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The standard clinical technique for using repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder (MDD) is associated with limited efficacy to date. Such limited efficacy may be due to reliance on scalp-based targeting rather than state-of-the-science methods which incorporate fMRI-guided neuronavigation based on a specific model of neurocircuit dysfunction. In this review, we examine such a specific model drawn from regulatory focus theory, which postulates two brain/behavior systems, the promotion and prevention systems, underlying goal pursuit. Individual differences in these systems have been shown to predict vulnerability to MDD as well as to comorbid generalized anxiety disorder (GAD). Activation of an individual's promotion or prevention goals via priming leads to motivational and affective responses modulated by the individual's appraisal of their progress in attaining the goal. In addition, priming promotion vs. prevention goals induces discriminable patterns of brain activation that are sensitive to the effects of depression and anxiety: MDD is associated with promotion system failure, anhedonic/dysphoric symptoms, and hypoactivation in specific regions in left prefrontal cortex, whereas GAD is associated with prevention system failure, hypervigilant/agitated symptoms, and hyperactivation in right prefrontal cortex (PFC). These left and right PFC locations can be directly targeted in an individualized manner for TMS. Additionally, this individually targeted rTMS can be integrated with cognitive interventions designed to activate the neural circuitry associated with promotion vs. prevention, thus allowing the neuroplasticity induced by the rTMS to benefit the systems likely to be involved in remediating depression. Targeted engagement of cortical systems involved in emotion regulation using individualized fMRI guidance may help increase the efficacy of rTMS in depression. •rTMS for depression using scalp-based targeting has shown limited efficacy to date•Using fMRI-guided neuronavigation along with a model of neurocircuit dysfunction may improve the efficacy of rTMS•In this article we introduce a model of depression drawn from regulatory focus theory•Our model allows for individually targeted rTMS that engages cortical systems involved in emotion regulation and for combining interventions targeting the same putative circuit

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.

Transcranial magnetic stimulation (TMS) is a noninvasive method to stimulate the cerebral cortex that has applications in psychiatry, such as in the treatment of depression and anxiety. Although many TMS targeting methods that use figure-8 coils exist, many do not account for individual differences in anatomy or are not generalizable across target sites. This protocol combines functional magnetic resonance imaging (fMRI) and iterative electric-field (E-field) modeling in a generalized approach to subject-specific TMS targeting that is capable of optimizing the stimulation site and TMS coil orientation. To apply this protocol, the user should (i) operationally define a region of interest (ROI), (ii) generate the head model from the structural MRI data, (iii) preprocess the functional MRI data, (iv) identify the single-subject stimulation site within the ROI, and (iv) conduct E-field modeling to identify the optimal coil orientation. In comparison with standard targeting methods, this approach demonstrates (i) reduced variability in the stimulation site across subjects, (ii) reduced scalp-to-cortical-target distance, and (iii) reduced variability in optimal coil orientation. Execution of this protocol requires intermediate-level skills in structural and functional MRI processing. This protocol takes ~24 h to complete and demonstrates how constrained fMRI targeting combined with iterative E-field modeling can be used as a general method to optimize both the TMS coil site and its orientation. The authors describe an approach for optimizing transcranial magnetic stimulation (TMS) targeting by combining functional magnetic resonance imaging and iterative electric-field stimulation.

The Stroop task is a well-established tool to investigate the influence of competing visual categories on decision making. Neuroimaging as well as rTMS studies have demonstrated the involvement of parietal structures, particularly the intraparietal sulcus (IPS), in this task. Given its reliability, the numerical Stroop task was used to compare the effects of different TMS targeting approaches by Sack and colleagues (Sack AT 2009), who elegantly demonstrated the superiority of individualized fMRI targeting. We performed the present study to test whether fMRI-guided rTMS effects on numerical Stroop task performance could still be observed while using more advanced techniques that have emerged in the last decade (e.g., electrical sham, robotic coil holder system, etc.). To do so we used a traditional reaction time analysis and we performed, post-hoc, a more advanced comprehensive drift diffusion modeling approach. Fifteen participants performed the numerical Stroop task while active or sham 10 Hz rTMS was applied over the region of the right intraparietal sulcus (IPS) showing the strongest functional activation in the Incongruent > Congruent contrast. This target was determined based on individualized fMRI data collected during a separate session. Contrary to our assumption, the classical reaction time analysis did not show any superiority of active rTMS over sham, probably due to confounds such as potential cumulative rTMS effects, and the effect of practice. However, the modeling approach revealed a robust effect of rTMS on the drift rate variable, suggesting differential processing of congruent and incongruent properties in perceptual decision-making, and more generally, illustrating that more advanced computational analysis of performance can elucidate the effects of rTMS on the brain where simpler methods may not.

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.

