Additional Info

  • Other Names:
    John P. Coetzee

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All Publications

  • Evaluation of temperature elevation associated with low-intensity focused ultrasound (LIFU) stimulation with or without a deep brain electrode. Brain stimulation Rao, V., Coetzee, J., Perez, L., Penalba, A., Adamson, M., Yoon, B. C. 2025

    View details for DOI 10.1016/j.brs.2025.10.003

    View details for PubMedID 41067685

  • Trigeminal Nerve Stimulation as a Semi-Active Control Condition in TMS Clinical Trials: Evidence From Heart-Brain Coupling and Clinical Outcomes. Brain stimulation Arns, M., Williams, N., Downar, J., Dojnov, A., Coetzee, J., Goya-Maldonado, R. 2025

    Abstract

    The inertness of sham controls in transcranial magnetic stimulation (TMS) studies, particularly those involving Transcutaneous Electrical Nerve Stimulation (TENS), remains controversial. Using heart-brain coupling (HBC) as a frontal-vagal engagement measure, we analyzed pilot data and data from two placebo-controlled accelerated intermittent theta burst stimulation (aiTBS) trials (combined N=100). Active-TMS induced significantly stronger HBC compared to sham in both studies, with the effect size for TENS-sham considerably attenuated, and significantly stronger HBC for TENS-sham relative to SAINT-sham (d=0.9). HBC in the TENS-sham group was associated with clinical improvement (d=1.12), reflecting antidepressant effects of trigeminal nerve stimulation. These findings suggest TENS-sham should be seen as a semi-active control condition, also controlling for trigeminal nerve stimulation, resulting in downstream vagal and cortical engagement and thus controlling for this non-specific effect of TMS. Future studies should be aware of this semi-active effect and conduct power-analyses accordingly, modifying the expected effect size. Furthermore, HBC could be used to titrate the intensity of TENS-stimulation to minimize semi-active effects.

    View details for DOI 10.1016/j.brs.2025.07.004

    View details for PubMedID 40651660

  • A new flexible coil setup to measure interleaved TMS-fMRI response during accelerated iTBS. Brain stimulation Tik, M., Coetzee, J., Kerr, A., Johnson, N., Geoly, A., Sridhar, M., Hunegnaw, S. A., Veerapal, C., Rolle, C., Williams, N. 2025

    View details for DOI 10.1016/j.brs.2025.06.006

    View details for PubMedID 40494481

  • Predicting brain age for veterans with traumatic brain injuries and healthy controls: an exploratory analysis FRONTIERS IN AGING NEUROSCIENCE Coetzee, J. P., Kang, X., Liou-Johnson, V., Luttenbacher, I., Seenivasan, S., Eshghi, E., Grewal, D., Shah, S., Hillary, F., Dennis, E. L., Adamson, M. M. 2025; 17: 1472207

    Abstract

    Traumatic brain injury (TBI) is associated with increased dementia risk. This may be driven by underlying biological changes resulting from the injury. Machine learning algorithms can use structural MRIs to give a predicted brain age (pBA). When the estimated age is greater than the chronological age (CA), this is called the brain age gap (BAg). We analyzed this outcome in men and women with and without TBI.To determine whether factors that contribute to BAg, as estimated using the brainageR algorithm, differ between men and women who are US military Veterans with and without TBI.In an exploratory, hypothesis-generating analysis, we analyzed data from 85 TBI patients and 22 healthy controls (HCs). High-resolution T1W images were processed using FreeSurfer 7.0. pBAs were calculated from T1s. Differences between the two groups were tested using the Mann-Whitney U. Associations between the BAg and other factors were tested using partial Pearson's r within groups, controlling for CA, followed by construction of regression models.After correcting for multiple comparisons, TBI patients and HCs differed on PCL score (higher for TBI patients) and cortical thickness (CT) in both hemispheres (higher for HCs). Among women TBI patients, BAg was correlated with pBA and hippocampal volume (HV), and among men TBI patients, BAg was correlated with pBA and CT. Among both men and women HCs, BAg was correlated only with CA. Four hierarchical regression models were constructed to predict BAg in each group, which controlled for CA and excluded pBA for multicollinearity. These models showed that HV predicted BAg among women with TBI, while CT predicted BAg among men with TBI, while only CA predicted BAg among HCs.These results offer tentative support to the view the factors associated with BAg among individuals with TBI differ from factors associated with BAg among HCs, and between men and women. Specifically, BAg among individuals with TBI is predicted by neuroanatomical factors, while among HCs it is predicted only by CA. This may reflect features of the algorithm, an underlying biological process, or both.

