Evoked EEG Responses to TMS Targeting Regions Outside the Primary Motor Cortex and Their Test-Retest Reliability.

Transcranial magnetic stimulation (TMS)-evoked electroencephalography (EEG) potentials (TEPs) provide unique insights into cortical excitability and connectivity. However, confounding EEG signals from auditory and somatosensory co-stimulation complicate TEP interpretation. Our optimized sham procedure established with TMS of primary motor cortex (Gordon in JAMA 245:118708, 2021) differentiates direct cortical EEG responses to TMS from those caused by peripheral sensory inputs. Using this approach, this study aimed to investigate TEPs and their test-retest reliability when targeting regions outside the primary motor cortex, specifically the left angular gyrus, supplementary motor area, and medial prefrontal cortex. We conducted three identical TMS-EEG sessions one week apart involving 24 healthy participants. In each session, we targeted the three areas separately using a figure-of-eight TMS coil for active TMS, while a second coil away from the head produced auditory input for sham TMS. Masking noise and electric scalp stimulation were applied in both conditions to achieve matched EEG responses to peripheral sensory inputs. High test-retest reliability was observed in both conditions. However, reliability declined for the 'cleaned' TEPs, resulting from the subtraction of evoked EEG response to the sham TMS from those to the active, particularly for latencies > 100 ms following the TMS pulse. Significant EEG differences were found between active and sham TMS at latencies < 90 ms for all targeted areas, exhibiting distinct spatiotemporal characteristics specific to each target. In conclusion, our optimized sham procedure effectively reveals EEG responses to direct cortical activation by TMS in brain areas outside primary motor cortex. Moreover, we demonstrate the impact of peripheral sensory inputs on test-retest reliability of TMS-EEG responses.

Adapted Beamforming: A Robust and Flexible Approach for Removing Various Types of Artifacts from TMS-EEG Data.

Electroencephalogram (EEG) recorded as response to transcranial magnetic stimulation (TMS) can be highly informative of cortical reactivity and connectivity. Reliable EEG interpretation requires artifact removal as the TMS-evoked EEG can contain high-amplitude artifacts. Several methods have been proposed to uncover clean neuronal EEG responses. In practice, determining which method to select for different types of artifacts is often difficult. Here, we used a unified data cleaning framework based on beamforming to improve the algorithm selection and adaptation to the recorded signals. Beamforming properties are well understood, so they can be used to yield customized methods for EEG cleaning based on prior knowledge of the artifacts and the data. The beamforming implementations also cover, but are not limited to, the popular TMS-EEG cleaning methods: independent component analysis (ICA), signal-space projection (SSP), signal-space-projection-source-informed-reconstruction method (SSP-SIR), the source-estimate-utilizing noise-discarding algorithm (SOUND), data-driven Wiener filter (DDWiener), and the multiple-source approach. In addition to these established methods, beamforming provides a flexible way to derive novel artifact suppression algorithms by considering the properties of the recorded data. With simulated and measured TMS-EEG data, we show how to adapt the beamforming-based cleaning to different data and artifact types, namely TMS-evoked muscle artifacts, ocular artifacts, TMS-related peripheral responses, and channel noise. Importantly, beamforming implementations are fast to execute: We demonstrate how the SOUND algorithm becomes orders of magnitudes faster via beamforming. Overall, the beamforming-based spatial filtering framework can greatly enhance the selection, adaptability, and speed of EEG artifact removal.

Untangling TMS-EEG responses caused by TMS versus sensory input using optimized sham control and GABAergic challenge.

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) elegantly probes the excitability and connectivity of the human brain. However, TMS-EEG signals inevitably also contain sensory-evoked responses caused by TMS-associated auditory and somatosensory inputs, constituting a substantial confounding factor. Here we applied our recently established optimized SHAM protocol (Gordon et al., Neuroimage 2021:118708) to disentangle TMS-EEG responses caused by TMS vs. sensory input. One unresolved question is whether these responses superimpose without relevant interaction, a requirement for their disaggregation by the optimized SHAM approach. We applied in 20 healthy subjects a pharmacological intervention using a single oral dose of 20 mg of diazepam, a positive modulator of GABAA receptors. Diazepam decreased the amplitudes of the P60 and P150 components specifically in the ACTIVE TMS and/or the ACTIVE TMS minus SHAM conditions but not in the SHAM condition, pointing to a response caused by TMS. In contrast, diazepam suppressed the amplitude of the N100 component indiscriminately in the ACTIVE TMS and SHAM conditions but not in the ACTIVE TMS minus SHAM condition, pointing to a response caused by sensory input. Moreover, diazepam suppressed the beta-band response observed in the motor cortex specifically after ACTIVE TMS and ACTIVE TMS minus SHAM. These findings demonstrate a lack of interaction of TMS-EEG responses caused by TMS vs. sensory input and validate optimized SHAM-controlled TMS-EEG as an appropriate approach to untangle these TMS-EEG responses. This knowledge will enable the proficient use of TMS-EEG to probe the physiology of the human cortex. KEY POINTS: Optimized SHAM disentangles TMS-EEG responses caused by TMS vs. sensory input. Diazepam differentially modulates TMS-EEG responses caused by TMS vs. sensory input. Diazepam modulation of P60 and P150 indicate TMS-EEG responses caused by TMS. Diazepam modulation of N100 indicate a TMS-EEG response caused by sensory input.

