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Introduction: Focal brain stimulation has potential as a treatment for posttraumatic stress disorder (PTSD). In this review, we aim to inform selection of focal brain stimulation targets for treating PTSD by examining studies of the functional neuroanatomy of PTSD and treatment response. We first briefly review data on brain stimulation interventions for PTSD. Although published data suggest good efficacy overall, the neurobiological rationale for each stimulation target is not always clear., Methods: Therefore, we assess pre- and post-treatment (predominantly psychotherapy) functional neuroimaging studies in PTSD to determine which brain changes seem critical to treatment response. Results of these studies are presented within a previously proposed functional neural systems model of PTSD., Results: While not completely consistent, research suggests that downregulating the fear learning and threat and salience detection circuits (i.e., amygdala, dorsal anterior cingulate cortex and insula) and upregulating the emotion regulation and executive function and contextual processing circuits (i.e., prefrontal cortical regions and hippocampus) may mediate PTSD treatment response., Conclusion: This literature review provides some justification for current focal brain stimulation targets. However, the examination of treatment effects on neural networks is limited, and studies that include the stimulation targets are lacking. Further, additional targets, such as the cingulate, medial prefrontal cortex, and inferior parietal lobe, may also be worth investigation, especially when considering how to achieve network level changes. Additional research combining PTSD treatment with functional neuroimaging will help move the field forward by identifying and validating novel targets, providing better rationale for specific treatment parameters and personalizing treatment for PTSD., (© 2021 Wiley Periodicals LLC.)

Objective: Transcranial direct current stimulation (tDCS) has been found to have antidepressant effects and may have beneficial neurocognitive effects. However, prior research has produced an unclear understanding of the neurocognitive effects of repeated exposure to tDCS. The study's aim was to determine the neurocognitive effects following tDCS treatment in participants with unipolar or bipolar depression., Method: The study was a triple-masked, randomized, controlled clinical trial across six international academic medical centers. Participants were randomized to high dose (2.5 mA for 30 min) or low dose (0.034 mA, for 30 min) tDCS for 20 sessions over 4 weeks, followed by an optional 4 weeks of open-label high dose treatment. The tDCS anode was centered over the left dorsolateral prefrontal cortex at F3 (10/20 EEG system) and the cathode over F8. Participants completed clinical and neurocognitive assessments before and after tDCS. Genotype (BDNF Val66Met and catechol-o-methyltransferase [COMT] Val158Met polymorphisms) were explored as potential moderators of neurocognitive effects., Results: The study randomized 130 participants. Across the participants, tDCS treatment (high and low dose) resulted in improvements in verbal learning and recall, selective attention, information processing speed, and working memory, which were independent of mood effects. Similar improvements were observed in the subsample of participants with bipolar disorder. There was no observed significant effect of tDCS dose. However, BDNF Val66Met and COMT Val158Met polymorphisms interacted with tDCS dose and affected verbal memory and verbal fluency outcomes, respectively., Conclusions: These findings suggest that tDCS could have positive neurocognitive effects in unipolar and bipolar depression. Thus, tDCS stimulation parameters may interact with interindividual differences in BDNF and COMT polymorphisms to affect neurocognitive outcomes, which warrants further investigation., (© 2020 Wiley Periodicals, Inc.)

Psychotic symptoms are common, disabling non-motor features of Parkinson's disease (PD). Despite noted heterogeneity in clinical features, natural history and therapy response, current dogma posits that psychosis generally progresses in a stereotypic manner through a cascade of events that begins with minor hallucinations and evolves to severe hallucinations and delusions. Further, the occurrence of psychotic symptoms is believed to indicate a poor prognosis. Here we propose a classification scheme that outlines the pathogenesis of psychosis as it relates to dysfunction of several neurotransmitter systems. We hypothesize that several subtypes exist, and that PD psychosis is not consistently indicative of a progressive cascade and poor prognosis. The literature was reviewed from 1990 to 2017. An overview of the features of PD psychosis is followed by a review of data indicating the existence of neurotransmitter-related subtypes of psychosis. We found that ample evidence exists to demonstrate the presence of multiple subtypes of PD psychosis, which are traced to dysfunction of the following neurotransmitter systems: dopamine, serotonin and acetylcholine. Dysfunction of each of these systems is recognizable through their clinical features and correlates, and the varied long-term prognoses. Identifying which neurotransmitter system is dysfunctional may help to develop targeted therapies. PD psychosis has various subtypes that differ in clinical features, underlying pathology and pathophysiology, treatment response and prognosis. A novel classification scheme is presented that describes the clinical subtypes with different outcomes, which could lead to the development of targeted therapies. Future research should focus on testing the viability of this classification., (© 2017 EAN.)

