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Neurobiology of Aging Feb 2020Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI)... (Meta-Analysis)
Meta-Analysis
Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Currently, however, the effectiveness of this therapy is unclear because of the low statistical power and heterogeneity of previous trials. The purpose of the meta-analysis was to systematically characterize the effectiveness of various combinations of rTMS parameters on different cognitive domains in patients with MCI and AD. Thirteen studies comprising 293 patients with MCI or AD were included in this analysis. Random-effects analysis revealed an overall medium-to-large effect size (0.77) favoring active rTMS over sham rTMS in the improvement of cognitive functions. Subgroup analyses revealed that (1) high-frequency rTMS over the left dorsolateral prefrontal cortex and low-frequency rTMS at the right dorsolateral prefrontal cortex significantly improved memory functions; (2) high-frequency rTMS targeting the right inferior frontal gyrus significantly enhanced executive performance; and (3) the effects of 5-30 consecutive rTMS sessions could last for 4-12 weeks. Potential mechanisms of rTMS effects on cognitive functions are discussed.
Topics: Alzheimer Disease; Cognition; Cognitive Dysfunction; Humans; Memory; Prefrontal Cortex; Transcranial Magnetic Stimulation
PubMed: 31783330
DOI: 10.1016/j.neurobiolaging.2019.08.020 -
JAMA Psychiatry Mar 2021This study assesses whether treatment response for depression could be improved via a single one-site-fits-all dorsolateral prefrontal cortex target, representing the... (Clinical Trial)
Clinical Trial
This study assesses whether treatment response for depression could be improved via a single one-site-fits-all dorsolateral prefrontal cortex target, representing the group average optimal site of subgenual cingulate cortex functional connectivity, or whether target site personalization is necessary.
Topics: Adult; Brain Mapping; Depressive Disorder, Major; Dorsolateral Prefrontal Cortex; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Outcome and Process Assessment, Health Care; Transcranial Magnetic Stimulation
PubMed: 33237320
DOI: 10.1001/jamapsychiatry.2020.3794 -
Brain Stimulation 2020Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an effective treatment for major depressive disorder (MDD), but... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an effective treatment for major depressive disorder (MDD), but response rates are low and effect sizes small. Synchronizing TMS pulses with instantaneous brain oscillations can reduce variability and increase efficacy of TMS-induced plasticity.
OBJECTIVE
To study whether brain oscillation-synchronized rTMS is feasible, safe and has neuromodulatory effects when targeting the DLPFC of patients with MDD.
METHODS
Using real-time EEG-triggered TMS we conducted a pseudo-randomized controlled single-session crossover trial of brain oscillation-synchronized rTMS of left DLPFC in 17 adult patients with antidepressant-resistant MDD. Stimulation conditions in separate sessions were: (1) rTMS triggered at the negative EEG peak of instantaneous alpha oscillations (alpha-synchronized rTMS), (2) a variation of intermittent theta-burst stimulation (modified iTBS), and (3) a random alpha phase control condition.
RESULTS
Triggering TMS at the negative peak of instantaneous alpha oscillations by real-time analysis of the electrode F5 EEG signal was successful in 15 subjects. Two subjects reported mild transient discomfort at the site of stimulation during stimulation; no serious adverse events were reported. Alpha-synchronized rTMS, but not modified iTBS or the random alpha phase control condition, reduced resting-state alpha activity in left DLPFC and increased TMS-induced beta oscillations over frontocentral channels.
CONCLUSIONS
Alpha-synchronized rTMS of left DLPFC is feasible, safe and has specific single-session neuromodulatory effects in patients with antidepressant-resistant MDD. Future studies need to further elucidate the mechanisms, optimize the parameters and investigate the therapeutic potential and efficacy of brain oscillation-synchronized rTMS in MDD.
Topics: Adolescent; Adult; Alpha Rhythm; Depressive Disorder, Major; Electroencephalography; Female; Humans; Male; Prefrontal Cortex; Transcranial Magnetic Stimulation
PubMed: 31631058
DOI: 10.1016/j.brs.2019.10.007 -
Trends in Cognitive Sciences Jun 2020Motivation plays a central role in human behavior and cognition but is not well captured by widely used artificial intelligence (AI) and computational modeling... (Review)
Review
Motivation plays a central role in human behavior and cognition but is not well captured by widely used artificial intelligence (AI) and computational modeling frameworks. This Opinion article addresses two central questions regarding the nature of motivation: what are the nature and dynamics of the internal goals that drive our motivational system and how can this system be sufficiently flexible to support our ability to rapidly adapt to novel situations, tasks, etc.? In reviewing existing systems and neuroscience research and theorizing on these questions, a wealth of insights to constrain the development of computational models of motivation can be found.
