Reduced Mirror Neuron Activity in Schizophrenia and Its Association With Theory of Mind Deficits: Evidence From a Transcranial Magnetic Stimulation Study

Background: Studies have implicated hypofrontality in the pathogenesis of impaired theory of mind (ToM) and executive function (EF) in major depressive disorder (MDD). These symptoms are usually resistant to treatment. Repetitive transcranial magnetic stimulation (rTMS) has been shown to reverse hypofrontality. Moreover, BDNF is an effective biomarker of antidepressant effects, but there have been very few studies on the correlation between BDNF and rTMS. We aimed to evaluate the efficacy of 20 sessions of a 10 Hz unilateral rTMS intervention over the left dorsolateral prefrontal cortex (DLPFC) in improving ToM and EF in patients with MDD and its correlation with BDNF. Methods: A total of 120 MDD patients were enrolled in this randomized, sham-controlled, double-blind trial. Each participant received 20 sessions of rTMS at 10 Hz frequency through the active or the sham coil over 4 weeks. ToM was assessed with the facial emotion identification test (FEIT) and hinting task (HT). EF was assessed with the Wisconsin card sorting test (WCST). BDNF assessments were carried out at baseline and 2-, 4-, 12-, and 24-week follow-ups. Results: The improvement in the ToM (FEIT, HT) in the active rTMS group was significantly different from that in the sham rTMS group (F = 18.09, p < 0.001; F = 5.02, p = 0.026). There were significant differences in the WCST (categories completed, response errors, response perseverative errors, non-response perseverative errors) after logarithmic transformation at different time points in the active rTMS group (F = 14.71, p < 0.001; F = 5.99, p = 0.046; F = 8.90, p = 0.031; F = 2.31, p = 0.048). However, there was no significant difference in log transformed BDNF concentration between the two groups (t = 0.07 to t = 1.29, p > 0.05). BDNF was negatively correlated with WCST categories completed at the 24th week (r = −0.258, p = 0.046). Conclusions: The results show that rTMS may improve the ToM and EF of patients with MDD and there was no significant correlation with serum BDNF concentration. RTMS can not only be used for treatment of patients with MDD but also has a positive effect on ToM and EF.

Download Full-text

Transcranial magnetic stimulation of the ventromedial prefrontal cortex impairs theory of mind learning

European Psychiatry ◽

10.1016/j.eurpsy.2010.11.008 ◽

2012 ◽

Vol 27 (4) ◽

pp. 285-289 ◽

Cited By ~ 22

Author(s):

S. Lev-Ran ◽

S.G. Shamay-Tsoory ◽

A. Zangen ◽

Y. Levkovitz

Keyword(s):

Prefrontal Cortex ◽

Transcranial Magnetic Stimulation ◽

Theory Of Mind ◽

Magnetic Stimulation ◽

Repetitive Transcranial Magnetic Stimulation ◽

Ventromedial Prefrontal Cortex ◽

Learning Performance ◽

Control Task ◽

Normal Functioning ◽

Lesion Studies

AbstractImaging and lesion studies indicate that the prefrontal cortex plays a prominent role in mediating theory of mind (ToM) functioning. Particularly, the ventromedial prefrontal cortex (VMPFC) appears to be involved in mediating ToM functioning. This study utilized slow repetitive transcranial magnetic stimulation (rTMS) over the VMPFC in 13 healthy subjects in order to test whether normal functioning of the VMPFC is necessary for ToM functioning. We found that rTMS to the VMPFC, but not sham-rTMS, significantly disrupted ToM learning. Performance on a control task, not involving affective ToM functioning, was not significantly altered after applying rTMS to the VMPFC or sham-rTMS. In an additional experiment, rTMS to the vertex did not significantly affect ToM learning, confirming specificity of the VMPFC region. These findings indicate that the VMPFC is critical for intact ToM learning and shed further light on the concept and localization of ToM in particular and empathic functioning in general.

Download Full-text

Transcranial magnetic stimulation studies of the human mirror neuron system

International Congress Series ◽

10.1016/s0531-5131(01)00729-4 ◽

2002 ◽

Vol 1232 ◽

pp. 889-894 ◽

Cited By ~ 10

Author(s):

Fumiko Maeda ◽

John Mazziotta ◽

Marco Iacoboni

Keyword(s):

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Mirror Neuron System ◽

Mirror Neuron ◽

Neuron System

Download Full-text

Timing of cortical excitability changes during the reaction time of movements superimposed on tonic motor activity

Journal of Applied Physiology ◽

10.1152/japplphysiol.00542.2004 ◽

2004 ◽

Vol 97 (6) ◽

pp. 2220-2227 ◽

Cited By ~ 32

Author(s):

Cyril Schneider ◽

Brigitte A. Lavoie ◽

Hugues Barbeau ◽

Charles Capaday

Keyword(s):

Reaction Time ◽

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Muscle Activation ◽

Motor Evoked Potential ◽

Voluntary Contraction ◽

Neuron Activity ◽

Emg Activity ◽

Magnetic Stimulus ◽

Near Threshold

Seated subjects were instructed to react to an auditory cue by simultaneously contracting the tibialis anterior (TA) muscle of each ankle isometrically. Focal transcranial magnetic stimulation of the leg area of the motor cortex (MCx) was used to determine the time course of changes in motor-evoked potential amplitude (MEP) during the reaction time (RT). In one condition the voluntary contraction was superimposed on tonic EMG activity maintained at 10% of maximal voluntary contraction. In the other condition the voluntary contraction was made starting from rest. MEPs in the TA contralateral to the stimulation coil were evoked at various times during the RT in each condition. These were compared to the control MEPs evoked during tonic voluntary activity or with the subject at rest. The RT was measured trial by trial from the EMG activity of the TA ipsilateral to the magnetic stimulus, taking into account the nearly constant time difference between the two sides. The MEPs became far greater than control MEPs during the RT (mean = 332%, SD = 44 %, of control MEPs, P < 0.001) without any measurable change in the background level of EMG activity. The onset of this facilitation occurred on average 12.80 ms (SD = 7.55 ms) before the RT. There was no difference in the onset of facilitation between the two conditions. Because MEPs were facilitated without a change in the background EMG activity, it is concluded that this facilitation is specifically due to an increase of MCx excitability just before voluntary muscle activation. This conclusion is further reinforced by the observation that MEPs evoked by near-threshold anodal stimuli to the MCx were not facilitated during the RT, in contrast to those evoked by near-threshold transcranial magnetic stimulation. However, several observations in the present and previous studies indicate that MEP amplitude may be more sensitive to α-motoneuron activity than to motor cortical neuron activity, an idea that has important methodological implications.

Download Full-text