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Author: Zafiris J Daskalakis (241)



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Dec
1969

Electroconvulsive therapy is effective in treatment-resistant schizophrenia (TRS) but use is limited due to stigma and concerns around cognitive adverse effects. Magnetic seizure therapy (MST) is a promising new neuromodulation technique that uses transcranial magnetic stimulation to induce therapeutic seizures. Studies of MST in depression have shown clinical improvement with a favorable adverse effect profile.

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Jan
2018

Magnetic seizure therapy (MST) is a novel brain stimulation technique that uses a high-powered transcranial magnetic stimulation device to produce therapeutic seizures. Preliminary MST studies have found antidepressant effects in the absence of cognitive side effects but its efficacy compared to electroconvulsive therapy (ECT) remains unclear. The aim of this study was to investigate the therapeutic efficacy and cognitive profile of MST compared to standard right unilateral ECT treatment.

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Dec
2017

Based on the success of deep brain stimulation (DBS) for treating movement disorders, there is growing interest in using DBS to treat schizophrenia (SZ). We review the unmet needs of patients with SZ and the scientific rationale behind the DBS targets proposed in the literature in order to guide future development of DBS to treat this vulnerable patient population. SZ remains a devastating disorder despite treatment.

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Dec
2017

GABAergic and glutamatergic dysfunction in the dorsolateral prefrontal cortex (DLPFC) are thought to be the core pathophysiological mechanisms of schizophrenia. Recently, we have established a method to index these functions from the DLPFC using the paired transcranial magnetic stimulation (TMS) paradigms of short interval intracortical inhibition (SICI) and facilitation (ICF) combined with electroencephalography (EEG). In this study, we aimed to evaluate neurophysiological indicators related to GABAand glutamate receptor-mediated functions respectively from the DLPFC in patients with schizophrenia using these paradigms, compared to healthy controls.

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Nov
2017

Modulating the function of the insular cortex could be a novel therapeutic strategy to treat addiction to a variety of drugs of abuse as this region has been implicated in mediating drug reward and addictive processes. The recent advent of the H-coil has permitted the targeting of deeper brain structures which was not previously feasible. The goal of this study was to bilaterally target the insular region using the H-coil with repetitive Transcranial Magnetic Stimulation (rTMS) and subsequently measure changes in dopamine levels using Positron Emission Tomography (PET) with [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO).

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Jan
2018

Conventional rTMS in major depressive disorder (MDD) targets the dorsolateral prefrontal cortex (DLPFC). However, many patients do not respond to DLPFC-rTMS. Recent evidence suggests that the right lateral orbitofrontal cortex (OFC) plays a key role in 'non-reward' functions and shows hyperconnectivity in MDD.

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Jan
2018

Repetitive transcranial magnetic stimulation (rTMS) shows efficacy in the treatment of major depressive episodes (MDEs), but can require ≥4-6 weeks for maximal effect. Recent studies suggest that multiple daily sessions of rTMS can accelerate response without reducing therapeutic efficacy. However, it is unresolved whether therapeutic effects track cumulative number of pulses, or cumulative number of sessions.

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Jan
2018

The impact of comorbid borderline personality disorder (BPD) or post-traumatic stress disorder (PTSD) on clinical and cognitive outcomes of electroconvulsive therapy (ECT) in patients with major depressive episodes (MDE) is unknown.
Compare clinical response and adverse cognitive effects for MDE patients with comorbid BPD or PTSD to MDE only.
In a matched retrospective cohort study of 75 patients treated with ECT at an academic psychiatric hospital with DSM-IV MDE and either comorbid BPD, PTSD or both (MDE + BPD/PTSD), 75 MDE patients without BPD or PTSD (MDE-only) were matched.

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Jan
2018

Predicting rTMS nonresponse could be helpful in sparing patients from futile treatment, and in improving use of limited rTMS resources. While several predictive biomarkers have been proposed, few are accurate for individual-level prediction; none have entered routine use. An alternative approach in pharmacotherapy predicts outcome from early response; patients showing minimal (e.

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Dec
2017

The extent of dorsolateral prefrontal cortex (DLPFC) plasticity in Alzheimer disease (AD) and its association with working memory are not known.
To determine whether participants with AD had impaired DLPFC plasticity compared with healthy control participants, to compare working memory between participants with AD and controls, and to determine whether DLPFC plasticity was associated with working memory.
This cross-sectional study included 32 participants with AD who were 65 years or older and met diagnostic criteria for dementia due to probable AD with a score of at least 17 on the Mini-Mental State Examination and 16 age-matched control participants.

