The role of lateral occipital face and object areas in the face inversion effect

Stimulus inversion impairs face discrimination to a greater extent than discrimination of other non-face object categories. This finding has led to suggestions that upright faces are represented by mechanisms specialized for upright faces whereas inverted face representation depends on more general object recognition mechanisms. In the present study we tested the causal role of face-selective and object-selective cortical areas for upright and inverted face discrimination by transiently disrupting neural processing using transcranial magnetic stimulation (TMS). Participants matched upright and inverted faces while TMS was delivered over each participant's functionally localized right occipital face area (rOFA) or right lateral occipital area (rLO). TMS delivered over rOFA disrupted the discrimination of upright and inverted faces while TMS delivered over rLO impaired inverted face discrimination only. These results provide causal evidence that upright faces are represented by face-specific mechanisms whereas inverted faces are represented by both face-specific and object-specific mechanisms. The similar sensitivity of the OFA to upright and inverted faces is consistent with the hypothesis that the OFA processes facial features at an early stage of face processing.     

The lateral‐occipital and the inferior‐frontal cortex play different roles during the naming of visually presented objects

We reasoned that if an area is devoted to processing only the visual features of objects, then transcranial magnetic stimulation (TMS) applied to this area in either hemisphere would affect the naming of objects presented in contralateral but not ipsilateral space. In contrast, if an area is involved in language, then one might expect to see effects of TMS when applied over the left but not the right hemisphere, regardless whether objects are in contralateral or ipsilateral space. Our experiments reveal two important findings. First, TMS delivered to the lateral‐occipital complex (LOC), a visual‐form area, affected the naming of objects presented in contralateral but not ipsilateral space, independent of which hemisphere was stimulated. In two additional experiments, when participants named the color of objects or made judgments about the size of stimuli as shown physically on a computer screen, TMS over the contralateral LOC did not affect color naming but did affect the participants' ability to make size judgments. Second, TMS delivered to the left but not the right posterior inferior‐frontal gyrus (pIFG) affected the naming of objects irrespective of whether objects were presented in contralateral or ipsilateral space. In a separate experiment, when participants were asked to either read or categorize words, TMS over the left but not the right pIFG affected word categorization but not word reading. On the basis of these findings, we propose that when people name visually‐presented objects, LOC processes the visual form of objects while the left pIFG processes the semantics of objects. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Increases of corticospinal excitability in self-related processing

Involvement of fronto‐parietal structures within the right hemisphere in bodily self recognition has gained convergent support from behavioural, neuropsychological and neuroimaging studies. Increases in corticospinal excitability via transcranial magnetic stimulation (TMS) also testify to right hemisphere self‐related processing. However, evidence for self‐dependent modulations of motor excitability is limited to the processing of face‐related information that, by definition, conveys someone’s identity. Here we tested the hypothesis that vision of one’s own hand, as compared with vision of somebody else’s hand, would also engage specific self‐hand processing in the right hemisphere. Healthy participants were submitted to a classic TMS paradigm to assess changes in corticospinal excitability of the right (Experiment 1) and left (Experiment 2) motor cortex, while viewing pictures of a (contralateral) still hand, which could either be their own (Self) or not (Other). As a control for body selectivity, subjects were also presented with pictures of a hand‐related, but non‐corporeal object, i.e. a mobile phone, which could similarly be their own or not. Results showed a selective right hemisphere increase in corticospinal excitability with self‐hand and self‐phone stimuli with respect to Other stimuli. Such a Self vs. Other modulation of primary motor cortex appeared at 600 ms and was maintained at 900 ms, but was not present at earlier timings (100 and 300 ms) and was completely absent following stimulation of the left hemisphere. A similar pattern observed for self‐hand and self‐phone stimuli suggests that owned hands and objects may undergo similar self‐processing, possibly via a different cortical network from that responsible for self‐face processing.     

Revisiting the backward masking deficit in schizophrenia: individual differences in performance and modeling with transcranial magnetic stimulation.