    View details for DOI 10.3389/fnagi.2025.1472207

    View details for Web of Science ID 001497956100001

    View details for PubMedID 40443792

    View details for PubMedCentralID PMC12119580

  • Higher Intensity of Mystical Experience Following Magnesium-Ibogaine is Associated With Larger Decreases in PTSD Severity Brown, R., Coetzee, J., Lissemore, J., Faerman, A., Olash, C., Buchanan, D., Geoly, A., Cherian, K., Adamson, M., Rolle, C., Williams, N. ELSEVIER SCIENCE INC. 2025: S274-S275

    View details for Web of Science ID 001483254800099

  • Corrigendum to "Low-intensity focused ultrasound (LIFU) for the treatment of post-traumatic headache (PTH) in veterans: A feasibility study" [Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, vol. 17 (2024), pg. 1290-1292/No. 6]. Brain stimulation Yoon, B. C., Coetzee, J. P., Kang, X., Brar, R., Timmerman, M., Harris, O., Madrigal, E., Adamson, M. M. 2025; 18 (2): 211

    View details for DOI 10.1016/j.brs.2025.01.019

    View details for PubMedID 39965459

  • Effect of DLPFC rTMS on anhedonia and alpha asymmetry in depressed patients. Scientific reports Kazemi, R., Rostami, R., Hadipour, A. L., Zandbagleh, A., Khomami, S., Kiaee, N., Coetzee, J. P., Philips, A., Mausoof Adamson, M. 2025; 15 (1): 899

    Abstract

    Anhedonia, a core symptom of depression, has been defined as the loss of pleasure or lack of reactivity to pleasurable stimuli. Considering the relevance of alpha asymmetry to MDD and anhedonia, we explored the effect of dorsolateral prefrontal cortex (DLPFC) stimulation on frontal and posterior EEG alpha asymmetry (FAA and PAA, respectively), in this exploratory investigation. 61 participants randomly received sham (n = 11), bilateral (BS; n = 25), or unilateral stimulation (US; n = 25) of the DLPFC. The Snaith-Hamilton Pleasure Scale (SHAPS) was administered. FAA and PAA were calculated by subtracting the natural log-transformed alpha power of the right (F8 or T6) from that of the left (F7 or T5) EEG channel. Furthermore, alpha peak was defined as the frequency where alpha power was at its maximum. BS and US both reduced anhedonia symptoms in the active compared to the sham group. Even non-responders in the BS group showed a decreased anhedonia. Interestingly in the BS group, only the patients who showed a right-lateralized FAA or PAA at baseline showed a reduction in anhedonia. However, in the US group, only patients with left-lateralized FAA or right-lateralized PAA showed a decrease in anhedonia. PAA at baseline predicted symptoms post treatment. Furthermore, a significant positive correlation between baseline alpha peak values and SHAPS scores post treatment were found in the BS group. PAA was a better predictor of anhedonia and reduction of depressive symptoms in both groups. BS may produce larger effects with regard to anhedonia.

    View details for DOI 10.1038/s41598-024-85057-w

    View details for PubMedID 39762503

    View details for PubMedCentralID PMC11704047

  • Low-intensity focused ultrasound (LIFU) for the treatment of post-traumatic headache (PTH) in veterans: a feasibility study. Brain stimulation Yoon, B. C., Coetzee, J. P., Kang, X., Brar, R., Timmerman, M., Harris, O., Madrigal, E., Adamson, M. M. 2024

