Transcranial direct current stimulation of the prefrontal and visual cortices diversely affects early and late perceptual learning.

BACKGROUND: Research has shown that visual perceptual learning (VPL) is related to modifying neural activity in higher level decision-making regions. However, the causal roles of the prefrontal and visual cortexes in VPL are still unclear. Here, we investigated how anodal transcranial direct current stimulation (tDCS) of the prefrontal and visual cortices modulates VPL in the early and later phases and the role of multiple brain regions. METHODS: Perceptual learning on the coherent motion direction identification task included early and later stages. After early training, participants needed to continuously train to reach a plateau; once the plateau was reached, participants entered a later stage. Sixty participants were randomly divided into five groups. Regardless of the training at the early and later stages, four groups received multitarget tDCS over the right dorsolateral prefrontal cortex (rDLPFC) and right middle temporal area (rMT), single-target tDCS over the rDLPFC, and single-target tDCS over the rMT or sham stimulation, and one group was stimulated at the ipsilateral brain region (i.e., left MT). RESULTS: Compared with sham stimulation, multitarget and two single-target tDCS over the rDLPFC or rMT improved posttest performance and accelerated learning during the early period. However, multitarget tDCS and two single-target tDCS led to equivalent benefits for VPL. Additionally, these beneficial effects were absent when anodal tDCS was applied to the ipsilateral brain region. For the later period, the above facilitating effects on VPL induced by multitarget or single-target tDCS disappeared. CONCLUSIONS: This study suggested the causal role of the prefrontal and visual cortices in visual motion perceptual learning by anodal tDCS but failed to find greater beneficial effects by simultaneously stimulating the prefrontal and visual cortices. Future research should investigate the functional associations between multiple brain regions to further promote VPL.

Transcranial Direct Current Stimulation for Food Craving in Women Affected by Overweight and Obesity: A Randomized Controlled Trial.

INTRODUCTION: Craving is a multifactorial behavior caused by central circuit imbalance. The proposed treatments involve exercise and reduced food intake. However, the treatments frequently fail. This study aimed to investigate the effect of 10 consecutive sessions of anodal transcranial direct current stimulation over the right dorsolateral prefrontal cortex on food craving and eating consumption of women affected by overweight and obesity. METHODS: A randomized double-blind controlled trial with 50 volunteers was divided into two groups (active-tDCS: n = 25 and sham-tDCS: n = 25). There were a total of 10 consecutive tDCS sessions (2 mA, for 20 min) with an F4 anodal-F3 cathodal montage. We evaluated the effects on eating behavior (food craving, uncontrolled eating, emotional eating, and cognitive restriction), food consumption (calories and macronutrients), and anthropometric and body composition variables (weight, body mass index, waist circumference, and body fat percentage). RESULTS: There were no statistically significant results between groups at the baseline regarding sociodemographic and clinical characteristics. Also, there was no significant interaction between time versus group for any of the variables studied. Treatment with tDCS was well tolerated and there were no serious adverse effects. CONCLUSIONS: In women affected by overweight and obesity with food cravings, 10 sessions of F4 (anodal) and F3 (cathodal) tDCS did not produce changes in eating behavior, food consumption, and anthropometric and body composition.

Regional brain activity and neural network changes in cognitive-motor dual-task interference: A functional near-infrared spectroscopy study.

Previous neuroimaging studies have reported dual-task interference (DTi) and deterioration of task performance in a cognitive-motor dual task (DT) compared to that in a single task (ST). Greater frontoparietal activity is a neural signature of DTi; nonetheless, the underlying mechanism of cortical network in DTi still remains unclear. This study aimed to investigate the regional brain activity and neural network changes during DTi induced by highly demanding cognitive-motor DT. Thirty-four right-handed healthy young adults performed the spiral-drawing task. They underwent a paced auditory serial addition test (PASAT) simultaneously or independently while their cortical activity was measured using functional near-infrared spectroscopy. Motor performance was determined using the balanced integration score (BIS), a balanced index of drawing speed and precision. The cognitive task of the PASAT was administered with two difficulty levels defined by 1 s (PASAT-1 s) and 2 s (PASAT-2 s) intervals, allowing for the serial addition of numbers. Cognitive performance was determined using the percentage of correct responses. These motor and cognitive performances were significantly reduced during DT, which combined a drawing and a cognitive task at either difficulty level, compared to those in the corresponding ST conditions. The DT conditions were also characterized by significantly increased activity in the right dorsolateral prefrontal cortex (DLPFC) compared to that in the ST conditions. Multivariate Granger causality (GC) analysis of cortical activity in the selected frontoparietal regions of interest further revealed selective top-down causal connectivity from the right DLPFC to the right inferior parietal cortex during DTs. Furthermore, changes in the frontoparietal GC connectivity strength between the PASAT-2 s DT and ST conditions significantly correlated negatively with changes in the percentage of correct responses. Therefore, DTi can occur even in cognitively proficient young adults, and the right DLPFC and frontoparietal network being crucial neural mechanisms underlying DTi. These findings provide new insights into DTi and its underlying neural mechanisms and have implications for the clinical utility of cognitive-motor DTs applied to clinical populations with cognitive decline, such as those with psychiatric and brain disorders.

