The effect of repetitive transcranial magnetic stimulation on gamma oscillatory activity in schizophrenia

Abstract

Background: Gamma (γ) oscillations (30-50 Hz) have been shown to be excessive in patients with schizophrenia (SCZ) during working memory (WM). WM is a cognitive process that involves the online maintenance and manipulation of information that is mediated largely by the dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS) represents a non-invasive method to stimulate the cortex that has been shown to enhance cognition and γ oscillatory activity during WM.

Methodology and principal findings: We examined the effect of 20 Hz rTMS over the DLPFC on γ oscillatory activity elicited during the N-back task in 24 patients with SCZ compared to 22 healthy subjects. Prior to rTMS, patients with SCZ elicited excessive γ oscillatory activity compared to healthy subjects across WM load. Active rTMS resulted in the reduction of frontal γ oscillatory activity in patients with SCZ, while potentiating activity in healthy subjects in the 3-back, the most difficult condition. Further, these effects on γ oscillatory activity were found to be specific to the frontal brain region and were absent in the parieto-occipital brain region.

Conclusions and significance: We suggest that this opposing effect of rTMS on γ oscillatory activity in patients with SCZ versus healthy subjects may be related to homeostatic plasticity leading to differential effects of rTMS on γ oscillatory activity depending on baseline differences. These findings provide important insights into the neurophysiological mechanisms underlying WM deficits in SCZ and demonstrated that rTMS can modulate γ oscillatory activity that may be a possible avenue for cognitive potentiation in this disorder.

Figure 1. A representation of the 1-, 2- and 3-back conditions that were completed in a randomized order by patients with schizophrenia (SCZ) and healthy subjects (HS) pre-post rTMS.

Subjects were required to push one button (target) if the current letter was identical to the letter presented “N” trials back; otherwise the participants pushed a different button (non-target). Correct responses for target (TC) and non-target (NTC) were included in the data analysis (A). The timing of one trial from the presentation of a one letter separated by a (+) sign followed by a subsequent letter for a total time of 3000 msec (B).

Figure 2. Targeting the Dorsolateral Prefrontal Cortex (DLPFC) for rTMS stimulation.

Transverse view from a single subject with exposed cortex and overlap of Brodmann areas 9 & 46, highlighted (white) on a T1-weighted 3D MRI. Using MRI-to-MiniBird co-registration, the centre of the TMS coil was held over this region.

Figure 3. Mean log transformed gamma oscillatory power (γ; 30–50 Hz; uV²) for target correct (TC) and non-target correct (NTC) responses during the N-back task pre-post rTMS in healthy subjects (HS; N = 22) versus patients with schizophrenia (SCZ; N = 24) (A).

Mean log transformed γ oscillatory power (uV²) for target correct (TC) and non-target correct (NTC) responses during the 3-back condition measured from the frontal and parieto-occipitalbrain regions pre-post rTMS in patients with schizophrenia (SCZ; N = 24) and healthy subjects (HS; N = 22) (B). Bars represent (±) 1 standard deviation.

Figure 4. Mean log transformed oscillatory power (uV²) for target correct (TC) and non-target correct (NTC) responses during the N-back task pre-post rTMS in healthy subjects (HS; N = 22) versus patients with schizophrenia (SCZ; N = 24) across delta (δ; 1–3.5 Hz), theta (θ; 4–7 Hz), alpha (α; 8–12 Hz), and beta (β; 12.5–28 Hz) frequency ranges.

Bars represent (±) 1 standard deviation.