Electric Field Characteristics of Rotating Permanent Magnet Stimulation.

Neurostimulation devices that use rotating permanent magnets are being explored for their potential therapeutic benefits in patients with psychiatric and neurological disorders. This study aims to characterize the electric field (E-field) for ten configurations of rotating magnets using finite element analysis and phantom measurements. Various configurations were modeled, including single or multiple magnets, and bipolar or multipolar magnets, rotated at 10, 13.3, and 350 revolutions per second (rps). E-field strengths were also measured using a hollow sphere (r=9.2 cm) filled with a 0.9% sodium chloride solution and with a dipole probe. The E-field spatial distribution is determined by the magnets' dimensions, number of poles, direction of the magnetization, and axis of rotation, while the E-field strength is determined by the magnets' rotational frequency and magnetic field strength. The induced E-field strength on the surface of the head ranged between 0.0092 and 0.52 V/m. In the range of rotational frequencies applied, the induced E-field strengths were approximately an order or two of magnitude lower than those delivered by conventional transcranial magnetic stimulation. The impact of rotational frequency on E-field strength represents a confound in clinical trials that seek to tailor rotational frequency to individual neural oscillations. This factor could explain some of the variability observed in clinical trial outcomes.

Electric field characteristics of rotating permanent magnet stimulation.

Neurostimulation devices that use rotating permanent magnets are being explored for their potential therapeutic benefits in patients with psychiatric and neurological disorders. This study aims to characterize the electric field (E-field) for ten configurations of rotating magnets using finite element analysis and phantom measurements. Various configurations were modeled, including single or multiple magnets, bipolar or multipolar magnets, rotated at 10, 13.3, and 400 Hz. E-field strengths were also measured using a hollow sphere ( r = 9.2 cm) filled with a 0.9% sodium chloride solution and with a dipole probe. The E-field spatial distribution is determined by the magnets' dimensions, number of poles, direction of the magnetization, and axis of rotation, while the E-field strength is determined by the magnets' rotational frequency and magnetic field strength. The induced E-field strength on the surface of the head ranged between 0.0092 and 0.59 V/m. At the range of rotational frequencies applied, the induced E-field strengths were approximately an order or two of magnitude lower than those delivered by conventional transcranial magnetic stimulation. The impact of rotational frequency on E-field strength represents a previously unrecognized confound in clinical trials that seek to personalize stimulation frequency to individual neural oscillations and may represent a mechanism to explain some clinical trial results.

Electroconvulsive Therapy in the United States: A 2022 Survey of Practice.

OBJECTIVES: This study aimed to describe current US electroconvulsive therapy (ECT) practice, identify practice changes over time, and inform discussion of practice. METHOD: Our anonymous survey was open on SurveyMonkey.com from January to June 2022. We sent invitations to providers identified using a Medicare provider database, an advanced PubMed search function, and professional group listservs. Participants were instructed to submit 1 survey per ECT site. We examined frequency of responses, tabulated individual comments, and grouped data for comparison. RESULTS: We received responses from 74 US practice sites encompassing 283 providers. Forty-nine percent (n = 36) of respondents practiced at general academic medical centers, 23% (n = 17) at general medical centers, 16% (n = 12) at freestanding psychiatric hospitals, and 7% (n = 5) at Veterans Affairs medical centers. Proportions of female (29%) and Black or African American (AA) (1%) ECT providers were markedly lower than proportions of female (60%) and Black or African American ECT patients (10%). The median number of treatments for a major depressive episode was 10. The preferred electrode placement was right unilateral (66%, n = 45). The favored dosing strategy was seizure threshold titration. Quantitative outcome measures were used by 89% (n = 66) of sites for depressive symptoms and 84% (n = 62) for cognitive adverse effects. CONCLUSIONS: This survey is the first nationwide survey of ECT practice in nearly 40 years. Our results describe changes in practice over time and highlight the need to increase the number of female and Black or African American ECT providers. A comprehensive network of ECT sites could facilitate more frequent nationwide surveys.

Design and methodology for a proof of mechanism study of individualized neuronavigated continuous Theta burst stimulation for auditory processing in adolescents with autism spectrum disorder.