Transcranial Direct Current Stimulation (tDCS) over the left dorsolateral prefrontal cortex reduced attentional bias toward natural emotional sounds.

Previous research has indicated that the left dorsolateral prefrontal cortex (DLPFC) exerts an influence on attentional bias toward visual emotional information. However, it remains unclear whether the left DLPFC also play an important role in attentional bias toward natural emotional sounds. The current research employed the emotional spatial cueing paradigm, incorporating natural emotional sounds of considerable ecological validity as auditory cues. Additionally, high-definition transcranial direct current stimulation (HD-tDCS) was utilized to examine the impact of left dorsolateral prefrontal cortex (DLPFC) on attentional bias and its subcomponents, namely attentional engagement and attentional disengagement. The results showed that (1) compared to sham condition, anodal HD-tDCS over the left DLPFC reduced the attentional bias toward positive and negative sounds; (2) anodal HD-tDCS over the left DLPFC reduced the attentional engagement toward positive and negative sounds, whereas it did not affect attentional disengagement away from natural emotional sounds. Taken together, the present study has shown that left DLPFC, which was closely related with the top-down attention regulatory function, plays an important role in auditory emotional attentional bias.

Repetitive Transcranial Magnetic Stimulation in Fibromyalgia: Exploring the Necessity of Neuronavigation for Targeting New Brain Regions.

Fibromyalgia and osteoarthritis are among the most prevalent rheumatic conditions worldwide. Nonpharmacological interventions have gained scientific endorsements as the preferred initial treatments before resorting to pharmacological modalities. Repetitive transcranial magnetic stimulation (rTMS) is among the most widely researched neuromodulation techniques, though it has not yet been officially recommended for fibromyalgia. This review aims to summarize the current evidence supporting rTMS for treating various fibromyalgia symptoms. Recent findings: High-frequency rTMS directed at the primary motor cortex (M1) has the strongest support in the literature for reducing pain intensity, with new research examining its long-term effectiveness. Nonetheless, some individuals may not respond to M1-targeted rTMS, and symptoms beyond pain can be prominent. Ongoing research aims to improve the efficacy of rTMS by exploring new brain targets, using innovative stimulation parameters, incorporating neuronavigation, and better identifying patients likely to benefit from this treatment. Summary: Noninvasive brain stimulation with rTMS over M1 is a well-tolerated treatment that can improve chronic pain and overall quality of life in fibromyalgia patients. However, the data are highly heterogeneous, with a limited level of evidence, posing a significant challenge to the inclusion of rTMS in official treatment guidelines. Research is ongoing to enhance its effectiveness, with future perspectives exploring its impact by targeting additional areas of the brain such as the medial prefrontal cortex, anterior cingulate cortex, and inferior parietal lobe, as well as selecting the right patients who could benefit from this treatment.

Deficits in prefrontal metabotropic glutamate receptor 5 are associated with functional alterations during emotional processing in bipolar disorder.

