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Article ; Online: Doubling Down on Combined Neurology-Psychiatry Residency Training and Behavioral Neurology & Neuropsychiatry Fellowship Training: Reply to Perez.

Brown, Joshua C

The Journal of neuropsychiatry and clinical neurosciences

2024 Volume 36, Issue 1, Page(s) 79–81

MeSH term(s)	Humans ; Neuropsychiatry ; Fellowships and Scholarships ; Internship and Residency ; Psychiatry
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Letter
ZDB-ID	1036340-3
ISSN	1545-7222 ; 0895-0172
ISSN (online)	1545-7222
ISSN	0895-0172
DOI	10.1176/appi.neuropsych.20230163
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Article: The Problem and Potential of TMS' Infinite Parameter Space: A Targeted Review and Road Map Forward.

Caulfield, Kevin A / Brown, Joshua C

Frontiers in psychiatry

2022 Volume 13, Page(s) 867091

Abstract: Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive, effective, and FDA-approved brain stimulation method. However, rTMS parameter selection remains largely unexplored, with great potential for optimization. In this review, ...

Abstract	Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive, effective, and FDA-approved brain stimulation method. However, rTMS parameter selection remains largely unexplored, with great potential for optimization. In this review, we highlight key studies underlying next generation rTMS therapies, particularly focusing on: (1) rTMS Parameters, (2) rTMS Target Engagement, (3) rTMS Interactions with Endogenous Brain Activity, and (4) Heritable Predisposition to Brain Stimulation Treatments. Methods: We performed a targeted review of pre-clinical and clinical rTMS studies. Results: Current evidence suggests that rTMS pattern, intensity, frequency, train duration, intertrain interval, intersession interval, pulse and session number, pulse width, and pulse shape can alter motor excitability, long term potentiation (LTP)-like facilitation, and clinical antidepressant response. Additionally, an emerging theme is how endogenous brain state impacts rTMS response. Researchers have used resting state functional magnetic resonance imaging (rsfMRI) analyses to identify personalized rTMS targets. Electroencephalography (EEG) may measure endogenous alpha rhythms that preferentially respond to personalized stimulation frequencies, or in closed-loop EEG, may be synchronized with endogenous oscillations and even phase to optimize response. Lastly, neuroimaging and genotyping have identified individual predispositions that may underlie rTMS efficacy. Conclusions: We envision next generation rTMS will be delivered using optimized stimulation parameters to rsfMRI-determined targets at intensities determined by energy delivered to the cortex, and frequency personalized and synchronized to endogenous alpha-rhythms. Further research is needed to define the dose-response curve of each parameter on plasticity and clinical response at the group level, to determine how these parameters interact, and to ultimately personalize these parameters.
Language	English
Publishing date	2022-05-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564218-2
ISSN	1664-0640
ISSN	1664-0640
DOI	10.3389/fpsyt.2022.867091
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Article: An Interventional Psychiatry Track.

Brown, Joshua C

The American journal of psychiatry residents' journal

2019 Volume 15, Issue 1, Page(s) 11–14

Abstract: Interventional psychiatry" has been proposed as a name for the emerging psychiatric subspecialty of neuromodulation, or brain stimulation. The practices of electroconvulsive therapy and transcranial magnetic stimulation are rapidly expanding. Moreover, ... ...

Abstract	"Interventional psychiatry" has been proposed as a name for the emerging psychiatric subspecialty of neuromodulation, or brain stimulation. The practices of electroconvulsive therapy and transcranial magnetic stimulation are rapidly expanding. Moreover, research techniques, such as neuronavigation and electrophysiology, are already translating to the clinic, further emphasizing the need for training paradigms to keep pace. The purpose of this article is to provide practical guidance for psychiatry residents who seek further training in this emerging subspecialty. It describes a training track developed at the Medical University of South Carolina that can be adopted by residents at other institutions.
Language	English
Publishing date	2019-09-06
Publishing country	United States
Document type	Journal Article
ISSN	2474-4662
ISSN	2474-4662
DOI	10.1176/appi.ajp-rj.2019.150110
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Article ; Online: Older age associated with better antidepressant response to H1-coil transcranial magnetic stimulation in female patients.

