Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique increasingly used in clinical and research practices around the world. Historically, the ethical considerations guiding the therapeutic practice of TMS were largely concerned with aspects of subject safety in clinical trials. While safety remains of paramount importance, the recent US Food and Drug Administration approval of the Neuronetics NeuroStar TMS device for the treatment of specific medication-resistant depression has raised a number of additional ethical concerns, including (...) marketing, off-label use and technician certification. This article provides an overview of the history of TMS and highlights the ethical questions that are likely arise as the therapeutic use of TMS continues to expand. (shrink)

We can understand viewed scenes and extract task-relevant information within a few hundred milliseconds. This process is generally supported by three cortical regions that show selectivity for scene images: parahippocampal place area (PPA), medial place area (MPA) and occipital place area (OPA). Prior studies have focused on the visual information each region is responsive to, usually within the context of recognition or navigation. Here, we move beyond these tasks to investigate gaze allocation during scene viewing. Eye movements rely on a (...) scene’s visual representation to direct saccades, and thus foveal vision. In particular, we focus on the contribution of OPA, which is i) located in occipito-parietal cortex, likely feeding information into parts of the dorsal pathway critical for eye movements, and ii) contains strong retinotopic representations of the contralateral visual field. Participants viewed scene images for 1034 ms while their eye movements were recorded. On half of the trials, a 500 ms train of five transcranial magnetic stimulation (TMS) pulses was applied to the participant’s cortex, starting at scene onset. TMS was applied to the right hemisphere over either OPA or the occipital face area (OFA), which also exhibits a contralateral visual field bias but shows selectivity for face stimuli. Participants generally made an overall left-to-right, top-to-bottom pattern of eye movements across all conditions. When TMS was applied to OPA, there was an increased saccade latency for eye movements toward the contralateral relative to the ipsilateral visual field after the final TMS pulse (400ms). Additionally, TMS to the OPA biased fixation positions away from the contralateral side of the scene compared to the control condition, while the OFA group showed no such effect. There was no effect on horizontal saccade amplitudes. These combined results suggest that OPA might serve to represent local scene information that can then be utilized by visuomotor control networks to guide gaze allocation in natural scenes. (shrink)

In order to study whether there exist a period of activity in the human early visual cortex that contributes exclusively to visual awareness, we applied transcranial magnetic stimulation over the early visual cortex and measured subjective visual awareness during visual forced-choice symbol or orientation discrimination tasks. TMS produced one dip in awareness 60–120 ms after stimulus onset, while forced-choice orientation discrimination was suppressed between 60 and 90 ms and symbol discrimination between 60 and 120 ms. Thus, a (...) time window specific to visual awareness was found only in the orientation condition at 120 ms. The results imply that both conscious and unconscious perception depend on activity in early visual areas. On the basis of previous estimates of neural processing speed, we suggest that the late part of the activity period most likely involve local extrastriate–striate interactions which provide the contents for visual awareness but are not themselves sufficient for awareness to arise. (shrink)

Transcranial magnetic stimulation (TMS) is a method capable of transiently modulating neural excitability. Depending on the stimulation parameters information processing in the brain can be either enhanced or disrupted. This way the contribution of different brain areas involved in mental processes can be studied, allowing a functional decomposition of cognitive behavior both in the temporal and spatial domain, hence providing a functional resolution of brain/mind processes. The aim of the present paper is to argue that TMS (...) with its ability to draw causal inferences on function and its neural representations is a valuable neurophysiological tool for investigating the causal basis of neuronal functions and can provide substantive insight into the modern interdisciplinary and (anti)reductionist neurophilosophical debates concerning the relationships between brain functions and mental abilities. Thus, TMS can serve as a heuristic method for resolving causal issues in an arena where only correlative tools have traditionally been available. (shrink)

Single-pulse and repetitive transcranial magnetic stimulation are used in clinical practice for diagnostic and therapeutic purposes. However, rTMS-based therapies that lead to a significant and sustained reduction in neuropsychiatric symptoms remain scarce. While it is generally accepted that the stimulation frequency plays a crucial role in producing the therapeutic effects of rTMS, less attention has been dedicated to determining the role of the electric field strength. Conventional threshold-based intensity selection approaches, such as the resting motor threshold, (...) produce variable stimulation intensities and electric fields across participants and cortical regions. Insufficient standardization of electric field strength may contribute to the variability of rTMS effects and thus therapeutic success. Computational approaches that can prospectively optimize the electric field and standardize it across patients and cortical targets may overcome some of these limitations. Here, we discuss these approaches and propose that electric field standardization will be instrumental for translational science frameworks aimed at deciphering the subcellular, cellular, and network mechanisms of rTMS. Advances in understanding these mechanisms will be important for optimizing rTMS-based therapies in psychiatry. (shrink)

