Deep Transcranial Magnetic Stimulation for the Treatment of Negative Symptoms in Schizophrenia: Beyond an Antidepressant Effect.

BACKGROUND: Negative symptoms of schizophrenia show limited response to both typical and atypical antipsychotics. Repetitive transcranial magnetic stimulation applied over the prefrontal cortex (PFC) has been proposed as an adjuvant to pharmacological treatment of negative symptoms in schizophrenia, but whether the improvements obtained are specific to negative symptoms or attributable to antidepressant effects is still unclear. OBJECTIVE: The aim of the present study is to determine to which extent the improvements in negative symptoms of schizophrenia obtained after high-frequency stimulation of the bilateral PFC using deep TMS (dTMS) are attributable to antidepressant effects. METHODS: Repetitive dTMS was administered to the PFC in a cohort of 16 patients with schizophrenia under successful pharmacological control of positive symptoms and predominant negative symptoms. Patients were treated using high-frequency (18 Hz) bilateral stimulation applied over the lateral PFC bilaterally using Brainsway H-2 coil. The effects of dTMS on negative symptoms were measured using the Scale for the Assessment of Negative Symptoms and the Positive and Negative Syndrome Scales. We then compared the improvements in negative symptoms obtained in patients showing depressive symptoms (≥7 points) with those found in patients without depression (>7 points), as determined by the Calgary Scale for Depression. RESULTS: Repetitive dTMS treatment induced significant improvements in negative symptoms as assessed using both Scale for the Assessment of Negative Symptoms and Positive and Negative Syndrome Scales. Comparison of the improvements obtained in patients with or without depression at the beginning of treatment revealed similar improvements in negative symptoms, irrespective of subjacent depression. CONCLUSIONS: Our data suggest that the beneficial effects of high frequency dTMS of the PFC cannot be attributed solely to its antidepressant effects.

Immediate Effects of Transcranial Direct Current Stimulation on Obsession-Induced Anxiety in Refractory Obsessive-Compulsive Disorder: A Pilot Study.

OBJECTIVE: Studies have shown that transcranial direct current stimulation (tDCS) has immediate effects on brain activity. The aim of this study was to investigate the potential use of tDCS to regulate obsession-induced anxiety immediately after symptom provocation in patients with refractory obsessive-compulsive disorder (OCD). METHODS: Twelve patients with refractory OCD received cathode, anode, and sham transcranial direct current stimulation over the medial prefrontal cortex conjugant to pharmacological treatment in a crossover design. Before and after the DC stimulation, patients graded the intensity of their anxiety after a short exposure to a provoking stimulus using the visual analogue scale. Clinical questionnaires assessing symptoms severity were also applied before each stimulation mode. RESULTS: We found a statistically significant decrease in the severity of the obsession-induced anxiety (decreased visual analogue scale) as a result of cathode tDCS in comparison with the anode and sham stimulation. Reduction in obsession-induced anxiety was consistent, yet short lasting, and was independent of symptom severity. CONCLUSIONS: Cathode tDCS could be potentially used to regulate obsession-induced anxiety in refractory OCD patients. Further studies are warranted to confirm our results as well as to determine whether tDCS can achieve prolonged benefits in OCD and be of aid in behavioral treatments based on exposure.

Enhanced cognition and emotional recognition, and reduced obsessive compulsive symptoms in two adults with high-functioning autism as a result of deep Transcranial Magnetic Stimulation (dTMS): a case report.

We report reduced repetitive behaviors similar to obsessive compulsive disorder and improved emotional recognition and cognitive abilities in two young patients diagnosed with high-functioning Autism as a result of deep transcranial magnetic stimulation (dTMS). The patients received daily high-frequency (5 Hz) dTMS with HAUT-coil over the medial prefrontal cortex for a period of 5-6 weeks. A computerized cognitive battery, tasks for testing emotional recognition, and clinical questionnaires were used to measure the effects of treatment. TMS might have modulated networks related to metalizing abilities and self-referential processes since both patients reported improved sociability and communication skills.