It has been suggested that aberrant excitation/inhibition (E/I) balance and dysfunctional structure and function of relevant brain networks may underlie the symptoms of autism spectrum disorder (ASD). However, the nomological network linking these constructs to quantifiable measures and mechanistically relating these constructs to behavioral symptoms of ASD is lacking. Herein we describe a within-subject, controlled, proof-of-mechanism study investigating the pathophysiology of auditory/language processing in adolescents with ASD. We utilize neurophysiological and neuroimaging techniques including magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG) metrics of language network structure and function. Additionally, we apply a single, individually targeted session of continuous theta burst stimulation (cTBS) as an experimental probe of the impact of perturbation of the system on these neurophysiological and neuroimaging outcomes. MRS, fMRI, and MEG measures are evaluated at baseline and immediately prior to and following cTBS over the posterior superior temporal cortex (pSTC), a region involved in auditory and language processing deficits in ASD. Also, behavioral measures of ASD and language processing and DWI measures of auditory/language network structures are obtained at baseline to characterize the relationship between the neuroimaging and neurophysiological measures and baseline symptom presentation. We hypothesize that local gamma-aminobutyric acid (GABA) and glutamate concentrations (measured with MRS), and structural and functional activity and network connectivity (measured with DWI and fMRI), will significantly predict MEG indices of auditory/language processing and behavioral deficits in ASD. Furthermore, a single session of cTBS over left pSTC is hypothesized to lead to significant, acute changes in local glutamate and GABA concentration, functional activity and network connectivity, and MEG indices of auditory/language processing. We have completed the pilot phase of the study (n=20 Healthy Volunteer adults) and have begun enrollment for the main phase with adolescents with ASD (n=86; age 14-17). If successful, this study will establish a nomological network linking local E/I balance measures to functional and structural connectivity within relevant brain networks, ultimately connecting them to ASD symptoms. Furthermore, this study will inform future therapeutic trials using cTBS to treat the symptoms of ASD.

The use of noninvasive brain stimulation techniques in autism spectrum disorder.

Noninvasive brain stimulation (NIBS) techniques, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), have recently emerged as alternative, nonpharmacological interventions for a variety of psychiatric, neurological, and neurodevelopmental conditions. NIBS is beginning to be applied in both research and clinical settings for the treatment of core and associated symptoms of autism spectrum disorder (ASD) including social communication deficits, restricted and repetitive behaviors, irritability, hyperactivity, depression and impairments in executive functioning and sensorimotor integration. Though there is much promise for these targeted device-based interventions, in other disorders (including adult major depressive disorder (MDD) and obsessive compulsive disorder (OCD) where rTMS is FDA cleared), data on the safety and efficacy of these interventions in individuals with ASD is limited especially in younger children when neurodevelopmental interventions typically begin. Most studies are open-label, small scale, and/or focused on a restricted subgroup of individuals with ASD. There is a need for larger, randomized controlled trials that incorporate neuroimaging in order to develop predictive biomarkers of treatment response and optimize treatment parameters. We contend that until such studies are conducted, we do not have adequate estimates of the safety and efficacy of NIBS interventions in children across the spectrum. Thus, broad off-label use of these techniques in this population is not supported by currently available evidence. Here we discuss the existing data on the use of NIBS to treat symptoms related to ASD and discuss future directions for the field.

Clinical Outcomes of Magnetic Seizure Therapy vs Electroconvulsive Therapy for Major Depressive Episode: A Randomized Clinical Trial.

