Repetitive transcranial magnetic stimulation influences mood in healthy male volunteers

The influence of repetitive transcranial magnetic stimulation (rTMS) on mood in healthy people is uncertain, as former studies show divergent results. Previous studies in healthy volunteers focused exclusively on the immediate effect of a single session of rTMS. In contrast the aim of this randomised sham-controlled study was to analyse the influence on mood of a series of 9 High Frequency (HF) rTMS stimulations of the left dorsolateral prefrontal cortex (DLPFC).44 young healthy male volunteers were randomly assigned to receive 9 sessions of active HF-rTMS (n = 22) or sham rTMS (n = 22) over the left DLPFC. Each session in the active group consisted of 15 trains of 25 Hz starting with 100% of motor threshold. Sham stimulation was performed following the same protocol, but using a sham coil. The variables of interest were the Beck Depression Inventory (BDI) and six Visual Analogue Scales (VAS) which quantified “mood”, “enjoyment” and “energy”. We found a significant reduction of the BDI sum score in the active group (GLM, p < 0.001) whereas no significant changes of the BDI sum score were caused by sham stimulation (GLM, p = 0.109). The BDI single item analyses revealed within and between group differences supporting the modifying effect of rTMS on BDI. According to the employed VAS we did not find significant differences caused by active or sham stimulation in five of six VAS. In the VAS labelled lively/gloomy the active group was found to be more “gloomy” (p = 0.0111) immediately after stimulation. Our data show that a 9-day long series of HF-rTMS of the left DLPFC improves mood, analysed by BDI in healthy young men, whereas no significant long-term changes were found in VAS.     

The effects of high frequency rTMS on negative attentional bias are influenced by baseline state anxiety

High frequency (HF) repetitive Transcranial Magnetic Stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) has been shown to induce an attentional bias towards threatening information in healthy adults, associated with decreased activation in the right DLPFC and increased activation in the right amygdala. Additionally, it has been shown that healthy individuals with higher state anxiety portray similar negative attentional biases and cortico-subcortical activation patterns to those induced by HF-rTMS of the right DLPFC. Therefore, the aim of this study is to investigate whether inter-individual differences in state anxiety levels prior to the administration of HF-rTMS of the right DLPFC might be related to the degree to which rTMS induces such a negative attentional bias in healthy volunteers. We administered HF-rTMS of the right DLPFC to a group of 28 healthy female individuals. In line with previous research, a single session of HF-rTMS of the right DLPFC induced an attentional bias towards threatening information. Moreover, self-report measures of state anxiety (STAI-State) prior to stimulation correlated positively with the magnitude of the induced attentional bias. More specifically, we found that healthy individuals who scored higher on self-reports of state anxiety acquired more attentional bias towards negative information after HF-rTMS. Therefore, the effects of a single placebo-controlled rTMS session of the right DLPFC is consistent with the effects of a disrupted prefrontal-amygdala circuitry. The effects on attentional bias are largest in those participants reporting higher state anxiety scores, possibly because underlying amygdala activation is highest.     

The influence of endogenous estrogen on high-frequency prefrontal transcranial magnetic stimulation

BackgroundThe use of repetitive transcranial magnetic stimulation (rTMS) as both therapeutic and experimental tools has grown enormously over the past decade. However, variability in response to rTMS is one challenge that remains to be solved. Estrogen can impact neural plasticity and may also affect plastic changes following rTMS. The present study investigated whether estrogen levels influence the neurophysiological effects of high-frequency (HF) rTMS in the left dorsolateral prefrontal cortex (DLPFC).HypothesisIt was hypothesised that individuals with higher endogenous estrogen would demonstrate greater rTMS-induced changes in cortical reactivity.Methods29 healthy adults (15M/14F) received HF-rTMS over left DLPFC. Females attended two sessions, one during a high-estrogen (HE) phase of the menstrual cycle, another during a low-estrogen (LE) phase. Males attended one session. Estrogen level was verified via blood assay. TMS-EEG was used to probe changes in cortical plasticity and comparisons were made using cluster-based permutation statistics and Bayesian analysis.ResultsIn females, a significant increase in TMS-evoked P60 amplitude, and decrease in N45, N100 and P180 amplitudes was observed during HE. A less pervasive pattern of change was observed during LE. No significant changes in TEPs were seen in males. Between-condition comparisons revealed higher likelihood of the change in N100 and/or P180 being larger in females during HE compared to both females during LE and males.ConclusionsThese preliminary findings indicate that a greater neuroplastic response to prefrontal HF-rTMS is seen in women when estrogen is at its highest compared to men, suggesting that endogenous estrogen levels contribute to variability in response to HF-rTMS.     

