Stimulation Of Control Site Research Articles

Transcranial ultrasound stimulation to human middle temporal complex improves visual motion detection and modulates electrophysiological responses

BackgroundTranscranial ultrasound stimulation (TUS) holds promise as a novel technology for non-invasive neuromodulation, with greater spatial precision than other available methods and the ability to target deep brain structures. However, its safety and efficacy for behavioural and electrophysiological modulation remains controversial and it is not yet clear whether it can be used to manipulate the neural mechanisms supporting higher cognitive function in humans. Moreover, concerns have been raised about a potential TUS-induced auditory confound. ObjectivesWe aimed to investigate whether TUS can be used to modulate higher-order visual function in humans in an anatomically-specific way whilst controlling for auditory confounds. MethodsWe used participant-specific skull maps, functional localisation of brain targets, acoustic modelling and neuronavigation to guide TUS delivery to human visual motion processing cortex (hMT+) whilst participants performed a visual motion detection task. We compared the effects of hMT+ stimulation with sham and control site stimulation and examined EEG data for modulation of task-specific event-related potentials. An auditory mask was applied which prevented participants from distinguishing between stimulation and sham trials. ResultsCompared with sham and control site stimulation, TUS to hMT+ improved accuracy and reduced response times of visual motion detection. TUS also led to modulation of the task-specific event-related EEG potential. The amplitude of this modulation correlated with the performance benefit induced by TUS. No pathological changes were observed comparing structural MRI obtained before and after stimulation. ConclusionsThe results demonstrate for the first time the precision, efficacy and safety of TUS for stimulation of higher-order cortex and cognitive function in humans whilst controlling for auditory confounds.

Online transcranial magnetic stimulation reveals differential effects of transitivity in left inferior parietal cortex but not premotor cortex during action naming

Accumulating evidence indicates two cortical regions, the left ventral premotor cortex (PMv) and left intraparietal sulcus (IPS), are involved in spoken verb production. Some evidence also indicates these regions may be differentially engaged by transitive (i.e., object-oriented) versus intransitive actions. We explored the role of these regions during action picture naming in two experiments, each employing high frequency (10 Hz) online repetitive Transcranial Magnetic Stimulation (rTMS) in 20 participants. In Experiment 1, participants named intransitive action pictures (e.g., LAUGH) accompanied by active and sham rTMS to the left PMv, left IPS, and right superior parietal lobule (SPL; control site). Application of rTMS to PMv resulted in slower naming latencies compared to sham and control site stimulation, whereas stimulation of the IPS did not result in any significant effects. Experiment 2 employed active and sham rTMS identical to Experiment 1 with transitive action pictures (e.g., PUSH). Stimulation of both regions induced changes in naming latencies compared to sham and control site stimulation, with rTMS applied to PMv slowing responses and IPS stimulation facilitating them. Surprisingly, stimulation of the right SPL control site also slowed naming compared to sham across both Experiments. Overall, these findings indicate different roles for PMv and IPS during action picture naming. Specifically, the divergent effects of PMv and IPS stimulation in the transitive action naming task indicate different processes likely operate in the two regions during verb production. Involvement of the right SPL across both transitive and intransitive action naming might reflect visuospatial or general attention mechanisms rather than language processes per se.

Episodic Memory Precision and Reality Monitoring Following Stimulation of Angular Gyrus.

The qualities of remembered experiences are often used to inform "reality monitoring" judgments, our ability to distinguish real and imagined events. Previous experiments have tended to investigate only whether reality monitoring decisions are accurate or not, providing little insight into the extent to which reality monitoring may be affected by qualities of the underlying mnemonic representations. We used a continuous-response memory precision task to measure the quality of remembered experiences that underlie two different types of reality monitoring decisions: self/experimenter decisions that distinguish actions performed by participants and the experimenter and imagined/perceived decisions that distinguish imagined and perceived experiences. The data revealed memory precision to be associated with higher accuracy in both self/experimenter and imagined/perceived reality monitoring decisions, with lower precision linked with a tendency to misattribute self-generated experiences to external sources. We then sought to investigate the possible neurocognitive basis of these observed associations by applying brain stimulation to a region that has been implicated in precise recollection of personal events, the left angular gyrus. Stimulation of angular gyrus selectively reduced the association between memory precision and self-referential reality monitoring decisions, relative to control site stimulation. The angular gyrus may, therefore, be important for the mnemonic processes involved in representing remembered experiences that give rise to a sense of self-agency, a key component of "autonoetic consciousness" that characterizes episodic memory.

