Although repetitive Transcranial Magnetic Stimulation (rTMS) is frequently used to examine emotio... more 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.We carried out a sham-controlled single-blind crossover study using fMRI, we examined in 20 right-handed healthy female volunteers whether a single high frequency (HF)-rTMS session applied to the left dorsolateral prefrontal cortex (DLPFC) could influence emotional processing while focussing on blocks of positively and negatively valenced baby faces. A single HF-rTMS session selectively influenced the processing of positively and negatively valenced baby faces. In essence, our results indicate that the effects of one left-sided HF-rTMS sessions results in improved processing of positive emotions and reduced negative emotional processing in never depressed female subjects.
Objectives: We aimed to examine the effects and safety of accelerated intermittent Theta Burst St... more Objectives: We aimed to examine the effects and safety of accelerated intermittent Theta Burst Stimulation (iTBS) on suicide risk in a group of treatment-resistant unipolar depressed patients, using an extensive suicide assessment scale. Methods: In 50 therapy-resistant, antidepressant-free depressed patients, an intensive protocol of accelerated iTBS was applied over the left dorsolateral prefrontal cortex (DLPFC) in a randomized, sham-controlled crossover design. Patients received 20 iTBS sessions over 4 days. Suicide risk was assessed using the Beck Scale of Suicide ideation (BSI). The iTBS protocol was safe and well tolerated. We observed a significant decrease of the BSI score over time, unrelated to active or sham stimulation and unrelated to depression-response. No worsening of suicidal ideation was observed. The effects of accelerated iTBS on mood and depression severity are reported in . The decrease in suicide risk lasted up to 1 month after baseline, even in depression non-responders. Conclusions: This accelerated iTBS protocol was safe. The observed significant decrease in suicide risk was unrelated to active or sham stimulation and unrelated to depression response. Further sham-controlled research in suicidal depressed patients is necessary. (Clinicaltrials.gov identifier: NCT01832805).
Repetitive Transcranial Magnetic Stimulation (rTMS) is as a promising therapeutic tool for major ... more Repetitive Transcranial Magnetic Stimulation (rTMS) is as a promising therapeutic tool for major depressive disorder. However, the degree of clinical improvement following rTMS treatment still remains questionable. This pilot study aimed at investigating potential working mechanisms of rTMS by examining the effects on attentional processing towards negative information, a proposed underlying cognitive vulnerability factor for depression. The antidepressant effect of high-frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex and possible effects on the inhibitory processing of emotional information was assessed in a sample of fourteen depressed patients immediately after the first stimulation session and at the end of a two week treatment period. One session of rTMS caused neither significant self-reported mood changes, nor improvements in inhibitory control towards negative information. After a 10-day treatment period, nine out of our fourteen patients demonstrated significant mood improvements, as indexed by a reduction of more than 50 % on the Hamilton depression rating scale. Responders also demonstrated significant improvements in the inhibitory processing of negative information. This study contributed to the existing evidence of the antidepressant effect of rTMS in the treatment of depression and additionally was able to demonstrate improvements in underlying deficiencies in inhibitory processes towards negative information.
Aims: As alcohol dependency is characterized by severe executive function deficits, we examined t... more Aims: As alcohol dependency is characterized by severe executive function deficits, we examined the influence of high-frequency (HF) -repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex (DLPFC) on executive functioning in recently detoxified alcohol dependent patients. In this randomized, single blind, sham (placebo)-controlled crossover study we included fifty detoxified alcohol dependent patients. We examined the effect of a single right DLPFC HF-rTMS session on commission errors, mean reaction times (RT) and intra-individual reaction time variability (IIRTV) during a Go-NoGo task (50% Go / 50% NoGo condition) in 29 alcohol dependent patients. Patients completed this cognitive task immediately before and immediately after the stimulation session. In order to avoid carry-over effects between stimulation sessions, a one-week intersession interval was respected. Because rTMS treatment has been shown to affect subjective craving all patients were also assessed with the Obsessive Compulsive Drinking Scale (OCDS). Results: After both stimulation conditions we observed a significant decrease of commission errors, without differences between active and sham HF-rTMS stimulation. No significant difference was observed between active and sham stimulation on mean RT. However, only active stimulation resulted in a significant decrease in IIRTV. No effects of stimulation were found for the craving measurements. Our findings suggest that in recently detoxified alcohol dependent patients, one right-sided HF-rTMS session stabilizes cognitive performance during executive control tasks, implying that active stimulation reduces patients' proneness to attentional lapses.