    View details for DOI 10.1016/j.brs.2024.11.007

    View details for PubMedID 39566597

  • Magnesium-ibogaine therapy in veterans with traumatic brain injuries. Nature medicine Cherian, K. N., Keynan, J. N., Anker, L., Faerman, A., Brown, R. E., Shamma, A., Keynan, O., Coetzee, J. P., Batail, J., Phillips, A., Bassano, N. J., Sahlem, G. L., Inzunza, J., Millar, T., Dickinson, J., Rolle, C. E., Keller, J., Adamson, M., Kratter, I. H., Williams, N. R. 2024

    Abstract

    Traumatic brain injury (TBI) is a leading cause of disability. Sequelae can include functional impairments and psychiatric syndromes such as post-traumatic stress disorder (PTSD), depression and anxiety. Special Operations Forces (SOF) veterans (SOVs) may be at an elevated risk for these complications, leading some to seek underexplored treatment alternatives such as the oneirogen ibogaine, a plant-derived compound known to interact with multiple neurotransmitter systems that has been studied primarily as a treatment for substance use disorders. Ibogaine has been associated with instances of fatal cardiac arrhythmia, but coadministration of magnesium may mitigate this concern. In the present study, we report a prospective observational study of the Magnesium-Ibogaine: the Stanford Traumatic Injury to the CNS protocol (MISTIC), provided together with complementary treatment modalities, in 30 male SOVs with predominantly mild TBI. We assessed changes in the World Health Organization Disability Assessment Schedule from baseline to immediately (primary outcome) and 1month (secondary outcome) after treatment. Additional secondary outcomes included changes in PTSD (Clinician-Administered PTSD Scale for DSM-5), depression (Montgomery-Asberg Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale). MISTIC resulted in significant improvements in functioning both immediately (Pcorrected<0.001, Cohen's d=0.74) and 1month (Pcorrected< 0.001, d=2.20) after treatment and in PTSD (Pcorrected<0.001, d=2.54), depression (Pcorrected<0.001, d=2.80) and anxiety (Pcorrected<0.001, d=2.13) at 1month after treatment. There were no unexpected or serious adverse events. Controlled clinical trials to assess safety and efficacy are needed to validate these initial open-label findings. ClinicalTrials.gov registration: NCT04313712 .

    View details for DOI 10.1038/s41591-023-02705-w

    View details for PubMedID 38182784

  • Transcranial Magnetic Stimulation-Induced Heart-Brain Coupling: Implications for Site Selection and Frontal Thresholding-Preliminary Findings. Biological psychiatry global open science Dijkstra, E., van Dijk, H., Vila-Rodriguez, F., Zwienenberg, L., Rouwhorst, R., Coetzee, J. P., Blumberger, D. M., Downar, J., Williams, N., Sack, A. T., Arns, M. 2023; 3 (4): 939-947

    Abstract

    Background: Neurocardiac-guided transcranial magnetic stimulation (TMS) uses repetitive TMS (rTMS)-induced heart rate deceleration to confirm activation of the frontal-vagal pathway. Here, we test a novel neurocardiac-guided TMS method that utilizes heart-brain coupling (HBC) to quantify rTMS-induced entrainment of the interbeat interval as a function of TMS cycle time. Because prior neurocardiac-guided TMS studies indicated no association between motor and frontal excitability threshold, we also introduce the approach of using HBC to establish individualized frontal excitability thresholds for optimally dosing frontal TMS.Methods: In studies 1A and 1B, we validated intermittent theta burst stimulation (iTBS)-induced HBC (2 seconds iTBS on; 8 seconds off: HBC= 0.1 Hz) in 15 (1A) and 22 (1B) patients with major depressive disorder from 2 double-blind placebo-controlled studies. In study 2, HBC was measured in 10 healthy subjects during the 10-Hz "Dash" protocol (5 seconds 10-Hz on; 11 seconds off: HBC= 0.0625 Hz) applied with 15 increasing intensities to 4 evidence-based TMS locations.Results: Using blinded electrocardiogram-based HBC analysis, we successfully identified sham from real iTBS sessions (accuracy: study 1A= 83%, study 1B= 89.5%) and found a significantly stronger HBC at 0.1 Hz in active compared with sham iTBS (d= 1.37) (study 1A). In study 2, clear dose-dependent entrainment (p= .002) was observed at 0.0625 Hz in a site-specific manner.Conclusions: We demonstrated rTMS-induced HBC as a function of TMS cycle time for 2 commonly used clinical protocols (iTBS and 10-Hz Dash). These preliminary results supported individual site specificity and dose-response effects, indicating that this is a potentially valuable method for clinical rTMS site stratification and frontal thresholding. Further research should control for TMS side effects, such as pain of stimulation, to confirm these findings.