Stimulating parietal regions of the multiple-demand cortex impairs novel vocabulary learning

Neuroimaging research demonstrated that the early stages of learning engage domain-general networks, non-specialist brain regions that process a wide variety of cognitive tasks. Those networks gradually disengage as learning progresses and learned information becomes processed in brain networks specialised for the specific function (e.g., language). In the current study, we used repetitive transcranial magnetic stimulation (rTMS) in the form of continuous theta burst stimulation (cTBS) to test whether stimulation of the bilateral parietal region of the domain-general network impairs learning new vocabulary, indicating its causal engagement in this process. Twenty participants, with no prior knowledge of Polish, learned Polish words for well-known objects across three training stages. The first training stage started with cTBS applied to either the experimental domain-general bilateral parietal site or the control bilateral precentral site. Immediately after cTBS, the vocabulary training commenced. A different set of words was learned for each site. Immediately after the training stage, participants performed a novel vocabulary test, designed to measure their knowledge of the new words and the effect of stimulation on learning. To measure stimulation effect when the words were more established in the mental lexicon, participants received additional training on the same words but without cTBS (second training stage) and then the full procedures from the first training stage were repeated (third training stage). Results demonstrated that stimulation impaired novel word learning when applied to the bilateral parietal site at the first stage of learning only. This effect was not present when newly learned words were used more proficiently in the third training stage, or at any learning stage during control site stimulation. Our results show that the bilateral parietal region of the domain-general network causally contributes to the successful learning of novel words.

Non-invasive stimulation of the auditory feedback area for improved articulation in Parkinson's disease

IntroductionHypokinetic dysarthria (HD) is a common symptom of Parkinson's disease (PD) which does not respond well to PD treatments. We investigated acute effects of repetitive transcranial magnetic stimulation (rTMS) of the motor and auditory feedback area on HD in PD using acoustic analysis of speech. MethodsWe used 10 Hz and 1 Hz stimulation protocols and applied rTMS over the left orofacial primary motor area, the right superior temporal gyrus (STG), and over the vertex (a control stimulation site) in 16 PD patients with HD. A cross-over design was used. Stimulation sites and protocols were randomised across subjects and sessions. Acoustic analysis of a sentence reading task performed inside the MR scanner was used to evaluate rTMS-induced effects on motor speech. Acute fMRI changes due to rTMS were also analysed. ResultsThe 1 Hz STG stimulation produced significant increases of the relative standard deviation of the 2nd formant (p = 0.019), i.e. an acoustic parameter describing the tongue and jaw movements. The effects were superior to the control site stimulation and were accompanied by increased resting state functional connectivity between the stimulated region and the right parahippocampal gyrus. The rTMS-induced acoustic changes were correlated with the reading task-related BOLD signal increases of the stimulated area (R = 0.654, p = 0.029). ConclusionOur results demonstrate for the first time that low-frequency stimulation of the temporal auditory feedback area may improve articulation in PD and enhance functional connectivity between the STG and the cortical region involved in an overt speech control.

Effects of High-Definition and Conventional tDCS on Response Inhibition.