Importance: Electroconvulsive therapy (ECT) is highly effective and rapid in treating depression, but it carries a risk of significant cognitive adverse effects. Magnetic seizure therapy (MST), an investigational antidepressant treatment, may maintain the robust antidepressant efficacy of ECT while substantially reducing adverse effects due to its enhanced focality and weaker stimulation strength; however, previous clinical trials of MST were limited by small sample sizes. Objective: To compare the antidepressant efficacy of MST vs ultrabrief pulse right unilateral (RUL) ECT. Design, Setting, and Participants: A between-participants, double-blinded, randomized clinical trial was conducted at 3 academic hospitals from June 2007 to August 2012. Adults aged 18 to 90 years who were referred for treatment with ECT, had a major depressive episode in the context of major depressive disorder or bipolar disorder, and had a baseline 24-item Hamilton Depression Rating Scale (HDRS-24) total score of 18 or higher were included. Participants were randomly assigned 1:1 to treatment with MST or ultrabrief pulse RUL ECT. After the treatment course, patients were naturalistically followed up for up to 6 months to examine the durability of clinical effects. Interventions: Treatment with MST, applied at 100 Hz at 100% of the maximum device power for 10 seconds, or ultrabrief pulse RUL ECT, applied at 6 times seizure threshold. Main Outcomes and Measures: The primary outcome was change from baseline in HDRS-24 total score, with patients followed up for up to 6 months. A reduction of at least 50% in the HDRS-24 score indicated response, and at least a 60% decrease in the HDRS-24 score and a total score of 8 or less indicated remission. Results: Of the 73 participants (41 [56.2%] female; mean [SD] age, 48 [14.1] years), 35 were randomized to MST and 38 to ECT. Among them, 53 (72.6%) were classified as completers (29 in the MST group and 24 in the ECT group). Both MST and ECT demonstrated clinically meaningful antidepressant effects. In the intent-to-treat sample, 18 participants (51.4%) in the MST group and 16 (42.1%) in the ECT group met response criteria; 13 (37.1%) in the MST group and 10 (26.3%) in the ECT group met remission criteria. Among completers, 17 of 29 (58.6%) in the MST group and 15 of 24 (62.5%) in the ECT group met response criteria; 13 of 29 (44.8%) in the MST group and 10 of 24 (41.7%) in the ECT group met remission criteria. There was no significant difference between MST and ECT for either response or remission rates. However, the mean (SD) number of treatments needed to achieve remission was 9.0 (3.1) with MST and 6.7 (3.3) with ECT, a difference of 2.3 treatments (t71.0 = 3.1; P = .003). Both MST and ECT showed a sustained benefit over a 6-month follow-up period, again with no significant difference between them. Compared with MST, ECT had significantly longer time to orientation after treatment (threshold level: F1,56 = 10.0; P = .003) and greater severity of subjective adverse effects, particularly in the physical and cognitive domains. Conclusions and Relevance: This randomized clinical trial found that the efficacy of MST was indistinguishable from that of ultrabrief pulse RUL ECT, the safest form of ECT currently available. These results support the continued development of MST and provide evidence for advantages relative to state-of-the-art ECT. Trial Registration: ClinicalTrials.gov Identifier: NCT00488748.

How electroconvulsive therapy works in the treatment of depression: is it the seizure, the electricity, or both?

We have known for nearly a century that triggering seizures can treat serious mental illness, but what we do not know is why. Electroconvulsive Therapy (ECT) works faster and better than conventional pharmacological interventions; however, those benefits come with a burden of side effects, most notably memory loss. Disentangling the mechanisms by which ECT exerts rapid therapeutic benefit from the mechanisms driving adverse effects could enable the development of the next generation of seizure therapies that lack the downside of ECT. The latest research suggests that this goal may be attainable because modifications of ECT technique have already yielded improvements in cognitive outcomes without sacrificing efficacy. These modifications involve changes in how the electricity is administered (both where in the brain, and how much), which in turn impacts the characteristics of the resulting seizure. What we do not completely understand is whether it is the changes in the applied electricity, or in the resulting seizure, or both, that are responsible for improved safety. Answering this question may be key to developing the next generation of seizure therapies that lack these adverse side effects, and ushering in novel interventions that are better, faster, and safer than ECT.

Network-level dynamics underlying a combined rTMS and psychotherapy treatment for major depressive disorder: An exploratory network analysis

Background: Despite the growing use of repetitive transcranial magnetic stimulation (rTMS) as a treatment for depression, there is a limited understanding of the mechanisms of action and how potential treatment-related brain changes help to characterize treatment response. To address this gap in understanding we investigated the effects of an approach combining rTMS with simultaneous psychotherapy on global functional connectivity. Method: We compared task-related functional connectomes based on an idiographic goal priming task tied to emotional regulation acquired before and after simultaneous rTMS/psychotherapy treatment for patients with major depressive disorders and compared these changes to normative connectivity patterns from a set of healthy volunteers (HV) performing the same task. Results: At baseline, compared to HVs, patients demonstrated hyperconnectivity of the DMN, cerebellum and limbic system, and hypoconnectivity of the fronto-parietal dorsal-attention network and visual cortex. Simultaneous rTMS/psychotherapy helped to normalize these differences, which were reduced after treatment. This finding suggests that the rTMS/therapy treatment regularizes connectivity patterns in both hyperactive and hypoactive brain networks. Conclusions: These results help to link treatment to a comprehensive model of the neurocircuitry underlying depression and pave the way for future studies using network-guided principles to significantly improve rTMS efficacy for depression. (AU)

Electroconvulsive Therapy Across Nations: A 2022 Survey of Practice.