Neuromodulation: Technology at the Neural Interface, 2021
Objectives: Accelerated intermittent theta burst stimulation (aiTBS) is a promising treatment opt... more Objectives: Accelerated intermittent theta burst stimulation (aiTBS) is a promising treatment option for depressed patients. However, there is a large interindividual variability in clinical effectiveness and individual biomarkers to guide treatment outcome are needed. Materials and Methods: Here, the relation between cortical thickness and clinical response (17-item Hamilton Depression Rating Scale) was studied using anatomical MRI data of 50 depressed patients who were included in a randomized, sham-controlled, double-blinded, cross-over aiTBS design (NCT01832805). Results: Baseline cortical thickness in the right caudal part of the anterior cingulate cortex (cACC) was significantly correlated with direct clinical responses in the subgroup who received active aiTBS during the first stimulation week. No correlations were found between baseline cortical thickness and delayed clinical effectiveness. In this particular region, longitudinal changes in cortical thickness were significantly correlated with clinical effectiveness. Furthermore, direct changes in cortical thickness in the right cACC showed predictive potential of delayed clinical responses. Cortical thickness within the right cACC might be an important biomarker to predict clinical responses to aiTBS. Additional studies are warranted to substantiate the specific biomarker potential of these parts of the ACC.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Introduction: Non-invasive brain stimulation (NIBS) as monotherapy has been increasingly used to ... more Introduction: Non-invasive brain stimulation (NIBS) as monotherapy has been increasingly used to enhance the activity of brain networks. However, it is unclear whether a combination of distinct NIBS approaches could enhance prefrontal cortical (PFC) activity. Objective: We propose to investigate the combined and standalone effects of two NIBS modalities on the PFC through a working memory task, single photon emission computed tomography (SPECT), and salivary cortisol. We hypothesize that the combined protocol will provoke greater changes in the collected measures compared to the remining protocols. Methods: A randomized, double-blind, sham-controlled, full-factorial design will be conducted. The effects of transcranial direct current stimulation (tDCS) and intermittent theta-burst stimulation (iTBS) will be investigated over four different sessions (sham tDCS + sham iTBS, anodal tDCS + sham iTBS, anodal tDCS + active iTBS and sham tDCS + active iTBS) in 30 healthy adult volunteers. A 99mTcethylene cysteine dimer (99mTC-ECD) will be administered during the NIBS session and neuroimaging will be acquired within one hour. Salivary cortisol will be collected before and after each session and an n-back working memory task will be applied after the end of each NIBS session. The outcomes will be cerebral perfusion alterations (99mTC-ECD SPECT), accuracy and reaction time in the n-back task, and changes in salivary cortisol level. The results from this trial can guide future therapeutic protocols for NIBS treatments stimulating the PFC by demonstrating that the combination of NIBS techniques is feasible, tolerable, and can lead to greater enhancement of PFC activity.
The left dorsolateral prefrontal cortex (lDLPFC) is implicated in anticipatory (i.e. during antic... more The left dorsolateral prefrontal cortex (lDLPFC) is implicated in anticipatory (i.e. during anticipation of emotional stimuli) and online (i.e. during confrontation with emotional stimuli) emotion regulatory processes. However, research that investigates the causal role of the lDLPFC in these processes is lacking. In this study, 74 participants received active or sham transcranial direct current stimulation (tDCS) over the lDLPFC. Participants were told strangers evaluated them. These (rigged) social evaluations were presented, and in 50% of the trials, participants could anticipate the valence (positive or negative) of the upcoming social feedback. Pupil dilation (a marker of cognitive resource allocation) and skin conductance responses (a marker of arousal) were measured. The results indicate that active (compared to sham) tDCS reduced arousal during the confrontation with anticipated feedback but only marginally during the confrontation with unanticipated feedback. When participa...
Previous research supports the distinction between proactive and reactive control. Although the d... more 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 trial...
The prefrontal cortex, and especially the Dorsolateral Prefrontal Cortex (DLPFC), plays an inhibi... more The prefrontal cortex, and especially the Dorsolateral Prefrontal Cortex (DLPFC), plays an inhibitory role in the regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis under stressful situations. Moreover, recent evidence suggests that a sustained DLPFC activation is associated with adaptive stress regulation in anticipation of a stressful event, leading to a reduced stress-induced amygdala response, and facilitating the confrontation with the stressor. However, studies using experimental manipulation of the activity of the DLPFC before a stressor are scarce, and more research is needed to understand the specific role of this brain area in the stress-induced physiological response. This preregistered study investigated the effect on stress regulation of a single excitatory high frequency (versus sham) repetitive transcranial magnetic stimulation (HF-rTMS) session over the left DLPFC applied before the Trier Social Stress Test in 75 healthy young women (M=21.05, SD=2.60). Heart rate variability (HRV) and salivary cortisol were assessed throughout the experimental protocol. The active HF-rTMS and the sham group showed a similar cognitive appraisal of the stress task. No differences in HRV were observed during both the anticipation and the actual confrontation with the stress task and therefore, our results did not reflect DLPFC-related adaptive anticipatory adjustments. Importantly, participants in the active HF-rTMS group showed a lower cortisol response to the stress. The effect of left prefrontal HF-rTMS on the stress system provides further critical experimental evidence for the inhibitory role played by the DLPFC in the regulation of the HPA axis.
Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cog... more Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although nonimplantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms
Dysregulation of autonomic cardiovascular homeostasis is an important cardiological and neurologi... more Dysregulation of autonomic cardiovascular homeostasis is an important cardiological and neurological risk factor. Cortical regions including the prefrontal and insular cortices exert tonic control over cardiovascular autonomic functions. Transcranial Magnetic Stimulation (TMS) may be a suitable approach for studying topdown control of visceromotor processes. However, there is inconsistent evidence as to whether TMS can modify cardiovascular autonomic states. One reason for the inconsistency may arise from the lack of studies accounting for the acute affective states of participants with respect to the stimulation procedures. To gain more insights into these processes, we evaluated the effects of intermittent and continuous theta-burst stimulation (TBS) to the right frontotemporal cortex on state anxiety and cardiovascular responses in a preliminary study. State anxiety significantly increased for both intermittent and continuous TBS relative to sham. Intermittent TBS also significantly increased heart-rate variability (HRV) at natural and slow-paced breathing rates. The effect of intermittent TBS on vagally-mediated HRV was attenuated after accounting for stimulation-induced anxiety, suggesting that increased HRV after stimulation may reflect a response to a transient stressor (i.e., the stimulation itself), rather than TBS effects on visceromotor networks. In contrast, continuous TBS increased pulse transit time latency across breathing rates, an effect that was enhanced after accounting for state anxiety. TMS is a promising approach to study cortical involvement in cardiovascular autonomic regulation. The findings show that TBS induces effects on visceromotor networks, and that analysis of state covariates such as anxiety can be important for increasing the precision of these estimates. Future non-invasive brain stimulation studies of topdown neurocardiac regulation should account for the potential influence of non-specific arousal or anxiety responses to stimulation.
The application of repetitive transcranial magnetic stimulation has been shown to rapidly decreas... more The application of repetitive transcranial magnetic stimulation has been shown to rapidly decrease suicidal ideation in major depressive disorder (MDD). However, the neural working mechanisms behind this prompt attenuation of suicidal thoughts remains to be determined. Here, we examined how placebo-accelerated intermittent theta burst stimulation (aiTBS) may influence brain perfusion and suicidal thoughts using arterial spin labeling (ASL). In a randomized double-blind sham-controlled crossover trial, 45 MDD patients received aiTBS applied to the left dorsolateral prefrontal cortex (Trial registration: http://clinicaltrials.gov/show/NCT01832805). With each ASL scan measurement, suicidal ideation was assessed with the Beck Scale for Suicidal Ideation (BSI) and depression severity with the Beck Depression Inventory (BDI). Compared with active stimulation, the attenuation of suicidal ideation after 4 days of placebo aiTBS was related to significant frontopolar prefrontal perfusion decr...
The Dorsolateral prefrontal cortex (DLPFC) is implicated in cognitive and emotional responses. Ye... more The Dorsolateral prefrontal cortex (DLPFC) is implicated in cognitive and emotional responses. Yet, research that investigates the causal role of the left versus right DLPFC during the processes of emotion appraisal is lacking. In the current study, transcranial direct current stimulation (tDCS) was used to disentangle the functional lateralization of the DLPFC on emotional processing in response to the anticipation of, and subsequent confrontation with emotional stimuli in healthy volunteers. Forty-eight subjects received both active and sham (on separate days) anodal tDCS over either the left (N = 24) or right (N = 24) DLPFC. Subjects' pupil dilation (PD, a physiological marker of cognitive resource allocation) was recorded while performing an appraisal task in which negative and positive emotion eliciting images were presented, each preceded by an informative cue indicating the valence of the upcoming stimulus. As compared to sham stimulation, left DLPFC anodal tDCS resulted in increased PD when confronted with negative emotional images, whereas right DLPFC anodal tDCS resulted in decreased PD when confronted with emotional images, irrespective of valence. The interpretation of pupil dilation in response to emotional stimuli is limited. These findings suggest inverse lateralized DLPFC effects on cognitive resource allocation (as measured by pupillary responses) when confronted with emotional stimuli. The current
Attention to relevant emotional information in the environment is an important process related to... more Attention to relevant emotional information in the environment is an important process related to vulnerability and resilience for mood and anxiety disorders. In the present study, the effects of left and right dorsolateral prefrontal cortex (i.e., DLPFC) stimulation on attentional mechanisms of emotional processing were tested and contrasted. A sample of 54 healthy participants received 20 min of active and sham anodal transcranial direct current stimulation (i.e., tDCS) either of the left (n = 27) or of the right DLPFC (n = 27) on two separate days. The anode electrode was placed over the left or the right DLPFC, the cathode over the corresponding contra lateral supraorbital area. After each neurostimulation session, participants completed an eye-tracking task assessing direct processes of attentional engagement towards and attentional disengagement away from emotional faces (happy, disgusted, and sad expressions). Compared to sham, active tDCS over the left DLPFC led to faster ga...