The standard clinical technique for using repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder (MDD) is associated with limited efficacy to date. Such limited efficacy may be due to reliance on scalp-based targeting rather than state-of-the-science methods which incorporate fMRI-guided neuronavigation based on a specific model of neurocircuit dysfunction. In this review, we examine such a specific model drawn from regulatory focus theory, which postulates two brain/behavior systems, the promotion and prevention systems, underlying goal pursuit. Individual differences in these systems have been shown to predict vulnerability to MDD as well as to comorbid generalized anxiety disorder (GAD). Activation of an individual's promotion or prevention goals via priming leads to motivational and affective responses modulated by the individual's appraisal of their progress in attaining the goal. In addition, priming promotion vs. prevention goals induces discriminable patterns of brain activation that are sensitive to the effects of depression and anxiety: MDD is associated with promotion system failure, anhedonic/dysphoric symptoms, and hypoactivation in specific regions in left prefrontal cortex, whereas GAD is associated with prevention system failure, hypervigilant/agitated symptoms, and hyperactivation in right prefrontal cortex (PFC). These left and right PFC locations can be directly targeted in an individualized manner for TMS. Additionally, this individually targeted rTMS can be integrated with cognitive interventions designed to activate the neural circuitry associated with promotion vs. prevention, thus allowing the neuroplasticity induced by the rTMS to benefit the systems likely to be involved in remediating depression. Targeted engagement of cortical systems involved in emotion regulation using individualized fMRI guidance may help increase the efficacy of rTMS in depression. •rTMS for depression using scalp-based targeting has shown limited efficacy to date.•Using fMRI-guided neuronavigation along with model of neurocircuit dysfunction may improve the efficacy of rTMS.•In this article we introduce a model of depression drawn from regulatory focus theory.•Our model allows for individually targeted rTMS that engages cortical systems involved in emotion regulation and for combining interventions targeting the same putative circuit.

For a coherent and meaningful life, conscious self-representation is mandatory. Such explicit \"autonoetic consciousness\" is thought to emerge by retrieval of memory of personally experienced events (\"episodic memory\"). During episodic retrieval, functional imaging studies consistently show differential activity in medial prefrontal and medial parietal cortices. With positron-emission tomography, we here show that these medial regions are functionally connected and interact with lateral regions that are activated according to the degree of self-reference. During retrieval of previous judgments of Oneself, Best Friend, and the Danish Queen, activation increased in the left lateral temporal cortex and decreased in the right inferior parietal region with decreasing self-reference. Functionally, the former region was preferentially connected to medial prefrontal cortex, the latter to medial parietal. The medial parietal region may, then, be conceived of as a nodal structure in self-representation, functionally connected to both the right parietal and the medial prefrontal cortices. To determine whether medial parietal cortex in this network is essential for episodic memory retrieval with self-representation, we used transcranial magnetic stimulation over the region to transiently disturb neuronal circuitry. There was a decrease in the efficiency of retrieval of previous judgment of mental Self compared with retrieval of judgment of Other with transcranial magnetic stimulation at a latency of 160 ms, confirming the hypothesis. This network is strikingly similar to the network of the resting conscious state, suggesting that self-monitoring is a core function in resting consciousness.

Whereas previous research has focused on the role of the rTPJ when consciously inhibiting mimicry, we test the role of the rTPJ on mimicry within a social interaction, during which mimicking occurs nonconsciously. We wanted to determine whether higher rTPJ activation always inhibits the tendency to imitate (regardless of the context) or whether it facilitates mimicry during social interactions (when mimicking is an adaptive response). Participants received either active or sham intermittent theta-burst stimulation (iTBS: a type of stimulation that increases cortical activation) to the rTPJ. Next, we measured how much participants mimicked the hair and face touching of another person. Participants in the active stimulation condition engaged in significantly less mimicry than those in the sham stimulation condition. This finding suggests that even in a context in which mimicking is adaptive, rTPJ inhibits mimicry rather than facilitating it, supporting the hypothesis that rTPJ enhances representations of self over other regardless of the goals within a given context.

Purpose of Review Sleep deprivation is a global health issue, and the resultant cognitive deficits can be debilitating. A series of studies reported success with individually neuronavigated transcranial magnetic stimulation (TMS), coupled with online task performance, in substantially reducing performance deficits in working memory in healthy adults caused by 2 days of total sleep depression. This paradigm of coupling TMS with online task performance has been referred to as Cognitive Paired Associative Stimulation (C-PAS). This review describes those studies and the research since using various TMS paradigms to remediate working memory deficits in sleep deprivation. Recent Findings Three such studies were found, but none replicated the earlier findings. However, in each case, there were differences in study design that might explain the negative findings and inform future methodological choices and to underline the need to combine TMS with brain imaging guidance. Summary Online task performance during TMS, as done in the C-PAS paradigm, appears to be essential to demonstrating lasting remediation of working memory deficits induced by sleep deprivation. This observation highlights the importance of state-dependency in determining the effects of TMS. Further work needs to be done to clarify the potential role of C-PAS in alleviating the effects of sleep deprivation and studying cognitive processes affected by sleep.

Background: Resting-state functional connectivity (RSFC) is widely used to identify abnormal brain function associated with depression. Resting-state functional magnetic resonance imaging (fMRI) scans have many potential confounds, and task-based FC might provide complementary information leading to better insight on brain function. Methods: We used MATLAB’s (version 2024b) CONN toolbox (version 22a) to evaluate FC in 40 adults with and without major depressive disorder (MDD) (nMDD = 23, nHC = 17). fMRI acquisition was performed while participants were at rest and while performing the Selves Task, an individualized goal priming task. Seed-based analyses were performed using two seeds: medial prefrontal cortex (mPFC) and left hippocampus. Results: Both groups showed strong positive RSFC between the mPFC and other DMN regions, including the anterior cingulate cortex and precuneus, which had more focal positive FC to the mPFC during the task in both groups. Additionally, the MDD group had significantly lower RSFC between the mPFC and several regions, including the right inferior temporal gyrus. The left hippocampus seed-based analysis revealed a pattern of hypoconnectivity to multiple brain regions in MDD, including the cerebellum, which was present at rest and during the task. Conclusions: Our results indicated multiple FC differences between adults with and without MDD, as well as distinct FC patterns and contrast results in resting state and task-based analyses, including differential FC between mPFC–cerebellum and hippocampus–cerebellum. These results emphasize that resting-state and task-based fMRI capture distinct patterns of brain connectivity. Further investigation into combining resting-state and task-based FC could inform future neuroimaging research.