BACKGROUND: Elucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the metabotropic glutamate receptor 5 (mGlu5) in the pathology of BD, here, we therefore test the hypothesis that recently identified deficits in mGlu5 are associated with functional brain differences during emotion processing in BD. METHODS: Positron emission tomography (PET) with [18F]FPEB was used to measure mGlu5 receptor availability and functional imaging (fMRI) was performed while participants completed an emotion processing task. Data were analyzed from 62 individuals (33 ± 12 years, 45 % female) who completed both PET and fMRI, including individuals with BD (n = 18), major depressive disorder (MDD: n = 20), and psychiatrically healthy comparisons (HC: n = 25). RESULTS: Consistent with some prior reports, the BD group displayed greater activation during fear processing relative to MDD and HC, notably in right lateralized frontal and parietal brain regions. In BD, (but not MDD or HC) lower prefrontal mGlu5 availability was associated with greater activation in bilateral pre/postcentral gyri and cuneus during fear processing. Furthermore, greater prefrontal mGlu5-related brain activity in BD was associated with difficulties in psychomotor function (r≥0.904, p≤0.005) and attention (r≥0.809, p≤0.028). LIMITATIONS: The modest sample size is the primary limitation. CONCLUSIONS: Deficits in prefrontal mGlu5 in BD were linked to increased cortical activation during fear processing, which in turn was associated with impulsivity and attentional difficulties. These data further implicate an mGlu5-related mechanism unique to BD. More generally these data suggest integrating PET and fMRI can provide novel mechanistic insights.

Medial anterior prefrontal cortex stimulation downregulates implicit reactions to threats and prevents the return of fear.

Downregulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is critical for top-down modulatory processes, and despite previous studies adopting repetitive transcranial magnetic stimulation (rTMS) over this region provided encouraging results in enhancing extinction, no studies have hitherto explored the effects of stimulating the medial anterior PFC (aPFC, encompassing the Brodmann area 10) on threat memory and generalization. Here we showed that rTMS over the aPFC applied before threat memory retrieval immediately decreases implicit reactions to learned and novel stimuli in humans. These effects enduringly persisted 1 week later in the absence of rTMS. No effects were detected on explicit recognition. Critically, rTMS over the aPFC resulted in a more pronounced reduction of defensive responses compared to rTMS targeting the dorsolateral PFC. These findings reveal a previously unexplored prefrontal region, the modulation of which can efficiently and durably inhibit implicit reactions to learned threats. This represents a significant advancement toward the long-term deactivation of exaggerated responses to threats.

Non-additive effects of electrical stimulation of the dorsolateral prefrontal cortex and the vestibular system on muscle sympathetic nerve activity in humans.

Sinusoidal galvanic vestibular stimulation (sGVS) induces robust modulation of muscle sympathetic nerve activity (MSNA) alongside perceptions of side-to-side movement, sometimes with an accompanying feeling of nausea. We recently showed that transcranial alternating current stimulation (tACS) of the dorsolateral prefrontal cortex (dlPFC) also modulates MSNA, but does not generate any perceptions. Here, we tested the hypothesis that when the two stimuli are given concurrently, the modulation of MSNA would be additive. MSNA was recorded from 11 awake participants via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve at the fibular head. Sinusoidal stimuli (± 2 mA, 0.08 Hz, 100 cycles) were applied in randomised order as follows: (i) tACS of the dlPFC at electroencephalogram (EEG) site F4 and referenced to the nasion; (ii) bilateral sGVS applied to the vestibular apparatuses via the mastoid processes; and (iii) tACS and sGVS together. Previously obtained data from 12 participants supplemented the data for stimulation protocols (i) and (ii). Cross-correlation analysis revealed that each stimulation protocol caused significant modulation of MSNA (modulation index (paired data): 35.2 ± 19.4% for sGVS; 27.8 ± 15.2% for tACS), but there were no additive effects when tACS and sGVS were delivered concurrently (32.1 ± 18.5%). This implies that the vestibulosympathetic reflexes are attenuated with concurrent dlPFC stimulation. These results suggest that the dlPFC is capable of blocking the processing of vestibular inputs through the brainstem and, hence, the generation of vestibulosympathetic reflexes.

Efficacy of non-invasive brain stimulation and neuronavigation for major depressive disorder: a systematic review and meta-analysis.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are increasingly used for major depressive disorder (MDD). Most tDCS and rTMS studies target the left dorsolateral prefrontal cortex, either with or without neuronavigation. We examined the effect of rTMS and tDCS, and the added value of neuronavigation in the treatment of MDD. METHODS: A search on PubMed, Embase, and Cochrane databases for rTMS or tDCS randomized controlled trials of MDD up to 1 February 2023, yielded 89 studies. We then performed meta-analyses comparing tDCS efficacy to non-neuronavigated rTMS, tDCS to neuronavigated rTMS, and neuronavigated rTMS to non-neuronavigated rTMS. We assessed the significance of the effect in subgroups and in the whole meta-analysis with a z-test and subgroup differences with a chi-square test. RESULTS: We found small-to-medium effects of both tDCS and rTMS on MDD, with a slightly greater effect from rTMS. No significant difference was found between neuronavigation and non-neuronavigation. CONCLUSION: Although both tDCS and rTMS are effective in treating MDD, many patients do not respond. Additionally, current neuronavigation methods are not significantly improving MDD treatment. It is therefore imperative to seek personalized methods for these interventions.