Response inhibition is a critical executive function, enabling the adaptive control of behavior in a changing environment. The inferior frontal cortex (IFC) is considered to be critical for response inhibition, leading researchers to develop transcranial direct current stimulation (tDCS) montages attempting to target the IFC and improve inhibitory performance. However, conventional tDCS montages produce diffuse current through the brain, making it difficult to establish causality between stimulation of any one given brain region and resulting behavioral changes. Recently, high-definition tDCS (HD-tDCS) methods have been developed to target brain regions with increased focality relative to conventional tDCS. Remarkably few studies have utilized HD-tDCS to improve cognitive task performance, however, and no study has directly compared the behavioral effects of HD-tDCS to conventional tDCS. In the present study, participants received either HD-tDCS or conventional tDCS to the IFC during performance of a response inhibition task (stop-signal task, SST) or a control task (choice reaction time task, CRT). A third group of participants completed the same behavioral protocols, but received tDCS to a control site (mid-occipital cortex). Post-stimulation improvement in SST performance was analyzed as a function of tDCS group and the task performed during stimulation using both conventional and Bayesian parameter estimation analyses. Bayesian estimation of the effects of HD- and conventional tDCS to IFC relative to control site stimulation demonstrated enhanced response inhibition for both conditions. No improvements were found after control task (CRT) training in any tDCS condition. Results support the use of both HD- and conventional tDCS to the IFC for improving response inhibition, providing empirical evidence that HD-tDCS can be used to facilitate performance on an executive function task.

Chronometric Electrical Stimulation of Right Inferior Frontal Cortex Increases Motor Braking

The right inferior frontal cortex (rIFC) is important for stopping responses. Recent research shows that it is also activated when response emission is slowed down when stopping is anticipated. This suggests that rIFC also functions as a goal-driven brake. Here, we investigated the causal role of rIFC in goal-driven braking by using computer-controlled, event-related (chronometric), direct electrical stimulation (DES). We compared the effects of rIFC stimulation on trials in which responses were made in the presence versus absence of a stopping-goal ("Maybe Stop" [MS] vs "No Stop" [NS]). We show that DES of rIFC slowed down responses (compared with control-site stimulation) and that rIFC stimulation induced more slowing when motor braking was required (MS) compared with when it was not (NS). Our results strongly support a causal role of a rIFC-based network in inhibitory motor control. Importantly, the results extend this causal role beyond externally driven stopping to goal-driven inhibitory control, which is a richer model of human self-control. These results also provide the first demonstration of double-blind chronometric DES of human prefrontal cortex, and suggest that--in the case of rIFC--this could lead to augmentation of motor braking.

P 106. High-frequency rTMS stimulation improves the facial mimicry and detection responses in an empathic emotional task

Facial expression detection and facial mimicry behavior in response to an emotional empathic task were analyzed in the present research. We supposed a “simulation mechanism” may be related to emotional face detection, and that it could be supported by prefrontal cortical structures ( Balconi et al., 2011 ). High frequency rTMS (repeated Transcranial Magnetic Stimulation) was applied to MPFC to induce an increased response to facial expression of emotions when subjects ( N = 16) were required to emotionally empathize with the facial stimuli. The stimulus valence was also varied (negative vs positive vs. neutral faces) to explore also the emotional content effect on empathic behavior. Autonomic (facial zygomatic and corrugator EMG subjective response) and detection (correct recognitions, CRs; RTs, response times) measures were found to be modulated by MPFC activity ( Balconi and Bortolotti, 2012 ). Specifically, when prefrontal structures were activated (in comparison with sham effect and control site stimulation) an increased performance was observed in terms of increased CRs and reduced RTs for face recognition from one hand; of increased emotion-specific EMG response for the other hand. In fact, zygomatic muscle was more responsive in case of positive emotion (happiness), whereas corrugator activity was related to negative emotions (fear, anger, disgust). A higher effect was revealed for negative, and potentially aversive, faces in comparison respectively with positive and neutral faces. Finally, a direct correlation was found between the psychophysiological and detection measures. Taken together, these results suggest a “simulation mechanism” underlying emotion detection in an empathic situation that includes both EMG and behavioral responses ( Balconi and Bortolotti, 2012 ). This mechanism appears to be supported and regulated by MPFC area.