Effects of HF-rTMS over the left and right DLPFC on proactive and reactive cognitive control

Previous research supports the distinction between proactive and reactive control. Although the dorsolateral prefrontal cortex (DLPFC) has been consistently related to these processes, lateralization of proactive and reactive control is still under debate. We manipulated brain activity to investigate the role of the left and right DLPFC in proactive and reactive cognitive control. Using a single-blind, sham-controlled crossover within-subjects design, 25 young healthy females performed the ‘AX’ Continuous Performance Task after receiving sham vs active high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to increase left and right DLPFC activity. Reaction times (RTs) and pupillometry were used to assess patterns of proactive and reactive cognitive control and task-related resource allocation, respectively. We observed that, compared to sham, HF-rTMS over the left DLPFC increased proactive control. After right DLPFC HF-rTMS, participants showed slower RTs on AX trials, suggesting more reactive control. However, this latter result was not supported by RTs on BX trials (i.e. the trial that specifically assess reactive control). Pupil measures showed a sustained increase in resource allocation after both active left and right HF-rTMS. Our results with RT data provide evidence on the role of the left DLPFC in proactive control and suggest that the right DLPFC is implicated in reactive control.     

High-frequency rTMS over the dorsolateral prefrontal cortex on chronic and provoked pain: A systematic review and meta-analysis

BackgroundHigh-frequency rTMS over the dorsolateral prefrontal cortex (DLPFC) has demonstrated mixed effects on chronic and provoked pain.Objectives/MethodsIn this study, a meta-analysis was conducted to characterise the potential analgesic effects of high-frequency rTMS over the DLPFC on both chronic and provoked pain.ResultsA total of 626 studies were identified in a systematic search. Twenty-six eligible studies were included for the quantitative review, among which 17 modulated chronic pain and the remaining investigated the influence on provoked pain. The left side DLPFC was uniformly targeted in the chronic pain studies. While our data identified no overall effect of TMS across chronic pain conditions, there was a significant short-term analgesia in neuropathic pain conditions only (SMD = −0.87). In terms of long-lasting analgesia, there was an overall pain reduction in the midterm (SMD = −0.53, 24.6 days average) and long term (SMD = −0.63, 3 months average) post DLPFC stimulation, although these effects were not observed within specific chronic pain conditions. Surprisingly, the number of sessions was demonstrated to have no impact on rTMS analgesia. In the analysis of provoked pain, our data also indicated a significant analgesic effect following HF-rTMS over the DLPFC (SMD = −0.73). Importantly, we identified a publication bias in the studies of provoked pain but not for chronic pain conditions.ConclusionsOverall, our findings support that HF-DLPFC stimulation is able to induce an analgesic effect in chronic pain and in response to provoked pain. These results highlight the potential of DLPFC-rTMS in the management of certain chronic pain conditions and future directions are discussed to enhance the potential long-term analgesic effects.     

Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex Decreases Cue-induced Nicotine Craving and EEG Delta Power

BackgroundTMS has high potential as smoking cessation treatment. However, the neural mechanisms underlying TMS induced reduction of tobacco craving remain unclear. Electroencephalographic (EEG) delta frequency has been associated with the activity of the dopaminergic brain reward system, which is crucial for nicotine induced effects, and decreases after nicotine admission in smokers.ObjectiveThe aim of this study was to investigate EEG delta power changes induced by hf rTMS of the left dorsolateral prefrontal cortex (DLPFC) in nicotine deprived smokers and it's relation to cue-induced nicotine craving.MethodsFourteen healthy smokers meeting ICD-10 criteria for tobacco addiction participated in this within-subject sham controlled study. Participants had to abstain from smoking 6 h before the experiment. Effects of high-frequency repetitive TMS (hf rTMS) (10 Hz) for verum (left DLPFC) and sham (vertex) stimulations on cue-induced nicotine craving and resting state EEG delta power were assessed before and three times within 40 min after rTMS.ResultsBoth craving (P = 0.046) and EEG delta power (P = 0.048) were significantly lower after verum stimulation compared to sham stimulation across the whole post stimulation time period assessed. However, changes of craving ratings and delta power did not correlate.ConclusionHf rTMS applied to the left DLPFC reduces nicotine craving in short-term abstinent smokers. Changes in delta activity support the idea that stimulation induced effects are mediated by the dopaminergic brain reward system, which presumably plays a prominent, but probably not exclusive, role in this stimulation induced behavioral modulation, making this method a promising smoking cessation treatment candidate.     