Benefits of Deep Transcranial Magnetic Stimulation in Alzheimer Disease: Case Series.

BACKGROUND: Patients diagnosed with Alzheimer disease (AD) show severe cognitive deficits. Decline in memory, language, and executive function have repeatedly been reported. Although AD affects 60% to 80% of demented elderly patients, there is currently no cure and limited treatment alternatives. OBJECTIVES: The aim of the study was to evaluate the feasibility of stimulating prefrontal cortex (PFC) with deep transcranial magnetic stimulation (dTMS) to ameliorate cognitive deficits in patients suffering from AD. METHODS: Eleven patients (6 males; mean [SD] age, 76 [7] years) in moderate to severe stages of AD received dTMS over the PFC for 20 sessions. Computerized battery (Mindstreams [MS]) and neuropsychological testing (Addenbrooke Cognitive Examination [ACE]) were used to assess cognitive performance before and after treatment. RESULTS: Compared with baseline, 60% of patients performed better on the MS battery and 77% of patients performed better on the ACE testing at the end of dTMS treatment. None of the patients performed worse on both tests at the end of treatment. The DTMS effects on the group mean in ACE and MS approached significance (P = 0.065 and P = 0.086, respectively). A dTMS-induced improvement in the ACE was significant (P = 0.001) on patients in more progressed stage (n = 6). Change in ACE negatively correlated with score at baseline. CONCLUSIONS: In sum, the current report of this novel technique indicates that deep stimulation might lead to preservation and even improvement of cognitive functions, at least during the time of treatment. Further examinations should report of long-term effects of this technique.

Utilization of psychiatry services in the emergency department following a terror event in Israel.

In October 2023, Israel sustained a massive terror attack, with 1,300 people murdered, over 240 kidnapped, and millions exposed to the horrors. This study's aim is to examine the profile of patients arriving to the emergency department (ED) for psychiatric services during the month following the attack, compared to a similar period the year prior. In this cohort study, we compared patients arriving to the ED of a large general hospital in the center of Tel Aviv for psychiatric services during the month post-attack with the previous year using t-tests and chi-square exams. In 2023, 256 patients arrived in the ED for psychiatric evaluation and/or treatment, 46 % more than in 2022. Of these, 64 % were examined due to symptoms related to the terror attack. In 2023, significantly fewer patients had a prior psychiatric diagnosis (68% vs. 89 %). Significantly more patients were diagnosed with acute stress reaction or acute stress disorder in the ED, compared to almost no such diagnoses in 2022 (14 % and 43% vs. 0 % and 1 %). Major terror incidents profoundly influence psychiatric ED visits. Planning efforts for major emergencies should be adapted accordingly.

Electrical brain stimulation improves cognitive performance by modulating functional connectivity and task-specific activation.

Excitatory anodal transcranial direct current stimulation (atDCS) can improve human cognitive functions, but neural underpinnings of its mode of action remain elusive. In a cross-over placebo ("sham") controlled study we used functional magnetic resonance imaging (fMRI) to investigate neurofunctional correlates of improved language functions induced by atDCS over a core language area, the left inferior frontal gyrus (IFG). Intrascanner transcranial direct current stimulation-induced changes in overt semantic word generation assessed behavioral modulation; task-related and task-independent (resting-state) fMRI characterized language network changes. Improved word-retrieval during atDCS was paralleled by selectively reduced task-related activation in the left ventral IFG, an area specifically implicated in semantic retrieval processes. Under atDCS, resting-state fMRI revealed increased connectivity of the left IFG and additional major hubs overlapping with the language network. In conclusion, atDCS modulates endogenous low-frequency oscillations in a distributed set of functionally connected brain areas, possibly inducing more efficient processing in critical task-relevant areas and improved behavioral performance.

