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The Lancet. Psychiatry Apr 2023The left dorsolateral prefrontal cortex is a prime target for repetitive transcranial magnetic stimulation (TMS) to treat neuropsychiatric disorders; thus, abundant... (Meta-Analysis)
Meta-Analysis
Effects of repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex on symptom domains in neuropsychiatric disorders: a systematic review and cross-diagnostic meta-analysis.
BACKGROUND
The left dorsolateral prefrontal cortex is a prime target for repetitive transcranial magnetic stimulation (TMS) to treat neuropsychiatric disorders; thus, abundant efficacy data from controlled trials are available. A cross-diagnostic meta-analysis was conducted to identify the symptom domains susceptible to repetitive TMS to the left dorsolateral prefrontal cortex.
METHODS
This systematic review and meta-analysis investigated the effects of repetitive TMS to the left dorsolateral prefrontal cortex on neuropsychiatric symptoms presenting across diagnoses. We searched PubMed, MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform for randomised and sham controlled trials published from inception to Aug 17, 2022. Included studies assessed symptoms using clinical measures and reported sufficient data to calculate effect sizes pooled with a random effects model. Two independent reviewers conducted screening and used the Cochrane risk-of-bias tool for quality assessment. Summary data were extracted from published reports. The main outcome was the therapeutic effects of repetitive TMS of the left dorsolateral prefrontal cortex on distinct symptom domains. This study is registered with PROSPERO (CRD42021278458).
FINDINGS
Of 9056 studies identified (6704 from databases and 2352 from registers), 174 were included in the analysis including 7905 patients. 163 of 174 studies reported gender data; 3908 (52·35%) of 7465 patients were male individuals, and 3557 (47·65%) were female individuals. Mean age was 44·63 years (range 19·79-72·80). Ethnicity data were mostly not available. Effect size was large for craving (Hedges'g -0·803 [95% CI -1·099 to -0·507], p<0·0001; I=82·40%), medium for depressive symptoms (-0·725 [-0·889 to -0·561], p<0·0001; I=85·66%), small for anxiety, obsessions or compulsions, pain, global cognition, declarative memory, working memory, cognitive control, and motor coordination (Hedges'g -0·198 to -0·491), and non-significant for attention, suicidal ideation, language, walking ability, fatigue, and sleep.
INTERPRETATION
The cross-diagnostic meta-analysis shows the efficacy of repetitive TMS of the left dorsolateral prefrontal cortex on distinct symptom domains, providing a novel framework for assessing target or efficacy interactions of repetitive TMS, and informing personalised applications for conditions for which regular trials are uninformative.
FUNDING
The University Grants Committee of Hong Kong and the Mental Health Research Center, The Hong Kong Polytechnic University.
Topics: Humans; Male; Female; Young Adult; Adult; Middle Aged; Aged; Transcranial Magnetic Stimulation; Dorsolateral Prefrontal Cortex; Pain; Anxiety Disorders; Cognition
PubMed: 36898403
DOI: 10.1016/S2215-0366(23)00026-3 -
Handbook of Clinical Neurology 2019The frontal lobes contain a complex set of diverse anatomic regions that form multiple distinct, complex networks with cortical and subcortical regions. Damage to these... (Review)
Review
The frontal lobes contain a complex set of diverse anatomic regions that form multiple distinct, complex networks with cortical and subcortical regions. Damage to these cortical-subcortical networks can have dramatic behavioral consequences, ranging from apathy to impairments in executive functioning. This chapter provides a brief overview of the common syndromes caused by damage to the mediodorsal and dorsolateral prefrontal circuits, followed by a more detailed review of the syndrome-sometimes referred to as pseudopsychopathy or acquired sociopathy-associated with damage to the ventromedial prefrontal circuit.
Topics: Agnosia; Apathy; Emotions; Executive Function; Frontal Lobe; Frontotemporal Dementia; Humans; Motivation; Nerve Net; Neuropsychological Tests
PubMed: 31590727
DOI: 10.1016/B978-0-12-804281-6.00008-2 -
Progress in Brain Research 2022This chapter summarizes early electrophysiological and lesion studies to elucidate cortical, subcortical and cerebellar mechanisms for extracting visual target motion...
This chapter summarizes early electrophysiological and lesion studies to elucidate cortical, subcortical and cerebellar mechanisms for extracting visual target motion and programming a smooth-pursuit response. The importance of a descending pursuit pathway from the middle temporal (MT) cortical visual area, which extracts the speed and direction of a moving target, the projections to dorsolateral pontine nuclei, and onto the cerebellum are outlined. Contributions of the cerebellum to pursuit are discussed and models are presented to account for the ways in which floccular gaze Purkinje cells behave during smooth pursuit, combined eye-head tracking, and during head rotation while viewing a stationary target.
Topics: Cerebellum; Humans; Neurophysiology; Purkinje Cells; Pursuit, Smooth; Reflex, Vestibulo-Ocular
PubMed: 35074066
DOI: 10.1016/bs.pbr.2021.10.021 -
Biological Psychiatry Jun 2021Takeda G protein-coupled receptor 5 (TGR5) is recognized as a promising target for type 2 diabetes and metabolic syndrome; its expression has been demonstrated in the...
BACKGROUND
Takeda G protein-coupled receptor 5 (TGR5) is recognized as a promising target for type 2 diabetes and metabolic syndrome; its expression has been demonstrated in the brain and is thought to be neuroprotective. Here, we hypothesize that dysfunction of central TGR5 may contribute to the pathogenesis of depression.
METHODS
In well-established chronic social defeat stress (CSDS) and chronic restraint stress (CRS) models of depression, we investigated the functional roles of TGR5 in CA3 pyramidal neurons (PyNs) and underlying mechanisms of the neuronal circuit in depression (for in vivo studies, n = 10; for in vitro studies, n = 5-10) using fiber photometry; optogenetic, chemogenetic, pharmacological, and molecular profiling techniques; and behavioral tests.