Left and right High Frequency repetitive Transcranial Magnetic Stimulation of the dorsolateral prefrontal cortex does not affect mood in female volunteers.

OBJECTIVE: High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) has yielded divergent results concerning its effect on mood in normal volunteers. In a former study, we were unable to demonstrate negative mood effects after one session of HF-rTMS on the left dorsolateral prefrontal cortex (DLPFC) in a large group of healthy female volunteers: researchers had focused mainly on negative mood changes, overlooking a possible positive mood induction, while no studies had yet examined mood effects of HF-rTMS delivered on the right prefrontal cortex. In this study, we have tried to replicate our previous HF-rTMS findings on the left DLPFC in a new (large) group of healthy female subjects, and we focused especially on positive mood changes. We also extended our former research by stimulating the right DLPFC in a different but comparable (large) group of healthy female volunteers with the same HF-rTMS parameters. METHODS: In this sham-controlled, single blind, crossover HF-rTMS study, stimulus parameters were an exact copy of our previous healthy volunteer study. To exclude individual anatomical differences, the left and right DLPFC were targeted under magnetic resonance (MRI) guidance. To examine subjective mood changes we used Visual Analogue Scales (VAS), the Profile of Mood States (POMS), and the Positive Affect and Negative Affect Schedule (PANAS), the latter to assure assessment of positive emotions. To detect any delayed mood changes, assessments were also re-administered 30min post-HF-rTMS. RESULTS: We were unable to demonstrate immediate or delayed mood changes after one single active HF-rTMS session on the left or right DLPFC. CONCLUSIONS: Although we took into account several methodological problems which might have confounded previous rTMS mood induction studies, the hypothesis that one single session of HF-rTMS on the left or on the right DLPFC can influence mood in healthy female volunteers was not supported. SIGNIFICANCE: One HF-rTMS session has no effect on subjective mood in healthy female volunteers.     

Transcranial Direct Current Stimulation (tDCS) Enhances Reconsolidation of Long-Term Memory

A new and weak memory trace undergoes consolidation to gain resistance against interfering stimuli. When an encoded memory is recalled, it becomes labile and another round of consolidation, or reconsolidation, is required to restore its stability. Transcranial direct current stimulation (tDCS) is a non-invasive method of altering cortical excitability. The aim of this study was to examine the effects of tDCS on the reconsolidation of long-term verbal memory. Participants (n = 15) memorized words in the encoding session, then reactivated the memory of the words 3 h later using an old–new recognition task under anodal, cathodal and sham stimulation to the left dorsolateral prefrontal cortex (DLPFC). Finally, after another 5 h, they performed another round of the old–new recognition task and rated their confidence. Anodal tDCS during the second session resulted in significantly more words recognized in the third session as compared to cathodal and sham stimulation. Cathodal tDCS did not affect the recognition performance compared to sham stimulation. These results cannot be attributed to differences in response times and confidence ratings, as they were comparable in all conditions. In order to study whether the activation of a memory was crucial for the enhancing effects of anodal tDCS, a group of controls (n = 15) did not perform the recognition task in the second session but still underwent stimulation. Contrary to the main group, anodal stimulation did not enhance the memory performance for the control group. This result suggests that anodal tDCS over the left DLPFC can enhance the reconsolidation of long-term memory only when the memory has been reactivated.     

Effect of Two Weeks of rTMS on Brain Activity in Healthy Subjects During an n-Back Task: A Randomized Double Blind Study

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has shown significant efficiency in the treatment of several psychiatric disorders. In depressive disorders, the dorsolateral prefrontal cortex (DLPFC) is the main target for rTMS, but the effects of this stimulation on cognitive functions and their neural correlates are not well known. Previous works have established that the left DLPFC is reliably activated during the n-back working memory task.ObjectiveThe aim of this randomized double-blind study was to determine the impact of rTMS applied to the DLPFC on brain activity during an n-back task in healthy subjects.MethodsAfter randomization, twenty subjects received either active treatment (10 sessions; 1 session a day; frequency = 10 Hz; intensity = 110% of motor threshold) or placebo treatment (sham coil). Subjects performed an n-back task during two functional magnetic resonance imaging sessions (one before stimulation, and one after 10 active or sham rTMS sessions).ResultsNo significant changes, neither in mood nor in performance in the n-back task, were shown. A significant group-by-time interaction effect was found in the bilateral middle frontal gyrus and in the left caudate nucleus.ConclusionsThese results show that rTMS applied on the left DLPFC had close and remote effects on brain areas involved in working memory.     

