Cortical processing depends on finely tuned excitatory and inhibitory connections in neuronal microcircuits. Reduced inhibition by somatostatin-expressing interneurons is a key component of altered associated with treatment-resistant major depressive disorder (depression), which implicated cognitive deficits rumination, but the link remains to be better established mechanistically humans. Here we test effect reduced somatostatin interneuron-mediated cortical human microcircuits using...

Reduced cortical inhibition by somatostatin-expressing (SST) interneurons has been strongly associated with treatment-resistant depression. However, due to technical limitations it is impossible establish experimentally in humans whether the effects of reduced SST interneuron on microcircuit activity have signatures detectable clinically-relevant brain signals such as electroencephalography (EEG). To overcome these limitations, we simulated resting-state and EEG using detailed models human...

Transcranial magnetic stimulation (TMS) is an emerging alternative to existing treatments for major depressive disorder (MDD). The effects of TMS on both brain physiology and therapeutic outcomes are known be highly variable from subject subject, however. Proposed reasons this variability include individual differences in neurophysiology, cortical geometry, connectivity. Standard approaches target site definition tend focus coordinates or landmarks within the regions implicated MDD, such as...

Abstract Reduced inhibition by somatostatin-expressing interneurons is associated with depression. Administration of positive allosteric modulators α5 subunit-containing GABA A receptor (α5-PAM) that selectively target this lost exhibit antidepressant and pro-cognitive effects in rodent models chronic stress. However, the functional α5-PAM on human brain vivo are unknown, currently cannot be assessed experimentally. We modeled tonic as measured neurons, tested silico detailed cortical...

Non-invasive brain stimulation (NIBS) is emerging as a robust treatment alternative for major depressive disorder, with potential achieving higher remission rates by providing targeted to underlying networks, such the salience network (SN). Growing evidence suggests that these therapeutic effects are dependent on frequency and phase synchrony between SN oscillations well task-specific state of during stimulation. However, development phase-synchronized non-invasive has proved challenging...

Abstract Reduced cortical inhibition mediated by gamma-aminobutyric acid (GABA) is reported in depression, anxiety disorders, and aging. Novel positive allosteric modulator that specifically target α5-GABA A receptor subunit (α5-PAM), ligand GL-II-73, shows anxiolytic, antidepressant, pro-cognitive effects without the common side associated with non-specific modulation benzodiazepines such as diazepam (DZP), thus suggesting novel therapeutic potential. However, it unknown if α5-PAM has...

<title>Abstract</title> <bold>Objective: </bold>It is increasingly being recognized that depression clinically heterogeneous in terms of clinical presentation and neuroimaging. Repetitive transcranial magnetic stimulation (rTMS) a neuroanatomically focal treatment for may be used to probe this heterogeneity. Here, we examine the predictors correlates response rTMS targeting dorsolateral prefrontal cortex (DLPFC), dorsomedial (DMPFC), or orbitofrontal (OFC). It expected each target will...

Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depressive disorder (MDD); however, this currently lacks reliable biomarkers of response. TMS-evoked potentials (TEPs), measured using TMS-electroencephalography (TMS-EEG), have been suggested as potential biomarker candidates, with the N100 peak being one most promising. This study investigated association between baseline amplitude 1 Hz right dorsolateral prefrontal cortex (R-DLPFC) accelerated...

Abstract Reduced cortical inhibition by parvalbumin-expressing (PV) interneurons has been associated with impaired processing in the prefrontal cortex (PFC) and altered EEG signals such as oddball mismatch negativity (MMN) schizophrenia. However, establishing link between reduced PV interneuron MMN experimentally humans is currently not possible. To overcome these challenges, we used detailed computational models of human PFC microcircuits, modeled schizophrenia microcircuits integrating...

Abstract Cortical processing depends on finely-tuned excitatory and inhibitory connections in neuronal microcircuits. Reduced inhibition by somatostatin-expressing interneurons is a key component of altered associated with treatment-resistant major depressive disorder (depression), which implicated cognitive deficits rumination, but the link remains to be better established mechanistically humans. Here, we tested impact reduced somatostatin interneuron mediated cortical human microcircuits...