Structural and functional neural patterns among sub-threshold bulimia nervosa: Abnormalities in dorsolateral prefrontal cortex and orbitofrontal cortex.

BACKGROUND: Disordered eating behaviors are prevalent among youngsters and highly associated with dysfunction in neurocognitive systems. We aimed to identify the potential changes in individuals with bulimia symptoms (sub-BN) to generate insights to understand developmental pathophysiology of bulimia nervosa. METHODS: We investigated group differences in terms of degree centrality (DC) and gray matter volume (GMV) among 145 undergraduates with bulimia symptoms and 140 matched control undergraduates, with the secondary analysis of the whole brain connectivity in these regions of interest showing differences in static functional connectivity (FC). RESULTS: The sub-BN group exhibited abnormalities of the right dorsolateral prefrontal cortex and right orbitofrontal cortex in both GMV and DC, and displayed decreased FC between these regions and the precuneus. We also observed that sub-BN presented with reduced FC between the calcarine and superior temporal gyrus, middle temporal gyrus and inferior parietal gyrus. Additionally, brain-behavioral associations suggest a distinct relationship between these FCs and psychopathological symptoms in sub-BN group. CONCLUSIONS: Our study demonstrated that individuals with bulimia symptoms present with aberrant neural patterns that mainly involved in cognitive control and reward processing, as well as attentional and self-referential processing, which could provide important insights into the pathology of BN.

Functional near-infrared spectroscopy-based neurofeedback training regulates time-on-task effects and enhances sustained cognitive performance.

Time-on-task effect is a common consequence of long-term cognitive demand work, which reflects reduced behavioral performance and increases the risk of accidents. Neurofeedback is a neuromodulation method that can guide individuals to regulate their brain activity and manifest as changes in related symptoms and cognitive behaviors. This study aimed to examine the effects of functional near-infrared spectroscopy-based neurofeedback training on time-on-task effects and sustained cognitive performance. A randomized, single-blind, sham-controlled study was performed: 17 participants received feedback signals of their own dorsolateral prefrontal cortex activity (neurofeedback group), and 16 participants received feedback signals of dorsolateral prefrontal cortex activity from the neurofeedback group (sham-neurofeedback group). All participants received 5 neurofeedback training sessions and completed 2 sustained cognitive tasks, including a 2-back task and a psychomotor vigilance task, to evaluate behavioral performance changes following neurofeedback training. Results showed that neurofeedback relative to the sham-neurofeedback group exhibited increased dorsolateral prefrontal cortex activation, increased accuracy in the 2-back task, and decreased mean response time in the psychomotor vigilance task after neurofeedback training. In addition, the neurofeedback group showed slower decline performance during the sustained 2-back task after neurofeedback training compared with sham-neurofeedback group. These findings demonstrate that neurofeedback training could regulate time-on-task effects on difficult task and enhance performance on sustained cognitive tasks by increasing dorsolateral prefrontal cortex activity.

Moral decision-making in context: Behavioral and neural processes underlying allocations based on need, merit, and equality.

How to fairly allocate goods is a key issue of social decision-making. Extensive research demonstrates that people do not selfishly maximize their own benefits, but instead also consider how others are affected. However, most accounts of the psychological processes underlying fairness-related behavior implicitly assume that assessments of fairness are somewhat stable. In this paper, we present results of a novel task, the Re-Allocation Game, in which two players receive an allocation determined by the computer and, on half of the trials, one player has the subsequent possibility to change this allocation. Importantly, prior to the receipt of the allocation, players were shown either their respective financial situations, their respective performance on a previous simple task, or random information, while being scanned using functional neuroimaging. As expected, our results demonstrate when given the opportunity, participants allocated on average almost half the money to anonymous others. However, our findings further show that participants used the provided information in a dynamic manner, revealing the underlying principle based on which people re-allocate money - namely based on merit, need, or equality - switches dynamically. On the neural level, we identified activity in the right and left dorsolateral prefrontal cortices related to context-independent inequity and context-dependent fairness information respectively when viewing the computer-generated allocations. At the same time, activity in the temporoparietal and precuneus represented these different types of fairness-related information in adjacent and partially overlapping clusters. Finally, we observed that the activity pattern in the precuneus and putamen was most clearly related to participants' subsequent re-allocation decisions. Together, our findings suggest that participants judge an allocation as fair or unfair using a network associated with cognitive control and theory-of-mind, while dynamically switching between what might constitute a fair allocation in a particular context.