Bridging language barriers in developing valid health policy research tools: insights from the translation and validation process of the SHEMESH questionnaire.

BACKGROUND: The use of research tools developed and validated in one cultural and linguistic context to another often faces challenges. One major challenge is poor performance of the tool in the new context. This potentially impact the legitimacy of health policy research conducted with informal adaptations of existing tools which have not been subjected to formal validation. Best practices exist to guide researchers in adapting and validating research tools effectively. We present here, as an extended example, our validation of the SHEMESH questionnaire ('Organizational Readiness to Change Assessment'; In Hebrew: 'SHE'elon Muchanut Ergunit le'SHinuy'), a Hebrew-language version of the Organizational Readiness to Change Assessment (ORCA). SHEMESH is tailored to support implementation science projects, whose aim is to promote a more rapid and complete adoption of evidence-based health policies and practices. METHODS: The SHEMESH included originally eleven questions from the Evidence (item 1-4) and Context (items 5-11) domains. We validated SHEMESH through the following steps: 1. Professional translation to Hebrew and discussion of the translation by multidisciplinary committee; 2. Back-translation into English by a different translator to detect discrepancies; 3. Eleven cognitive interviews with psychiatric emergency department physicians and nurses; and 4. Pilot testing and psychometric analyses, including Cronbach's alpha for subscales and factor analyses. RESULTS: Following translation and cognitive interviews, SHEMESH was administered to 222 psychiatrists and nurses. Pearson correlation showed significant and strong correlations of items 1-4 to the Evidence construct and items 6-11 to the Context construct. Item 5 did not correlate with the other items, and therefore was removed from the other psychometric procedures and eventually from the SHEMESH. Factor analysis with the remaining 10 items yielded two factors, which together explained a total of 69.7% of variance. Cronbach's Alpha scores for the two subscales were high (Evidence, 0.887, and Context, 0.852). CONCLUSIONS: This multi-step validation process of the SHEMESH questionnaire may serve as a comprehensive guideline for others who are willing to adapt research tools that were developed in other languages. Practically, SHEMESH has been validated for use in implementation science research projects in Israel.

Enabling Expedited Disposition of Emergencies Using Telepsychiatry in Israel: Protocol for a Hybrid Implementation Study.

BACKGROUND: Telepsychiatry is the use of virtual communication, such as a video link, to deliver mental health assessment, treatment, and follow-up. Previous studies have shown telepsychiatry to be feasible, accurate compared with in-person practice, and satisfying for psychiatrists and patients. Telepsychiatry has also been associated with reduced waiting times for evaluation and, in some studies, lower admission rates. However, most previous studies focused on using telepsychiatry in community settings and not on involuntary admission. OBJECTIVE: The aim of this study is to examine the effectiveness and implementation process of patient assessment for involuntary admissions in the psychiatric emergency department (ED) using a video link. METHODS: This type 1 hybrid implementation study will examine telepsychiatry effectiveness and the implementation process, by comparing telepsychiatry (n=240) with historical controls who had a face-to-face evaluation (n=240) during the previous, usual care period in 5 psychiatric EDs in Israel. A temporary waiver of the standing policy requiring in-person evaluations only, for the purpose of research, was obtained from the Israeli Ministry of Health. During the telepsychiatry phase, clinical staff and patients will join a video call from the ED, while the attending physician will log in elsewhere. The Promoting Action on Research Implementation in Health Services (PARIHS) framework will guide the evaluation of the telepsychiatry implementation process in the ED. PARIHS has the following 3 constructs: (1) evidence: staff's opinions regarding the innovation's viability and practicality, their satisfaction levels with its use, and patients' perceptions of the change; (2) context: level of approval of new strategies in the ED, decision-making processes, and the manner in which clinical teams converse and work together; (3) facilitation: adequacy of the facilitation efforts using champions reports. Primary clinical outcomes include ED length of stay and violent incidents obtained from medical records. RESULTS: This study received Helsinki approval from the Ethics Committee of Abarbanel Mental Health Center (174; March 13, 2023), Jerusalem Mental Health Center (22-21; November 6, 2022), Lev-Hasharon Mental Health Medical Center (LH12023; February 12, 2023), Tel-Aviv Medical Center (TLV-22-0656; January 3, 2023), and Sha'ar Menashe (1-4-23; April 18, 2023). Data collection began in July 2023 in 2 study sites and will begin soon at the others. CONCLUSIONS: Telepsychiatry could have significant benefits for patients in the psychiatric ED. Examining telepsychiatry effectiveness in the ED, in addition to identifying the facilitators and barriers of implementing it in different emergency settings, will facilitate better policy decisions regarding its implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05771545; https://clinicaltrials.gov/study/NCT05771545. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49405.