Transcranial direct current stimulation (tDCS) is a potential treatment strategy for mood and anx... more Transcranial direct current stimulation (tDCS) is a potential treatment strategy for mood and anxiety disorders, but how this application may influence emotional processes, and whether this is related to individual characteristics, is not well understood. It has been proposed that perceived criticism (PC) may represent a vulnerability factor for the development of such mental illnesses. To decipher whether neural mechanisms of action of tDCS potentially differ depending on PC status (low vs. high), we evaluated mood and brain perfusion before and after applying MRI-compatible tDCS, and after participants were exposed to verbal criticism in the scanner. Experimental design 30 healthy nondepressed females were included in a sham-controlled crossover MRI-compatible tDCS study. Brain perfusion was measured by means of arterial spin labeling (ASL) before and after tDCS applied to the left dorsolateral prefrontal cortex (DLPFC), and after hearing criticism. Before the experiment, all part...
Cognitive, Affective, & Behavioral Neuroscience, 2016
The aim of this study was to increase insight in the neural substrates of attention processes inv... more The aim of this study was to increase insight in the neural substrates of attention processes involved in emotion regulation. The effects of right dorsolateral prefrontal cortex (i.e., DLPFC) stimulation on attentional processing of emotional information were evaluated. A novel attention task allowing a straightforward measurement of attentional engagement toward, and attentional disengagement away from emotional faces was used. A sample of healthy participants received 20 minutes of active and sham anodal transcranial direct current stimulation (i.e., tDCS) applied over the right DLPFC on 2 separate days and completed the attention task after receiving real or sham stimulation. Compared to sham stimulation, tDCS over the right DLPFC led to impairments in attentional disengagement from both positive and negative faces. Findings demonstrate a causal role of right DLPFC activity in the generation of attentional impairments that are implicated in emotional disturbances such as depression and anxiety.
Transcranial direct current stimulation (tDCS) is a non-invasive, non-convulsive technique for mo... more Transcranial direct current stimulation (tDCS) is a non-invasive, non-convulsive technique for modulating brain function. In contrast to other non-invasive brain stimulation techniques, where costs, clinical applicability, and availability limit their large-scale use in clinical practices, the low-cost, portable, and easy-to-use tDCS devices may overcome these restrictions. Despite numerous clinical applications in large numbers of patients suffering from psychiatric disorders, it is not quite clear how tDCS influences the mentally affected human brain. In order to decipher potential neural mechanisms of action of tDCS in patients with psychiatric conditions, we focused on the combination of tDCS with neuroimaging techniques. We propose a contemporary overview on the currently available neurophysiological and neuroimaging data where tDCS has been used as a research or treatment tool in patients with psychiatric disorders. Over a reasonably short period of time, tDCS has been broadly...
Although negative results have been reported, an important aspect of the physiology of repetitive... more Although negative results have been reported, an important aspect of the physiology of repetitive transcranial magnetic stimulation (rTMS) could be related to the endocrinological response of the hypothalamic-pituitary-adrenal (HPA) axis, such as cortisol secretion. Because endocrinological responses are influenced by anxiety states, this could influence the effect of rTMS in healthy individuals. In this sham-controlled, "single blind" crossover study, we examined whether one session of HF-rTMS could affect the HPA-system, when taking into account individual state anxiety scores based on the State-Trait Anxiety Inventory (STAI). Twenty-four healthy rTMS naïve females received one sham-controlled high frequency (HF)-rTMS session delivered on the right dorsolateral prefrontal cortex (DLPFC). The Profile of Mood States (POMS) questionnaire, together with salivary cortisol samples, was collected before, just after and 30 min post HF-rTMS. To examine whether state anxiety could...