    View details for DOI 10.1016/j.bpsgos.2023.01.003

    View details for PubMedID 37881544

  • Predictors of brain age gap among patients with traumatic brain injuries and healthy controls Adamson, M., Coetzee, J., Kang, X., Luttenbacher, I., Liou-Johnson, V., Seenivasan, S., Dennis, E., Hillary, F. TAYLOR & FRANCIS LTD. 2023: 195-196

    View details for Web of Science ID 001092280000373

  • Dissociating Language and Thought in Human Reasoning. Brain sciences Coetzee, J. P., Johnson, M. A., Lee, Y., Wu, A. D., Iacoboni, M., Monti, M. M. 2022; 13 (1)

    Abstract

    What is the relationship between language and complex thought? In the context of deductive reasoning there are two main views. Under the first, which we label here the language-centric view, language is central to the syntax-like combinatorial operations of complex reasoning. Under the second, which we label here the language-independent view, these operations are dissociable from the mechanisms of natural language. We applied continuous theta burst stimulation (cTBS), a form of noninvasive neuromodulation, to healthy adult participants to transiently inhibit a subregion of Broca's area (left BA44) associated in prior work with parsing the syntactic relations of natural language. We similarly inhibited a subregion of dorsomedial frontal cortex (left medial BA8) which has been associated with core features of logical reasoning. There was a significant interaction between task and stimulation site. Post hoc tests revealed that performance on a linguistic reasoning task, but not deductive reasoning task, was significantly impaired after inhibition of left BA44, and performance on a deductive reasoning task, but not linguistic reasoning task, was decreased after inhibition of left medial BA8 (however not significantly). Subsequent linear contrasts supported this pattern. These novel results suggest that deductive reasoning may be dissociable from linguistic processes in the adult human brain, consistent with the language-independent view.

    View details for DOI 10.3390/brainsci13010067

    View details for PubMedID 36672048

  • Electrophysiological and behavioral effects of unilateral and bilateral rTMS; A randomized clinical trial on rumination and depression. Journal of affective disorders Kazemi, R., Rostami, R., Nasiri, Z., Hadipour, A. L., Kiaee, N., Coetzee, J. P., Philips, A., Brown, R., Seenivasan, S., Adamson, M. M. 2022

    Abstract

    BACKGROUND: Rumination is significantly frequent in major depressive disorder (MDD). However, not a lot of studies have investigated the effects of repetitive transcranial magnetic stimulation (rTMS) on rumination.METHODS: 61 participants with a minimum Hamilton Depression Rating Scale (HAM-D) score of 20 were randomly assigned to sham, bilateral stimulation (BS) or unilateral stimulation (US) groups. EEG, The Ruminative Response Scale (RRS), and HAM-D were administered before and after the 20 sessions of rTMS. Phase locked values (PLV) were calculated as a measure of connectivity.RESULTS: There was a significant decrease in HAM-D scores in both BS and US. In responders, BS and US differed significantly in RRS total scores, with greater reduction in BS. PLV significantly changed in the default mode network (DMN) in delta, theta, alpha, and beta in BS, in responders of which PLV decreased in the DMN in beta and gamma. Positive correlations between PLV and brooding in delta and theta, and negative correlations between PLV and reflection were found in theta, alpha, and beta. In US, connectivity in the DMN increased in beta, and PLV increased in theta and beta, and decreased in alpha and beta in its responders. Positive correlations between PLV and brooding in the delta and theta, as well as negative correlations between PLV and reflection in theta were observed in the DMN.CONCLUSION: US and BS resulted in different modulations in the DMN, however, both could alleviate both rumination and depression. Reductions in the beta and alpha frequency bands in the DMN can be considered as potential EEG-based markers of response to bilateral and unilateral rTMS, respectively.