A multimodal approach for the ecological investigation of sustained attention: A pilot study.

Natural fluctuations in sustained attention can lead to attentional failures in everyday tasks and even dangerous incidences. These fluctuations depend on personal factors, as well as task characteristics. So far, our understanding of sustained attention is partly due to the common usage of laboratory setups and tasks, and the complex interplay between behavior and brain activity. The focus of the current study was thus to test the feasibility of applying a single-channel wireless EEG to monitor patterns of sustained attention during a set of ecological tasks. An EEG marker of attention (BEI-Brain Engagement Index) was continuously recorded from 42 healthy volunteers during auditory and visual tasks from the Test of Everyday Attention (TEA) and Trail Making Test (TMT). We found a descending pattern of both performance and BEI in the auditory tasks as task complexity increases, while the increase in performance and decrease in BEI on the visual task. In addition, patterns of BEI in the complex tasks were used to detect outliers and the optimal range of attention through exploratory models. The current study supports the feasibility of combined electrophysiological and neurocognitive investigation of sustained attention in ecological tasks yielding unique insights on patterns of sustained attention as a function of task modality and task complexity.

The interactive effects of test-retest and methylphenidate administration on cognitive performance in youth with ADHD: A double-blind placebo-controlled crossover study.

Studies have shown that Methylphenidate (MPH) affects cognitive performance on the neuropsychological tests and clinical symptoms of individuals diagnosed with attention deficit/hyperactivity disorder (ADHD). This study investigated the acute effects of MPH on neuropsychological tests to explore the interaction between MPH and test-retest effects. Twenty youths with ADHD were tested before and after MPH intake in a double-blind placebo-controlled crossover design and compared to twenty matched controls. Participants were tested on a range of standardized tasks including sustained attention to response, N-Back, and Word/Color Stroop. Identical tasks were administered twice each testing day, before and 1 hour after MPH/Placebo administration. Healthy controls were tested similarly with no intervention. Decreases in response time (RT) variability across tasks and in commission errors were found in ADHD after MPH. Conversely, a significant increase in RT variability and increase in omission errors were observed after the placebo. In the control group, RT variability and omission errors increased whereas commission errors decreased, suggesting fatigue and practice effects, respectively. Test-retest reliability was higher in controls than ADHD. It is suggested that cognitive tests are sensitive objective measures for the assessment of responses to MPH in ADHD but are also affected by repetition and fatigue.

Ruminative Tendency Relates to Ventral Striatum Functionality: Evidence From Task and Resting-State fMRI.