The Painfulness of Active,but not Sham,Transcranial Magnetic Stimulation Decreases Rapidly Over Time: Results From the Double-Blind Phase of the OPT-TMS Trial

BackgroundDaily left prefrontal repetitive transcranial magnetic stimulation (rTMS) over several weeks is an FDA approved treatment for major depression. Although rTMS is generally safe when administered using the FDA guidelines, there are a number of side effects that can make it difficult for patients to complete a course of rTMS. Many patients report that rTMS is painful, although patients appear to accommodate to the initial painfulness. The reduction in pain is hypothesized to be due to prefrontal stimulation and is not solely explained by accommodation to the stimulation.MethodsIn a recent 4 site randomized controlled trial (using an active electrical sham stimulation system) investigating the antidepressant effects of daily left dorsolateral prefrontal rTMS (Optimization of TMS, or OPT-TMS), the procedural painfulness of TMS was assessed before and after each treatment session. Computerized visual analog scale ratings were gathered before and after each TMS session in the OPT-TMS trial. Stimulation was delivered with an iron core figure-8 coil (Neuronetics) with the following parameters: 10 Hz, 120% MT (EMG-defined), 4 s pulse train, 26 s inter-train interval, 3000 pulses per session, one 37.5 min session per day. After each session, procedural pain (pain at the beginning of the TMS session, pain toward the middle, and pain toward then end of the session) ratings were collected at all 4 sites. From the 199 patients randomized, we had usable data from 142 subjects for the initial 15 TMS sessions (double-blind phase) delivered over 3 weeks (142 × 2 × 15 = 4260 rating sessions).ResultsThe painfulness of real TMS was initially higher than that of the active sham condition. Over the 15 treatment sessions, subjective reports of the painfulness of rTMS (during the beginning, middle and end of the session) decreased significantly 37% from baseline in those receiving active TMS, with no change in painfulness in those receiving sham. This reduction, although greatest in the first few days, continued steadily over the 3 weeks. Overall, there was a decay rate of 1.56 VAS points per session in subjective painfulness of the procedure in those receiving active TMS.DiscussionThe procedural pain of left, prefrontal rTMS decreases over time, independently of other emotional changes, and only in those receiving active TMS. These data suggest that actual TMS stimulation of prefrontal cortex maybe related to the reduction in pain, and that it is not a non-specific accommodation to pain. This painfulness reduction softly corresponds with later clinical outcome. Further work is needed to better understand this phenomenon and whether acute within-session or over time painfulness changes might be used as short-term biomarkers of antidepressant response.     

Evidence for a Role of the Right Dorsolateral Prefrontal Cortex in Controlling Stimulus-response Integration: A Transcranial Direct Current Stimulation (tDCS) Study

BackgroundActing coherently upon stimuli requires some kind of integration of stimulus and response features across various distinct cortical feature maps (one aspect of the binding problem). Although the process of feature binding proper seems rather automatic, recent studies revealed that the management of stimulus-response bindings is less efficient in populations with impaired cognitive-control processes.ObjectiveHere, we investigated whether the cognitive control of stimulus-response feature bindings (“event files”) in healthy participants is affected by non-invasive brain stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC)—a main component of the cognitive-control network.MethodIn different sessions, participants received anodal, cathodal, or sham tDCS (2 mA, 20 min) while performing an audio-visual event-file task assessing the creation and retrieval of stimulus–stimulus and stimulus-response feature bindings. The general findings from this task indicate that performance suffers when some, but not all of the features are repeated (the so-called partial repetition cost).ResultsStimulation over the right, but not the left DLPFC reduced control of stimulus-response bindings and produced outcome patterns similar to those previously observed in autistic children, people with lower fluid intelligence, and older adults.ConclusionsThis finding provides empirical support for a role of the right DLPFC in feature-binding management, which might consist in preventing the stimulus-induced activation of previously created, but now task-irrelevant, episodic bindings. From a methodological perspective, the finding may suggest that tDCS could be used as a temporary, reversible “brain lesion” generator in healthy subjects, enabling experimental investigation of how the brain works.     