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Dec
1969

There has been a distinct shift in neuroimaging from localization of function into a more network based approach focused on connectivity. While fMRI has proven very fruitful for this, the hemodynamic signal is inherently slow which limits the temporal resolution of fMRI-only connectivity measures. The brain, however, works on a time scale of milliseconds.

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Aug
2017

Subsequent to global initiatives in mapping the human brain and investigations of neurobiological markers for brain disorders, the number of multi-site studies involving the collection and sharing of large volumes of brain data, including electroencephalography (EEG), has been increasing. Among the complexities of conducting multi-site studies and increasing the shelf life of biological data beyond the original study are timely standardization and documentation of relevant study parameters. We present the insights gained and guidelines established within the EEG working group of the Canadian Biomarker Integration Network in Depression (CAN-BIND).

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Dec
2017

This study aims to investigate the clinical effects of benzodiazepines or anticonvulsant use during a course of electroconvulsive therapy (ECT).
A case report study of a patient who received ECT with and without concomitant flurazepam and pregabalin is presented. The literature on the use of benzodiazepines and anticonvulsants during ECT is reviewed.

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Oct
2017

Parcellating brain regions into functionally homogeneous subdivisions is critical for understanding normal and abnormal brain functions.
In this study, we developed a new sparse representation-based parcellation method for functional magnetic resonance imaging (fMRI) data, and applied the new method to investigate functional insular subdivisions in treatment-resistant major depressive disorder (MDD). Realistic simulations were implemented to demonstrate the feasibility of the method.

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Jul
2017

Previous studies have demonstrated that alcohol consumption impairs neuroplasticity in the motor cortex. However, it is unknown whether alcohol produces a similar impairment of neuroplasticity in the dorsolateral prefrontal cortex (DLPFC), a brain region that plays an important role in cognitive functioning. The aim of the current study was to evaluate the effect of alcohol intoxication on neuroplasticity in the DLPFC.

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Dec
1969

Adolescent depression is a prevalent disorder with substantial morbidity and mortality. Current treatment interventions do not target relevant pathophysiology and are frequently ineffective, thereby leading to a substantial burden for individuals, families, and society. During adolescence, the prefrontal cortex undergoes extensive structural and functional changes.

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Oct
2017

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation modality that has been increasingly used for major depressive disorder (MDD) treatment. Although studies in healthy volunteers showed that the technique is well-tolerated, tDCS safety and acceptability have not been sufficiently explored in patients with MDD.
We collected individual patient data from 6 randomized clinical trials that had been previously identified in a systematic review and meta-analysis.

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Dec
1969

The objective of this study was to evaluate the feasibility of using paired-associative stimulation (PAS) to study excitatory and inhibitory plasticity in adolescents while examining variables that may moderate plasticity (such as sex and environment).
We recruited 34 healthy adolescents (aged 13-19, 13 males, 21 females). To evaluate excitatory plasticity, we compared mean motor-evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS) before and after PAS at 0, 15, and 30 min.

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Jan
2018

Cortical inhibition (CI) occurs largely through GABA receptor-mediated inhibitory neurotransmission, which can be modulated by cholinergic, dopaminergic, and glutamatergic inputs. Transcranial magnetic stimulation (TMS) can be used to index CI through a paradigm known as long-interval CI (LICI). When TMS is combined with electroencephalography (EEG), LICI can index GABA receptor-mediated inhibitory neurotransmission in the dorsolateral prefrontal cortex (DLPFC).

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Dec
1969

Combining transcranial magnetic stimulation (TMS) with electroencephalography (EEG) allows for the assessment of various neurophysiological processes in the human cortex. One of these paradigms, short-latency afferent inhibition (SAI), is thought to be a sensitive measure of cholinergic activity. In a previous study, we demonstrated the temporal pattern of this paradigm from both the motor (M1) and dorsolateral prefrontal cortex (DLPFC) using simultaneous TMS-EEG recording.

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Aug
2017

Treatment resistant depression (TRD) remains a clinical challenge, and finding biomarkers that predict treatment response are a long sought goal to precisely indicate treatments. This pilot study aims to characterize brain dysfunction in TRD patients who underwent rTMS to define neuroimaging biomarkers that discriminate non-responders (NR) from responders (R).
20 TRD patients who underwent a course of rTMS to the left DLPFC were categorized into R and NR groups based on a >50% reduction in HRSD scores.

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Dec
1969

An overly negative self-schema is a proposed cognitive mechanism of major depressive disorder (MDD). Self-schema - one's core conception of self, including how strongly one believes one possesses various characteristics - is part of semantic memory (SM), our knowledge about concepts and their relationships. We used the N400 event-related potential (ERP) - elicited by meaningful stimuli, and reduced by greater association of the stimulus with preceding context - to measure association strength between self-concept and positive, negative, and neutral characteristics in SM.