BACKGROUND: Ruminative responding involves repetitive and passive thinking about one's negative affect. This tendency interferes with initiation of goal-directed rewarding strategies, which could alleviate depressive states. Such reward-directed response selection has been shown to be mediated by ventral striatum/nucleus accumbens (VS/NAcc) function. However, to date, no study has examined whether trait rumination relates to VS/NAcc functionality. Here, we tested whether rumination moderates VS/NAcc function both in response to reward and during a ruminative state. METHODS: Trait rumination was considered dimensionally using Rumination Response Scale (RRS) scores. Our sample (N = 80) consisted of individuals from a community sample and from patients diagnosed with major depressive disorder, providing a broad range of RRS scores. Participants underwent fMRI to assess two modes of VS/NAcc functionality: 1) in response to reward, and 2) during resting-state, as a proxy for ruminative state. We then tested for associations between RRS scores and VS/NAcc functional profiles, statistically controlling for overall depressive symptom severity. RESULTS: RRS scores correlated positively with VS/NAcc response to reward. Furthermore, we noted that higher RRS scores were associated with increased ruminative-dependent resting-state functional connectivity of the VS/NAcc with the left orbitofrontal cortex. CONCLUSIONS: These findings suggest that ruminative tendencies manifest in VS/NAcc reward- and rumination-related functions, providing support for a theoretical-clinical perspective of rumination as a habitual impairment in selection of rewarding, adaptive coping strategies.

Modulation of Gestural-verbal Semantic Integration by tDCS.

BACKGROUND: Understanding actions based on either language or observation of gestures is presumed to involve the motor system, and reflect the engagement of an embodied conceptual network. The role of the left inferior frontal gyrus (IFG) in language tasks is well established, but the role of the right hemisphere is unclear with some imaging evidence suggesting right IFG activation when gestures mismatch speech. OBJECTIVE: Using transcranial direct current stimulation (tDCS), we explored the hemispheric asymmetries in the assumed cognitive embodiment required for gestural-verbal integration. METHODS: Symbolic gestures served as primes for verbal targets. Primes were clips of symbolic gestures taken from a rich set of emblems and pantomimes. Participants responded by performing a semantic relatedness-judgment under 3 stimulation conditions - anodal tDCS (atDCS) over the left IFG, atDCS over the right IFG, and sham. There was also a non-semantic control task of attentional load. RESULTS: AtDCS of the right IFG generated faster responses to symbolic gestures than atDCS over the left IFG or sham stimulation. For the attentional load task, no differences were observed across the three stimulation conditions. These results support a right-lateralization bias of the human mirror neuron system in processing gestural-verbal stimuli. CONCLUSION: Gesture comprehension may be enhanced by improved gesture and language integration.

Cerebral autoregulation and brain networks in occlusive processes of the internal carotid artery.

Patients with unilateral occlusive processes of the internal carotid artery (ICA) show subtle cognitive deficits. Decline in cerebral autoregulation and in functional and structural integrity of brain networks have previously been reported in the affected hemisphere (AH). However, the association between cerebral autoregulation, brain networks, and cognition remains to be elucidated. Fourteen neurologically asymptomatic patients (65±11 years) with either ICA occlusion or high-grade ICA stenosis and 11 age-matched healthy controls (HC) (67±6 years) received neuropsychologic testing, transcranial Doppler sonography to assess cerebral autoregulation using vasomotor reactivity (VMR), and magnetic resonance imaging to probe white matter microstructure and resting-state functional connectivity (RSFC). Patients performed worse on memory and executive tasks when compared with controls. Vasomotor reactivity, white matter microstructure, and RSFC were lower in the AH of the patients when compared with the unaffected hemisphere and with controls. Lower VMR of the AH was associated with several ipsilateral clusters of lower white matter microstructure and lower bilateral RSFC in patients. No correlations were found between VMR and cognitive scores. In sum, impaired cerebral autoregulation was associated with reduced structural and functional connectivity in cerebral networks, indicating possible mechanisms by which severe unilateral occlusive processes of the ICA lead to cognitive decline.

Changes in cerebellar activity and inter-hemispheric coherence accompany improved reading performance following Quadrato Motor Training.

