RESUMEN
BACKGROUND: Suicide attempts and completed suicides are common, yet there are no proven acute medication or device treatments for treating a suicidal crisis. Repeated daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) for 4-6 weeks is a new FDA-approved treatment for acute depression. Some open-label rTMS studies have found rapid reductions in suicidality. DESIGN: This study tests whether a high dose of rTMS to suicidal inpatients is feasible and safe, and also whether this higher dosing might rapidly improve suicidal thinking. This prospective, 2-site, randomized, active sham-controlled (1:1 randomization) design incorporated 9 sessions of rTMS over 3 days as adjunctive to usual inpatient suicidality treatment. The setting was two inpatient military hospital wards (one VA, the other DOD). PATIENTS: Research staff screened approximately 377 inpatients, yielding 41 adults admitted for suicidal crisis. Because of the funding source, all patients also had either post-traumatic stress disorder, mild traumatic brain injury, or both. TMS METHODS: Repetitive TMS (rTMS) was delivered to the left prefrontal cortex with a figure-eight solid core coil at 120% motor threshold, 10 Hertz (Hz), 5 second (s) train duration, 10 s intertrain interval for 30 minutes (6000 pulses) 3 times daily for 3 days (total 9 sessions; 54,000 stimuli). Sham rTMS used a similar coil that contained a metal insert blocking the magnetic field and utilized electrodes on the scalp, which delivered a matched somatosensory sensation. MAIN OUTCOME MEASURE: Primary outcomes were the daily change in severity of suicidal thinking as measured by the Beck Scale of Suicidal Ideation (SSI) administered at baseline and then daily, as well as subjective visual analog scale measures before and after each TMS session. Mixed model repeated measures (MMRM) analysis was performed on modified intent to treat (mITT) and completer populations. RESULTS: This intense schedule of rTMS with suicidal inpatients was feasible and safe. Minimal side effects occurred, none differing by arm, and the 3-day retention rate was 88%. No one died of suicide within the 6 month followup. From the mITT analyses, SSI scores declined rapidly over the 3 days for both groups (sham change -15.3 points, active change -15.4 points), with a trend for more rapid decline on the first day with active rTMS (sham change -6.4 points, active -10.7 points, P = 0.12). This decline was more pronounced in the completers subgroup [sham change -5.9 (95% CI: -10.1, -1.7), active -13 points (95% CI: -18.7, -7.4); P = 0.054]. Subjective ratings of 'being bothered by thoughts of suicide' declined non-significantly more with active rTMS than with sham at the end of 9 sessions of treatment in the mITT analysis [sham change -31.9 (95% CI: -41.7, -22.0), active change -42.5 (95% CI: -53.8, -31.2); P = 0.17]. There was a significant decrease in the completers sample [sham change -24.9 (95% CI: -34.4, -15.3), active change -43.8 (95% CI: -57.2, -30.3); P = 0.028]. CONCLUSIONS: Delivering high doses of left prefrontal rTMS over three days (54,000 stimuli) to suicidal inpatients is possible and safe, with few side effects and no worsening of suicidal thinking. The suggestions of a rapid anti-suicide effect (day 1 SSI data, Visual Analogue Scale data over the 3 days) need to be tested for replication in a larger sample. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01212848, TMS for suicidal ideation.
Asunto(s)
Trastorno Depresivo/terapia , Corteza Prefrontal/fisiopatología , Intento de Suicidio/prevención & control , Estimulación Magnética Transcraneal/métodos , Adulto , Afecto , Femenino , Hospitalización , Hospitales Militares , Hospitales de Veteranos , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Dolor , Dimensión del Dolor , Estudios Prospectivos , Trastornos por Estrés Postraumático , Resultado del TratamientoRESUMEN
Learning a new word consists of two primary tasks that have often been conflated into a single process: referent selection, in which a child must determine the correct referent of a novel label, and referent retention, which is the ability to store this newly formed label-object mapping in memory for later use. In addition, children must be capable of performing these tasks rapidly and repeatedly as they are frequently exposed to novel words during the course of natural conversation. Here we used a preferential pointing task to investigate 2-year-olds' (N=72) ability to infer the referent of a novel noun from a single ambiguous exposure and their ability to retain this mapping over time. Children were asked to identify the referent of a novel label on six critical trials distributed throughout the course of a 10-min study involving many familiar and novel objects. On these critical trials, images of a known object and a novel object (e.g., a ball and a nameless artifact constructed in the laboratory) appeared on two computer screens and a voice asked children to "point at the _____ [e.g., glark]." Following label onset, children were allowed only 3s during which to infer the correct referent, point at it, and potentially store this new word-object mapping. In a final posttest trial, all previously labeled novel objects appeared and children were asked to point to one of them (e.g., "Can you find the glark?"). To succeed, children needed to have initially mapped the novel labels correctly and retained these mappings over the course of the study. Despite the difficult demands of the current task, children successfully identified the target object on the retention trial. We conclude that 2-year-olds are able to fast map novel nouns during a brief single exposure under ambiguous labeling conditions.