BACKGROUND: Deficits in backward masking have been variably reported in schizophrenia patients, but individual differences in the expression of these deficits have not been explicitly investigated. In addition, increased knowledge of the visual system has opened the door for new techniques such as transcranial magnetic stimulation (TMS) to explore these deficits physiologically. METHODS: Patients with schizophrenia and healthy controls were tested using a backward masking paradigm. In order to examine the functionality of visual pathways involved in backward masking, subjects were retested on a backward masking paradigm using single pulse TMS applied to occipital cortex in lieu of the masking stimuli. RESULTS: Compared with controls, patients had significantly delayed recovery from visual backward masking. However, 23.5% of patients (compared to 5% of controls) never recovered to levels approaching unmasked performance. When these subjects were segregated from the analysis, group differences vanished. In addition, stimulus masking with occipital TMS followed the same pattern in both patients and controls. CONCLUSIONS: Observations of individual differences in visual masking performance may identify a subgroup of schizophrenia patients. The TMS data suggest that this deficit may not localize to the occipital cortex. However, TMS can be a useful tool for localizing processing deficits in schizophrenia.     

Electric field calculations in brain stimulation based on finite elements: An optimized processing pipeline for the generation and usage of accurate individual head models

The need for realistic electric field calculations in human noninvasive brain stimulation is undisputed to more accurately determine the affected brain areas. However, using numerical techniques such as the finite element method (FEM) is methodologically complex, starting with the creation of accurate head models to the integration of the models in the numerical calculations. These problems substantially limit a more widespread application of numerical methods in brain stimulation up to now. We introduce an optimized processing pipeline allowing for the automatic generation of individualized high‐quality head models from magnetic resonance images and their usage in subsequent field calculations based on the FEM. The pipeline starts by extracting the borders between skin, skull, cerebrospinal fluid, gray and white matter. The quality of the resulting surfaces is subsequently improved, allowing for the creation of tetrahedral volume head meshes that can finally be used in the numerical calculations. The pipeline integrates and extends established (and mainly free) software for neuroimaging, computer graphics, and FEM calculations into one easy‐to‐use solution. We demonstrate the successful usage of the pipeline in six subjects, including field calculations for transcranial magnetic stimulation and transcranial direct current stimulation. The quality of the head volume meshes is validated both in terms of capturing the underlying anatomy and of the well‐shapedness of the mesh elements. The latter is crucial to guarantee the numerical robustness of the FEM calculations. The pipeline will be released as open‐source, allowing for the first time to perform realistic field calculations at an acceptable methodological complexity and moderate costs. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Reward processing abnormalities in Parkinson's disease

The primary motor cortex is important for motor learning and response selection, functions that require information on the expected and actual outcomes of behavior. Therefore, it should receive signals related to reward. Pathways from reward centers to motor cortex exist in primates. Previously, we showed that gamma aminobutyric acid–A–mediated inhibition in the motor cortex, measured by paired transcranial magnetic stimulation, changes with expectation and uncertainty of money rewards generated by a slot machine simulation. We examined the role of dopamine in this phenomenon by testing 13 mildly affected patients with Parkinson's disease, off and on dopaminergic medications, and 13 healthy, age‐matched controls. Consistent with a dopaminergic mechanism, reward expectation or predictability modulated the response to paired transcranial magnetic stimulation in controls, but not in unmedicated patients. A single dose of pramipexole restored this effect of reward, mainly by increasing the paired transcranial magnetic stimulation response amplitude during low expectation. Levodopa produced no such effect. Both pramipexole and levodopa increased risk‐taking behavior on the Iowa Gambling Task. However, pramipexole increased risk‐taking behavior more in patients showing lower paired transcranial magnetic stimulation response amplitude during low expectation. These results provide evidence that modulation of motor cortex inhibition by reward is mediated by dopamine signaling and that the physiological state of the motor cortex changes with risk‐taking tendency in patients on pramipexole. The cortical response to reward expectation may represent an endophenotype for risk‐taking behavior in patients on agonist treatment. © 2011 Movement Disorder Society     

Causal role of the right temporoparietal junction in selfishness depends on the social partner

The right temporoparietal junction (rTPJ) is a hub of the mentalizing network, but its causal role in social decisions remains an area of active investigation. While prior studies using causal neurostimulation methods have confirmed the role of the rTPJ in mentalizing and strategic social interactions, most of the evidence for its role in resource-sharing decisions comes from correlational neuroimaging studies. Further, it remains unclear if the influence of the rTPJ on decisions about sharing resources depends on whether the other person is salient and identifiable. To clarify the causal role of the rTPJ in social decision making, we examined the effects of putatively inhibitory rTPJ transcranial magnetic stimulation (TMS) on Dictator Game behavior with one partner that was physically present and one that was only minimally identified. Under control conditions, participants tended to create more advantageous inequity toward the partner that was only minimally identified, selfishly keeping more resources themselves. rTPJ TMS reduced this differential treatment of the two partners. Clarifying prior mixed findings, results suggest that the rTPJ may play a role in differentiating between others when deciding how equitably to divide resources, but may not play a general role in reducing selfishness by promoting aversion to advantageous inequity.     