Dyslexia is a multifactorial reading deficit that involves multiple brain systems. Among other theories, it has been suggested that cerebellar dysfunction may be involved in dyslexia. This theory has been supported by findings from anatomical and functional imaging. A possible rationale for cerebellar involvement in dyslexia could lie in the cerebellum's role as an oscillator, producing synchronized activity within neuronal networks including sensorimotor networks critical for reading. If these findings are causally related to dyslexia, a training regimen that enhances cerebellar oscillatory activity should improve reading performance. We examined the cognitive and neural effects of Quadrato Motor Training (QMT), a structured sensorimotor training program that involves sequencing of motor responses based on verbal commands. Twenty-two adult Hebrew readers (12 dyslexics and 10 controls) were recruited for the study. Using Magnetoencephalography (MEG), we measured changes in alpha power and coherence following QMT in a within-subject design. Reading performance was assessed pre- and post-training using a comprehensive battery of behavioral tests. Our results demonstrate improved performance on a speeded reading task following one month of intensive QMT in both the dyslexic and control groups. Dyslexic participants, but not controls, showed significant increase in cerebellar oscillatory alpha power following training. In addition, across both time points, inter-hemispheric alpha coherence was higher in the dyslexic group compared to the control group. In conclusion, the current findings suggest that the combination of motor and language training embedded in QMT increases cerebellar oscillatory activity in dyslexics and improves reading performance. These results support the hypothesis that the cerebellum plays a role in skilled reading, and begin to unravel the underlying mechanisms that mediate cerebellar contribution in cognitive and neuronal augmentation.

Transcranial direct current stimulation over multiple days improves learning and maintenance of a novel vocabulary.

INTRODUCTION: Recently, growing interest emerged in the enhancement of human potential by means of non-invasive brain stimulation. In particular, anodal transcranial direct current stimulation (atDCS) has been shown to exert beneficial effects on motor and higher cognitive functions. However, the majority of transcranial direct current stimulation (tDCS) studies have assessed effects of single stimulation sessions that are mediated by transient neural modulation. Studies assessing the impact of multiple stimulation sessions on learning that may induce long-lasting behavioural and neural changes are scarce and have not yet been accomplished in the language domain in healthy individuals. METHOD: The present study probed the potential of atDCS to enhance language learning over multiple days by employing an explicit word learning paradigm. Forty healthy young participants were randomized to learning with either simultaneous atDCS or sham stimulation (N = 20/group; comparable regarding demographic variables and neurocognitive status). All participants acquired a novel vocabulary (familiar and novel object picture - non-word pairs) over five consecutive days. Two memory tasks (free recall; forced choice recognition tasks) were administered immediately after each training session. A one week follow-up tested the maintenance of learning success. RESULTS: Linear mixed effects model analysis revealed superior learning during atDCS compared to sham stimulation for both familiar and novel objects. atDCS yielded a steeper learning curve and significantly more pronounced learning at the end of the training during the recall task. During the recognition task, the atDCS group reached ceiling levels earlier and overall learning success was greater. For both tasks, beneficial atDCS effects were maintained during the follow-up assessment. CONCLUSIONS: The present study provides direct evidence that atDCS administered during multiple learning sessions facilitates language learning and that effects are maintained over time. This study contributes important novel information about the extent of stimulation effects in the healthy brain, thereby highlighting the potential of atDCS to enhance language recovery after stroke.

Improving emotional prosody detection in the attending ear by cathodal tDCS suppression of the competing channel.

Currently it is assumed that cathodal stimulation (in transcranial direct current stimulation, tDCS) degrades the neural firing rate, and thus it is believed to degrade cognitive performance. Here we challenge this assumption by predicting that under high competition the cathodal stimulation might act as a noise filter, leading to an improved performance. We presented auditory targets with different emotional valence using a dichotic listening paradigm. We found that cathodal, but not anodal stimulation of the right IFG generated better prosody comprehension. Cathodal stimulation in competitive situations, such as the dichotic listening paradigm, can act like a noise filter, and may in fact enhance cognitive performance. This study contributes to understanding the way the IFG is engaged with prosody functions, and explains the cathodal effects of tDCS. This might lead to the development of more efficient brain stimulation protocols.