Mapping cortical excitability in the human dorsolateral prefrontal cortex.

BACKGROUND: Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (dlPFC) is an effective treatment for depression, but the neural effects after TMS remains unclear. TMS paired with electroencephalography (TMS-EEG) can causally probe these neural effects. Nonetheless, variability in single pulse TMS-evoked potentials (TEPs) across dlPFC subregions, and potential artifact induced by muscle activation, necessitate detailed mapping for accurate treatment monitoring. OBJECTIVE: To characterize early TEPs anatomically and temporally (20-50 ms) close to the TMS pulse (EL-TEPs), as well as associated muscle artifacts (<20 ms), across the dlPFC. We hypothesized that TMS location and angle influence EL-TEPs, and specifically that conditions with larger muscle artifact may exhibit lower observed EL-TEPs due to over-rejection during preprocessing. Additionally, we sought to determine an optimal group-level TMS target and angle, while investigating the potential benefits of a personalized approach. METHODS: In 16 healthy participants, we applied single-pulse TMS to six targets within the dlPFC at two coil angles and measured EEG responses. RESULTS: Stimulation location significantly influenced observed EL-TEPs, with posterior and medial targets yielding larger EL-TEPs. Regions with high EL-TEP amplitude had less muscle artifact, and vice versa. The best group-level target yielded 102% larger EL-TEP responses compared to other dlPFC targets. Optimal dlPFC target differed across subjects, suggesting that a personalized targeting approach might boost the EL-TEP by an additional 36%. SIGNIFICANCE: EL-TEPs can be probed without significant muscle-related confounds in posterior-medial regions of the dlPFC. The identification of an optimal group-level target and the potential for further refinement through personalized targeting hold significant implications for optimizing depression treatment protocols.

Effect of dorsolateral prefrontal cortex structural measures on neuroplasticity and response to paired-associative stimulation in Alzheimer's dementia.

Long-term potentiation (LTP)-like activity can be induced by stimulation protocols such as paired associative stimulation (PAS). We aimed to determine whether PAS-induced LTP-like activity (PAS-LTP) of the dorsolateral prefrontal cortex (DLPFC) is associated with cortical thickness and other structural measures impaired in Alzheimer's dementia (AD). We also explored longitudinal relationships between these brain structures and PAS-LTP response after a repetitive PAS (rPAS) intervention. Mediation and regression analyses were conducted using data from randomized controlled trials with AD and healthy control participants. PAS-electroencephalography assessed DLPFC PAS-LTP. DLPFC thickness and surface area were acquired from T1-weighted magnetic resonance imaging. Fractional anisotropy and mean diffusivity (MD) of the superior longitudinal fasciculus (SLF)-a tract important to induce PAS-LTP-were measured with diffusion-weighted imaging. AD participants exhibited reduced DLPFC thickness and increased SLF MD. There was also some evidence that reduction in DLPFC thickness mediates DLPFC PAS-LTP impairment. Longitudinal analyses showed preliminary evidence that SLF MD, and to a lesser extent DLPFC thickness, is associated with DLPFC PAS-LTP response to active rPAS. This study expands our understanding of the relationships between brain structural changes and neuroplasticity. It provides promising evidence for a structural predictor to improving neuroplasticity in AD with neurostimulation. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

A tale of two n-backs: Diverging associations of dorsolateral prefrontal cortex activation with n-back task performance.