Transcranial magnetic stimulation (TMS) is a method capable of transiently modulating neural excitability. Depending on the stimulation parameters information processing in the brain can be either enhanced or disrupted. This way the contribution of different brain areas involved in mental processes can be studied, allowing a functional decomposition of cognitive behavior both in the temporal and spatial domain, hence providing a functional resolution of brain/mind processes. The aim of the present paper is to argue that TMS (...) with its ability to draw causal inferences on function and its neural representations is a valuable neurophysiological tool for investigating the causal basis of neuronal functions and can provide substantive insight into the modern interdisciplinary and (anti)reductionist neurophilosophical debates concerning the relationships between brain functions and mental abilities. Thus, TMS can serve as a heuristic method for resolving causal issues in an arena where only correlative tools have traditionally been available. (shrink)

Transcranial magnetic stimulation is a relatively non-invasive technique to interfere with the function of small cortical areas through currents induced by alternating magnetic fields emanating from a handheld coil placed directly above the targeted area. This technique has clear effects on a whole range of measures of brain function and has become an important research tool in neuropsychiatry. More recently, TMS has been studied in psychiatry mainly to assess its putative therapeutic effects in the treatment of (...) refractory major depression. Most studies indicate that both low-frequency TMS and higher frequency repetitive TMS may have some antidepressant properties. This is most interesting and opens a whole new avenue of low invasive techniques to stimulate the brain in major depression. However, definite therapeutic effects of clinical significance still remain to be demonstrated. (shrink)

Neuropsychological patients exhibiting category-selective visual agnosias provide unique insights into the cognitive functions of the human brain. Transcranial magnetic stimulation, in contrast, can be used to draw causal inferences, as one of the effects of the cortical disruption induced by magnetic stimulation is to act as a “virtual lesion” lasting from tens of milliseconds up to approximately one hour, depending on the type of stimulation. This specificity offers a unique advantage in psychological testing as (...) TMS can be used to test where and when cognitive computations are performed. This article briefly describes TMS, considers the small but growing number of studies that use TMS to disrupt face processing. It discusses how TMS can be used in the future to understand better how faces are cortically represented in the human brain. (shrink)

PurposeTo explore the changes of cerebral blood flow and fractional anisotropy in stroke patients with motor dysfunction after repetitive transcranial magnetic stimulation treatment, and to better understand the role of rTMS on motor rehabilitation of subcortical stroke patients from the perfusion and structural level.Materials and MethodsIn total, 23 first-episode acute ischemic stroke patients and sixteen healthy controls were included. The patients were divided into the rTMS and sham group. The rehabilitation assessments and examination of perfusion and structural (...) MRI were performed before and after rTMS therapy for each patient. Voxel-based analysis was used to detect the difference in CBF and FA among all three groups. The Pearson correlation analysis was conducted to evaluate the relationship between the CBF/FA value and the motor scales.ResultsAfter rTMS, significantly increased CBF was found in the ipsilesional supplementary motor area, postcentral gyrus, precentral gyrus, pons, medulla oblongata, contralesional midbrain, superior cerebellar peduncle, and middle cerebellar peduncle compared to that during the prestimulation and in the sham group, these fasciculi comprise the cortex-pontine-cerebellum-cortex loop. Besides, altered CBF in the ipsilesional precentral gyrus, postcentral gyrus, and pons was positively associated with the improved Fugl-Meyer assessment scores. Significantly decreased FA was found in the contralesional precentral gyrus, increased FA was found in the ipsilesional postcentral gyrus, precentral gyrus, contralesional supplementary motor area, and bilateral cerebellum, these fasciculi comprise the corticospinal tract. The change of FMA score was positively correlated with altered FA value in the ipsilesional postcentral gyrus and negatively correlated with altered FA value in the contralesional precentral gyrus.ConclusionOur results suggested that rTMS could facilitate the motor recovery of stroke patients. High frequency could promote the improvement of functional activity of ipsilesional CPC loop and the recovery of the microstructure of CST. (shrink)