    View details for DOI 10.1016/j.jad.2022.08.098

    View details for PubMedID 36055535

  • Ultrasonic Deep Brain Neuromodulation in Acute Disorders of Consciousness: A Proof-of-Concept. Brain sciences Cain, J. A., Spivak, N. M., Coetzee, J. P., Crone, J. S., Johnson, M. A., Lutkenhoff, E. S., Real, C., Buitrago-Blanco, M., Vespa, P. M., Schnakers, C., Monti, M. M. 2022; 12 (4)

    Abstract

    The promotion of recovery in patients who have entered a disorder of consciousness (DOC; e.g., coma or vegetative states) following severe brain injury remains an enduring medical challenge despite an ever-growing scientific understanding of these conditions. Indeed, recent work has consistently implicated altered cortical modulation by deep brain structures (e.g., the thalamus and the basal ganglia) following brain damage in the arising of, and recovery from, DOCs. The (re)emergence of low-intensity focused ultrasound (LIFU) neuromodulation may provide a means to selectively modulate the activity of deep brain structures noninvasively for the study and treatment of DOCs. This technique is unique in its combination of relatively high spatial precision and noninvasive implementation. Given the consistent implication of the thalamus in DOCs and prior results inducing behavioral recovery through invasive thalamic stimulation, here we applied ultrasound to the central thalamus in 11 acute DOC patients, measured behavioral responsiveness before and after sonication, and applied functional MRI during sonication. With respect to behavioral responsiveness, we observed significant recovery in the week following thalamic LIFU compared with baseline. With respect to functional imaging, we found decreased BOLD signals in the frontal cortex and basal ganglia during LIFU compared with baseline. In addition, we also found a relationship between altered connectivity of the sonicated thalamus and the degree of recovery observed post-LIFU.

    View details for DOI 10.3390/brainsci12040428

    View details for PubMedID 35447960

  • Prediction of Brain Age for Healthy Individuals and Patients with Traumatic Brain Injuries Adamson, M., Kang, X., Luttenbacher, I., Coetzee, J., Liou-Johnson, V., Dennis, E., Hillary, F. TAYLOR & FRANCIS LTD. 2022: 98-99

    View details for Web of Science ID 000761085700199

  • Fiber tract integrity in patients with brain injury and chronic health symptoms. Neuroimage. Reports Kang, X., Coetzee, J. P., Main, K. L., Seenivasan, S., Zhu, K., Adamson, M. M. 2021; 1 (4): 100047

    Abstract

    Patients with traumatic brain injuries (TBI), especially those with chronic health symptoms, often experience behavioral impairments attributable to white matter (WM) microstructural degeneration. Diffusion tensor imaging (DTI) is sensitive to these WM abnormalities, which are frequently a consequence of diffuse axonal injuries precipitated by the original trauma. In this study, tract profile analyses using an automated fiber quantification (AFQ) procedure compared diffusion properties along 20 major fiber tracts in a total of 46 participants, including individuals with TBI, who either have (n = 17) or did not have (n = 16) chronic symptoms, and a control group (n = 13). The tract profile analyses indicated that fractional anisotropy (FA) and radial diffusivity (RD) are more sensitive biomarkers of WM integrity than other commonly used diffusion measures, such as the linear anisotropy coefficient (CL) and mean diffusivity (MD). For all participants with TBI, FA was significantly lower and RD significantly higher in the middle portion of the left cingulum hippocampus (as compared to the control group). Additionally, FA was significantly lower in the inside segment of the left uncinate and the posterior segment of the inferior longitudinal fasciculus for TBI participants with chronic symptoms compared to the controls, but this was not the case for individuals with TBI without chronic symptoms. TBI participants with chronic symptoms also exhibited significantly lower fiber volume (VOL) in three other fiber tracts. This study provides evidence that the diffusion properties of discrete segments along the major fiber tracts, as measured by AFQ, can serve as biomarkers of WM abnormalities, especially for individuals with TBI and chronic health symptoms.