Background: In studying the neural correlates of working memory (WM) ability via functional magnetic resonance imaging (fMRI) in health and disease, it is relatively uncommon for investigators to report associations between brain activation and measures of task performance. Additionally, how the choice of WM task impacts observed activation-performance relationships is poorly understood. We sought to illustrate the impact of WM task on brain-behavior correlations using two large, publicly available datasets. Methods: We conducted between-participants analyses of task-based fMRI data from two publicly available datasets: the Human Connectome Project (HCP; n = 866) and the Queensland Twin Imaging (QTIM) Study (n = 459). Participants performed two distinct variations of the n-back WM task with different stimuli, timings, and response paradigms. Associations between brain activation ([2-back - 0-back] contrast) and task performance (2-back % correct) were investigated separately in each dataset, as well as across datasets, within the dorsolateral prefrontal cortex (dlPFC), medial prefrontal cortex, and whole cortex. Results: Global patterns of activation to task were similar in both datasets. However, opposite associations between activation and task performance were observed in bilateral pre-supplementary motor area and left middle frontal gyrus. Within the dlPFC, HCP participants exhibited a significantly greater activation-performance relationship in bilateral middle frontal gyrus relative to QTIM Study participants. Conclusions: The observation of diverging activation-performance relationships between two large datasets performing variations of the n-back task serves as a critical reminder for investigators to exercise caution when selecting WM tasks and interpreting neural activation in response to a WM task.

Real-time optimization to enhance noninvasive cortical excitability assessment in the human dorsolateral prefrontal cortex.

Objective: We currently lack a robust noninvasive method to measure prefrontal excitability in humans. Concurrent TMS and EEG in the prefrontal cortex is usually confounded by artifacts. Here we asked if real-time optimization could reduce artifacts and enhance a TMS-EEG measure of left prefrontal excitability. Methods: This closed-loop optimization procedure adjusts left dlPFC TMS coil location, angle, and intensity in real-time based on the EEG response to TMS. Our outcome measure was the left prefrontal early (20-60 ms) and local TMS-evoked potential (EL-TEP). Results: In 18 healthy participants, this optimization of coil angle and brain target significantly reduced artifacts by 63% and, when combined with an increase in intensity, increased EL-TEP magnitude by 75% compared to a non-optimized approach. Conclusions: Real-time optimization of TMS parameters during dlPFC stimulation can enhance the EL-TEP. Significance: Enhancing our ability to measure prefrontal excitability is important for monitoring pathological states and treatment response.

Cognitive impairment in schizophrenia is associated with prefrontal-striatal functional hypoconnectivity and striatal dopaminergic abnormalities.

BACKGROUND: A better understanding of the mechanisms underlying cognitive impairment in schizophrenia is imperative, as it causes poor functional outcomes and a lack of effective treatments. AIMS: This study aimed to investigate the relationships of two proposed main pathophysiology of schizophrenia, altered prefrontal-striatal connectivity and the dopamine system, with cognitive impairment and their interactions. METHODS: Thirty-three patients with schizophrenia and 27 healthy controls (HCs) who are right-handed and matched for age and sex were recruited. We evaluated their cognition, functional connectivity (FC) between the dorsolateral prefrontal cortex (DLPFC)/middle frontal gyrus (MiFG) and striatum, and the availability of striatal dopamine transporter (DAT) using a cognitive battery investigating attention, memory, and executive function, resting-state functional magnetic resonance imaging with group independent component analysis and single-photon emission computed tomography with 99mTc-TRODAT. RESULTS: Patients with schizophrenia exhibited poorer cognitive performance, reduced FC between DLPFC/MiFG and the caudate nucleus (CN) or putamen, decreased DAT availability in the left CN, and decreased right-left DAT asymmetry in the CN compared to HCs. In patients with schizophrenia, altered imaging markers are associated with cognitive impairments, especially the relationship between DLPFC/MiFG-putamen FC and attention and between DAT asymmetry in the CN and executive function. CONCLUSIONS: This study is the first to demonstrate how prefrontal-striatal hypoconnectivity and altered striatal DAT markers are associated with different domains of cognitive impairment in schizophrenia. More research is needed to evaluate their complex relationships and potential therapeutic implications.

Role of Repetitive Transcranial Magnetic Stimulation in Treatment of Fibromyalgia: A Randomized Controlled Trial.

