Test-retest assessment of cortical activation induced by repetitive transcranial magnetic stimulation with brain atlas-guided optical topography.

Repetitive transcranial magnetic stimulation (rTMS) is a technology that stimulates neurons with rapidly changing magnetic pulses with demonstrated therapeutic applications for various neuropsychiatric disorders. Functional near-infrared spectroscopy (fNIRS) is a suitable tool to assess rTMS-evoked brain responses without interference from the magnetic or electric fields generated by the TMS coil. We have previously reported a channel-wise study of combined rTMS/fNIRS on the motor and prefrontal cortices, showing a robust decrease of oxygenated hemoglobin concentration (Δ[HbO2]) at the sites of 1-Hz rTMS and the contralateral brain regions. However, the reliability of this putative clinical tool is unknown. In this study, we develop a rapid optical topography approach to spatially characterize the rTMS-evoked hemodynamic responses on a standard brain atlas. A hemispherical approximation of the brain is employed to convert the three-dimensional topography on the complex brain surface to a two-dimensional topography in the spherical coordinate system. The test-retest reliability of the combined rTMS/fNIRS is assessed using repeated measurements performed two to three days apart. The results demonstrate that the Δ[HbO2] amplitudes have moderate-to-high reliability at the group level; and the spatial patterns of the topographic images have high reproducibility in size and a moderate degree of overlap at the individual level.

Neural correlates of successful response inhibition in unmedicated patients with late-life depression.

OBJECTIVE: Accumulating evidence implicates a strong association between abnormal frontostriatal-limbic brain circuits, executive dysfunction, and late-life depression (LLD). The stop signal task (SST) was designed by Rubia et al. for use with functional magnetic resonance imaging (fMRI) to identify the neural correlates of motor response inhibition, a well-characterized executive function. In this study, we compared brain activation between a group of unmedicated participants with LLD and an unmedicated healthy cohort during SST performance. METHODS: Participants 55-85 years of age were screened, clinically evaluated, and entered into either the LLD (n = 15) or healthy comparison group (n = 13). Both groups underwent neuroimaging while performing the SST under similar conditions. The brain circuitry of successful motor inhibition was evaluated by contrasting the condition of correctly inhibiting responses with the condition of correctly responding to Go signals. Differential areas of brain activation between the LLD and comparison groups were determined with FMRIB Software Library. RESULTS: Despite comparable SST performance measures, LLD participants demonstrated greater blood oxygen level dependent activation relative to the comparison group in predominantly left-lateralized frontostriatal-limbic circuitry that included the bilateral superior frontal cortices and left-hemispheric orbitofrontal gyri, insular cortex, cingulate cortex, caudate, and putamen. Conversely, the healthy comparison group did not exhibit any areas of greater activation than the LLD group. CONCLUSION: Unmedicated participants with LLD activate additional areas within frontostriatal-limbic brain circuitry when performing the SST at a level comparable to a healthy cohort.

Functional connectivity of brain structures correlates with treatment outcome in major depressive disorder.

Identifying biosignatures to assess the probability of response to an antidepressant for patients with major depressive disorder (MDD) is critically needed. Functional connectivity MRI (fcMRI) offers the promise to provide such a measure. Previous work with fcMRI demonstrated that the correlation in signal from one region to another is a measure of functional connectivity. In this pilot work, a baseline non-task fcMRI was acquired in 14 adults with MDD who were free of all medications. Participants were then treated for 8 weeks with an antidepressant and then clinically re-evaluated. Probabilistic anatomic regions of interest (ROI) were defined for 16 brain regions (eight for each hemisphere) previously identified as being important in mood disorders. These ROIs were used to determine mean time courses for each individual's baseline non-task fcMRI. The correlations in time courses between 16 brain regions were calculated. These calculated correlations were considered to signify measures of functional connectivity. The degree of connectivity for each participant was correlated with treatment outcome. Among 13 participants with 8 weeks follow-up data, connectivity measures in several regions, especially the subcallosal cortex, were highly correlated with treatment outcome. These connectivity measures could provide a means to evaluate how likely a patient is to respond to an antidepressant treatment. Further work using larger samples is required to confirm these findings and to assess if measures of functional connectivity can be used to predict differential outcomes between antidepressant treatments.

Replication of Functional MRI Detection of Deception.

BACKGROUND: Several studies support the use of fMRI for detecting deception. There have been, however, no reported replications on different scanners or at different locations. In a previous study, deception was accurately detected in at least 90% of the participants in two independent cohorts. This study attempted to replicate those findings using a different scanner and location. METHODS: Healthy participants 18-50 years of age were recruited from the local community. After providing written informed consent, participants were screened to ensure that they were healthy, not taking any medications, and safe to have an MRI. For the testing paradigm, subjects chose one of two objects (ring or watch) to "steal" and placed it in their locker. Participants were then scanned while being visually presented with a series of questions. Functional MRI analysis was performed in the same manner as described in Kozel et al. 2005. A Chi-Squared test was used to test for a significant difference between the results in the previous study and in this replication study. RESULTS: Thirty subjects (20 women, mean age 29.0+/-6.5 years) were scanned with one subject being noncompliant with the protocol. Twenty-five of twenty-nine (86%) participants were correctly identified when being deceptive. There was no statistical difference between the accuracy rate obtained in this study (25/29) versus the previous study (28/31) (Chi-Squared, chi(2)=0.246, p=0.6197). CONCLUSIONS: Our methodology for detecting deception was successfully replicated at a different site suggesting that this methodology is robust and independent of both scanner and location.

Using simultaneous repetitive Transcranial Magnetic Stimulation/functional Near Infrared Spectroscopy (rTMS/fNIRS) to measure brain activation and connectivity.

INTRODUCTION: Simultaneously acquiring functional Near Infrared Spectroscopy (fNIRS) during Transcranial Magnetic Stimulation (rTMS) offers the possibility of directly investigating superficial cortical brain activation and connectivity. In addition, the effects of rTMS in distinct brain regions without quantifiable behavioral changes can be objectively measured. METHODS: Healthy, nonmedicated participants age 18-50 years were recruited from the local community. After written informed consent was obtained, the participants were screened to ensure that they met inclusion criteria. They underwent two visits of simultaneous rTMS/fNIRS separated by 2 to 3 days. In each visit, the motor cortex and subsequently the prefrontal cortex (5 cm anterior to the motor cortex) were stimulated (1 Hz, max 120% MT, 10 s on with 80 s off, for 15 trains) while simultaneous fNIRS data were acquired from the ipsilateral and contralateral brain regions. RESULTS: Twelve healthy volunteers were enrolled with one excluded prior to stimulation. The 11 participants studied (9 male) had a mean age of 31.8 (s.d. 10.2, range 20-49) years. There was no significant difference in fNIRS between Visit 1 and Visit 2. Stimulation of both the motor and prefrontal cortices resulted in a significant decrease in oxygenated hemoglobin (HbO(2)) concentration in both the ipsilateral and contralateral cortices. The ipsilateral and contralateral changes showed high temporal consistency. DISCUSSION: Simultaneous rTMS/fNIRS provides a reliable measure of regional cortical brain activation and connectivity that could be very useful in studying brain disorders as well as cortical changes induced by rTMS.