Kryatova, Maria S / Seiner, Stephen J / Brown, Joshua C / Siddiqi, Shan H

Journal of affective disorders

2024 Volume 351, Page(s) 66–73

Abstract: Background: TMS is increasingly used to treat depression, but predictors of treatment outcomes remain unclear. We assessed the association between age and TMS response given inconsistent prior reports limited by small sample size, heterogeneity, ... ...

Abstract	Background: TMS is increasingly used to treat depression, but predictors of treatment outcomes remain unclear. We assessed the association between age and TMS response given inconsistent prior reports limited by small sample size, heterogeneity, outdated TMS parameters, lack of assessment of H1-coil TMS, and lack of an a priori hypothesis. We hypothesized that older age would be associated with better treatment response based on trends in recent large exploratory analyses. Methods: We conducted a naturalistic retrospective analysis of patients (n = 378) ages 18-80 with depression (baseline Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) > 5) who received 29-35 sessions of TMS between 2014 and 2021. Response was assessed using percent reduction of QIDS-SR. The relationship between percent response or remission and age group was assessed using the chi-square test. Results: 85 % of patients received the standard protocol of H1-coil TMS to the left DLPFC. Percent response and remission rates for the entire study sample increased with age (response: p = .026; remission: p = .0023). This finding was stronger in female patients (response: p = .0033; remission: p = .00098) and was not observed in male patients (response: p = .73; remission: p = .26). This was confirmed in a sub-analysis of patients who only received the standard protocol with the H1-coil for the entire treatment course. Limitations: Naturalistic retrospective analysis from one academic center. Conclusions: Older age is associated with a better antidepressant response to H1-coil TMS in female patients. This was demonstrated in a hypothesis-driven confirmation of prior exploratory findings in a large sample size with a homogeneous data collection protocol across all participants.
MeSH term(s)	Humans ; Male ; Female ; Aged ; Transcranial Magnetic Stimulation/methods ; Retrospective Studies ; Treatment Outcome ; Antidepressive Agents/therapeutic use ; Sample Size
Chemical Substances	Antidepressive Agents
Language	English
Publishing date	2024-01-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	135449-8
ISSN	1573-2517 ; 0165-0327
ISSN (online)	1573-2517
ISSN	0165-0327
DOI	10.1016/j.jad.2024.01.160
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Article ; Online: BRAG about (s)lots.

Brown, Joshua C / Hell, Johannes W / Gerges, Nashaat Z

The Journal of cell biology

2023 Volume 222, Issue 12

Abstract: Mutations in IQSEC2/BRAG1 cause intellectual dysfunction by impairing ARF-GEF activity and long-term depression. In this issue, Bai et al. (https://doi.org/10.1083/jcb.202307117) discover how constitutive ARF-GEF activity is regulated by a closed ... ...

Abstract	Mutations in IQSEC2/BRAG1 cause intellectual dysfunction by impairing ARF-GEF activity and long-term depression. In this issue, Bai et al. (https://doi.org/10.1083/jcb.202307117) discover how constitutive ARF-GEF activity is regulated by a closed conformation which opens in the presence of Ca2+. Two known pathogenic mutations cause "leaky" autoinhibition with reduced synaptic dynamic range and impaired cognitive performance.
MeSH term(s)	Mutation ; Neuronal Plasticity ; Guanine Nucleotide Exchange Factors/genetics ; Guanine Nucleotide Exchange Factors/physiology ; Calcium ; Cognition
Chemical Substances	Guanine Nucleotide Exchange Factors ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2023-11-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.202310023
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Article ; Online: Lamotrigine-Associated Progressive Dysphasia and Cognitive Dysfunction.

Brown, Joshua C / Broadway, Jessica L

OBM neurobiology

2021 Volume 5, Issue 2

Abstract: Lamotrigine is generally accepted as a well-tolerated medication with few cognitive side effects. Here, we report a case of a 62-year old female with a severe, rapidly progressive dementia-like process which was completely reversed after reduction of ... ...

Abstract	Lamotrigine is generally accepted as a well-tolerated medication with few cognitive side effects. Here, we report a case of a 62-year old female with a severe, rapidly progressive dementia-like process which was completely reversed after reduction of lamotrigine. Associated findings included hyperreflexia with clonus, ataxia, Wernicke-like dysphasia, global cognitive impairment, burst suppression on electroencephalogram (EEG), and bilateral parietal hypo-metabolism on fluorodeoxyglucose-Positron Emission Tomography (FDG-PET). To our knowledge, this is the first case of a severe neuropsychiatric syndrome attributed to lamotrigine at the Food and Drug administration (FDA) recommended dose and not associated with epileptic activity.
Language	English
Publishing date	2021-04-20
Publishing country	United States
Document type	Journal Article
ISSN	2573-4407
ISSN (online)	2573-4407
DOI	10.21926/obm.neurobiol.2102091
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Article ; Online: Pharmacological adjuncts and transcranial magnetic stimulation-induced synaptic plasticity: a systematic review.