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Jan
2018

Cholinergic dysfunction is increasingly assumed to be involved in the pathophysiology of schizophrenia. Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation (TMS) paradigm that has been shown to assay central cholinergic activity from the motor cortex (M1). Recently, we established a method to index SAI from the dorsolateral prefrontal cortex (DLPFC), an area implicated in the pathophysiology of schizophrenia.

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Jun
2017

Executive function (EF) deficits in patients with autism spectrum disorder (ASD) are ubiquitous and understudied. Further, there are no effective, neuroscience-based treatments to address this impairing feature of ASD. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated promise in addressing EF deficits in adult neuropsychiatric disorders.

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Apr
2017

Over 350 million people worldwide suffer from depression, a third of whom are medication-resistant. Seizure therapy remains the most effective treatment in depression, even when many treatments fail. The utility of seizure therapy is limited due to its cognitive side effects and stigma.

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Apr
2017

To determine the clinical effectiveness and cognitive impact of electroconvulsive therapy (ECT) in a large clinical sample of patients with schizophrenia and explore factors associated with treatment response and transient cognitive impairment.
We examined the clinical records of 144 patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were treated at an academic mental health hospital from October 2009 to August 2014. These patients received 171 acute courses of ECT; we attempted to determine their treatment response and transient cognitive impairment from ECT.

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Feb
2017

Deficits in GABAergic inhibitory neurotransmission are a reliable finding in schizophrenia (SCZ) patients. Previous studies have reported that unaffected first-degree relatives of patients with SCZ demonstrate neurophysiological abnormalities that are intermediate between probands and healthy controls. In this study, first-degree relatives of patients with SCZ and their related probands were investigated to assess frontal cortical inhibition.

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Dec
1969

Dementia frequently presents with aggression, agitation, and disorganized behavior for which current treatment is partially effective and is associated with significant adverse effects.
The aim of this study was to retrospectively assess the clinical effectiveness and tolerability of electroconvulsive therapy (ECT) in a sample of patients with neuropsychiatric symptoms of dementia (NPS) and to explore factors associated with response and with cognitive adverse effects.
We examined the clinical records of 25 patients with dementia and a pre-existing psychiatric disorder treated with ECT at an academic mental health hospital between April 1, 2010 and January 28, 2016.

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Feb
2017

Gamma-aminobutyric acid (GABA)ergic and glutamatergic neurotransmissions in the prefrontal cortex decreases with age. Further, cognitive function mediated through the dorsolateral prefrontal cortex (DLPFC) also declines with age. Although neuroimaging studies have demonstrated decreased levels of these substances, direct neurophysiological data investigating the effect of aging in the DLPFC in human subjects is lacking.

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Mar
2017

We aimed to investigate neuromodulatory effects of high-frequency left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) on resting-state electroencephalography (EEG) and their clinical and cognitive correlates in patients with depression.
Thirty-one patients diagnosed with depression included in the present study. Resting-state gamma power and theta-gamma coupling (TGC) were calculated before and after a course of rTMS.

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Nov
2017

Working memory deficits represent a core feature of schizophrenia. These deficits have been associated with dysfunctional dorsolateral prefrontal cortex (DLPFC) cortical oscillations. Theta-gamma coupling describes the modulation of gamma oscillations by theta phasic activity that has been directly associated with the ordering of information during working memory performance.

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Dec
2017

Bipolar depression (BD) is a highly prevalent condition with limited therapeutic options. Deep (H1-coil) transcranial magnetic stimulation (dTMS) is a novel TMS modality with established efficacy for unipolar depression. We conducted a randomized sham-controlled trial to evaluate the efficacy and safety of dTMS in treatment-resistant BD patients.

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Feb
2017

Although several strategies of repetitive transcranial magnetic stimulation (rTMS) have been investigated as treatment of major depressive disorder (MDD), their comparative efficacy and acceptability is unknown.
To establish the relative efficacy and acceptability of the different modalities of rTMS used for MDD by performing a network meta-analysis, obtaining a clinically meaningful treatment hierarchy.
PubMed/MEDLINE, EMBASE, PsycInfo, and Web of Science were searched up until October 1, 2016.