Transcranial magnetic stimulation is used to make inferences about relationships between brain areas and their functions because, in contrast to neuroimaging tools, it modulates neuronal activity. The central aim of this article is to critically evaluate to what extent it is possible to draw causal inferences from repetitive TMS data. To that end, we describe the logical limitations of inferences based on rTMS experiments. The presented analysis suggests that rTMS alone does not provide the sort of premises (...) that are sufficient to warrant strong inferences about the direct causal properties of targeted brain structures. Overcoming these limitations demands a close look at the designs of rTMS studies, especially the methodological and theoretical conditions which are necessary for the functional decomposition of the relations between brain areas and cognitive functions. The main points of this article are that TMS-based inferences are limited in that stimulation-related causal effects are not equivalent to structure-related causal effects due to TMS side effects, the electric field distribution, and the sensitivity of neuroimaging and behavioral methods in detecting structure-related effects and disentangling them from confounds. Moreover, the postulated causal effects can be based on indirect effects. A few suggestions on how to manage some of these limitations are presented. We discuss the benefits of combining rTMS with neuroimaging in experimental reasoning and we address the restrictions and requirements of rTMS control conditions. The use of neuroimaging and control conditions allows stronger inferences to be gained, but the strength of the inferences that can be drawn depends on the individual experiment’s designs. Moreover, in some cases, TMS might not be an appropriate method of answering causality-related questions or the hypotheses have to account for the limitations of this technique. We hope this summary and formalization of the reasoning behind rTMS research can be of use not only for scientists and clinicians who intend to interpret rTMS results causally but also for philosophers interested in causal inferences based on brain stimulation research. (shrink)

BackgroundHigh frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex has shown significant efficiency in the treatment of resistant depression. However in healthy subjects, the effects of rTMS remain unclear.ObjectiveOur aim was to determine the impact of 10 sessions of rTMS applied to the DLPFC on mood and emotion recognition in healthy subjects.DesignIn a randomised double-blind study, 20 subjects received 10 daily sessions of active or sham rTMS. The TMS coil was positioned on the left (...) DLPFC through neuronavigation. Several dimensions of mood and emotion processing were assessed at baseline and after rTMS with clinical scales, visual analogue scales, and the Ekman 60 faces test.ResultsThe 10 rTMS sessions targeting the DLPFC were well tolerated. No significant difference was found between the active group and the control group for clinical scales and the Ekman 60 faces test. Compared to the control group, the active rTM... (shrink)

ObjectiveThe effects and possible mechanisms of cerebellar high-frequency repetitive transcranial magnetic stimulation on swallowing-related neural networks were studied using resting-state functional magnetic resonance imaging.MethodA total of 23 healthy volunteers were recruited, and 19 healthy volunteers were finally included for the statistical analysis. Before stimulation, the cerebellar hemisphere dominant for swallowing was determined by the single-pulse TMS. The cerebellar representation of the suprahyoid muscles of this hemisphere was selected as the target for stimulation with 10 (...) Hz rTMS, 100% resting motor threshold, and 250 pulses, with every 1 s of stimulation followed by an interval of 9 s. The motor evoked potential amplitude of the suprahyoid muscles in the bilateral cerebral cortex was measured before and after stimulation to evaluate the cortical excitability. Forty-eight hours after elution, rTMS was reapplied on the dominant cerebellar representation of the suprahyoid muscles with the same stimulation parameters. Rs-fMRI was performed before and after stimulation to observe the changes in amplitude of low-frequency fluctuation and regional homology at 0.01–0.08 Hz, 0.01–0.027 Hz, and 0.027–0.073 Hz.ResultsAfter cerebellar high-frequency rTMS, MEP recorded from swallowing-related bilateral cerebral cortex was increased. The results of rs-fMRI showed that at 0.01–0.08 Hz, ALFF was increased at the pons, right cerebellum, and medulla and decreased at the left temporal lobe, and ReHo was decreased at the left insular lobe, right temporal lobe, and corpus callosum. At 0.01–0.027 Hz, ALFF was decreased at the left temporal lobe, and ReHo was decreased at the right temporal lobe, left putamen, and left supplementary motor area.ConclusionRepetitive transcranial magnetic stimulation of the swallowing cortex in the dominant cerebellar hemisphere increased the bilateral cerebral swallowing cortex excitability and enhanced pontine, bulbar, and cerebellar spontaneous neural activity, suggesting that unilateral high-frequency stimulation of the cerebellum can excite both brainstem and cortical swallowing centers. These findings all provide favorable support for the application of cerebellar rTMS in the clinical practice. (shrink)