Sohn, Myren N / Brown, Joshua C / Sharma, Prayushi / Ziemann, Ulf / McGirr, Alexander

Journal of psychiatry & neuroscience : JPN

2024 Volume 49, Issue 1, Page(s) E59–E76

Abstract: Background: Transcranial magnetic stimulation (TMS) is a noninvasive neurostimulation modality that has been used to study human synaptic plasticity. Leveraging work in ex vivo preparations, mechanistically informed pharmacological adjuncts to TMS have ... ...

Abstract	Background: Transcranial magnetic stimulation (TMS) is a noninvasive neurostimulation modality that has been used to study human synaptic plasticity. Leveraging work in ex vivo preparations, mechanistically informed pharmacological adjuncts to TMS have been used to improve our fundamental understanding of TMS-induced synaptic plasticity. Methods: We systematically reviewed the literature pairing pharmacological adjuncts with TMS plasticity-induction protocols in humans. We searched MEDLINE, PsycINFO, and Embase from 2013 to Mar. 10, 2023. Studies published before 2013 were extracted from a previous systematic review. We included studies using repetitive TMS, theta-burst stimulation, paired associative stimulation, and quadripulse stimulation paradigms in healthy and clinical populations. Results: Thirty-six studies met our inclusion criteria (28 in healthy and 8 in clinical populations). Most pharmacological agents have targeted the glutamatergic Limitations: This review is limited by the predominance in the literature of studies with small sample sizes and crossover designs. Conclusion: Pharmacologically enhanced TMS largely parallels findings from ex vivo preparations. As this area expands and novel targets are tested, adequately powered samples in healthy and clinical populations will inform the mechanisms of TMS-induced plasticity in health and disease.
MeSH term(s)	Humans ; Transcranial Magnetic Stimulation/methods ; Neuronal Plasticity/physiology ; Motor Cortex ; Dopamine ; Calcium ; Evoked Potentials, Motor/physiology
Chemical Substances	Dopamine (VTD58H1Z2X) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2024-02-15
Publishing country	Canada
Document type	Systematic Review ; Journal Article
ZDB-ID	1077443-9
ISSN	1488-2434 ; 1180-4882
ISSN (online)	1488-2434
ISSN	1180-4882
DOI	10.1503/jpn.230090
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Article ; Online: An Evaluation of the Emerging Techniques in Sports-Related Concussion.

Brown, Joshua C / Goldszer, Isaac M / Brooks, Madison C / Milano, Nicholas J

Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society

2023 Volume 40, Issue 5, Page(s) 384–390

Abstract: Summary: Sports-related concussion is now in public awareness more than ever before. Investigations into underlying pathophysiology and methods of assessment have correspondingly increased at an exponential rate. In this review, we aim to highlight some ...

Abstract	Summary: Sports-related concussion is now in public awareness more than ever before. Investigations into underlying pathophysiology and methods of assessment have correspondingly increased at an exponential rate. In this review, we aim to highlight some of the evidence supporting emerging techniques in the fields of neurophysiology, neuroimaging, vestibular, oculomotor, autonomics, head sensor, and accelerometer technology in the setting of the current standard: clinical diagnosis and management. In summary, the evidence we reviewed suggests that (1) head impact sensors and accelerometers may detect possible concussions that would not otherwise receive evaluation; (2) clinical diagnosis may be aided by sideline vestibular, oculomotor, and portable EEG techniques; (3) clinical decisions on return-to-play eligibility are currently not sensitive at capturing the neurometabolic, cerebrovascular, neurophysiologic, and microstructural changes that biomarkers have consistently detected days and weeks after clinical clearance. Such biomarkers include heart rate variability, quantitative electroencephalography, as well as functional, metabolic, and microstructural neuroimaging. The current challenge is overcoming the lack of consistency and replicability of any one particular technique to reach consensus.
MeSH term(s)	Humans ; Athletic Injuries/diagnosis ; Brain Concussion/diagnosis ; Neuroimaging ; Electroencephalography
Language	English
Publishing date	2023-03-16
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	605640-4
ISSN	1537-1603 ; 0736-0258
ISSN (online)	1537-1603
ISSN	0736-0258
DOI	10.1097/WNP.0000000000000879
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Article: Synapses, predictions, and prediction errors: A neocortical computational study of MDD using the temporal memory algorithm of HTM.

