the inferior frontal gyrus. Language mapping by use of neuro-navigated transcranial magnetic stimulation (TMS) is frequently applied in clinical research to identify language-related cortical regions. Recently, we proposed a high spatial resolution approach for more detailed language mapping of cortical sub-areas such as Broca's region. Here, we employed a phonological picture-word interference paradigm in healthy subjects to reveal functional specialization in Broca's region for phonological processing. The behavioral phonological priming effect is characterized by accelerated naming responses to target pictures accompanied by phonologically related auditory distractor words. We hypothesized that the inhibitory effects of TMS on language processing would reduce phonological priming only at stimulation sites involved in phonological processing. In active as compared to sham TMS, we found reduced phonological facilitation specifically at sites overlapping with the probabilistic cytoarchitectonic area 44. Our findings complemented functional imaging data by revealing structure-function relationship in Broca's region. The introduction of a reaction time based interference paradigm into TMS language mapping increases the objectivity of the method and allows to explore functional specificity with high temporal resolution. Findings may help to interpret results in clinical applications.

Cognitive Control Structures in the Imitation Learning of Spatial Sequences and Rhythms-An fMRI Study.

Imitation learning involves the acquisition of novel motor patterns based on action observation (AO). We used event-related functional magnetic resonance imaging to study the imitation learning of spatial sequences and rhythms during AO, motor imagery (MI), and imitative execution in nonmusicians and musicians. While both tasks engaged the fronto-parietal mirror circuit, the spatial sequence task recruited posterior parietal and dorsal premotor regions more strongly. The rhythm task involved an additional network for auditory working memory. This partial dissociation supports the concept of task-specific mirror mechanisms. Two regions of cognitive control were identified: 1) dorsolateral prefrontal cortex (DLPFC) was found to be more strongly activated during MI of novel spatial sequences, which allowed us to extend the 2-level model of imitation learning by Buccino et al. (2004) to spatial sequences. 2) During imitative execution of both tasks, the posterior medial frontal cortex was robustly activated, along with the DLPFC, which suggests that both regions are involved in the cognitive control of imitation learning. The musicians' selective behavioral advantage for rhythm imitation was reflected cortically in enhanced sensory-motor processing during AO and by the absence of practice-related activation differences in DLPFC during rhythm execution.

High-resolution language mapping of Broca's region with transcranial magnetic stimulation.

Broca's region, corresponding roughly to cytoarchitectonic areas 44 and 45 in the inferior frontal cortex, holds a multifunctional role in language processing, as shown, e.g., by functional imaging data. Neuro-navigated transcranial magnetic stimulation (TMS) enables complementary non-invasive mapping of cortical functions with high spatial resolution. Here, we report on detailed TMS language mapping of Broca's region in 12 healthy participants. The test protocol with an object naming task was adapted for high-resolution and semi-quantitative mapping of TMS-induced effects on speech and language performance. Hierarchical cluster analysis of normalized ratings of error frequency and severity revealed a clear focus of TMS impact at dorso-posterior target sites, close to the inferior frontal junction. Adjacent clusters of moderate and slightly affected stimulation sites yielded a posterosuperior-to-anteroinferior gradient of TMS susceptibility. Our findings indicate that the part of Broca's region most susceptible to TMS-induced language inhibition in object naming is located in the dorsal area 44.

Affordance processing in segregated parieto-frontal dorsal stream sub-pathways.

The concept of affordances indicates "action possibilities" as characterized by object properties the environment provides to interacting organisms. Affordances relate to both perception and action and refer to sensory-motor processes emerging from goal-directed object interaction. In contrast to stable properties, affordances may vary with environmental context. A sub-classification into stable and variable affordances was proposed in the framework of the ROSSI project (Borghi et al., 2010; Borghi and Riggio, 2015, 2009). Here, we present a coordinate-based meta-analysis of functional imaging studies on object interaction targeting consistent anatomical correlates of these different types of affordances. Our review revealed the existence of two parallel (but to some extent overlapping) functional pathways. The network for stable affordances consists of predominantly left inferior parietal and frontal cortices in the ventro-dorsal stream, whereas the network for variable affordances is localized preferentially in the dorso-dorsal stream. This is in line with the proposal of differentiated affordances: stable affordances are characterized by the knowledge of invariant object features, whereas variable affordances underlie adaptation to changing object properties.

Are abstract action words embodied? An fMRI investigation at the interface between language and motor cognition.

The cognitive and neural representation of abstract words is still an open question for theories of embodied cognition. Generally, it is proposed that abstract words are grounded in the activation of sensorimotor or at least experiential properties, exactly as concrete words. Further behavioral theories propose multiple representations evoked by abstract and concrete words. We conducted a functional magnetic resonance imaging (fMRI) study to investigate the neural correlates of concrete and abstract multi-word expressions in an action context. Participants were required to read simple sentences which combined each concrete noun with an adequate concrete verb and an adequate abstract verb, as well as an adequate abstract noun with either kind of verbs previously used. Thus, our experimental design included a continuum from pure concreteness to mere abstractness. As expected, comprehension of both concrete and abstract language content activated the core areas of the sensorimotor neural network namely the left lateral (precentral gyrus) and medial (supplementary motor area) premotor cortex. While the purely concrete multi-word expressions elicited activations within the left inferior frontal gyrus (pars triangularis) and two foci within the left inferior parietal cortex, the purely abstract multi-word expressions were represented in the anterior part of left middle temporal gyrus that is part of the language processing system. Although the sensorimotor neural network is engaged in both concrete and abstract language contents, the present findings show that concrete multi-word processing relies more on the sensorimotor system, and abstract multi-word processing relies more on the linguistic system.

Motion class dependency in observers' motor areas revealed by functional magnetic resonance imaging.

Human and animal data suggest that the mere observation of biological motion activates those premotor areas that also underlie the initiation of the same motion. However, data also indicate that the human premotor cortex (PM), in contrast to the monkey PM, responds not only to the observation of goal-directed (transitive) motion but also to intransitive motion. The present study used functional magnetic resonance imaging to test this hypothesis directly. Participants were presented cycles of intransitive motion specified as belonging to the distal (fingers and mouth), proximal (knee, ankle, elbow, and wrist), or axial (trunk and shoulder) motion class. Attention to motion was behaviorally tested by a forced-choice task on motion acceleration and deceleration. Results revealed extended PM activation for each motion condition. However, direct contrasts showed that the most significant activations were elicited in ventrolateral PM by distal motion, in dorsolateral PM by proximal motion, and medial PM (supplementary motor area) by axial motion. Findings confirm observed intransitive motions to engage premotor areas along a gross-scaled somatotopy.

Motor areas beyond motor performance: deficits in serial prediction following ventrolateral premotor lesions.

Previous functional MRI findings have indicated that a premotor-parietal network is involved in the perceptual processing of sequential information. Given that premotor functions have traditionally been restricted to behaviors requiring motor or sensorimotor computations, the goal of the present patient study was to further investigate whether the lateral premotor cortex is critical in purely perceptual sequencing. Patients with either ventral premotor or inferior parietal lesions, in addition to patients with prefrontal lesions and age- and gender-matched healthy controls, were tested during the processing of temporal, object-specific, and spatial sequences. Results revealed that premotor patients as well as parietal patients showed significantly higher error rates than did healthy controls on all sequence tasks. In contrast, prefrontal patients showed no behavioral deficits. These findings support the significance of the ventrolateral premotor cortex, in addition to parietal areas, in nonmotor (attentional) functions.