Although repetitive Transcranial Magnetic Stimulation (rTMS) is frequently used to examine emotio... more 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.We carried out a sham-controlled single-blind crossover study using fMRI, we examined in 20 right-handed healthy female volunteers whether a single high frequency (HF)-rTMS session applied to the left dorsolateral prefrontal cortex (DLPFC) could influence emotional processing while focussing on blocks of positively and negatively valenced baby faces. A single HF-rTMS session selectively influenced the processing of positively and negatively valenced baby faces. In essence, our results indicate that the effects of one left-sided HF-rTMS sessions results in improved processing of positive emotions and reduced negative emotional processing in never depressed female subjects.
Objectives: We aimed to examine the effects and safety of accelerated intermittent Theta Burst St... more Objectives: We aimed to examine the effects and safety of accelerated intermittent Theta Burst Stimulation (iTBS) on suicide risk in a group of treatment-resistant unipolar depressed patients, using an extensive suicide assessment scale. Methods: In 50 therapy-resistant, antidepressant-free depressed patients, an intensive protocol of accelerated iTBS was applied over the left dorsolateral prefrontal cortex (DLPFC) in a randomized, sham-controlled crossover design. Patients received 20 iTBS sessions over 4 days. Suicide risk was assessed using the Beck Scale of Suicide ideation (BSI). The iTBS protocol was safe and well tolerated. We observed a significant decrease of the BSI score over time, unrelated to active or sham stimulation and unrelated to depression-response. No worsening of suicidal ideation was observed. The effects of accelerated iTBS on mood and depression severity are reported in . The decrease in suicide risk lasted up to 1 month after baseline, even in depression non-responders. Conclusions: This accelerated iTBS protocol was safe. The observed significant decrease in suicide risk was unrelated to active or sham stimulation and unrelated to depression response. Further sham-controlled research in suicidal depressed patients is necessary. (Clinicaltrials.gov identifier: NCT01832805).
Repetitive Transcranial Magnetic Stimulation (rTMS) is as a promising therapeutic tool for major ... more Repetitive Transcranial Magnetic Stimulation (rTMS) is as a promising therapeutic tool for major depressive disorder. However, the degree of clinical improvement following rTMS treatment still remains questionable. This pilot study aimed at investigating potential working mechanisms of rTMS by examining the effects on attentional processing towards negative information, a proposed underlying cognitive vulnerability factor for depression. The antidepressant effect of high-frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex and possible effects on the inhibitory processing of emotional information was assessed in a sample of fourteen depressed patients immediately after the first stimulation session and at the end of a two week treatment period. One session of rTMS caused neither significant self-reported mood changes, nor improvements in inhibitory control towards negative information. After a 10-day treatment period, nine out of our fourteen patients demonstrated significant mood improvements, as indexed by a reduction of more than 50 % on the Hamilton depression rating scale. Responders also demonstrated significant improvements in the inhibitory processing of negative information. This study contributed to the existing evidence of the antidepressant effect of rTMS in the treatment of depression and additionally was able to demonstrate improvements in underlying deficiencies in inhibitory processes towards negative information.
Aims: As alcohol dependency is characterized by severe executive function deficits, we examined t... more Aims: As alcohol dependency is characterized by severe executive function deficits, we examined the influence of high-frequency (HF) -repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex (DLPFC) on executive functioning in recently detoxified alcohol dependent patients. In this randomized, single blind, sham (placebo)-controlled crossover study we included fifty detoxified alcohol dependent patients. We examined the effect of a single right DLPFC HF-rTMS session on commission errors, mean reaction times (RT) and intra-individual reaction time variability (IIRTV) during a Go-NoGo task (50% Go / 50% NoGo condition) in 29 alcohol dependent patients. Patients completed this cognitive task immediately before and immediately after the stimulation session. In order to avoid carry-over effects between stimulation sessions, a one-week intersession interval was respected. Because rTMS treatment has been shown to affect subjective craving all patients were also assessed with the Obsessive Compulsive Drinking Scale (OCDS). Results: After both stimulation conditions we observed a significant decrease of commission errors, without differences between active and sham HF-rTMS stimulation. No significant difference was observed between active and sham stimulation on mean RT. However, only active stimulation resulted in a significant decrease in IIRTV. No effects of stimulation were found for the craving measurements. Our findings suggest that in recently detoxified alcohol dependent patients, one right-sided HF-rTMS session stabilizes cognitive performance during executive control tasks, implying that active stimulation reduces patients' proneness to attentional lapses.