Background and Objective: Fibromyalgia syndrome (FMS) is a chronic disease characterized by widespread, persistent musculoskeletal pain in association with impaired health-related quality of life. Repetitive transcranial magnetic stimulation (rTMS) is an emerging tool for the management of fibromyalgia. There is no standardized protocol of rTMS for the treatment of FMS, and both low- and high-frequency stimulation of the dorsolateral prefrontal cortex (DLPFC) are described in the literature with variable efficacy. The objective of this study was to determine the effectiveness of rTMS in people with fibromyalgia and compare the response of low- and high-frequency stimulation with sham stimulation. Materials and Methods: This study was a single-blinded, randomized, placebo-controlled trial. Ninety patients with the diagnosis of FMS were randomly allocated into one of the following three groups: low-frequency (1 Hz) group, high-frequency (10 Hz) group, and sham group. Pain, depression, anxiety, and quality of life were measured using the Numerical Pain Rating Scale (NPRS), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HDRS), and Revised Fibromyalgia Impact Questionnaire (FIQR) immediately following treatment as well as at 1 and 3 months after treatment. The data was statistically analyzed using Statistical Package for the Social Sciences version 23 software. P value < 0.05 was considered statistically significant. Results: Intergroup analysis revealed a significant improvement in NPRS, HAM-A, HDRS, and FIQR scores in both low- and high- frequency groups immediately following treatment and for 3 months after treatment. No significant difference in the efficacy of low- and high-frequency stimulation was noticed. Conclusions: rTMS is an effective mode of treatment in people with FMS. Both low and high frequencies of stimulation at DLPFC are equally effective in reducing pain and associated symptoms.

Targeting the left DLPFC and right VLPFC in unmarried romantic relationship breakup (love trauma syndrome) with intensified electrical stimulation: A randomized, single-blind, parallel-group, sham-controlled study.

BACKGROUND: Ending a romantic relationship is one of the most painful losses an adult experience. Neuroimaging studies suggest that there is a neuropsychological link between breakup experiences and bereaved individuals, and that specific prefrontal regions are involved. The aim of this study was to determine whether enhancement of left DLPFC and right VLPFC activity with a novel intensified anodal transcranial direct current stimulation protocol reduces core symptoms of love trauma syndrome (LTS) and improves treatment-related variables. METHODS: In this randomized, sham-controlled, single-blind parallel trial, we assessed the efficacy of an intensified anodal stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) with two montages (left DLPFC vs right VLPFC) to reduce love trauma symptoms. 36 participants with love trauma syndrome were randomized in three tDCS condition (left DLPFC, right VLPFC, sham stimulation). LTS symptoms, treatment-related outcome variables (depressive state, anxiety, emotion regulation, positive and negative affect), and cognitive functions were assessed before, right after, and one month after intervention. RESULTS: Both DLPFC and VLPFC protocols significantly reduced LTS symptoms, and improved depressive state and anxiety after the intervention, as compared to the sham group. The improving effect of the DLPFC protocol on love trauma syndrome was significantly larger than that of the VLPFC protocol. For emotion regulation and positive and negative affect, improved regulation of emotions and positive affect and reduced negative affect were revealed after intervention in the two real stimulation conditions compared to the sham. For cognitive functions, no significant difference was observed between the groups, but again a positive effect of intervention within groups in the real stimulation conditions (DLPFC and VLPFC) was found for most components of the cognitive tasks. CONCLUSIONS: Enhancement of left DLPFC and right VLPFC activity with intensified stimulation improves LTS symptoms and treatment-related variables. For LTS symptoms, DLPFC stimulation was more efficient than VLPFC stimulation., For the other variables, no significant difference was observed between these two stimulation groups. These promising results require replication in larger trials.

A new angle on transcranial magnetic stimulation coil orientation: A targeted narrative review.

Transcranial magnetic stimulation (TMS) is used to treat several neuropsychiatric disorders including depression, where it is effective in approximately half of patients for whom pharmacological approaches have failed. Treatment response is related to stimulation parameters such as the stimulation frequency, pattern, intensity, location, total number of pulses and sessions applied, as well as target brain network engagement. One critical but underexplored component of the stimulation procedure is the orientation or yaw angle of the commonly used figure-of-eight TMS coil, which is known to impact neuronal response to TMS. However, coil orientation has remained largely unchanged since TMS was first used to treat depression and continues to be based on motor cortex anatomy which may not be optimal for the dorsolateral prefrontal cortex treatment site. This targeted narrative review evaluates experimental, clinical, and computational evidence indicating that optimizing coil orientation may potentially improve TMS treatment outcomes. The properties of the electric field induced by TMS, the changes to this field caused by the differing conductivities of head tissues, and the interaction between coil orientation and the underlying cortical anatomy are summarized. We describe evidence that the magnitude and site of cortical activation, surrogate markers of TMS dosing and brain network targeting considered central in clinical response to TMS, are influenced by coil orientation. We suggest that coil orientation should be considered when applying therapeutic TMS and propose several approaches to optimizing this potentially important treatment parameter.