Neuroanatomical correlates of therapeutic efficacy of low-frequency right prefrontal transcranial magnetic stimulation in treatment-resistant depression

Aims: Low‐frequency transcranial magnetic stimulation (TMS) to the right prefrontal cortex has been shown to be effective in treatment‐resistant depression. The aim of the present study was to investigate changes in regional cerebral blood flow (rCBF) after low‐frequency right prefrontal stimulation (LFRS), and neuroanatomical correlates of therapeutic efficacy of LFRS in treatment‐resistant depression. Methods: Twenty‐six patients with treatment‐resistant depression received five 60‐s 1‐Hz trains over the right prefrontal cortex, and 12 treatment sessions were administered during 3 weeks. Brain scans were acquired before and after LFRS using single photon emission computed tomography with ^99mTc‐ethyl cysteinate dimer. Severity of depression was assessed on the Hamilton Depression Rating Scale (HDRS). Results: Significant decreases in rCBF after LFRS were seen in the prefrontal cortex, orbitofrontal cortex, subgenual cingulate cortex, globus pallidus, thalamus, anterior and posterior insula, and midbrain in the right hemisphere. Therapeutic efficacy of LFRS was correlated with decreases in rCBF in the right prefrontal cortex, bilateral orbitofrontal cortex, right subgenual cingulate cortex, right putamen, and right anterior insula. Conclusion: The antidepressant effects of LFRS in treatment‐resistant depression may be associated with decreases in rCBF in the orbitofrontal cortex and the subgenual cingulate cortex via the right prefrontal cortex.     

Near and far space: Understanding the neural mechanisms of spatial attention

Visuospatial neglect is a multicomponent syndrome, and one dissociation reported is between neglect for near (peripersonal) and far (extrapersonal) space. Owing to patient heterogeneity and extensive lesions, it is difficult to determine the precise neural mechanisms underlying this dissociation using clinical methodology. In this study, transcranial magnetic stimulation was used to examine the involvement of three areas in the undamaged brain, while participants completed a conjunction search task in near and far space. The brain areas investigated were right posterior parietal cortex (rPPC), right frontal eye field (rFEF), and right ventral occipital cortex (rVO), each of which has been implicated in visuospatial processing. The results revealed a double dissociation, whereby rPPC was involved for search in near space only, whilst rVO only became necessary when the task was completed in far space. These data provide clear evidence for a dorsal and ventral dissociation between the processing of near and far space, which is compatible with the functional roles previously attributed to the two streams. For example, the involvement of the dorsal stream in near space reflects its role in vision for action, because it is within this spatial location that actions can be performed. The results also revealed that rFEF is involved in the processing of visual search in both near and far space and may contribute to visuospatial attention and/or the control of eye‐movements irrespective of spatial frame. We discuss our results with respect to their clear ramifications for clinical diagnosis and neurorehabilitation. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Probing the role of the right inferior frontal gyrus during Pain‐Related empathy processing: Evidence from fMRI and TMS

Recent studies have suggested that the right inferior frontal gyrus (rIFG) may be involved in pain‐related empathy. To verify the role of the rIFG, we performed a functional magnetic resonance imaging (fMRI) experiment to replicate previous research and further designed a noninvasive repetitive transcranial magnetic stimulation (rTMS) experiment to probe the causal role of the rIFG in pain‐related empathy processing. We assigned 74 volunteers (37 females) to three groups. Group 1 (n = 26) performed a task in which participants were required to perceive pain in others (task of pain: TP) and we used fMRI to observe the activity of the rIFG during pain‐related empathy processing. Then, we applied online rTMS to the rIFG and the vertex site (as reference site) to observe the performance of Group 2 (n = 24; performing TP) and Group 3 (n = 24; performing a control task of identifying body parts; task of body: TB). fMRI experiment demonstrated stronger activation in the rIFG than in the vertex during the perception of pain in others (p < .0001, Bonferroni‐corrected). rTMS experiment indicated that when the rIFG was temporarily disrupted, participants perceived pain in others significantly more slowly (p < .0001, Bonferroni‐corrected) than when the vertex was disrupted. Our results provide evidence that the rIFG is involved in pain‐related empathy processing, which yields insights into how the brain perceives pain in others.     

