title: Effects of alprazolam on cortical activity and tremors in patients with essential tremor.
abstract: BACKGROUND
  Essential tremor (ET) is characterised by postural and action tremors with a frequency of 4-12 Hz. Previous studies suggest that the tremor activity originates in the cerebello-thalamocortical pathways. Alprazolam is a short-acting benzodiazepine that attenuates tremors in ET. The mechanisms that mediate the therapeutic action of alprazolam are unknown; however, in healthy subjects, benzodiazepines increase cortical beta activity. In this study, we investigated the effect of alprazolam both on beta and tremor-related cortical activity and on alterations in tremor presentation in ET patients. Therefore, we characterised the dynamics of tremor and cortical activity in ET patients after alprazolam intake.
  
  
  METHODS
  We recorded hand tremors and contralateral cortical activity in four recordings before and after a single dose of alprazolam. We then computed the changes in tremors, cortico-muscular coherence, and cortical activity at the tremor frequency and in the beta band.
  
  
  RESULTS
  Alprazolam significantly attenuated tremors (EMG: 76.2 ± 22.68%), decreased cortical activity in the tremor frequency range and increased cortical beta activity in all patients (P<0.05). At the same time, the cortico-muscular coherence at the tremor frequency became non-significant (P<0.05). We also found a significant correlation (r = 0.757, P<0.001) between the reduction in tremor severity and the increased ratio of cortical activity in the beta band to the activity observed in the tremor frequency range.
  
  
  CONCLUSIONS
  This study provides the first quantitative analysis of tremor reduction following alprazolam intake. We observed that the tremor severity decreased in association with an increased ratio of beta to tremor-related cortical activity. We hypothesise that the increase in cortical beta activity may act as a blocking mechanism and may dampen the pathological oscillatory activity, which in turn attenuates the observed tremor.
authors.affiliation: Bioengineering Group, Consejo Superior de Investigaciones Científicas, Arganda del Rey, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Ibáñez
authors.affiliation: Department of Neurology, University Hospital "12 de Octubre", Madrid, Spain; Department of Medicine, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: González de la Aleja
authors.affiliation: Bioengineering Group, Consejo Superior de Investigaciones Científicas, Arganda del Rey, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Gallego
authors.affiliation: Department of Neurology, University Hospital "12 de Octubre", Madrid, Spain; Universidad Francisco de Vitoria, Pozuelo de Alarcón, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Romero
authors.affiliation: Department of Neurology, University Hospital "12 de Octubre", Madrid, Spain; Department of Medicine, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Rosana A
authors.initials: RA
authors.lastname: Saíz-Díaz
authors.affiliation: Department of Neurology, University Hospital "12 de Octubre", Madrid, Spain; Department of Medicine, Faculty of Medicine, Complutense University, Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Benito-León
authors.affiliation: Bioengineering Group, Consejo Superior de Investigaciones Científicas, Arganda del Rey, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rocon
mesh_terms: D000525:Alprazolam / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D004576:Electromyography; D020329:Essential Tremor / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects / Q000503:physiopathology; D014202:Tremor / Q000150:complications / Q000188:drug therapy*
chemical_list: D000525:Alprazolam