OBJECTIVES: We aimed to characterize worldwide electroconvulsive therapy (ECT) practice and compare practice across nations and global regions. METHOD: Our anonymous survey was open on SurveyMonkey.com from January to June 2022. We sent invitations to providers identified using a Medicare provider database, an advanced PubMed search function, and professional group listservs. Participants were instructed to submit one survey per ECT site. Response frequencies were pooled by global region and compared using nonparametric methods. RESULTS: Responses came from 126 sites, mostly in the United States (59%, n = 74), Europe (18%, n = 23), Canada (10%, n = 12), and South/East Asia (6%, n = 8). With some exceptions, sites were broadly consistent in practice as indicated by: a likely shift internationally from bitemporal to right unilateral electrode placement; predominant use of pulse widths <1 ms; preference for seizure threshold titration over age-based dosing methods; widespread availability of continuation/maintenance ECT (97%); and frequent use of quantitative outcome measures for depressive symptoms (88%) and cognitive adverse effects (80%). CONCLUSIONS: This is the first, published survey that aimed to characterize worldwide ECT practice. With some exceptions, responses suggest a concordance in practice. However, responses were primarily from the Global North. To obtain a truly worldwide characterization of practice, future surveys should include more responses from the Global South.

Distinguishing Convulsive Syncope From Seizure Induced by Repetitive Transcranial Magnetic Stimulation: A Case Report.

ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is Food and Drug Administration cleared for clinical use in treatment-resistant depression and a growing list of other disorders. The clinical uptake of rTMS has been facilitated by its relatively benign adverse-effect profile compared with other treatment modalities. Seizure is a rare but serious adverse event that has been reported with rTMS, when dosage exceeds safety guidelines or in individuals at increased risk for seizure. Fortunately, most rTMS-induced seizures are typically transient, with no adverse sequelae, but they may lead to treatment discontinuation. Seizure is not the only cause of loss of conscious and abnormal movements induced by rTMS. Convulsive syncope, a more common adverse event that involves loss of consciousness associated with myoclonic movements, can be difficult to differentiate from an rTMS-induced seizure. We report the case of a 52-year-old man with no known seizure risk factors, enrolled in an institutional review board-approved research study who developed what appeared to be a convulsive syncopal episode lasting 10 to 15 seconds during day 2 of a 30-day rTMS protocol (10 Hz, 120% of motor threshold, 4-second pulse train, 26-second intertrain interval, 3000 pulses per session), with no adverse sequelae. The patient's history, screening, physical examination, pertinent laboratory, neurology consult, electroencephalogram, and imaging findings are discussed. This case demonstrates that distinguishing between convulsive syncope and rTMS-induced seizure can be a diagnostic challenge. Clinicians and researchers delivering rTMS should be familiar with the risk factors for rTMS-induced seizures and rTMS-induced convulsive syncope, to screen for predisposing factors and to manage these rare adverse events if they occur.

Using latent profile analyses to classify subjects with anhedonia based on reward-related measures obtained in the FAST-MAS study.

BACKGROUND: Growing evidence indicates that anhedonia is a multifaceted construct. This study examined the possibility of identifying subgroups of people with anhedonia using multiple reward-related measures to provide greater understanding the Research Domain Criteria's Positive Valence Systems Domain and pathways for developing treatments. METHODS: Latent profile analysis of baseline data from a study that examined the effects of a novel kappa opioid receptor (KOR) antagonist drug on measures and biomarkers associated with anhedonia was used to identify subgroups. Measures included ventral striatal activation during the Monetary Incentive Delay task, response bias in the Probabilistic Reward Task, reward valuation scores from the Effort-Expenditure for Rewards Task, and scores from reward-related self-report measures. RESULTS: Two subgroups were identified, which differed on self-report measures of reward. Participants in the subgroup reporting more anhedonia also reported more depression and had greater illness severity and functional impairments. Graphs of change with treatment showed a trend for the less severe subgroup to demonstrate higher response to KOR antagonist treatment on the neuroimaging measure, probabilistic reward task, and ratings of functioning; the subgroup with greater severity showed a trend for higher treatment response on reward-related self-report measures. LIMITATIONS: The main limitations include the small sample size and exploratory nature of analyses. CONCLUSIONS: Evidence of possible dissociation between self-reported measures of anhedonia and other measures with respect to treatment response emerged. These results highlight the importance for future research to consider severity of self-reported reward-related deficits and how the relationship across measurement methods may vary with severity.