    View details for DOI 10.1016/j.ynirp.2021.100047

    View details for PubMedID 40568433

    View details for PubMedCentralID PMC12172828

  • Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. The American journal of psychiatry Cole, E. J., Phillips, A. L., Bentzley, B. S., Stimpson, K. H., Nejad, R., Barmak, F., Veerapal, C., Khan, N., Cherian, K., Felber, E., Brown, R., Choi, E., King, S., Pankow, H., Bishop, J. H., Azeez, A., Coetzee, J., Rapier, R., Odenwald, N., Carreon, D., Hawkins, J., Chang, M., Keller, J., Raj, K., DeBattista, C., Jo, B., Espil, F. M., Schatzberg, A. F., Sudheimer, K. D., Williams, N. R. 2021: appiajp202120101429

    Abstract

    OBJECTIVE: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of 90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression.METHODS: Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Asberg Depression Rating Scale (MADRS) 4 weeks after treatment.RESULTS: At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group.CONCLUSIONS: SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.

    View details for DOI 10.1176/appi.ajp.2021.20101429

    View details for PubMedID 34711062

  • Ultrasonic Thalamic Stimulation in Chronic Disorders of Consciousness. Brain stimulation Cain, J. A., Spivak, N. M., Coetzee, J. P., Crone, J. S., Johnson, M. A., Lutkenhoff, E. S., N P, C. R., Buitrago-Blanco, M., Vespa, P. M., Schnakers, C., Monti, M. M. 2021

    View details for DOI 10.1016/j.brs.2021.01.008

    View details for PubMedID 33465497

  • International Prevalence and Correlates of Psychological Stress during the Global COVID-19 Pandemic. International journal of environmental research and public health Adamson, M. M., Phillips, A. n., Seenivasan, S. n., Martinez, J. n., Grewal, H. n., Kang, X. n., Coetzee, J. n., Luttenbacher, I. n., Jester, A. n., Harris, O. A., Spiegel, D. n. 2020; 17 (24)

    Abstract

    This study reports perceived stress and associated sociodemographic factors from an international sample of adults, during the COVID-19 pandemic. The Perceived Stress Scale (PSS-10) along with socio-demographic questions were conducted between 8 April 2020 and 11 May 2020. The survey was translated from English into five languages. Recruitment was conducted worldwide using social media. A total of 1685 survey responses were collected across 57 countries with eleven countries (≥30 responses/country) included in the sub-analyses. Overall, the mean PSS-10 score was 19.08 (SD = 7.17), reflecting moderate stress compared to previously reported norms. Female gender was associated with a higher PSS score (3.03, p < 0.05) as well as four-year degree holders (3.29, p < 0.05), while adults over 75 years (-7.46, p < 0.05) had lower PSS scores. Personal care composite score (including hours of sleep, exercise, and meditation) was associated with lower PSS scores (-0.39, p < 0.01). Increases in personal care and changes in work expectations were associated with lower PSS scores (-1.30 (p < 0.05) and -0.38 (p < 0.01), respectively). Lower total PSS scores were reported in Germany (-4.82, p < 0.01) compared to the global response sample mean. This information, collected during the initial period of global mitigation orders, provides insight into potential mental health risks and protective factors during crises.

    View details for DOI 10.3390/ijerph17249248

    View details for PubMedID 33321950

  • Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. The American journal of psychiatry Cole, E. J., Stimpson, K. H., Bentzley, B. S., Gulser, M. n., Cherian, K. n., Tischler, C. n., Nejad, R. n., Pankow, H. n., Choi, E. n., Aaron, H. n., Espil, F. M., Pannu, J. n., Xiao, X. n., Duvio, D. n., Solvason, H. B., Hawkins, J. n., Guerra, A. n., Jo, B. n., Raj, K. S., Phillips, A. L., Barmak, F. n., Bishop, J. H., Coetzee, J. P., DeBattista, C. n., Keller, J. n., Schatzberg, A. F., Sudheimer, K. D., Williams, N. R. 2020: appiajp201919070720

    Abstract

    New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression.Twenty-two participants with treatment-resistant depression received open-label SAINT. fcMRI was used to individually target the region of the left DLPFC most anticorrelated with sgACC in each participant. Fifty iTBS sessions (1,800 pulses per session, 50-minute intersession interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT.One participant withdrew, leaving a sample size of 21. Nineteen of 21 participants (90.5%) met remission criteria (defined as a score <11 on the Montgomery-Åsberg Depression Rating Scale). In the intent-to-treat analysis, 19 of 22 participants (86.4%) met remission criteria. Neuropsychological testing demonstrated no negative cognitive side effects.SAINT, an accelerated, high-dose, iTBS protocol with fcMRI-guided targeting, was well tolerated and safe. Double-blinded sham-controlled trials are needed to confirm the remission rate observed in this initial study.