Recording brain responses to TMS of primary motor cortex by EEG - utility of an optimized sham procedure.

INTRODUCTION: Electroencephalography (EEG) is increasingly used to investigate brain responses to transcranial magnetic stimulation (TMS). A relevant issue is that TMS is associated with considerable auditory and somatosensory stimulation, causing peripherally evoked potentials (PEPs) in the EEG, which contaminate the direct cortical responses to TMS (TEPs). All previous attempts to control for PEPs suffer from significant limitations. OBJECTIVE/HYPOTHESIS: To design an optimized sham procedure to control all sensory input generated by subthreshold real TMS targeting the hand area of the primary motor cortex (M1), enabling reliable separation of TEPs from PEPs. METHODS: In 23 healthy (16 female) subjects, we recorded EEG activity evoked by an optimized sham TMS condition which masks and matches auditory and somatosensory co-stimulation during the real TMS condition: auditory control was achieved by noise masking and by using a second TMS coil that was placed on top of the real TMS coil and produced a calibrated sound pressure level. Somatosensory control was obtained by electric stimulation (ES) of the scalp with intensities sufficient to saturate somatosensory input. ES was applied in both the sham and real TMS conditions. Perception of auditory and somatosensory inputs in the sham and real TMS conditions were compared by psychophysical testing. Transcranially evoked EEG signal changes were identified by subtraction of EEG activity in the sham condition from EEG activity in the real TMS condition. RESULTS: Perception of auditory and somatosensory inputs in the sham vs. real TMS conditions was comparable. Both sham and real TMS evoked a series of similar EEG signal deflections and induced broadband power increase in oscillatory activity. Notably, the present procedure revealed EEG potentials and a transient increase in beta band power at the site of stimulation that were only present in the real TMS condition. DISCUSSION: The results validate the effectiveness of our optimized sham approach. Despite the presence of typical responses attributable to sensory input, the procedure provided evidence for direct cortical activation by subthreshold TMS of M1. The findings are relevant for future TMS-EEG experiments that aim at measuring regional brain target engagement controlled by an optimized sham procedure.

Clinical Implications of the National Institute of Neurological Disorders and Stroke Criteria for Diagnosing Psychosis in Parkinson's Disease.

The effect of psychotic symptoms in Parkinson's disease (PD) is variable among patients, and different methods to assess psychosis may yield conflicting results. A sample of 102 patients with a diagnosis of idiopathic PD underwent neurological, psychiatric, and neuropsychological assessment. Participants were divided into three groups: those who met DSM criteria for psychotic disorder, those who had psychotic symptoms but did not meet DSM criteria, and those without any psychotic symptoms. The first group had significantly worse sleep and worse cognitive and psychopathological symptoms compared with the other two groups. Results suggested that patients meeting DSM criteria for psychotic disorder comprise a separate clinical category.

Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder in Older Adults: Systematic Review and Meta-analysis.

BACKGROUND: Major depressive disorder (MDD) in older adults is a serious public health concern. Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological intervention approved for MDD treatment in adults, but its value in older adults remains unknown. This study aims to systematically review and meta-analyze evidence of rTMS efficacy in MDD treatment among older adults. METHODS: We systematically reviewed the literature for randomized controlled trials (RCTs) and open-label studies assessing rTMS for the treatment of MDD in patients older than 50 years, published until June 2020. Random-effects meta-analyses using standardized mean differences (SMDs) were conducted to assess change in depression severity score (primary outcome), while odds ratios (ORs) were used to assess secondary categorical outcomes (response and remission). Additionally, univariate meta-regression analyses were performed to identify potential predictors of change in depression severity scores. RESULTS: Fourteen RCTs were included in meta-analyses and 26 studies (10 RCTs and 16 open-label studies) in meta-regression. Active rTMS was significantly superior to sham treatment for reduction of severity (SMD = 0.36; 95% CI = 0.13-0.60), as well as response (OR = 3.26; 95% CI = 2.11-5.04) and remission (OR = 4.63; 95% CI = 2.24-9.55). Studies were of moderate to high quality, with funnel plots and Egger's regression test not suggestive of publication bias. In meta-regressions, higher mean age and number of sessions were significantly associated with greater improvement. CONCLUSIONS: Our results support that rTMS is an effective, safe, and well-tolerated treatment for MDD in older adults and that it should be considered in the treatment of this vulnerable population.

Comorbid epilepsy and psychogenic non-epileptic seizures: how well do patients and caregivers distinguish between the two.