tDCS-induced modulation of GABA concentration and dopamine release in the human brain: A combination study of magnetic resonance spectroscopy and positron emission tomography

BackgroundTranscranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) hypothetically modulates cognitive functions by facilitating or inhibiting neuronal activities chiefly in the cerebral cortex. The effect of tDCS in the deeper brain region, the basal ganglia-cortical circuit, remains unknown.ObjectiveTo investigate the interaction between γ-aminobutyric acid (GABA) concentrations and dopamine release following tDCS.MethodThis study used a randomized, placebo-controlled, double-blind, crossover design. Seventeen healthy male subjects underwent active and sham tDCS (13 min twice at an interval of 20 min) with the anode placed at the left DLPFC and the cathode at the right DLPFC, followed by examinations with [¹¹C]-raclopride positron emission topography (PET) and GABA-magnetic resonance spectroscopy (MRS). MRS voxels were set in the left DLPFC and bilateral striata. Paired t-tests and regression analyses were performed for PET and MRS parameters.ResultsMRS data analyses showed elevations in GABA in the left striatum along with moderate reductions in the right striatum and the left DLPFC after active tDCS. PET data analyses showed that reductions in [¹¹C]-raclopride binding potentials (increase in dopamine release) in the right striatum were inversely correlated with those in the left striatum after active tDCS. GABA reductions in the left DLPFC positively correlated with elevations in GABA in the left striatum and with increases in right striatal dopamine release and negatively correlated with increases in left striatal dopamine release.ConclusionThe present results suggest that tDCS to the DLPFC modulates dopamine-GABA functions in the basal ganglia-cortical circuit.     

Repeated stimulation of the dorsolateral-prefrontal cortex improves executive dysfunctions and craving in drug addiction: A randomized,double-blind,parallel-group study

BackgroundAccording to the neurocognitive model of addiction, the development and maintenance of drug addiction is associated with cognitive control deficits, as well as decreased activity of prefrontal regions, especially the dorsolateral prefrontal cortex (DLPFC). This study investigated how improving executive functions (EFs) impacts methamphetamine-use disorder, which has been less explored compared to craving, but might be a central aspect for the therapeutic efficacy of DLPFC stimulation in drug addiction.MethodsWe assessed the efficacy of 10 repeated sessions of transcranial direct current stimulation (tDCS) over the DLPFC on executive dysfunctions in methamphetamine-use disorder, and its association with craving alterations. 39 of 50 initially recruited individuals with methamphetamine-use disorder who were in the abstinent-course treatment were randomly assigned to “active” and “sham” stimulation groups in a randomized, double-blind parallel-group study. They received active (2 mA, 20 min) or sham tDCS for 10 sessions over 5 weeks. Performance on major EF tasks (e.g., working memory, inhibitory control, cognitive flexibility, and risk-taking behaviour) and craving were measured before, immediately after, and 1 month following the intervention. Participants reported abstinence from drug consumption throughout the experiment, verified by regular urine tests during the course of the study up to the follow-up measurement.ResultsThe group which received active DLPFC tDCS showed significantly improved task performance across all EFs immediately after and 1 month following the intervention, when compared to both pre-stimulation baseline and individuals who received sham tDCS. Similarly, a significant reduction in craving was observed immediately after and 1 month following the intervention in the active, but not sham stimulation group. A significant correlation between cognitive control improvement and craving reduction was found as well.ConclusionsImprovement of cognitive control functions is closely associated with reduced craving. Repeated DLPFC stimulation in order to improve executive control could be a promising approach for therapeutic interventions in drug addiction. However, the observed findings require further confirmation by studies that measure relapse/consumption of the respective substances over longer follow-up measurements.     