RESULTS
Both CSDS and CRS most significantly reduced TGR5 expression of hippocampal CA3 PyNs. Genetic overexpression of TGR5 in CA3 PyNs or intra-CA3 infusion of INT-777, a specific agonist, protected against CSDS and CRS, exerting significant antidepressant-like effects that were mediated via CA3 PyN activation. Conversely, genetic knockout or TGR5 knockdown in CA3 facilitated stress-induced depression-like behaviors. Re-expression of TGR5 in CA3 PyNs rather than infusion of INT-777 significantly improved depression-like behaviors in Tgr5 knockout mice exposed to CSDS or CRS. Silencing and stimulation of CA3 PyNs→somatostatin-GABAergic (gamma-aminobutyric acidergic) neurons of the dorsolateral septum circuit bidirectionally regulated depression-like behaviors, and blockade of this circuit abrogated the antidepressant-like effects from TGR5 activation of CA3 PyNs.
CONCLUSIONS
These findings indicate that TGR5 can regulate depression via CA3 PyNs→somatostatin-GABAergic neurons of dorsolateral septum transmission, suggesting that TGR5 could be a novel target for developing antidepressants.
Topics: Animals; CA3 Region, Hippocampal; Depression; Mice; Pyramidal Cells; Receptors, G-Protein-Coupled
PubMed: 33536132
DOI: 10.1016/j.biopsych.2020.11.018 -
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 -
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 -
Handbook of Clinical Neurology 2017Spinal subarachnoid hemorrhage (SAH) is a rare disease. Spinal aneurysms are even rarer and mostly undetected unless they rupture and become symptomatic. In this chapter... (Review)
Review
Spinal subarachnoid hemorrhage (SAH) is a rare disease. Spinal aneurysms are even rarer and mostly undetected unless they rupture and become symptomatic. In this chapter we aim to review the available literature about spinal subarachnoid hematoma with special emphasis on spinal aneurysms. As most reports of spinal aneurysms describe a single case or a small case series, the diagnostic algorithm is often lacking. The outcome is also different based on the etiologies; therefore management strategy must be individualized. We addressed these issues in this chapter. The reported incidence of spinal SAH is less than epidural hematoma and more than subdural hematoma. Spinal aneurysms can present as isolated entity or can be associated with other vascular anomalies. Microsurgical clipping and/or resection is possible, especially when they are located dorsally or dorsolaterally. Endovascular approach is also a feasible option unless negotiation of microcatheter becomes difficult in tortuous small-caliber arteries. Successful obliteration leads to good outcome, especially when present in posterior spinal artery. A detailed knowledge of spinal SAH and spinal aneurysms is important to detect them in time. Clinicians must consider several factors to choose an appropriate treatment strategy to ensure the safety of their patients.
Topics: Aneurysm; Humans; Spinal Cord; Spinal Cord Vascular Diseases; Subarachnoid Hemorrhage; Treatment Outcome; Vertebral Artery
PubMed: 28552143
DOI: 10.1016/B978-0-444-63640-9.00020-5 -
Proceedings of the National Academy of... May 2022Neurulation is the process in early vertebrate embryonic development during which the neural plate folds to form the neural tube. Spinal neural tube folding in the...
Neurulation is the process in early vertebrate embryonic development during which the neural plate folds to form the neural tube. Spinal neural tube folding in the posterior neuropore changes over time, first showing a median hinge point, then both the median hinge point and dorsolateral hinge points, followed by dorsolateral hinge points only. The biomechanical mechanism of hinge point formation in the mammalian neural tube is poorly understood. Here we employ a mechanical finite element model to study neural tube formation. The computational model mimics the mammalian neural tube using microscopy data from mouse and human embryos. While intrinsic curvature at the neural plate midline has been hypothesized to drive neural tube folding, intrinsic curvature was not sufficient for tube closure in our simulations. We achieved neural tube closure with an alternative model combining mesoderm expansion, nonneural ectoderm expansion, and neural plate adhesion to the notochord. Dorsolateral hinge points emerged in simulations with low mesoderm expansion and zippering. We propose that zippering provides the biomechanical force for dorsolateral hinge point formation in settings where the neural plate lateral sides extend above the mesoderm. Together, these results provide a perspective on the biomechanical and molecular mechanism of mammalian spinal neurulation.
Topics: Animals; Ectoderm; Humans; Mice; Neural Plate; Neural Tube; Neurulation; Notochord
PubMed: 35561223
DOI: 10.1073/pnas.2117075119 -
The Journal of the American Academy of... Oct 2018Bunionette deformity, historically known as tailor's bunion, is a forefoot protuberance laterally, dorsolaterally, or plantarlaterally along the fifth metatarsal head.... (Review)
Review
Bunionette deformity, historically known as tailor's bunion, is a forefoot protuberance laterally, dorsolaterally, or plantarlaterally along the fifth metatarsal head. Although bunionette deformity has been compared to hallux valgus deformity, it is likely due to a multifactorial, anatomic interplay between fifth metatarsal bony morphology and forefoot soft-tissue imbalance. Friction generated between the bony prominence, soft tissue, and associated constrictive footwear can result in keratosis, inflammation, pain, and ulceration. Symptomatic bunionettes are usually responsive to nonsurgical management. Surgical options are available based on the underlying bony deformity when nonsurgical treatment fails.
Topics: Bunion, Tailor's; Forefoot, Human; Humans; Osteotomy; Postoperative Complications; Risk Factors
PubMed: 30130354
DOI: 10.5435/JAAOS-D-17-00345