PURPOSE: To determine whether patients with comorbid epilepsy and psychogenic nonepileptic seizure (PNES) and their caregivers can distinguish between these two events at least one year after initial diagnosis, and to investigate factors associated with correct identification. METHODS: Adult patients with at least a one year diagnosis of both epilepsy and PNES, confirmed through video-electroencephalography (VEEG), were selected. Patients and a caregiver of their choice were interviewed and shown videos containing the patients' epileptic and PNES events. Variables associated with correct identification of events by patients and their caregivers were evaluated. RESULTS: Twenty-four patients participated in the study. Mean time between VEEG diagnosis and enrollment in the study was 26.8 months (±12.4). Six of patients correctly distinguished between the events shown. Factors associated with correct identification were the absence of intellectual disability, unremitted PNES, and a degree of preserved awareness during the PNES event. Twelve caregivers correctly distinguished between the events shown. Factors associated with correct identification among caregivers were the presentation of only one epileptic seizure type in the patient, and the participation of the caregiver during VEEG monitoring and communication of PNES diagnosis to the patient. CONCLUSION: A significant proportion of patients with epilepsy and PNES and their caregivers seem to be unable to discriminate between these events a year after diagnosis. These findings have implications for both clinical follow-up and research involving this population. Future research should further investigate methods that would allow patients and their caregivers to better distinguish between these two events.

Aspectos do acompanhamento psiquiátrico de pacientes obesos sob tratamento bariátrico: revisão / Aspects of psychiatric care for obese patients under bariatric treatment: a review

CONTEXTO: Nas últimas décadas, diversos estudos longitudinais têm demonstrado a eficácia da cirurgia bariátrica no controle de peso em longo prazo e na redução da mortalidade resultante de complicações clínicas associadas à obesidade. Contudo, os estudos também revelam aumento significativo da mortalidade devida a suicídio e comportamento impulsivo, por razões largamente desconhecidas, o que demonstra a escassez de informações relativas ao manejo clínico de pacientes bariátricos. O presente estudo tem como objetivo sintetizar o estado atual de conhecimentos referentes ao acompanhamento psiquiátrico de pacientes bariátricos. MÉTODO: Revisão seletiva da literatura envolvendo artigos indexados no Medline e PubMed até junho de 2010, utilizando-se os termos: "bariatric surgery", "psychiatry", "binge eating", "follow-up" e "outcome". RESULTADOS: Há relativo consenso na literatura de que não haja contraindicação psiquiátrica absoluta para a cirurgia bariátrica, embora a avaliação pré-operatória seja de extrema importância para o diagnóstico e tratamento de eventuais transtornos psiquiátricos, objetivando assegurar aderência ao tratamento multidisciplinar, melhor qualidade de vida e, possivelmente, melhor prognóstico pós-cirúrgico. Entre os transtornos mais prevalentes nessa população, encontra-se o transtorno da compulsão alimentar periódica (TCAP), que está relacionado com menor perda ponderal e pior qualidade de vida, especialmente quando presente no pós-operatório. No acompanhamento pós-operatório, também se deve atentar para o surgimento de sintomas impulsivos, incluindo abuso de álcool e outras substâncias. CONCLUSÃO: Diversos estudos indicam elevada prevalência de transtornos mentais e alterações psicopatológicas na população de pacientes bariátricos. Embora a maioria dos pacientes apresente adequado controle ponderal e melhora na qualidade de vida em médio e longo prazo, alguns pacientes desenvolvem alterações relativas ao comportamento alimentar,...

BACKGROUND: In recent decades, several longitudinal studies show the efficacy of bariatric surgery on long-term weight control and reductions in mortality due to clinical complications associated with obesity. However, studies also show significantly increased mortality due to suicide and impulsive behavior, for reasons largely unknown, which demonstrates the paucity of information concerning the clinical management of bariatric patients. This study aims to synthesize the current state of knowledge regarding the psychiatric care of bariatric patients. METHOD: A selective review of literature involving articles indexed on Medline and PubMed up to June 2010, using the terms: "bariatric surgery", "psychiatry", "binge eating", "follow-up", and "outcome". RESULTS: The literature is somehow consensual in which there is no absolute psychiatric contraindication for bariatric surgery, although the preoperative evaluation is of extreme importance for the diagnosis and treatment of any psychiatric disorder, to assure adherence to the multidisciplinary approach, improved quality of life and possibly a better prognosis after surgery. Among the most prevalent disorders in this population is the binge-eating disorder (BED), which is associated with lower weight loss and poor quality of life, especially when present in the postoperative period. In the postoperative follow-up one should also be alert to the emergence of impulsive symptoms, including abuse of alcohol and other substances. DISCUSSION: Several studies indicate high prevalence of mental disorders and psychopathology in the population of bariatric patients. Although most patients experience adequate weight control and improved quality of life in the medium and long term, some patients develop abnormal behavior relating to dysfunctional eating patterns, abuse of alcohol and other substances, and complications associated with impulsive behavior, which suggests etiological hypotheses involving from...