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Dec
1969

: Transcranial magnetic stimulation (TMS) research has suggested dysfunction in cortical glutamatergic systems in adolescent depression, while proton magnetic resonance spectroscopy (H-MRS) studies have demonstrated deficits in concentrations of glutamatergic metabolites in depressed individuals in several cortical regions, including the anterior cingulate cortex (ACC). However, few studies have combined TMS and MRS methods to examine relationships between glutamatergic neurochemistry and excitatory and inhibitory neural functions, and none have utilized TMS-MRS methodology in clinical populations or in youth. This exploratory study aimed to examine relationships between TMS measures of cortical excitability and inhibition and concentrations of glutamatergic metabolites as measured byH-MRS in depressed adolescents.

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Dec
1969

Cannabis is the most commonly used illicit substance among patients with schizophrenia. Cannabis exacerbates psychotic symptoms and leads to poor functional outcomes. Dysfunctional cortical inhibition has been implicated in the pathophysiology of schizophrenia; however, the effects of cannabis on this mechanism have been relatively unexamined.

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Dec
2016

Dysfunctional cortical inhibition (CI) is postulated as a key neurophysiological mechanism in major depressive disorder. Electroconvulsive therapy (ECT) is the treatment of choice for resistant depression and ECT has been associated with enhanced CI. The objective of this study was to evaluate the relationship between CI and ECT response in resistant depression.

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Mar
2017

Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines.
A systematic review of randomized antipsychotic clinical trials in treatment-resistant schizophrenia was performed, and definitions of treatment resistance were extracted.

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Dec
2017

Schizophrenia (SCZ) and obsessive-compulsive disorder (OCD) are psychiatric disorders with abnormalities in white matter structure. These disorders share high comorbidity and family history of OCD is a risk factor for SCZ which suggests some shared neurobiology. White matter was examined using diffusion tensor imaging in relativity large samples of SCZ (N = 48), OCD (N = 38) and non-psychiatric controls (N = 45).

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Dec
1969

Theta-burst stimulation is an emerging protocol for repetitive transcranial magnetic stimulation that takes 1-3 min to administer, yet offers equal/superior potency to conventional protocols lasting 30-60 min. However, preclinical evidence suggests that D2 receptor blockade may abolish the acute effects of theta-burst stimulation on synaptic facilitation or inhibition. As many patients presenting for repetitive transcranial magnetic stimulation are taking antipsychotic medications as augmentation for treatment-resistant depression, this finding is potentially concerning for the implementation of theta-burst stimulation in clinical settings.

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Nov
2016

Repetitive transcranial magnetic stimulation (rTMS) is a relatively recent addition to the neurostimulation armamentarium for treating individuals suffering from treatment refractory depression and has demonstrated efficacy in clinical trials. One of the proposed mechanisms of action underlying the therapeutic effects of rTMS for depression involves the modulation of depression-associated dysfunctional activity in distributed brain networks involving frontal cortical and subcortical limbic regions, via changes to aberrant functional and structural connectivity. Although there is currently a paucity of published data, we review changes to functional and structural connectivity following rTMS for depression.

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Dec
1969

Concurrent recording of electroencephalography (EEG) during transcranial magnetic stimulation (TMS) is an emerging and powerful tool for studying brain health and function. Despite a growing interest in adaptation of TMS-EEG across neuroscience disciplines, its widespread utility is limited by signal processing challenges. These challenges arise due to the nature of TMS and the sensitivity of EEG to artifacts that often mask TMS-evoked potentials (TEP)s.

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Dec
1969

The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies.

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Dec
1969

Nicotinic acetylcholine receptors (nAChR) have been implicated in the pathophysiology of schizophrenia, and deficits in this system may contribute to high rates of cigarette smoking in this population. nAChR stimulation may modulate neuroplasticity, or long-term potentiation (LTP), which is a key mediator of cognitive performance. Varenicline is a nAChR partial agonist that may improve cognitive deficits in both smokers and non-smokers with schizophrenia; however, the mechanism by which varenicline alters cognition in schizophrenia remains unclear.

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Sep
2016

The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.
Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses.

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Jan
2017

Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are noninvasive transcranial magnetic stimulation (TMS) measures of GABAreceptor-mediated inhibition and glutamatergic excitatory transmission, respectively. Conventionally these measures have been restricted to the motor cortex. We investigated whether SICI and ICF could be recorded from the dorsolateral prefrontal cortex (DLPFC) using combined TMS and electroencephalography (TMS-EEG).

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Aug
2016

Transcranial magnetic stimulation (TMS) is a non-invasive tool used for studying cortical excitability and plasticity in the human brain. This review aims to quantitatively synthesize the literature on age-related differences in cortical excitability and plasticity, examined by TMS.
A literature search was conducted using MEDLINE, Embase, and PsycINFO from 1980 to December 2015.

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