Depression is a widespread concern in the United States. Neuromodulation treatments are becoming more common but there is emerging concern for racial disparities in neuromodulation treatment utilization. This study focuses on Transcranial Magnetic Stimulation (TMS), a treatment for depression, and the structural and attitudinal barriers that racialized individuals face in accessing it. In January 2023 participants from the Twin Cities, Minnesota engaged in focus groups, coupled with an educational video intervention. Individuals self identified as non-white who had (...) no previous TMS exposure but had tried at least one treatment for their depression. Results revealed that the intervention did not notably change knowledge or stigma about TMS, but attitudes surrounding traveling for treatment changed. Notably, barriers like affordability, frequency of treatment, and lack of knowledge persist. Participants expressed a desire for more information, personal connection, and a tailored educational approach. The study suggests a need for multifaceted strategies to reduce disparities, focusing on education, community-based resources, and policy interventions. Immediate actions that can be taken include the creation of a TMS education program focused on patient engagement and awareness about TMS. (shrink)

BackgroundRepetitive transcranial magnetic stimulation applied to the mylohyoid cortical region has positive clinical effects on post-stroke. Therefore, we conducted a meta-analysis to investigate the efficacy of rTMS for patients with post-stroke dysphagia.MethodsAccording to PRISMA guidelines, we searched the databases of MEDLINE, Cochrane Library, Embase, Web of Science, CNKI, Wangfang. We searched for studies of randomized controlled trials of rTMS to treat dysphagia after stroke and screened by inclusion and exclusion criteria. Features of RCTs were extracted. The heterogeneity (...) of the trials was measured by I2 statistic.ResultsIn total, 11 RCTs with 463 dysphagia patients fulfilled our inclusion criteria. In our analysis, rTMS demonstrated a great beneficial effect for post-stroke dysphagia when combined with traditional swallowing exercises. Moreover, a greatly significant difference was noted based on stimulation frequency. Additionally, no significant difference was observed based on stimulation site.ConclusionsOverall, rTMS can effectively accelerate the improvement of swallowing function in patients with post-stroke swallowing disorders. (shrink)

The non-invasive stimulation techniques are already recognized as technology that allows neuroenhancement, specifically the Transcranial Magnetic Stimulation can be applied following potentiation protocols in order to enhance both cognitive and motor systems. Hand in hand with this capacity arises the ethical problem of its application. The objective of this contribution is to describe and discuss what ethical aspects have been established in relation to this current phenomenon. Thus, we will first describe the mechanisms and results of (...) non-invasive technology in relation to neuroenhancement, focusing on TMS enhancing protocols. Next, we will make a brief historical review of the ethical aspects established around the application of TMS and its ability to result in neuroenhancement. Finally, we will discuss the ethical aspects that have been described and new debates that arise from the previous ones, concluding in an expanded vision of addressing the discussion. (shrink)

After spinal cord injury (SCI), motoneuron death occurs at and around the level of injury which induces changes in function and organization throughout the nervous system, including cortical changes. Muscle affected by SCI may consist of both innervated (accessible to voluntary drive) and denervated (inaccessible to voluntary drive) muscle fibers. Voluntary activation measured with transcranial magnetic stimulation (VATMS) can quantify voluntary cortical/subcortical drive to muscle but is limited by technical challenges including suboptimal stimulation of target muscle (...) relative to its antagonist. The motor evoked potential (MEP) in the biceps compared to the triceps (i.e., MEP ratio) may be a key parameter in the measurement of biceps VATMS after SCI. We used paired pulse TMS, which can inhibit or facilitate MEPs, to determine whether the MEP ratio affects VATMS in individuals with tetraplegia. Ten individuals with tetraplegia following cervical SCI and ten non-impaired individuals completed single pulse and paired pulse VATMS protocols. Paired pulse stimulation was delivered at 1.5, 10, and 30 ms inter-stimulus intervals (ISI). In both the SCI and non-impaired groups, the main effect of the stimulation pulse (paired pulse compared to single pulse) on VATMS was not significant in the linear mixed-effects models. In both groups for the stimulation parameters we tested, the MEP ratio was not modulated across all effort levels and did not affect VATMS. Linearity of the voluntary moment and superimposed twitch moment relation was lower in SCI participants compared to non-impaired. Poor linearity in the SCI group limits interpretation of VATMS. Future work is needed to address methodological issues that limit clinical application of VATMS. (shrink)