High-Frequency Repetitive Transcranial Magnetic Stimulation over the Primary Foot Motor Area in Parkinson's Disease

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been reported to be clinically effective for treating motor symptoms in Parkinson's disease (PD). Few studies have been performed reporting the effects of rTMS on non-motor symptoms such as depression and apathy in PD.ObjectiveWe assessed the effects of high-frequency (HF) rTMS over the primary motor (M1) foot area on motor symptoms, depression and apathy scales, and sensory symptoms in PD.MethodsWe investigated the efficacy of 3 consecutive days of HF-rTMS over the M1 foot area in 21 patients with PD using a randomized, double-blind cross-over trial compared with sham stimulation. Motor effects were evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), the self-assessment motor score, the visual analog scale (VAS), the 10-m walking test, and finger tapping. Non-motor effects were analyzed using the Montgomery Asberg Depression Rating Scale, the Apathy Scale, and quantitative sensory testing.ResultsHF-rTMS significantly improved UPDRS-III (P < 0.001), VAS (P < 0.001), the walking test (P = 0.014), self-assessment motor score (P = 0.010), and finger tapping measurement (P < 0.05) compared to sham stimulation. In contrast, no significant improvement was observed in depression and apathy scales. Consecutive days of rTMS did not significantly increase the improvement in motor symptoms. There were no adverse effects following rTMS on patients with PD.ConclusionsWe confirmed that HF-rTMS over the M1 foot area significantly improved motor symptoms in patients with PD. In addition, daily repeated stimulation was not significantly more effective than a single session of stimulation, but may be effective for maintaining the improvement in motor symptoms in patients with PD.     

Prefrontal oscillatory stimulation modulates access to cognitive control references in retrospective metacognitive commentary

ObjectiveWe intended to examine how theta-rhythm transcranial alternating current stimulation (tACS) (versus sham non-active stimulation) modulated associations between working memory accuracy and later retrospective self-evaluation scores.MethodsHealthy participants were required to complete a verbal working memory task while receiving tACS bilaterally over the dorsolateral prefrontal cortex (DLPFC) versus sham DLPFC stimulation. After completion of the online and post-stimulation working memory tasks, participants were asked to rate the level of success-confidence on the two preceding working memory tasks.ResultsAs expected, online working memory accuracy was improved in the active bilateral DLPFC condition versus sham stimulation. Importantly, this working memory enhancement was related to post-stimulation self-evaluation scores.ConclusionsTheoretically, our findings indicated that cognitive-control representations (e.g., working memory accuracy) could serve as the optimal frame of reference for later retrospective metacognitive judgments.SignificanceNoninvasive application of bi-frontal oscillatory currents might enhance functional connectivity between prefrontal regulatory components of working memory and retrospective monitoring in humans. Importantly, along with recent electrophysiological finding indicating interaction of tACS with ongoing oscillatory activity, our preliminary findings support the feasibility of utilizing tACS to treat theta-rhythm functional disconnectivity and related cognitive impairments in schizophrenia.     

Impaired Activation in Cognitive Control Regions Predicts Reversal Learning in Schizophrenia

Reinforcement learning deficits have been associated with schizophrenia (SZ). However, the pathophysiology that gives rise to these abnormalities remains unclear. To address this question, SZ patients (N = 58) and controls (CN; N = 36) completed a probabilistic reversal-learning paradigm during functional magnetic resonance imaging scanning. During the task, participants choose between 2 stimuli. Initially, 1 stimulus was frequently rewarded (80%); the other was infrequently rewarded (20%). The reward contingencies reversed periodically because the participant learned the more rewarded stimulus. The results indicated that SZ patients achieved fewer reversals than CN, and demonstrated decreased winstay-loseshift decision-making behavior. On loseshift compared to winstay trials, SZ patients showed reduced Blood Oxygen Level Dependent activation compared to CN in a network of brain regions widely associated with cognitive control, and striatal regions. Importantly, relationships between group membership and behavior were mediated by alterations in the activity of cognitive control regions, but not striatum. These findings indicate an important role for the cognitive control network in mediating the use and updating of value representations in SZ. Such results provide biological targets for further inquiry because researchers attempt to better characterize decision-making neural circuitry in SZ as a means to discover new pathways for interventions.Key words: schizophrenia, cognitive control, fMRI, negative symptoms, reversal learning, reward processing, reinforcement learning     

The effect of one left-sided dorsolateral prefrontal sham-controlled HF-rTMS session on approach and withdrawal related emotional neuronal processes

Objective

Although repetitive Transcranial Magnetic Stimulation (rTMS) is frequently used to examine emotional changes in healthy volunteers, it remains largely unknown how rTMS is able to influence emotion.

Methods

In this sham-controlled, single-blind crossover study using fMRI, we examined in 20 right-handed healthy females whether a single high frequency (HF)-rTMS session applied to the left dorsolateral prefrontal cortex could influence emotional processing while focussing on blocks of positively and negatively valenced baby faces.