Objective: To examine the nature of the association between affective disorders and psychosis in Parkinson's disease (PD)., Background: In PD, psychosis and affective disorders are common and independently impact quality of life and mortality. Both depression and psychosis are correlated with the occurrence of cognitive dysfunction, suggesting that they may share neurobiological substrates. Anxiety has not been examined as a correlate of psychosis., Methods: 144 PD subjects were evaluated with the Schedule for Assessment of Positive Symptoms to assess psychotic features, while depression and anxiety were examined by the Structured Clinical Interview for DSM-IV-TR (SCID) and self-assessment scales Beck Depression Inventory II (BDI-II) and Beck Anxiety Inventory (BAI). Correlational analyses assessed associations between hallucinations and delusions with depression and anxiety., Results: A diagnosis of anxiety (SCID) was significantly (p=.015) associated with hallucinations (OR=4.81, CI=1.36-16.99). Severity of anxiety (BAI) significantly predicted (p=.03) the presence of hallucinations (OR=1.08, CI=1.01-1.15) and delusions (OR=1.09, CR=1.01-1.17). Current depression (SCID) was significantly (p=.001) associated with the presence of hallucinations (OR=6.12, CI=2.04-18.39) and delusions (OR=7.14, CI=2.23-22.93). Multiple linear regressions revealed that severity of anxiety remained an independent predictor (p<.05) of both the number of types of hallucinations (t=3.06, p=.003) and delusions (t=2.87, p=.005). Severity of depression was a significant predictor of the total number of delusions (t=2.28, p=.024)., Conclusions: This study demonstrates an association between depression and psychosis and, for the first time, an association between anxiety and psychosis. These associations may have implications on pathophysiology and treatment of psychosis in PD., Competing Interests: Conflict of interest There are no conflicts of interest from all authors that relate to the research covered in the article submitted.

We present the methodology utilized for development and clinimetric testing of the Comprehensive Cervical Dystonia (CD) Rating scale, or CCDRS. The CCDRS includes a revision of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-2), a newly developed psychiatric screening tool (TWSTRS-PSYCH), and the previously validated Cervical Dystonia Impact Profile (CDIP-58). For the revision of the TWSTRS, the original TWSTRS was examined by a committee of dystonia experts at a dystonia rating scales workshop organized by the Dystonia Medical Research Foundation. During this workshop, deficiencies in the standard TWSTRS were identified and recommendations for revision of the severity and pain subscales were incorporated into the TWSTRS-2. Given that no scale currently evaluates the psychiatric features of cervical dystonia (CD), we used a modified Delphi methodology and a reiterative process of item selection to develop the TWSTRS-PSYCH. We also included the CDIP-58 to capture the impact of CD on quality of life. The three scales (TWSTRS2, TWSTRS-PSYCH, and CDIP-58) were combined to construct the CCDRS. Clinimetric testing of reliability and validity of the CCDRS are described. The CCDRS was designed to be used in a modular fashion that can measure the full spectrum of CD. This scale will provide rigorous assessment for studies of natural history as well as novel symptom-based or disease-modifying therapies.

Background: A few studies have examined the durability of transcranial magnetic stimulation (TMS) antidepressant benefit once patients remitted. This study examined the long-term durability of clinical benefit from TMS using a protocol-specified TMS taper and either continuation pharmacotherapy or naturalistic follow-up., Methods: Patients were remitters from an acute double-blind sham-controlled trial of TMS (n = 18), or from an open-label extension in patients who did not respond to the acute trial (n = 43). Long-term durability of TMS acute effect was examined in remitters over a 12-week follow-up. Relapse, defined as 24-item Hamilton Depression Rating Scale (HDRS-24) ≥20, was the primary outcome., Results: Of 61 remitters in the acute trial, five entered naturalistic follow-up and 50 entered the TMS taper. Thirty-two patients completed TMS taper and 1-, 2-, and 3-month follow-up. At 3-month visit, 29 of 50 (58%) were classified as in remission (HDRS-24 ≤10), two of 50 (4%) as partial responders (30%≤ HDRS-24 reduction <50% from baseline), and one of 50 (2%) met criteria for relapse. During the entire 3-month follow-up, five of the 37 patients relapsed (relapse rate = 13.5%), but four of them regained remission by the end of the study. The average time to relapse in these five patients was 7.2 ± 3.3 weeks. Patients who relapsed had higher depression scores at 1 month., Conclusions: While one third of the sample was lost to follow-up, our results demonstrate that most patients contributing to observations experienced persistence of benefit from TMS followed by pharmacotherapy or no medication. Longer follow-up and more rigorous studies are needed to explore the true long-term durability of remission produced by TMS., (© 2012 Wiley Periodicals, Inc.)