Recent advances in electroconvulsive therapy in clinical practice and research.

Electroconvulsive therapy (ECT), the oldest somatic therapy still in use in psychiatry today, remains one of the most effective therapeutic interventions for a wide variety of psychiatric disorders. In this article, we review some of the recent advances in ECT that are currently being researched and implemented in clinical practice. We explore recent studies that point to the potential therapeutic benefit and safety of ECT in COVID-19-related neuropsychiatric complications and special populations (such as the elderly and pregnant persons) that are generally at higher risk of having adverse effects from psychotropic medications. We highlight studies that performed a head-to-head comparison of ECT and ketamine, which has shown promise for treatment-resistant depression and acute suicidality. Researchers continue to explore different ways of using ECT by modifying the treatment parameters to maintain efficacy and decrease side effects. Neurocognitive side effects remain one of the major drawbacks to its use and contribute to the negative stigma of this highly effective treatment. In this regard, we describe attempts to improve the safety of ECT by modifying dosing parameters, novel electrode placements, and the addition of augmenting agents with the aim of decreasing side effects and improving efficacy. This review identifies some of the recent advances in the last few years in ECT research while also highlighting areas where further research is needed.

New directions in psychiatric drug development: promising therapeutics in the pipeline.

INTRODUCTION: Psychiatric disorders are a leading cause of disability worldwide, calling for an urgent need for new treatments, early detection, early intervention, and precision medicine. Drug discovery and development in psychiatry continues to expand in new and exciting areas, with several new medications approved for psychiatric indications by the U.S. Food and Drug Administration (FDA) in the last 5 years. AREAS COVERED: In this review, the authors summarize recent new drug approvals and new molecular mechanisms in Phase 1-3 clinical development for psychiatric disorders. Advances in human genetics-driven target identification, emergent technologies such as artificial intelligence-enabled drug discovery, digital health technologies, and biomarker tools and strategies for testing novel mechanisms are highlighted. EXPERT OPINION: There continues to be a need for research focused on understanding the natural history, developmental trajectory, and pathophysiology of psychiatric disorders to identify new molecular and circuit-based targets. Looking to the future, a vision of precision psychiatry is emerging, taking advantage of advances in genetics, digital technology, and multimodal biomarkers to accelerate the development of next-generation therapies for individuals living with mental illnesses.

Future directions in psychiatric neurosurgery: Proceedings of the 2022 American Society for Stereotactic and Functional Neurosurgery meeting on surgical neuromodulation for psychiatric disorders.

OBJECTIVE: Despite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many as 30-40% of patients. Neuromodulation, including deep brain stimulation (DBS), has emerged as a potential therapy for persistent disabling disease, however it has not yet gained widespread adoption. In 2016, the American Society for Stereotactic and Functional Neurosurgery (ASSFN) convened a meeting with leaders in the field to discuss a roadmap for the path forward. A follow-up meeting in 2022 aimed to review the current state of the field and to identify critical barriers and milestones for progress. DESIGN: The ASSFN convened a meeting on June 3, 2022 in Atlanta, Georgia and included leaders from the fields of neurology, neurosurgery, and psychiatry along with colleagues from industry, government, ethics, and law. The goal was to review the current state of the field, assess for advances or setbacks in the interim six years, and suggest a future path forward. The participants focused on five areas of interest: interdisciplinary engagement, regulatory pathways and trial design, disease biomarkers, ethics of psychiatric surgery, and resource allocation/prioritization. The proceedings are summarized here. CONCLUSION: The field of surgical psychiatry has made significant progress since our last expert meeting. Although weakness and threats to the development of novel surgical therapies exist, the identified strengths and opportunities promise to move the field through methodically rigorous and biologically-based approaches. The experts agree that ethics, law, patient engagement, and multidisciplinary teams will be critical to any potential growth in this area.