Results

While positive information was being processed, we observed after one active HF-rTMS session enhanced neuronal activity in the left superior frontal cortex and right inferior parietal cortex. After sham HF-rTMS, we found significant decreases in neuronal activity in the left superior frontal cortex, the left inferior prefrontal cortex, as well as in the right posterior cingulate gyrus. When negative information was processed, one active stimulation attenuated neuronal activity in the right insula only.

Conclusions

Our findings suggest that during the processing of positive information one active session enhanced the ability to empathize with the depicted emotional stimuli, while during the processing of negative information it resulted in decreased psychophysiological reactions.

Significance

These results provide new information on the working mechanism of left-sided HF-rTMS.     

A reexamination of motor and prefrontal TMS in tobacco use disorder: Time for personalized dosing based on electric field modeling?

ObjectiveIn this study, we reexamined the use of 120% resting motor threshold (rMT) dosing for transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) using electric field modeling.MethodsWe computed electric field models in 38 tobacco use disorder (TUD) participants to compare figure-8 coil induced electric fields at 100% rMT over the primary motor cortex (M1), and 100% and 120% rMT over the DLPFC. We then calculated the percentage of rMT needed for motor-equivalent induced electric fields at the DLPFC and modeled this intensity for each person.ResultsElectric fields from 100% rMT stimulation over M1 were significantly larger than what was modeled in the DLPFC using 100% rMT (p < 0.001) and 120% rMT stimulation (p = 0.013). On average, TMS would need to be delivered at 133.5% rMT (range = 79.9 to 247.5%) to produce motor-equivalent induced electric fields at the DLPFC of 158.2 V/m.ConclusionsTMS would have to be applied at an average of 133.5% rMT over the left DLPFC to produce equivalent electric fields to 100% rMT stimulation over M1 in these 38 TUD patients. The high interindividual variability between motor and prefrontal electric fields for each participant supports using personalized electric field modeling for TMS dosing to ensure that each participant is not under- or over-stimulated.SignificanceThese electric field modeling in TUD data suggest that 120% rMT stimulation over the DLPFC delivers sub-motor equivalent electric fields in many individuals (73.7%). With further validation, electric field modeling may be an impactful method of individually dosing TMS.     

Unilateral and bilateral MRI-targeted repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled study

BackgroundSeveral factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance).MethodsWe recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate.ResultsA total of 121 patients participated in this study. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the HFL-rTMS group was intermediate and did not differ statistically from the rate in the 2 other groups. There were no significant differences in reduction of depression scores among the 3 groups.LimitationsThe number of pulses used per session in the unilateral group was somewhat lower in our trial than in more recent trials, and the sham condition did not involve active stimulation.ConclusionOur findings suggest that sequential bilateral rTMS is superior to sham rTMS; however, adjusting for coil-to-cortex distance did not yield enhanced efficacy rates.     

The Effects of Acute Transcranial Direct Current Stimulation on Attentional Bias in Pedophilic Disorder: A Preregistered Pilot Study

ObjectivesIndividuals with pedophilic disorder (PD) experience personal and interpersonal difficulties and are at risk of sexually offending against children. As such, innovative and empirically validated treatments are needed. Recent studies have indicated that men who have sexually offended against children (SOC) with PD display an automatic attention bias for child-related stimuli as well as reduced activity in the dorsolateral prefrontal cortex (dlPFC), a brain area involved in cognitive control, including control over sexual arousal. In this preregistered pilot study, we are the first to investigate whether acutely increasing prefrontal activity could reduce the putative pedophilic attention bias.Materials and MethodsWe delivered a single 20-min session of active anodal versus sham transcranial direct current stimulation (tDCS) over the left dlPFC to 16 SOC with PD and 16 matched healthy controls, while they performed a task requiring controlled attention to computer-generated images of clothed and nude children and adults. We collected responses unobtrusively by recording eye movements.ResultsOur results did not support the presence of the expected automatic attention bias across outcome measures. Nonetheless, we found a response facilitation with child targets in patients and, unexpectedly, in controls, likely due to unwanted salience effects. Active versus sham tDCS reduced this bias across groups, as indicated by a significant group*condition interaction (p = 0.04). However, no attentional bias and no tDCS effects on attentional responses to child and adult images emerged following tDCS.ConclusionsThese results suggest enhanced cognitive control in response to salient stimuli during active tDCS. Thus, to assist future studies on neuromodulation in PD, we provide suggestions for design improvement.