Neuromodulation: Technology at the Neural Interface, 2021
Objectives: Accelerated intermittent theta burst stimulation (aiTBS) is a promising treatment opt... more Objectives: Accelerated intermittent theta burst stimulation (aiTBS) is a promising treatment option for depressed patients. However, there is a large interindividual variability in clinical effectiveness and individual biomarkers to guide treatment outcome are needed. Materials and Methods: Here, the relation between cortical thickness and clinical response (17-item Hamilton Depression Rating Scale) was studied using anatomical MRI data of 50 depressed patients who were included in a randomized, sham-controlled, double-blinded, cross-over aiTBS design (NCT01832805). Results: Baseline cortical thickness in the right caudal part of the anterior cingulate cortex (cACC) was significantly correlated with direct clinical responses in the subgroup who received active aiTBS during the first stimulation week. No correlations were found between baseline cortical thickness and delayed clinical effectiveness. In this particular region, longitudinal changes in cortical thickness were significantly correlated with clinical effectiveness. Furthermore, direct changes in cortical thickness in the right cACC showed predictive potential of delayed clinical responses. Cortical thickness within the right cACC might be an important biomarker to predict clinical responses to aiTBS. Additional studies are warranted to substantiate the specific biomarker potential of these parts of the ACC.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Introduction: Non-invasive brain stimulation (NIBS) as monotherapy has been increasingly used to ... more Introduction: Non-invasive brain stimulation (NIBS) as monotherapy has been increasingly used to enhance the activity of brain networks. However, it is unclear whether a combination of distinct NIBS approaches could enhance prefrontal cortical (PFC) activity. Objective: We propose to investigate the combined and standalone effects of two NIBS modalities on the PFC through a working memory task, single photon emission computed tomography (SPECT), and salivary cortisol. We hypothesize that the combined protocol will provoke greater changes in the collected measures compared to the remining protocols. Methods: A randomized, double-blind, sham-controlled, full-factorial design will be conducted. The effects of transcranial direct current stimulation (tDCS) and intermittent theta-burst stimulation (iTBS) will be investigated over four different sessions (sham tDCS + sham iTBS, anodal tDCS + sham iTBS, anodal tDCS + active iTBS and sham tDCS + active iTBS) in 30 healthy adult volunteers. A 99mTcethylene cysteine dimer (99mTC-ECD) will be administered during the NIBS session and neuroimaging will be acquired within one hour. Salivary cortisol will be collected before and after each session and an n-back working memory task will be applied after the end of each NIBS session. The outcomes will be cerebral perfusion alterations (99mTC-ECD SPECT), accuracy and reaction time in the n-back task, and changes in salivary cortisol level. The results from this trial can guide future therapeutic protocols for NIBS treatments stimulating the PFC by demonstrating that the combination of NIBS techniques is feasible, tolerable, and can lead to greater enhancement of PFC activity.
The left dorsolateral prefrontal cortex (lDLPFC) is implicated in anticipatory (i.e. during antic... more The left dorsolateral prefrontal cortex (lDLPFC) is implicated in anticipatory (i.e. during anticipation of emotional stimuli) and online (i.e. during confrontation with emotional stimuli) emotion regulatory processes. However, research that investigates the causal role of the lDLPFC in these processes is lacking. In this study, 74 participants received active or sham transcranial direct current stimulation (tDCS) over the lDLPFC. Participants were told strangers evaluated them. These (rigged) social evaluations were presented, and in 50% of the trials, participants could anticipate the valence (positive or negative) of the upcoming social feedback. Pupil dilation (a marker of cognitive resource allocation) and skin conductance responses (a marker of arousal) were measured. The results indicate that active (compared to sham) tDCS reduced arousal during the confrontation with anticipated feedback but only marginally during the confrontation with unanticipated feedback. When participa...
Previous research supports the distinction between proactive and reactive control. Although the d... more 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 trial...
The prefrontal cortex, and especially the Dorsolateral Prefrontal Cortex (DLPFC), plays an inhibi... more The prefrontal cortex, and especially the Dorsolateral Prefrontal Cortex (DLPFC), plays an inhibitory role in the regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis under stressful situations. Moreover, recent evidence suggests that a sustained DLPFC activation is associated with adaptive stress regulation in anticipation of a stressful event, leading to a reduced stress-induced amygdala response, and facilitating the confrontation with the stressor. However, studies using experimental manipulation of the activity of the DLPFC before a stressor are scarce, and more research is needed to understand the specific role of this brain area in the stress-induced physiological response. This preregistered study investigated the effect on stress regulation of a single excitatory high frequency (versus sham) repetitive transcranial magnetic stimulation (HF-rTMS) session over the left DLPFC applied before the Trier Social Stress Test in 75 healthy young women (M=21.05, SD=2.60). Heart rate variability (HRV) and salivary cortisol were assessed throughout the experimental protocol. The active HF-rTMS and the sham group showed a similar cognitive appraisal of the stress task. No differences in HRV were observed during both the anticipation and the actual confrontation with the stress task and therefore, our results did not reflect DLPFC-related adaptive anticipatory adjustments. Importantly, participants in the active HF-rTMS group showed a lower cortisol response to the stress. The effect of left prefrontal HF-rTMS on the stress system provides further critical experimental evidence for the inhibitory role played by the DLPFC in the regulation of the HPA axis.
Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cog... more Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although nonimplantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms
Dysregulation of autonomic cardiovascular homeostasis is an important cardiological and neurologi... more Dysregulation of autonomic cardiovascular homeostasis is an important cardiological and neurological risk factor. Cortical regions including the prefrontal and insular cortices exert tonic control over cardiovascular autonomic functions. Transcranial Magnetic Stimulation (TMS) may be a suitable approach for studying topdown control of visceromotor processes. However, there is inconsistent evidence as to whether TMS can modify cardiovascular autonomic states. One reason for the inconsistency may arise from the lack of studies accounting for the acute affective states of participants with respect to the stimulation procedures. To gain more insights into these processes, we evaluated the effects of intermittent and continuous theta-burst stimulation (TBS) to the right frontotemporal cortex on state anxiety and cardiovascular responses in a preliminary study. State anxiety significantly increased for both intermittent and continuous TBS relative to sham. Intermittent TBS also significantly increased heart-rate variability (HRV) at natural and slow-paced breathing rates. The effect of intermittent TBS on vagally-mediated HRV was attenuated after accounting for stimulation-induced anxiety, suggesting that increased HRV after stimulation may reflect a response to a transient stressor (i.e., the stimulation itself), rather than TBS effects on visceromotor networks. In contrast, continuous TBS increased pulse transit time latency across breathing rates, an effect that was enhanced after accounting for state anxiety. TMS is a promising approach to study cortical involvement in cardiovascular autonomic regulation. The findings show that TBS induces effects on visceromotor networks, and that analysis of state covariates such as anxiety can be important for increasing the precision of these estimates. Future non-invasive brain stimulation studies of topdown neurocardiac regulation should account for the potential influence of non-specific arousal or anxiety responses to stimulation.
The application of repetitive transcranial magnetic stimulation has been shown to rapidly decreas... more The application of repetitive transcranial magnetic stimulation has been shown to rapidly decrease suicidal ideation in major depressive disorder (MDD). However, the neural working mechanisms behind this prompt attenuation of suicidal thoughts remains to be determined. Here, we examined how placebo-accelerated intermittent theta burst stimulation (aiTBS) may influence brain perfusion and suicidal thoughts using arterial spin labeling (ASL). In a randomized double-blind sham-controlled crossover trial, 45 MDD patients received aiTBS applied to the left dorsolateral prefrontal cortex (Trial registration: http://clinicaltrials.gov/show/NCT01832805). With each ASL scan measurement, suicidal ideation was assessed with the Beck Scale for Suicidal Ideation (BSI) and depression severity with the Beck Depression Inventory (BDI). Compared with active stimulation, the attenuation of suicidal ideation after 4 days of placebo aiTBS was related to significant frontopolar prefrontal perfusion decr...
The Dorsolateral prefrontal cortex (DLPFC) is implicated in cognitive and emotional responses. Ye... more The Dorsolateral prefrontal cortex (DLPFC) is implicated in cognitive and emotional responses. Yet, research that investigates the causal role of the left versus right DLPFC during the processes of emotion appraisal is lacking. In the current study, transcranial direct current stimulation (tDCS) was used to disentangle the functional lateralization of the DLPFC on emotional processing in response to the anticipation of, and subsequent confrontation with emotional stimuli in healthy volunteers. Forty-eight subjects received both active and sham (on separate days) anodal tDCS over either the left (N = 24) or right (N = 24) DLPFC. Subjects' pupil dilation (PD, a physiological marker of cognitive resource allocation) was recorded while performing an appraisal task in which negative and positive emotion eliciting images were presented, each preceded by an informative cue indicating the valence of the upcoming stimulus. As compared to sham stimulation, left DLPFC anodal tDCS resulted in increased PD when confronted with negative emotional images, whereas right DLPFC anodal tDCS resulted in decreased PD when confronted with emotional images, irrespective of valence. The interpretation of pupil dilation in response to emotional stimuli is limited. These findings suggest inverse lateralized DLPFC effects on cognitive resource allocation (as measured by pupillary responses) when confronted with emotional stimuli. The current
Attention to relevant emotional information in the environment is an important process related to... more Attention to relevant emotional information in the environment is an important process related to vulnerability and resilience for mood and anxiety disorders. In the present study, the effects of left and right dorsolateral prefrontal cortex (i.e., DLPFC) stimulation on attentional mechanisms of emotional processing were tested and contrasted. A sample of 54 healthy participants received 20 min of active and sham anodal transcranial direct current stimulation (i.e., tDCS) either of the left (n = 27) or of the right DLPFC (n = 27) on two separate days. The anode electrode was placed over the left or the right DLPFC, the cathode over the corresponding contra lateral supraorbital area. After each neurostimulation session, participants completed an eye-tracking task assessing direct processes of attentional engagement towards and attentional disengagement away from emotional faces (happy, disgusted, and sad expressions). Compared to sham, active tDCS over the left DLPFC led to faster ga...