Network-level dynamics underlying a combined rTMS and psychotherapy treatment for major depressive disorder: An exploratory network analysis.

Background: Despite the growing use of repetitive transcranial magnetic stimulation (rTMS) as a treatment for depression, there is a limited understanding of the mechanisms of action and how potential treatment-related brain changes help to characterize treatment response. To address this gap in understanding we investigated the effects of an approach combining rTMS with simultaneous psychotherapy on global functional connectivity. Method: We compared task-related functional connectomes based on an idiographic goal priming task tied to emotional regulation acquired before and after simultaneous rTMS/psychotherapy treatment for patients with major depressive disorders and compared these changes to normative connectivity patterns from a set of healthy volunteers (HV) performing the same task. Results: At baseline, compared to HVs, patients demonstrated hyperconnectivity of the DMN, cerebellum and limbic system, and hypoconnectivity of the fronto-parietal dorsal-attention network and visual cortex. Simultaneous rTMS/psychotherapy helped to normalize these differences, which were reduced after treatment. This finding suggests that the rTMS/therapy treatment regularizes connectivity patterns in both hyperactive and hypoactive brain networks. Conclusions: These results help to link treatment to a comprehensive model of the neurocircuitry underlying depression and pave the way for future studies using network-guided principles to significantly improve rTMS efficacy for depression.

Digitalized transcranial electrical stimulation: A consensus statement.

OBJECTIVE: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES. METHODS: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. RESULTS: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity. CONCLUSIONS: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. SIGNIFICANCE: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.

Effects of Online Single Pulse Transcranial Magnetic Stimulation on Prefrontal and Parietal Cortices in Deceptive Processing: A Preliminary Study.

Transcranial magnetic stimulation (TMS) was used to test the functional role of parietal and prefrontal cortical regions activated during a playing card Guilty Knowledge Task (GKT). Single-pulse TMS was applied to 15 healthy volunteers at each of three target sites: left and right dorsolateral prefrontal cortex and midline parietal cortex. TMS pulses were applied at each of five latencies (from 0 to 480 ms) after the onset of a card stimulus. TMS applied to the parietal cortex exerted a latency-specific increase in inverse efficiency score and in reaction time when subjects were instructed to lie relative to when asked to respond with the truth, and this effect was specific to when TMS was applied at 240 ms after stimulus onset. No effects of TMS were detected at left or right DLPFC sites. This manipulation with TMS of performance in a deception task appears to support a critical role for the parietal cortex in intentional false responding, particularly in stimulus selection processes needed to execute a deceptive response in the context of a GKT. However, this interpretation is only preliminary, as further experiments are needed to compare performance within and outside of a deceptive context to clarify the effects of deceptive intent.

Using diffusion tensor imaging to effectively target TMS to deep brain structures.

TMS has become a powerful tool to explore cortical function, and in parallel has proven promising in the development of therapies for various psychiatric and neurological disorders. Unfortunately, much of the inference of the direct effects of TMS has been assumed to be limited to the area a few centimeters beneath the scalp, though clearly more distant regions are likely to be influenced by structurally connected stimulation sites. In this study, we sought to develop a novel paradigm to individualize TMS coil placement to non-invasively achieve activation of specific deep brain targets of relevance to the treatment of psychiatric disorders. In ten subjects, structural diffusion imaging tractography data were used to identify an accessible cortical target in the right frontal pole that demonstrated both anatomic and functional connectivity to right Brodmann area 25 (BA25). Concurrent TMS-fMRI interleaving was used with a series of single, interleaved TMS pulses applied to the right frontal pole at four intensity levels ranging from 80% to 140% of motor threshold. In nine of ten subjects, TMS to the individualized frontal pole sites resulted in significant linear increase in BOLD activation of BA25 with increasing TMS intensity. The reliable activation of BA25 in a dosage-dependent manner suggests the possibility that the careful combination of imaging with TMS can make use of network properties to help overcome depth limitations and allow noninvasive brain stimulation to influence deep brain structures.