Sherif, Mohamed A / Khalil, Mostafa Z / Shukla, Rammohan / Brown, Joshua C / Carpenter, Linda L

Frontiers in psychiatry

2023 Volume 14, Page(s) 976921

Abstract: Introduction: Synapses and spines play a significant role in major depressive disorder (MDD) pathophysiology, recently highlighted by the rapid antidepressant effect of ketamine and psilocybin. According to the Bayesian brain and interoception ... ...

Abstract	Introduction: Synapses and spines play a significant role in major depressive disorder (MDD) pathophysiology, recently highlighted by the rapid antidepressant effect of ketamine and psilocybin. According to the Bayesian brain and interoception perspectives, MDD is formalized as being stuck in affective states constantly predicting negative energy balance. To understand how spines and synapses relate to the predictive function of the neocortex and thus to symptoms, we used the temporal memory (TM), an unsupervised machine-learning algorithm. TM models a single neocortical layer, learns in real-time, and extracts and predicts temporal sequences. TM exhibits neocortical biological features such as sparse firing and continuous online learning using local Hebbian-learning rules. Methods: We trained a TM model on random sequences of upper-case alphabetical letters, representing sequences of affective states. To model depression, we progressively destroyed synapses in the TM model and examined how that affected the predictive capacity of the network. We found that the number of predictions decreased non-linearly. Results: Destroying 50% of the synapses slightly reduced the number of predictions, followed by a marked drop with further destruction. However, reducing the synapses by 25% distinctly dropped the confidence in the predictions. Therefore, even though the network was making accurate predictions, the network was no longer confident about these predictions. Discussion: These findings explain how interoceptive cortices could be stuck in limited affective states with high prediction error. Connecting ketamine and psilocybin's proposed mechanism of action to depression pathophysiology, the growth of new synapses would allow representing more futuristic predictions with higher confidence. To our knowledge, this is the first study to use the TM model to connect changes happening at synaptic levels to the Bayesian formulation of psychiatric symptomatology. Linking neurobiological abnormalities to symptoms will allow us to understand the mechanisms of treatments and possibly, develop new ones.
Language	English
Publishing date	2023-02-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564218-2
ISSN	1664-0640
ISSN	1664-0640
DOI	10.3389/fpsyt.2023.976921
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Article: Chronic caffeine consumption curbs rTMS-induced plasticity.

Vigne, Megan / Kweon, Jamie / Sharma, Prayushi / Greenberg, Benjamin D / Carpenter, Linda L / Brown, Joshua C

Frontiers in psychiatry

2023 Volume 14, Page(s) 1137681

Abstract: Background: Caffeine is a widely used psychostimulant. In the brain, caffeine acts as a competitive, non-selective adenosine receptor antagonist of A1 and A2A, both known to modulate long-term potentiation (LTP), the cellular basis of learning and ... ...

Abstract	Background: Caffeine is a widely used psychostimulant. In the brain, caffeine acts as a competitive, non-selective adenosine receptor antagonist of A1 and A2A, both known to modulate long-term potentiation (LTP), the cellular basis of learning and memory. Repetitive transcranial magnetic stimulation (rTMS) is theorized to work through LTP induction and can modulate cortical excitability as measured by motor evoked potentials (MEPs). The acute effects of single caffeine doses diminish rTMS-induced corticomotor plasticity. However, plasticity in chronic daily caffeine users has not been examined. Method: We conducted a Results: In this hypothesis-generating pilot study, we observed enhanced MEP facilitation in non-caffeine users compared to caffeine users and placebo. Conclusion: These preliminary data highlight a need to directly test the effects of caffeine in prospective well-powered studies, because in theory, they suggest that chronic caffeine use could limit learning or plasticity, including rTMS effectiveness.
Language	English
Publishing date	2023-02-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564218-2
ISSN	1664-0640
ISSN	1664-0640
DOI	10.3389/fpsyt.2023.1137681
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