Transcranial direct current stimulation (tDCS) is a potential treatment strategy for mood and anx... more Transcranial direct current stimulation (tDCS) is a potential treatment strategy for mood and anxiety disorders, but how this application may influence emotional processes, and whether this is related to individual characteristics, is not well understood. It has been proposed that perceived criticism (PC) may represent a vulnerability factor for the development of such mental illnesses. To decipher whether neural mechanisms of action of tDCS potentially differ depending on PC status (low vs. high), we evaluated mood and brain perfusion before and after applying MRI-compatible tDCS, and after participants were exposed to verbal criticism in the scanner. Experimental design 30 healthy nondepressed females were included in a sham-controlled crossover MRI-compatible tDCS study. Brain perfusion was measured by means of arterial spin labeling (ASL) before and after tDCS applied to the left dorsolateral prefrontal cortex (DLPFC), and after hearing criticism. Before the experiment, all part...
Cognitive, Affective, & Behavioral Neuroscience, 2016
The aim of this study was to increase insight in the neural substrates of attention processes inv... more The aim of this study was to increase insight in the neural substrates of attention processes involved in emotion regulation. The effects of right dorsolateral prefrontal cortex (i.e., DLPFC) stimulation on attentional processing of emotional information were evaluated. A novel attention task allowing a straightforward measurement of attentional engagement toward, and attentional disengagement away from emotional faces was used. A sample of healthy participants received 20 minutes of active and sham anodal transcranial direct current stimulation (i.e., tDCS) applied over the right DLPFC on 2 separate days and completed the attention task after receiving real or sham stimulation. Compared to sham stimulation, tDCS over the right DLPFC led to impairments in attentional disengagement from both positive and negative faces. Findings demonstrate a causal role of right DLPFC activity in the generation of attentional impairments that are implicated in emotional disturbances such as depression and anxiety.
Transcranial direct current stimulation (tDCS) is a non-invasive, non-convulsive technique for mo... more Transcranial direct current stimulation (tDCS) is a non-invasive, non-convulsive technique for modulating brain function. In contrast to other non-invasive brain stimulation techniques, where costs, clinical applicability, and availability limit their large-scale use in clinical practices, the low-cost, portable, and easy-to-use tDCS devices may overcome these restrictions. Despite numerous clinical applications in large numbers of patients suffering from psychiatric disorders, it is not quite clear how tDCS influences the mentally affected human brain. In order to decipher potential neural mechanisms of action of tDCS in patients with psychiatric conditions, we focused on the combination of tDCS with neuroimaging techniques. We propose a contemporary overview on the currently available neurophysiological and neuroimaging data where tDCS has been used as a research or treatment tool in patients with psychiatric disorders. Over a reasonably short period of time, tDCS has been broadly...
Although negative results have been reported, an important aspect of the physiology of repetitive... more Although negative results have been reported, an important aspect of the physiology of repetitive transcranial magnetic stimulation (rTMS) could be related to the endocrinological response of the hypothalamic-pituitary-adrenal (HPA) axis, such as cortisol secretion. Because endocrinological responses are influenced by anxiety states, this could influence the effect of rTMS in healthy individuals. In this sham-controlled, "single blind" crossover study, we examined whether one session of HF-rTMS could affect the HPA-system, when taking into account individual state anxiety scores based on the State-Trait Anxiety Inventory (STAI). Twenty-four healthy rTMS naïve females received one sham-controlled high frequency (HF)-rTMS session delivered on the right dorsolateral prefrontal cortex (DLPFC). The Profile of Mood States (POMS) questionnaire, together with salivary cortisol samples, was collected before, just after and 30 min post HF-rTMS. To examine whether state anxiety could...
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Papers by Chris Baeken