BackgroundIndividuals who use methamphetamine for a long period of time may experience decreased inhibition and increased impulsivity. In order to reduce impulsivity or improve inhibitory control ability, high-frequency repetitive transcranial magnetic stimulation has attracted much attention of researchers. Recent studies on addiction have shown that rTMS can stimulate different brain regions to produce different therapeutic effects. Recent work also suggests that HF-rTMS over right dorsolateral prefrontal cortex does not affect the impulsivity of patients with alcohol use disorder; (...) while HF-rTMS over left DLPFC could improve the impulsivity of patients with alcohol use disorder and cigarette smokers. However, it should be noted that empirical studies applying HF-rTMS over left DLPFC of patients with MA use disorders are still lacking.MethodsTwenty-nine patients with MAUD underwent five sessions of HF-rTMS on the left DLPFC per week for 4 consecutive weeks. The cue-induced craving and stop-signal and NoGo task were assessed pre-rTMS and post-rTMS. In addition, 29 healthy controls were recruited. There was no rTMS intervention for the controls, the performance of the stop-signal and NoGo task was evaluated on them.ResultsIn total, HF-rTMS of the left DLPFC significantly decreased MA-dependent patients’ cue-induced craving and stop-signal reaction time. For SSRT, the pre-test of experimental group was significantly higher than the score of control group. In the experimental group, the pre-test score was significantly higher than the post-test score. For Go and stop-signal delay, the pre-test scores of the experimental group was significantly lower than the scores of the control group. No significant difference was found between the pre-test and the post-test scores of the experimental group.ConclusionAdd-on HF-rTMS of left DLPFC may be an effective intervention for reducing impulsivity and cue-induced craving of patients with MAUD. Future research with a control group of MAUD that does not undergo the treatment is needed to confirm the effectiveness. (shrink)

When we judge an action as morally right or wrong, we rely on our capacity to infer the actor's mental states. Here, we test the hypothesis that the right temporoparietal junction, an area involved in mental state reasoning, is necessary for making moral judgments. In two experiments, we used transcranial magnetic stimulation to disrupt neural activity in the RTPJ transiently before moral judgment and during moral judgment. In both experiments, TMS to the RTPJ led participants to rely (...) less on the actor's mental states. A particularly striking effect occurred for attempted harms : Relative to TMS to a control site, TMS to the RTPJ caused participants to judge attempted harms as less morally forbidden and more morally permissible. Thus, interfering with activity in the RTPJ disrupts the capacity to use mental states in moral judgment, especially in the case of attempted harms. (shrink)

Visual stimuli as well as transcranial magnetic stimulation can be used: to suppress the visibility of a target and to recover the visibility of a target that has been suppressed by another mask. Both types of stimulation thus provide useful methods for studying the microgenesis of object perception. We first review evidence of similarities between the processes by which a TMS mask and a visual mask can either suppress the visibility of targets or recover such suppressed (...) visibility. However, we then also point out a significant difference that has important implications for the study of the time course of unconscious and conscious visual information processing and for theoretical accounts of the processes involved. We present evidence and arguments showing: that visual masking techniques, by revealing more detailed aspects of target masking and target recovery, support a theoretical approach to visual masking and visual perception that must take into account activities in two separate neural channels or processing streams and, as a corollary, that at the current stage of methodological sophistication visual masks, by acting in more highly specifiable ways on these pathways, provide information about the microgenesis of form perception not available with TMS masks. (shrink)

The Role of Dorsal Premotor Cortex in Resolving Abstract Motor Rules provides alternative hypotheses about the cognitive functions affected by the application of repetitive transcranial magnetic stimulation. Their model simulated the effect of stimulation of the left dorsal premotor cortex right as participants provide a Models were used to demonstrate that the increased variability in observed response times can result from interference in replanning during the process of responding to the uninstructed stimulus.