Cortical oscillatory activity and the induction of plasticity in the human motor cortex

Repetitive transcranial magnetic stimulation paradigms such as continuous theta burst stimulation (cTBS) induce long-term potentiation- and long-term depression-like plasticity in the human motor cortex. However, responses to cTBS are highly variable and may depend on the activity of the cortex at the time of stimulation. We investigated whether power in different electroencephalogram (EEG) frequency bands predicted the response to subsequent cTBS, and conversely whether cTBS had after-effects on the EEG. cTBS may utilize similar mechanisms of plasticity to motor learning; thus, we conducted a parallel set of experiments to test whether ongoing electroencephalography could predict performance of a visuomotor training task, and whether training itself had effects on the EEG. Motor evoked potentials (MEPs) provided an index of cortical excitability pre- and post-intervention. The EEG was recorded over the motor cortex pre- and post-intervention, and power spectra were computed. cTBS reduced MEP amplitudes; however, baseline power in the delta, theta, alpha or beta frequencies did not predict responses to cTBS or learning of the visuomotor training task. cTBS had no effect on delta, theta, alpha or beta power. In contrast, there was an increase in alpha power following visuomotor training that was positively correlated with changes in MEP amplitude post-training. The results suggest that the EEG is not a useful state-marker for predicting responses to plasticity-inducing paradigms. The correlation between alpha power and changes in corticospinal excitability following visuomotor training requires further investigation, but may be related to disengagement of the somatosensory system important for motor memory consolidation.     

Lack of prefrontal repetitive transcranial magnetic stimulation effects in time production processing

The aim of the present study was to determine the effects of high frequency repetitive transcranial magnetic stimulation (rTMS) over different neuroanatomical areas [left and right doroslateral prefrontal cortex (DLPFC) and right cerebellar hemisphere] on time production task. The study was performed in 16 healthy right-handed men with a cross-over, within subject repeated measures design. There were four rTMS conditions: baseline without stimulation, high frequency rTMS over right, left DLPFC and over right cerebellum. The volunteers were asked to produce a 3-min interval by internal counting. The rTMS was applied during the task. No significantly differences were observed in absolute error scores in time estimation task with any rTMS condition. This preliminary study does not support the role of the prefrontal lobe in time production processes.     

Investigating the Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Cortical Excitability in Healthy Males

ObjectivesAs a potential treatment for epilepsy, transcutaneous auricular vagus nerve stimulation (taVNS) has yielded inconsistent results. Combining transcranial magnetic stimulation with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) can be used to investigate the effect of interventions on cortical excitability by evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs). The goal of this study is to objectively evaluate the effect of taVNS on cortical excitability with TMS-EMG and TMS-EEG. These findings are expected to provide insight in the mechanism of action and help identify more optimal stimulation paradigms.Materials and MethodsIn this prospective single-blind cross-over study, 15 healthy male subjects underwent active and sham taVNS for 60 min, using a maximum tolerated stimulation current. Single and paired pulse TMS was delivered over the right-sided motor hotspot to evaluate MEPs and TEPs before and after the intervention. MEP statistical analysis was conducted with a two-way repeated measures ANOVA. TEPs were analyzed with a cluster-based permutation analysis. Linear regression analysis was implemented to investigate an association with stimulation current.ResultsMEP and TEP measurements were not affected by taVNS in this study. An association was found between taVNS stimulation current and MEP outcome measures indicating a decrease in cortical excitability in participants who tolerated higher taVNS currents. A subanalysis of participants (n = 8) who tolerated a taVNS current ≥2.5 mA showed a significant increase in the resting motor threshold, decrease in MEP amplitude and modulation of the P60 and P180 TEP components.ConclusionstaVNS did not affect cortical excitability measurements in the overall population in this study. However, taVNS has the potential to modulate specific markers of cortical excitability in participants who tolerate higher stimulation levels. These findings indicate the need for adequate stimulation protocols based on the recording of objective outcome parameters.     

Transcranial magnetic stimulation in the treatment of psychiatric disorders

Transcranial magnetic stimulation (TMS) is a new technology that applies the principles of electromagnetism to deliver an electrical field to the cerebral cortices. Well established in diagnostic electrophysiology, TMS is now being studied as a treatment for psychiatric disorders. Evidence suggests this technique is safe and acceptable to patients. The future may see the application of TMS in obsessive-compulsive disorder, post-traumatic stress disorder and mania. There is strong evidence that it will become an accepted treatment of depression.     