    View details for DOI 10.1176/appi.ajp.2019.19070720

    View details for PubMedID 32252538

  • At the core of reasoning: Dissociating deductive and non-deductive load HUMAN BRAIN MAPPING Coetzee, J. P., Monti, M. M. 2018; 39 (4): 1850–61

    Abstract

    In recent years, neuroimaging methods have been used to investigate how the human mind carries out deductive reasoning. According to some, the neural substrate of language is integral to deductive reasoning. According to others, deductive reasoning is supported by a language-independent distributed network including left frontopolar and frontomedial cortices. However, it has been suggested that activity in these frontal regions might instead reflect non-deductive factors such as working memory load and general cognitive difficulty. To address this issue, 20 healthy volunteers participated in an fMRI experiment in which they evaluated matched simple and complex deductive and non-deductive arguments in a 2 × 2 design. The contrast of complex versus simple deductive trials resulted in a pattern of activation closely matching previous work, including frontopolar and frontomedial "core" areas of deduction as well as other "cognitive support" areas in frontoparietal cortices. Conversely, the contrast of complex and simple non-deductive trials resulted in a pattern of activation that does not include any of the aforementioned "core" areas. Direct comparison of the load effect across deductive and non-deductive trials further supports the view that activity in the regions previously interpreted as "core" to deductive reasoning cannot merely reflect non-deductive load, but instead might reflect processes specific to the deductive calculus. Finally, consistent with previous reports, the classical language areas in left inferior frontal gyrus and posterior temporal cortex do not appear to participate in deductive inference beyond their role in encoding stimuli presented in linguistic format.

    View details for DOI 10.1002/hbm.23979

    View details for Web of Science ID 000427117300030

    View details for PubMedID 29341386

  • Leukocyte telomere length predicts SSRI response in major depressive disorder: A preliminary report. Molecular neuropsychiatry Hough, C. M., Bersani, F. S., Mellon, S. H., Epel, E. S., Reus, V. I., Lindqvist, D. n., Lin, J. n., Mahan, L. n., Rosser, R. n., Burke, H. n., Coetzee, J. n., Nelson, J. C., Blackburn, E. H., Wolkowitz, O. M. 2016; 2 (2): 88–96

    Abstract

    Short leukocyte telomere length (LTL) may be associated with several psychiatric disorders, including major depressive disorder (MDD). Short LTL has previously been associated with poor response to psychiatric medications in bipolar disorder and schizophrenia, but no studies have prospectively assessed the relationship of LTL to SSRI response in MDD. We assessed pre-treatment LTL, depression severity (using the Hamilton Depression Rating Scale [HDRS]), and self-reported positive and negative affect in 27 healthy, unmedicated adults with MDD. Subjects then underwent open-label treatment with a selective serotonin reuptake inhibitor (SSRI) antidepressant for eight weeks, after which clinical ratings were repeated. Analyses were corrected for age, sex and BMI. "Non-responders" to treatment (HDRS improvement <50%) had significantly shorter pre-treatment LTL, compared to "Responders" (p=0.037). Further, shorter pre-treatment LTL was associated with less improvement in negative affect (p<0.010) but not with changes in positive affect (p=0.356). This preliminary study is the first to assess the relationship between LTL and SSRI response in MDD and among the first to prospectively assess its relationship to treatment outcome in any psychiatric illness. Our data suggest that short LTL may serve as a vulnerability index of poorer response to SSRI treatment, but this needs examination in larger samples.

    View details for DOI 10.1159/000446500

    View details for PubMedID 27429957

    View details for PubMedCentralID PMC4943759