ObjectivesSeveral studies have examined the effects of repetitive transcranial magnetic stimulation (rTMS) on associative memory (AM) but findings were inconsistent. Here, we aimed to test whether twice-daily rTMS could significantly improve AM.MethodsIn this single-blind, sham-controlled experiment, 40 participants were randomized to receive twice-daily sham or real rTMS sessions for five consecutive days (a total of 16,000 pulses). The stimulation target in left inferior parietal lobule (IPL) exhibiting peak functional connectivity to the left hippocampus was individually defined (...) for each participant. Participants completed both a picture-cued word association task and Stroop test at baseline and 1 day after the final real or sham rTMS session. Effects of twice-daily rTMS on AM and Stroop test performance were compared using two-way repeated measures analysis of variance with main factors Group (real vs. sham) and Time (baseline vs. post-rTMS).ResultsThere was a significant Group × Time interaction effect. AM score was significantly enhanced in the twice-daily real group after rTMS, but this difference could not survive the post hoc analysis after multiple comparison correction. Further, AM improvement in the twice-daily real group was not superior to a previously reported once-daily rTMS group receiving 8,000 pulses. Then, we combined the twice- and once-daily real groups, and found a significant Group × Time interaction effect. Post hoc analysis indicated that the AM score was significantly enhanced in the real group after multiple comparisons correction.ConclusionOur prospective experiment did not show significant rTMS effect on AM, but this effect may become significant if more participants could be recruited as revealed by our retrospective analysis. (shrink)

Transcranial magnetic stimulation, as a relatively new type of treatment, is a safe and non-invasive method for pain therapy. Here, we used CiteSpace software to visually analyze 440 studies concerning transcranial magnetic stimulation in pain research from 2010 to 2021, indexed by Web of Science, to clarify the research hotspots in different periods and characterize the process of discovery in this field. The United States ranked first in this field. Lefaucheur JP, Fregni F, and (...) Andrade ACD made great contributions to this field of study. The most prolific institution was University of São Paulo. The four main hot keywords were neuropathic pain, motor cortex, connectivity, and non-invasive brain stimulation. There were three main points that were generally accepted: definite analgesic effect of high-frequency rTMS of M1 contralateral to pain side in neuropathic pain; there are inconclusive recommendations regarding rTMS of the dorsolateral prefrontal cortex in fibromyalgia and neuropathic pain; there is low-quality evidence that single doses of high-frequency rTMS of the motor cortex may have short-term effects on chronic pain. This bibliometric analysis indicated that prospective, multi-center, large-sample, randomized controlled trials are still needed to further verify the effectiveness of various transcranial magnetic stimulation parameters in pain research. (shrink)

ObjectiveTwo subregions of the dorsolateral prefrontal cortex have been identified as effective repetitive transcranial magnetic stimulation targets for the “anxiosomatic” and “dysphoric” symptoms, respectively. We aimed to develop a convenient approach to locate these targets on the scalp.Materials and methodsIn a discovery experiment, the two personalized targets were precisely identified on 24 subjects using a neuronavigation system. Then, a localized approach was developed based on individual scalp landmarks. This “landmark-based approach” was replicated and validated in an independent (...) cohort. Reliability of the approach was tested by calculating the correlation of both the inter-rater and intra-rater results. Validity was tested by comparing the mean distance between the personalized and landmark-based targets to the TMS spatial resolution. We further conducted a total of 24 sham rTMS sessions to estimate the misplacement between the coil center and target during a 10-min stimulation without neuronavigation.ResultsThe parameters of the “landmark-based approach” in the discovery experiment were replicated well in an independent cohort. Using discovery parameters, we successfully identified the symptom-specific targets in the independent cohort. Specifically, the mean distance between the personalized and landmark-based targets on the cortex was not significantly larger than 5 mm. However, the personalized and landmark-based targets distance exceeded 5 mm in more than 50% of subjects. During the 10-min sham rTMS session, the average coil misplacement was significantly larger than 5 mm.ConclusionThe “landmark-based approach” can conveniently and reliably locate the two symptom-specific targets at group level. However, the accuracy was highly varied at individual level and further improvement is needed. (shrink)