Investigating object representations during change detection in human extrastriate cortex

Detecting a change in a visual stimulus is particularly difficult when it is accompanied by a visual disruption such as a saccade or flicker. In order to say whether a stimulus has changed across such a disruption, some neural trace must persist. Here we investigated whether two different regions of the human extrastriate visual cortex contain neuronal populations encoding such a trace. Participants viewed a stimulus that included various objects and a short blank period (flicker) made it difficult to distinguish whether an object in the stimulus had changed or not. By applying transcranial magnetic stimulation (TMS) during the visual disruption we show that the lateral occipital (LO) cortex, but not the occipital face area, contains a sustained representation of a visual stimulus. TMS over LO improved the sensitivity and response bias for detecting changes by selectively reducing false alarms. We suggest that TMS enhanced the initial object representation and thus boosted neural events associated with object repetition. Our findings show that neuronal signals in the human LO cortex carry a sustained neural trace that is necessary for detecting the repetition of a stimulus.     

Role of the right temporoparietal junction in intergroup bias in trust decisions

Intergroup bias, which is the tendency to behave more positively toward an in‐group member than toward an out‐group member, is pervasive in real life. In particular, intergroup bias in trust decisions substantially influences multiple areas of life and thus better understanding of this tendency can provide significant insights into human social behavior. Although previous functional magnetic resonance imaging studies showed the involvement of the right temporoparietal junction (TPJ) in intergroup trust bias, a causal relationship between the two has rarely been explored. By combining repetitive transcranial magnetic stimulation and a newly developed trust game task, we investigated the causal role of the right TPJ in intergroup bias in trust decisions. In the trust game task, the counterpart's group membership (in‐group or out‐group) and reciprocity were manipulated. We applied either neuronavigated inhibitory continuous theta burst stimulation (cTBS) or sham stimulation over the right TPJ before performing the trust game task in healthy volunteers. After the sham stimulation, the participants' degrees of investments with in‐group members were significantly higher than those with out‐group members. However, after cTBS to the right TPJ, this difference was not observed. The current results extend previous findings by showing that the causal roles of the right TPJ can be observed in intergroup bias in trust decisions. Our findings add to our understanding of the mechanisms of human social behavior.     

Brain stimulation: a therapeutic approach for the treatment of neurological disorders

Brain stimulation has become one of the most acceptable therapeutic approaches in recent years and a powerful tool in the remedy against neurological diseases. Brain stimulation is achieved through the application of electric currents using non-invasive as well as invasive techniques. Recent technological advancements have evolved into the development of precise devices with capacity to produce well-controlled and effective brain stimulation. Currently, most used non-invasive techniques are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), whereas the most common invasive technique is deep brain stimulation (DBS). In last decade, application of these brain stimulation techniques has not only exploded but also expanded to wide variety of neurological disorders. Therefore, in the current review, we will provide an overview of the potential of both non-invasive (rTMS and tDCS) and invasive (DBS) brain stimulation techniques in the treatment of such brain diseases.     

Slow right prefrontal transcranial magnetic stimulation as a treatment for medication-resistant depression: a double-blind, placebo-controlled study

Over the past decade, efforts have been made to assess the positive therapeutic effects of transcranial magnetic stimulation (TMS) by altering the excitability of the brain. We conducted a double-blind, placebo-controlled study to assess the efficacy of right prefrontal slow repetitive TMS in patients with treatment refractory major depression. This pilot study supports the therapeutic potential of rTMS in the low-frequency range of 1 Hz on right prefrontal cortex for the treatment of refractory major depression. Additional studies will be necessary to assess the efficacy of rTMS with different indices (frequency, intensity, and stimulation site) for major depression and other psychiatric diseases.     

Repetitive transcranial magnetic stimulation of language function in patients with refractory epilepsy A preliminary functional magnetic resonance imaging study

To investigate whether repetitive transcranial magnetic stimulation （rTMS） can improve language function in patients with refractory epilepsy, three right-handed, refractory epilepsy patients who had complained of language dysfunction, were recruited. Over 1 month, 1-Hz rTMS treatment was performed every 3 days. A battery of language production and functional MRI were evaluated in the patients using a standard verb generation task both before and 1 month after rTMS treatment. Significant and lasting improvement in verb production was observed following rTMS treatment. Functional MRI results revealed that the left frontal lobes of two patients were more activated than they had been prior to therapy, and activation was primarily concentrated in the language-related areas. Results demonstrated that low frequency rTMS has potential to improve language function in patients with refractory epilepsy.