Wiebke Struckmann

All Publications

• Modulation of dorsolateral prefrontal cortex functional connectivity after intermittent theta-burst stimulation in depression: Combining findings from fNIRS and fMRI NEUROIMAGE-CLINICAL Struckmann, W., Boden, R., Gingnell, M., Fallmar, D., Persson, J. 2022; 34: 103028

  Abstract

  Resting-state functional magnetic resonance imaging (fMRI) can assess modulation of functional connectivity networks following repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. Functional near-infrared spectroscopy (fNIRS) is well suited for the concurrent application during rTMS treatment sessions to capture immediate blood oxygenation (oxy-Hb) effects, however limited in spatial resolution.To understand the network effects behind such a prefrontal fNIRS response during rTMS, and to test whether the fNIRS signal may be predictive of treatment response, we linked data from fNIRS and fMRI within a clinical intervention study.42 patients with ongoing depression were recruited and randomized to receive active or sham intermittent theta-burst stimulation (iTBS) over the dorsomedial prefrontal cortex (dmPFC) twice daily for ten days at target intensity. Oxy-Hb was recorded with fNIRS during the first, fifth, and final day of iTBS, with the probe holders located laterally to the TMS coil over regions corresponding to the left and right dorsolateral prefrontal cortex (dlPFC). Resting-state fMRI scanning was performed before and after the whole iTBS treatment course. Functional connectivity analyses were then performed using dlPFC seeds from parcels of a brain atlas showing most overlap with the fNIRS probe locations during treatment.After active iTBS, left dlPFC-connectivity to the right insula/operculum was reduced compared to sham. The left insula showed a connectivity reduction to the left dlPFC that correlated with an improvement in symptoms. In addition, the posterior parietal cortex showed a connectivity reduction to the left dlPFC that correlated with the fNIRS signal following active iTBS. Finally, the fNIRS oxy-Hb signal from the left dlPFC-seed during the first treatment day was predictive of dlPFC-connectivity change to precentral and temporal cortex regions.By linking findings from these two different methods, this study suggests that changes within both the salience network and the central executive network affect the fNIRS response to iTBS.

  View details for DOI 10.1016/j.nicl.2022.103028

  View details for Web of Science ID 000806232600011

  View details for PubMedID 35537216

  View details for PubMedCentralID PMC9118162

• Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. Journal of affective disorders Bodén, R., Bengtsson, J., Thörnblom, E., Struckmann, W., Persson, J. 2021; 290: 308-315

  Abstract

  Intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex (DMPFC) has shown promise in open-label trials of depression.In this randomized, double-blind, sham controlled trial we evaluate iTBS over the DMPFC for anhedonia, avolition, and blunted affect in patients with schizophrenia or depression. Active iTBS was delivered over the DMPFC with 1200 pulses per session, twice daily over ten weekdays at target intensity with an angled figure-of eight coil. Sham condition comprised the magnetically shielded side of the coil and simultaneous transcutaneous electrical nerve stimulation. Primary outcome was change on the Clinical Assessment Interview for Negative Symptoms (CAINS).Twenty-eight patients were randomized to active iTBS and 28 to sham. Mean (standard deviation) change in CAINS score from baseline to the day after last treatment was -5.3 (8.1) in active iTBS and -2.1 (7.1) in sham. A linear model showed no significant effect of treatment, accounting for baseline scores p=.088. Sub analyses per diagnostic group showed a significant effect in patients with depression, p=.038, but not in the schizophrenia group, p=.850. However, overall depressive symptoms did not change significantly in patients with depression. There were three serious adverse events, all in the sham group.Possibly too short treatment course and few patients with schizophrenia.In this first transdiagnostic randomized controlled trial of iTBS over DMPFC for anhedonia, avolition, and blunted affect it can be concluded that it was generally tolerable and safe but only more effective than sham in the subgroup of patients with depression.

