Stimulation of subgenual cingulate area decreases limbic top-down effect on ventral visual stream: A DBS-EEG pilot study

101

Major depressive disorder (MDD) is a severe mental disorder associated with high morbidity and mortality rates, which remains difficult to treat, as both resistance and recurrence rates are high. Repetitive transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex (DLPFC) provides a safe and effective treatment for selected patients with treatment‐resistant MDD. Little is known about the mechanisms of action of TMS provided to the left DLPFC in MDD and we can currently not predict who will respond to this type of treatment, precluding effective patient selection. In order to shed some light on the mechanism of action, we applied single pulse TMS to the left DLPFC in 10 healthy participants using a unique TMS‐fMRI set‐up, in which we could record the direct effects of TMS. Stimulation of the DLPFC triggered activity in a number of connected brain regions, including the subgenual anterior cingulate cortex (sgACC) in four out of nine participants. The sgACC is of particular interest, because normalization of activity in this region has been associated with relief of depressive symptoms in MDD patients. This is the first direct evidence that TMS pulses delivered to the DLPFC can propagate to the sgACC. The propagation of TMS‐induced activity from the DLPFC to sgACC may be an accurate biomarker for rTMS efficacy. Further research is required to determine whether this method can contribute to the selection of patients with treatment resistant MDD who will respond to rTMS treatment.

Section: Discussionmentioning

confidence: 99%

A novel concurrent TMS‐fMRI method to reveal propagation patterns of prefrontal magnetic brain stimulation

Vink

Mandija

Petrov

et al. 2018

101

“…Analysis was focused on the N170 given its well-known sensitivity to facial expression (Hinojosa et al, 2015) and on our recent results on its dependency on stimulation of the sub-genual cingulate cortex in the same task (Kibleur et al, 2017). Moreover, this potential had the higher Signal to Noise ratio in our recordings (compared with the P100 or the P300 for instance), therefore, its modulation by the task conditions where sharper than the other potentials.…”

Section: Statistical Analysis and Eeg Processingmentioning

confidence: 93%

“…Thus, EEG recordings can be performed with DBS switched-ON and -OFF, which enables the interaction of DBS with the neural networks that underlie a subject's performance to be estimated from the evoked responses. Indeed, in a first EEG-DBS study of the emotional Stroop task, we recently showed how DBS of the sub-genual cingulate gyrus modulates the recorded event-related potentials in patients with depression (Kibleur et al, 2017). The highest amplitude evoked potential, thought to represent facial integration, corresponds to a negative infero-temporal deflection (N170) occurring around 170 ms after the presentation of a facial visual stimulus (Feuerriegel, Churches, Hofmann, & Keage, 2015;Hinojosa, Mercado, & Carretie, 2015;Vuilleumier & Pourtois, 2007).…”

Section: Deep Brain Stimulation Of the Subthalamic Nucleus (Stn Dbs)mentioning

confidence: 99%

“…It includes a control sub-task (nonemotional) where the subjects had to recognize the gender of neutral faces with the words "FEMME" and "HOMME" ("woman" and "man") superimposed on the pictures as the distractor. This paradigm was adapted from Etkin et al (2006) and it has been detailed previously (Fleury et al, 2014;Kibleur et al, 2017). Each sub-task (emotional and control) was presented in two blocks of 200 stimuli ( Figure 2).…”

Section: Emotional Stroop Taskmentioning

confidence: 99%

“…Indeed, EEG is being increasingly used to track emotional performance not only in healthy subjects but also in Parkinson's disease (Yuvaraj et al, 2014). Indeed, in a first EEG-DBS study of the emotional Stroop task, we recently showed how DBS of the sub-genual cingulate gyrus modulates the recorded event-related potentials in patients with depression (Kibleur et al, 2017). Thus, EEG recordings can be performed with DBS switched-ON and -OFF, which enables the interaction of DBS with the neural networks that underlie a subject's performance to be estimated from the evoked responses.…”

mentioning

confidence: 99%

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Different effects of levodopa and subthalamic stimulation on emotional conflict in Parkinson's disease

Martínez‐Fernández

Kibleur

Chabardès

et al. 2018

Self Cite

Parkinson's disease impairs the decoding of emotional stimuli reflecting alterations of the limbic cortico‐subcortical network. The objective of this study was to assess and compare the behavioral and electrophysiological effects of both levodopa and subthalamic stimulation on emotional processing in Parkinson's disease. Operated patients (n =16) and matched healthy subjects performed an emotional Stroop task, in which the emotion expressed by a face must be recognized while ignoring an emotional distractive word and that includes a neutral control sub‐task. Patients were tested in the four possible treatment conditions (off stim/off med; on stim/off med; off stim/on med; and on stim/on med). High‐resolution electroencephalography was recorded while performing the task. Patients made significantly more mistakes in facial emotion recognition than healthy subjects (p < .005). Untreated patients performed worse in the emotional trials than in the control sub‐task (p < .05). Fearful faces induced significantly slower reaction times than happy faces in patients (p = .0002), but not in the healthy subjects. The emotional Stroop effect with levodopa was significantly higher than with subthalamic stimulation when fearful faces were assessed (p = .0243). Conversely, treatments did not modulate the Stroop effect of the control sub‐task. EEG demonstrated that, compared with the untreated state, levodopa but not subthalamic stimulation significantly increases the amplitude of the event‐related potential N170 (p = .002 vs. p = .1, respectively), an electrophysiological biomarker of early aspects of facial processing. The activity of the N170 cortical sources within the right fusiform gyrus was increased by levodopa (p < .05) but not by stimulation. While levodopa normalizes the recognition of emotional facial expression and early EEG markers of emotional processing, subthalamic stimulation does not. Thus, operated patients require dopaminergic medication in addition to stimulation to treat emotional symptoms of Parkinson's disease.

Quantifying the axonal pathways directly stimulated in therapeutic subcallosal cingulate deep brain stimulation

Howell

Choi

Gunalan

et al. 2018

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is an emerging experimental therapy for treatment-resistant depression. New developments in SCC DBS surgical targeting are focused on identifying specific axonal pathways for stimulation that are estimated from patient-specific computational models. This connectomic-based biophysical modeling strategy has proven successful in improving the clinical response to SCC DBS therapy, but the DBS models used to date have been relatively simplistic, limiting the precision of the pathway activation estimates. Therefore, we used the most detailed patient-specific foundation for DBS modeling currently available (i.e., field-cable modeling) to evaluate SCC DBS in our most recent cohort of six subjects, all of which were responders to the therapy. We quantified activation of four major pathways in the SCC region: forceps minor (FM), cingulum bundle (CB), uncinate fasciculus (UF), and subcortical connections between the frontal pole and the thalamus or ventral striatum (FP). We then used the percentage of activated axons in each pathway as regressors in a linear model to predict the time it took patients to reach a stable response, or TSR. Our analysis suggests that stimulation of the left and right CBs, as well as FM are the most likely therapeutic targets for SCC DBS. In addition, the right CB alone predicted 84% of the variation in the TSR, and the correlation was positive, suggesting that activation of the right CB beyond a critical percentage may actually protract the recovery process.