High-frequency rTMS improves facial mimicry and detection responses in an empathic emotional task

In this study, we analysed facial expression detection and facial mimicry behaviour in response to an emotional empathic task. We posited that a “simulation mechanism” may be related to emotional face detection and that this mechanism could be supported by prefrontal cortical structures. To evaluate our hypothesis, we requested 16 subjects to emotionally empathise with facial stimuli and applied high frequency repeated transcranial magnetic stimulation (rTMS) to the medial prefrontal cortex (MPFC) in order to induce an increased response to the facial expressions of emotion. To determine whether emotional content affects empathic behaviour, we also varied the stimulus valence (negative vs. positive vs. neutral faces). We found that autonomic (facial zygomatic and corrugator electromyography (EMG) subjective response) and detection (correct responses (CRs); response times (RTs)) measures were modulated by the MPFC activity. Specifically, when prefrontal structures were activated, subjects displayed an increased performance in CRs and reduced RTs for face recognition, as well as increased emotion-specific EMG responses in comparison to sham effects and control site stimulation. In fact, the zygomatic muscle was more responsive in cases of positive emotion (happiness), whereas corrugator activity was more robust during periods of negative emotion (fear, anger, disgust). However, an overall stronger effect was observed in response to negative, and potentially aversive, faces when compared with responses to positive and neutral faces. Finally, a direct correlation was found between the psychophysiological responses and detection measures. In summary, these results suggest that a “simulation mechanism” underlies emotion detection in an empathic situation that includes both EMG and behavioural responses. This mechanism appears to be supported and regulated by the MPFC area.

Adaptation to Cortical Noise Induced by Transcranial Magnetic Stimulation to the Occipital Lobe

Transcranial magnetic stimulation (TMS) is increasingly used as a method to modify and study functional brain activity. However, results from various studies have produced conflicting theories on how TMS of cortical tissue influences ongoing visual processing. To investigate this issue, single pulse TMS was applied over left V1 in five healthy subjects during an orientation discrimination task (vertical vs. horizontal) using a Gabor patch (2 c/deg, presented 6° in the right visual field). Stimulus contrast was set to each individual's threshold, measured in the absence of TMS. When TMS was applied over V1 performance decreased in all observers (by 1.2–8.7%) compared to accuracy levels obtained during stimulation of a control site (Cz). Crucially, accuracy levels during V1 stimulation gradually improved across blocks of 200 trials in some subjects, whereas performance remained stable during control site stimulation. In contrast, this pattern of recovery was not found in an analogous backward masking paradi...

The effect of rTMS on auditory hallucinations: Clues from an EEG-rTMS study

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) to the temporoparietal region has been proposed as a therapeutic option for auditory verbal hallucinations (AVH). However, most large randomized controlled trials failed to demonstrate a superior effect of rTMS treatment as compared to sham. Previous studies applied daily rTMS sessions for one or more weeks to summate its effects. However, the effect of a single rTMS treatment on AVH-severity has never been studied, making it unclear if there is an initial effect that could be increased by repeated treatment. MethodsIn three separate sessions, twenty-four patients with a psychotic disorder received 1-Hz rTMS to the left temporoparietal cortex, its right-sided homologue or a centro-occipital control site. Severity of AVH was assessed before and after each rTMS session and resting-state EEGs were recorded to investigate the neuronal effects of rTMS. ResultsStimulation of the temporoparietal cortices was not more effective in reducing AVH-severity than control-site stimulation. In addition, EEG-related power and connectivity measures were not affected differently across stimulation sites and changes in neuronal activity did not correlate with changes in AVH-severity. ConclusionsThese results may suggest a placebo effect of a single session of 1-Hz rTMS treatment on AVH-severity.

Broca's area plays a causal role in morphosyntactic processing

Although there is strong evidence that Broca's area is important for syntax, this may simply be a by-product of greater working memory and/or cognitive control demands for more complex syntactic structures. Here we report an experiment with event-related transcranial magnetic stimulation (TMS) to investigate whether Broca's area plays a causal role in morphosyntactic processing when both working memory and cognitive control demands are low. Participants were presented with word pairs that could either agree or disagree in grammatical number or gender while receiving stimulation to Broca's area or to the right intraparietal sulcus (a control site). Stimulation of Broca's area significantly reduced the advantage for grammatical relative to ungrammatical word pairs. In contrast, stimulation of control site left this grammaticality advantage unchanged. The interaction between grammaticality and stimulation was specific to Broca's area, suggesting a clear involvement of the region in morphosyntactic processing.