Objective: To assess the efficacy of increasing the number of fast left repetitive transcranial magnetic stimulations (rTMS) (10 Hz @ 120% of motor threshold (MT) over the left dorsolateral prefrontal cortex (DLPFC)) needed to achieve remission in treatment-resistant depression (TRD). And, to determine if patients who do not remit to fast left will remit using slow right rTMS (1 Hz @ 120% MT over the right DLPFC)., Method: Patients were part of a multicenter sham-controlled trial investigating the efficacy of fast left rTMS. Patients who failed to meet minimal response criteria in the sham-controlled study could enroll in this open fast left rTMS study for an additional 3-6 weeks. Patients who failed to remit to fast left could switch to slow right rTMS for up to 4 additional weeks. The final outcome measure was remission, defined as a HAM-D score of <3 or 2 consecutive HAM-D scores less than 10., Results: Forty-three of 141 (30.5%) patients who enrolled in the open phase study eventually met criteria for remission. Patients who remitted during fast left treatment received a mean of 26 active treatments (90,000 pulses). Twenty-six percent of patients who failed fast left remitted during slow right treatment., Conclusion: The total number of rTMS stimulations needed to achieve remission in TRD may be higher than is used in most studies. TRD patients who do not respond to fast left rTMS may remit to slow right rTMS or additional rTMS stimulations., (© 2011 Wiley Periodicals, Inc.)

Background: Repetitive transcranial magnetic stimulation (rTMS) has shown safety and efficacy for treatment-resistant depression, but requires daily treatment for 4-6 weeks. Accelerated TMS, with all treatments delivered over a few days, would have significant advantages in terms of access and patient acceptance., Methods: Open-label accelerated TMS (aTMS), consisting of 15 rTMS sessions administered over 2 days, was tested in 14 depressed patients not responding to at least one antidepressant medication. Effects on depression, anxiety, and cognition were assessed the day following treatment, then after 3 and 6 weeks., Results: No seizure activity was observed and only one patient had a serious adverse event (increased suicidal ideation). Two patients failed to complete a full course of aTMS treatments, and 36% did not complete all study visits. Depression and anxiety significantly decreased following aTMS treatments and improvements persisted 3 and 6 weeks later. Response rates immediately following treatment and at 3 and 6 weeks were 43, 36, and 36%, respectively. Remission rates at the same timepoints were 29, 36, and 29%., Conclusions: Accelerated TMS demonstrated an excellent safety profile with efficacy comparable to that achieved in daily rTMS in other trials. Limitations primarily include open-label treatment and a small sample size., (Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc.)

A National Institutes of Health (National Institute of Neurological Disorders and Stroke; National Institute of Mental Health; National Institute on Aging) working group meeting focused on the non-motor aspects of Parkinson's disease (PD). Below is the summary of the meeting presentations and recommendations for a research agenda on the epidemiology, assessment, circuitry, therapeutic approaches, and clinical trials of Parkinson's disease co-morbid with depression. A second summary will focus on PD and dementia., (Copyright 2002 Wiley-Liss, Inc.)

It is a challenging task to review transcranial magnetic stimulation (TMS) studies in neuropsychiatric disorders alongside assessments of longstanding clinical applications of ECT as an empirical treatment. The task is challenging because TMS was developed as a probe of neural mechanisms, whereas, in marked contrast, ECT has been a clinical technique from its inception. Since the onset of modern psychopharmacology, the understanding of the potential applications of ECT to neuropsychiatric disorders is generally restricted to case reports of patients with intractable disease that have had at least a partial response to ECT. Studies of the possible efficacy of TMS in neuropsychiatric conditions have a significant advantage over ECT as the treatments are associated with less morbidity. The only serious known complication in TMS is a risk of seizures that may increase in patients with neuropsychiatric conditions such as course brain disease. Only cortical structures are themselves accessible to TMS using current technology. Present TMS techniques, however, seem capable of affecting activity in deeper brain structures that are functionally linked to cortical brain regions. TMS permits novel explorations of relationships between regional brain activity and symptoms of a number of neuropsychiatric disorders, as well as in research relating activity in functionally related brain regions to modulation of cognition and affective states in healthy individuals. This is particularly true at present because TMS and powerful neuroimaging and neuropsychological tools are all making rapid advances simultaneously.