  View details for DOI 10.1016/j.jad.2021.04.053

  View details for PubMedID 34020205

• Unchanged Cognitive Performance and Concurrent Prefrontal Blood Oxygenation After Accelerated Intermittent Theta-Burst Stimulation in Depression: A Sham-Controlled Study FRONTIERS IN PSYCHIATRY Struckmann, W., Persson, J., Gingnell, M., Weigl, W., Wass, C., Boden, R. 2021; 12: 659571

  Abstract

  Aim: Intermittent theta-burst stimulation (iTBS) delivered over the dorsomedial prefrontal cortex (DMPFC) has shown promise as a treatment for anhedonia and amotivation in patients with depression. Here, we investigated whether this protocol modulates cognitive performance and concurrent prefrontal blood oxygenation. We also examined whether depressed patients exhibit cognitive dysfunction and prefrontal hypoactivity at baseline compared to healthy controls. Methods: This sham-controlled study comprises 52 patients randomized to either active or sham accelerated iTBS over the DMPFC (applied twice daily) for 10 consecutive treatment days, and 55 healthy controls. Cognitive performance was assessed at baseline and once again 4 weeks later using a cognitive test battery targeting attention, inhibitory control, and numerical, verbal, and visual working memory. Concurrent prefrontal oxygenated hemoglobin (oxy-Hb) was captured with functional near-infrared spectroscopy. Results: Active iTBS over DMPFC did not affect cognitive performance or concurrent oxy-Hb change compared to sham iTBS in patients with depression. Compared to controls, patients at baseline showed impaired performance in the Trail Making Test, the Rey Auditory Verbal Learning Test, the Animal Naming Test, and the Digit Symbol Substitution Test, however no difference in prefrontal oxy-Hb was observed. Conclusion: Patients with treatment-resistant depression displayed cognitive deficits, however without prefrontal hypoactivity, compared to healthy controls at baseline. iTBS treatment did not alter cognitive performance, nor concurrent prefrontal blood oxygenation, in patients. Taken together, iTBS can likely be considered a cognitively safe treatment option in this sample of patients.

  View details for DOI 10.3389/fpsyt.2021.659571

  View details for Web of Science ID 000673242800001

  View details for PubMedID 34276437

  View details for PubMedCentralID PMC8278060

• Intermittent theta burst stimulation over the dorsomedial prefrontal cortex modulates resting-state connectivity in depressive patients: A sham-controlled study. Behavioural brain research Persson, J., Struckmann, W., Gingnell, M., Fällmar, D., Bodén, R. 2020; 394: 112834

  Abstract

  The mechanisms underlying repetitive transcranial magnetic stimulation (rTMS) treatment are largely unknown. Although there is a general lack of sham controlled studies, findings show altered functional connectivity to the stimulated region following treatment. When targeting the dorsolateral prefrontal cortex (dlPFC), connectivity with the subgenual anterior cingulate cortex (sgACC) is predictive of response, but less is known about the effects on functional connectivity of targeting the dorsomedial PFC (dmPFC). Here, 30 patients with an ongoing depressive episode were recruited and randomized to 20 sessions at target intensity of either active or sham intermittent theta burst stimulation (iTBS) over dmPFC. Those receiving sham were offered active treatment in a subsequent open phase. A seven minute resting-state scan and depressive symptom assessment was performed before and after treatment. After exclusions due to attrition and excessive head movements 23 patients remained for analysis. Seed-based resting-state connectivity was calculated using two seeds for the dmPFC target as well as the sgACC. A symptom related increase in dmPFC connectivity after active treatment, compared to sham treatment, was found. The effect was observed in a region overlapping the precuneus and the posterior cingulate cortex (PCC), suggesting an increase in the connectivity between the targeted salience network and the default mode network mediating improvement in depressive symptoms. Connectivity between the precuneus and both the sgACC and the treatment target was predictive of symptom improvement following active treatment. The findings have implications for understanding the mechanisms behind iTBS and may inform future efforts to individualize the treatment.