Topics: Artificial Intelligence; Cognition; Humans; Motivation; Prefrontal Cortex
PubMed: 32392468
DOI: 10.1016/j.tics.2020.03.001 -
ELife Jun 2023Opioids depress breathing by inhibition of interconnected respiratory nuclei in the pons and medulla. Mu opioid receptor (MOR) agonists directly hyperpolarize a...
Opioids depress breathing by inhibition of interconnected respiratory nuclei in the pons and medulla. Mu opioid receptor (MOR) agonists directly hyperpolarize a population of neurons in the dorsolateral pons, particularly the Kölliker-Fuse (KF) nucleus, that are key mediators of opioid-induced respiratory depression. However, the projection target and synaptic connections of MOR-expressing KF neurons are unknown. Here, we used retrograde labeling and brain slice electrophysiology to determine that MOR-expressing KF neurons project to respiratory nuclei in the ventrolateral medulla, including the preBötzinger complex (preBötC) and rostral ventral respiratory group (rVRG). These medullary-projecting, MOR-expressing dorsolateral pontine neurons express FoxP2 and are distinct from calcitonin gene-related peptide-expressing lateral parabrachial neurons. Furthermore, dorsolateral pontine neurons release glutamate onto excitatory preBötC and rVRG neurons via monosynaptic projections, which is inhibited by presynaptic opioid receptors. Surprisingly, the majority of excitatory preBötC and rVRG neurons receiving MOR-sensitive glutamatergic synaptic input from the dorsolateral pons are themselves hyperpolarized by opioids, suggesting a selective opioid-sensitive circuit from the KF to the ventrolateral medulla. Opioids inhibit this excitatory pontomedullary respiratory circuit by three distinct mechanisms-somatodendritic MORs on dorsolateral pontine and ventrolateral medullary neurons and presynaptic MORs on dorsolateral pontine neuron terminals in the ventrolateral medulla-all of which could contribute to opioid-induced respiratory depression.
Topics: Analgesics, Opioid; Medulla Oblongata; Neurons; Pons; Respiration
PubMed: 37314062
DOI: 10.7554/eLife.81119 -
Cell Reports Nov 2023The dorsal striatum is organized into functional territories defined by corticostriatal inputs onto both direct and indirect spiny projection neurons (SPNs), the major...
The dorsal striatum is organized into functional territories defined by corticostriatal inputs onto both direct and indirect spiny projection neurons (SPNs), the major cell types within the striatum. In addition to circuit connectivity, striatal domains are likely defined by the spatially determined transcriptomes of SPNs themselves. To identify cell-type-specific spatiomolecular signatures of direct and indirect SPNs within dorsomedial, dorsolateral, and ventrolateral dorsal striatum, we used RNA profiling in situ hybridization with probes to >98% of protein coding genes. We demonstrate that the molecular identity of SPNs is mediated by hundreds of differentially expressed genes across territories of the striatum, revealing extraordinary heterogeneity in the expression of genes that mediate synaptic function in both direct and indirect SPNs. This deep insight into the complex spatiomolecular organization of the striatum provides a foundation for understanding both normal striatal function and for dissecting region-specific dysfunction in disorders of the striatum.
Topics: Mice; Animals; Mice, Transgenic; Corpus Striatum; Interneurons; Neostriatum; Neurites
PubMed: 37952158
DOI: 10.1016/j.celrep.2023.113435 -
ELife Nov 2021Theoretical accounts distinguish between motivational ('wanting') and hedonic ('liking') dimensions of rewards. Previous animal and human research linked wanting and... (Randomized Controlled Trial)
Randomized Controlled Trial
Theoretical accounts distinguish between motivational ('wanting') and hedonic ('liking') dimensions of rewards. Previous animal and human research linked wanting and liking to anatomically and neurochemically distinct brain mechanisms, but it remains unknown how the different brain regions and neurotransmitter systems interact in processing distinct reward dimensions. Here, we assessed how pharmacological manipulations of opioid and dopamine receptor activation modulate the neural processing of wanting and liking in humans in a randomized, placebo-controlled, double-blind clinical trial. Reducing opioid receptor activation with naltrexone selectively reduced wanting of rewards, which on a neural level was reflected by stronger coupling between dorsolateral prefrontal cortex and the striatum under naltrexone compared with placebo. In contrast, reducing dopaminergic neurotransmission with amisulpride revealed no robust effects on behavior or neural activity. Our findings thus provide insights into how opioid receptors mediate neural connectivity related to specifically motivational, not hedonic, aspects of rewards.
Topics: Adult; Amisulpride; Corpus Striatum; Dopamine Antagonists; Dorsolateral Prefrontal Cortex; Double-Blind Method; Female; Healthy Volunteers; Humans; Magnetic Resonance Imaging; Male; Motivation; Naltrexone; Narcotic Antagonists; Reward
PubMed: 34761749
DOI: 10.7554/eLife.71077