Charting the road forward in psychiatric neurosurgery: proceedings of the 2016 American Society for Stereotactic and Functional Neurosurgery workshop on neuromodulation for psychiatric disorders.

Objective: Refractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive-compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials.

A pilot study of the comparative efficacy of 100 Hz magnetic seizure therapy and electroconvulsive therapy in persistent depression.

Background: 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.

Approaches to neuromodulation for schizophrenia.

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.

Evaluation of short interval cortical inhibition and intracortical facilitation from the dorsolateral prefrontal cortex in patients with schizophrenia.

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 GABA and glutamate receptor-mediated functions respectively from the DLPFC in patients with schizophrenia using these paradigms, compared to healthy controls.

Deep TMS of the insula using the H-coil modulates dopamine release: a crossover [C] PHNO-PET pilot trial in healthy humans.

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).

1Hz rTMS of the right orbitofrontal cortex for major depression: Safety, tolerability and clinical outcomes.

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.

Number of pulses or number of sessions? An open-label study of trajectories of improvement for once-vs. twice-daily dorsomedial prefrontal rTMS in major depression.

Background: 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.

Responders to rTMS for depression show increased fronto-midline theta and theta connectivity compared to non-responders.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, but only some individuals respond. Predicting response could reduce patient and clinical burden. Neural activity related to working memory (WM) has been related to mood improvements, so may represent a biomarker for response prediction.

Electroconvulsive therapy for depression with comorbid borderline personality disorder or post-traumatic stress disorder: A matched retrospective cohort study.

Background: 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.

Objective: Compare clinical response and adverse cognitive effects for MDE patients with comorbid BPD or PTSD to MDE only.

Methods: 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.

Early symptom improvement at 10 sessions as a predictor of rTMS treatment outcome in major depression.

Background: 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.

Extent of Dorsolateral Prefrontal Cortex Plasticity and Its Association With Working Memory in Patients With Alzheimer Disease.

Importance: The extent of dorsolateral prefrontal cortex (DLPFC) plasticity in Alzheimer disease (AD) and its association with working memory are not known.

Objectives: 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.

Design, Setting, And Participants: 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.

Low medical morbidity and mortality after acute courses of electroconvulsive therapy in a population-based sample.

Background: To determine event rates for specific medical events and mortality among individuals receiving electroconvulsive therapy (ECT).

Method: Population-based cohort study using health administrative data of acute ECT treatments delivered in Ontario, Canada, from 2003 to 2011. We measured the following medical event rates, per 10 000 ECT treatments, up to 7 and 30 days post-treatment: stroke, seizure, acute myocardial infarction, arrhythmia, pneumonia, pulmonary embolus, deep vein thrombosis, gastrointestinal bleeding, falls, hip fracture, and mortality.

Differing Time of Onset of Concurrent TMS-fMRI during Associative Memory Encoding: A Measure of Dynamic Connectivity.

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.

Standardization of electroencephalography for multi-site, multi-platform and multi-investigator studies: insights from the canadian biomarker integration network in depression.

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).

Should Benzodiazepines and Anticonvulsants Be Used During Electroconvulsive Therapy?: A Case Study and Literature Review.

Objective: This study aims to investigate the clinical effects of benzodiazepines or anticonvulsant use during a course of electroconvulsive therapy (ECT).

Method: 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.

A sparse representation-based method for parcellation of the resting brain and its application to treatment-resistant major depressive disorder.

Background: Parcellating brain regions into functionally homogeneous subdivisions is critical for understanding normal and abnormal brain functions.

New Method: 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.

Impairment of Neuroplasticity in the Dorsolateral Prefrontal Cortex by Alcohol.

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.

Transcranial Direct Current Stimulation: Considerations for Research in Adolescent Depression.

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.

Safety and acceptability of transcranial direct current stimulation for the acute treatment of major depressive episodes: Analysis of individual patient data.

Background: 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.

Methods: We collected individual patient data from 6 randomized clinical trials that had been previously identified in a systematic review and meta-analysis.

Paired-Associative Stimulation-Induced Long-term Potentiation-Like Motor Cortex Plasticity in Healthy Adolescents.

Objective: 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).

Methods: 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.

Pharmacological Manipulation of Cortical Inhibition in the Dorsolateral Prefrontal Cortex.

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).

Reduced Prefrontal Short-Latency Afferent Inhibition in Older Adults and Its Relation to Executive Function: A TMS-EEG Study.

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.

Abnormal functional connectivity within resting-state networks is related to rTMS-based therapy effects of treatment resistant depression: A pilot study.

Background: 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).

Methods: 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.