Abstract Reduced cortical inhibition by somatostatin-expressing (SST) interneurons has been strongly associated with treatment-resistant depression. However, whether the effects of reduced SST interneuron on microcircuit activity have signatures detectible in electroencephalography (EEG) signals remains unknown. We simulated resting-state and EEG using detailed models human microcircuits normal (healthy) or (depression). Healthy showed emergent key features EEG, depression exhibited...

Abstract Treatment for major depressive disorder (depression) often has partial efficacy and a large portion of patients are treatment resistant. Recent studies implicate reduced somatostatin (SST) interneuron inhibition in depression, new pharmacology boosting this via positive allosteric modulators α5-GABA A receptors (α5-PAM) offers promising effective treatment. However, testing the effect α5-PAM on human brain activity is limited, meriting use detailed simulations. We utilized our...

Abstract Major depressive disorder (depression) is associated with altered dendritic structure and function in excitatory cortical pyramidal neurons, due to decreased inhibition from somatostatin interneurons loss of spines synapses, as indicated postmortem human studies. Dendrites play an important role signal processing they receive the majority synaptic inputs exhibit nonlinear properties including backpropagating action potentials Na + spikes that enhance computational power neuron....

Reduced cortical inhibition mediated by GABA (gamma-aminobutyric acid) is reported in depression, anxiety disorders, and aging. A novel positive allosteric modulator that specifically targets the α5-GABAA receptor subunit (α5-PAM), ligand GL-II-73 shows anxiolytic, antidepressant, procognitive effects without common side associated with nonspecific modulation benzodiazepines such as diazepam, thus suggesting therapeutic potential. However, it unknown whether α5-PAM has detectable signatures...

Treatment for major depressive disorder (depression) often has partial efficacy and a large portion of patients are treatment resistant. Recent studies implicate reduced somatostatin (SST) interneuron inhibition in depression, new pharmacology boosting this via positive allosteric modulators α5-GABA A receptors (α5-PAM) offers promising effective treatment. However, testing the effect α5-PAM on human brain activity is limited, meriting use detailed simulations. We utilized our previous...

Abstract Reduced inhibition by somatostatin-expressing interneurons is associated with depression. Administration of positive allosteric modulators α5 subunit-containing GABA A receptor (α5-PAM) that selectively target this lost exhibit antidepressant and pro-cognitive effects in rodent models chronic stress. However, the functional α5-PAM on human brain vivo are unknown, currently cannot be assessed experimentally. We modeled tonic as measured neurons, tested silico detailed cortical...

Abstract Transcranial magnetic stimulation (TMS) is an emerging alternative to existing treatments for major depressive disorder (MDD). The effects of TMS on both brain physiology and therapeutic outcomes are known be highly variable from subject subject, however. Proposed reasons this variability include individual differences in neurophysiology, cortical geometry, connectivity. Standard approaches target site definition tend focus coordinates or landmarks within the regions implicated MDD,...

The objective was to determine if the installation of “healthy eating information” in a University dining hall would influence students’ food and beverage choices. This pre‐post, population nutrition intervention conducted buffet‐style cafeteria between September 2014 April 2015. encouraged students “fill half their plate with fruits vegetables” illustrated number minutes jogging it takes burn calories each option. choices, as well visits vegetable fruit bar, were recorded on twelve...

To compare the bioavailability of four temazepam 7.5-mg capsules (Restoril, Sandoz Pharmaceuticals) with that a single 30-mg capsule.Single-dose, open-label, two-period, crossover (replicated Latin square).Domiciled environment for clinical testing.Twenty-six healthy male volunteers aged 18-40 years; 25 completed study.Subjects randomly received either or one capsule. Blood samples were drawn at various time points after each period (0-48 h), and analyzed plasma concentration temazepam. The...

Transcranial magnetic stimulation (TMS) is an emerging alternative to existing treatments for major depressive disorder (MDD). The effects of TMS on both brain physiology and therapeutic outcomes are known be highly variable from subject subject, however. Proposed reasons this variability include individual differences in neurophysiology, cortical geometry, connectivity. Standard approaches target site definition tend focus coordinates or landmarks within the regions implicated MDD, such as...