  View details for DOI 10.1016/j.bbr.2020.112834

  View details for PubMedID 32726666

• Pain trajectories of dorsomedial prefrontal intermittent theta burst stimulation versus sham treatment in depression BMC NEUROLOGY Malm, E., Struckmann, W., Persson, J., Boden, R. 2020; 20 (1): 311

  Abstract

  Prefrontal repetitive transcranial magnetic stimulation is an established add-on treatment for major depressive disorder and is increasingly feasible with protocols of short duration, such as intermittent theta burst stimulation (iTBS). The most common and limiting side effect is pain at the site of application. Our objective was to investigate how pain develops over time in patients with depression receiving iTBS compared to sham stimulation.This is a subsample from a randomized clinical trial. Patients received daily sessions of 2400 pulses of dorsomedial prefrontal iTBS or sham stimulation with transcutaneous electric stimulation during 2 to 3 weeks. After unmasking of treatment allocation, patients receiving sham treatment were offered active iTBS in an open phase. Patients rated pain on a scale from 0 to 10 after the last train of stimulation on the first, fifth and final treatment day. A Mann-Whitney U-test was conducted to test for group differences and related-samples Friedman's tests to analyze changes in pain ratings over time.The scalp pain in the group receiving iTBS was rated higher than sham treatment on the first (U = 263.5, p = 0.035) and fifth day (U = 271.0, p = 0.020) but not on the final day (U = 210.5, p = 0.121). The pain decreased mainly during the first 5 days of treatment (χ2 = 0.875, p = 0.040). In the open phase the pain decreased from the first day to the final day (χ2 = 1.194, p = 0.001).The subjective pain perception of active dorsomedial iTBS was higher than sham treatment but decreased over time, indicating an analgesic effect, or habituation. The result from this study can be used to inform patients about what to expect regarding pain during an iTBS treatment course.Clinicaltrials.gov, NCT02905604 . Registered 19 September 2016.

  View details for DOI 10.1186/s12883-020-01881-3

  View details for Web of Science ID 000567125000002

  View details for PubMedID 32819321

  View details for PubMedCentralID PMC7439669

• Modulation of the prefrontal blood oxygenation response to intermittent theta-burst stimulation in depression: A sham-controlled study with functional near-infrared spectroscopy WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY Struckmann, W., Persson, J., Weigl, W., Gingnell, M., Boden, R. 2021; 22 (4): 247-256

  Abstract

  To better understand the neural mechanisms behind the effect of intermittent theta-burst stimulation (iTBS), we investigated how the prefrontal blood oxygenation response measured by changes in oxygenated haemoglobin (oxy-Hb) was modulated during a sham-controlled iTBS treatment course, and whether this was related to depressive symptom change.In this randomised, double-blind study, patients with ongoing treatment-resistant depression received either active (n = 18) or sham (n = 21) iTBS over the dorsomedial prefrontal cortex for ten to fifteen days with two sessions daily. Event-related functional near-infrared spectroscopy (fNIRS) was measured during each iTBS train, and resting-state oxy-Hb was compared before and after each iTBS session at the first, fifth, and last treatment day.Patients receiving active iTBS had an increase of the event-related oxy-Hb response compared to the sham group on the fifth (bilateral prefrontal cortices p < .001) and last (left prefrontal p = .007, right prefrontal p = .025) treatment day. Resting-state analysis showed suppressed oxy-Hb change in active iTBS compared to sham iTBS on the last treatment day (p = .024). Oxy-Hb change was unrelated to depressive symptom change (p = .474).This study describes a modulation of the blood oxygenation response over the prefrontal cortex that was built up during the course of active iTBS treatment in depression.

  View details for DOI 10.1080/15622975.2020.1785007

  View details for Web of Science ID 000547067400001

  View details for PubMedID 32640854