Low-frequency repetitive transcranial magnetic stimulation of the anterior temporal lobes does not dissociate social versus nonsocial semantic knowledge

Social conceptual knowledge is imperative to communicate with, interact with, and interpret human society; however, little is known about the neural basis of social concepts. Previous research has predominantly suggested that the right anterior temporal lobe (ATL) may specifically represent social conceptual knowledge, whereas the left ATL is necessary for general semantic processing. However, this view has not always been supported by empirical studies. Employing a lateralized design and two different semantic tasks and a nonsemantic control task, we aimed to clarify some of these ambiguities by potentially dissociating left from right functionality and social from nonsocial concepts, using inhibitory repetitive transcranial magnetic stimulation (rTMS) coupled with a sham and control site stimulation (N = 56). The results showed that stimulation of the left ATL led to overall faster processing times without affecting accuracy, whilst the right ATL and control groups did not significantly change in reaction times or accuracy. No difference occurred between social and nonsocial concepts after stimulation. This study is the first to show that inhibition of the left temporal lobe may improve performance on a semantic task and provides evidence that the ATLs may be lateralized in conceptual processing. The results do not confirm that the right temporal lobe is crucial for social conceptual processing, as inhibition did not significantly affect performance for social concepts.

The Role of the Dorsolateral Prefrontal Cortex in Bimodal Divided Attention: Two Transcranial Magnetic Stimulation Studies

The neural processes underlying the ability to divide attention between multiple sensory modalities remain poorly understood. To investigate the role of the dorsolateral prefrontal cortex (DLPFC) in bimodal divided attention, we completed two repetitive transcranial magnetic stimulation (rTMS) studies. We tested the hypothesis that the DLPFC is necessary in the ability to divide attention across modalities. This hypothesis originated as a result of a previous fMRI study in which the posterior DLPFC was active during a bimodal divided attention condition [Johnson, J. A., & Zatorre, R. J. Neural substrates for dividing and focusing attention between simultaneous auditory and visual events. Neuroimage, 2006]. In the current experiments, two separate groups of subjects underwent 10 min of slow rTMS to temporarily disrupt function of the DLPFC. In both groups, the ability to divide attention between unrelated auditory and visual stimuli decreased following DLPFC disruption compared to control site stimulation. Specifically, the ability to divide attention between modalities was hindered, leading to a pattern of behavior similar to bimodal selective attention (ability to attend to one or the other modality but not both). We discuss possible roles of the posterior DLPFC in bimodal divided attention and conclude that the area may be functioning to support the increased working memory load associated with divided, compared to selective attention.

Brainstem, thalamus, and cortex: FMRI evidence for midbrain reticular formation involvement in a human model of neuropathic pain

Hyperalgesia (often associated with neuropathic pain) is the clinical manifestation of plastic changes in pain processing. It can be evident at the site of injury - primary hyperalgesia – or outside it – secondary hyperalgesia. Our aim was to investigate the neural correlates of punctate mechanical secondary hyperalgesia. We used the heat/capsaicin sensitization model (45°C thermal stimulus followed by topical application of 0.075% capsaicin) to induce secondary hyperalgesia on the anteromedial surface of the lower legs in 12 healthy volunteers. We used whole-brain, high field (3T) functional magnetic resonance imaging (fMRI) to look at the brain activation elicited by mechanical stimulation with a 26 gram von Frey filament (254.8 mNewtons, 0.546 mm diameter) in the area of secondary hyperalgesia and compared it with the response to stimulation of normal, untreated skin, in the same subjects in a different session. Following heat/capsaicin treatment, all subjects developed an area of secondary hyperalgesia. The paired test between the brain activation maps in response to punctate stimulation of the secondary hyperalgesia area and the respective activation maps to control site stimulation showed activation in the cerebellum, the midbrain periaqueductal gray (PAG) and nucleus cuneiformis (NCF), the thalamus bilaterally, the left secondary somatosensory cortex (SII) and the left primary somatosensory cortex (SI), the anterior and posterior cingulate cortices, the right middle frontal gyrus, the right inferior parietal and right precuneus. Animal studies have established role for the rostral ventromedial medulla (RVM) in the development and maintenance of central sensitization and secondary hyperalgesia. The PAG and the NCF are the major source of input to the RVM and therefore in a position to modulate its output. We believe this is the first evidence in humans for a role of the NCF and PAG in secondary hyperalgesia.