title: Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease.
abstract: OBJECTIVE
  Recent transcranial magnetic stimulation (TMS) studies demonstrate that motor cortex excitability is increased in Alzheimer's disease (AD) and that intracortical inhibitory phenomena are impaired. The aim of the present study was to determine whether hyperexcitability is due to the impairment of intracortical inhibitory circuits or to an independent abnormality of excitatory circuits.
  
  
  METHODS
  We assessed the excitability of the motor cortex with TMS in 28 patients with AD using several TMS paradigms and compared the data of cortical excitability (evaluated by measuring resting motor threshold) with the amount of motor cortex disinhibition as evaluated using the test for motor cortex cholinergic inhibition (short latency afferent inhibition) and GABAergic inhibition (short latency intracortical inhibition). The data in AD patients were also compared with that from 12 age matched healthy individuals.
  
  
  RESULTS
  The mean resting motor threshold was significantly lower in AD patients than in controls. The amount of short latency afferent inhibition was significantly smaller in AD patients than in normal controls. There was also a tendency for AD patients to have less pronounced short latency intracortical inhibition than controls, but this difference was not significant. There was no correlation between resting motor threshold and measures of either short latency afferent or intracortical inhibition (r = -0.19 and 0.18 respectively, NS). In 14 AD patients the electrophysiological study was repeated after a single oral dose of the cholinesterase inhibitor rivastigmine. Resting motor threshold was not significantly modified by the administration of rivastigmine. In contrast, short latency afferent inhibition from the median nerve was significantly increased by the administration of rivastigmine.
  
  
  CONCLUSIONS
  The change in threshold did not seem to correlate with dysfunction of inhibitory intracortical cholinergic and GABAergic circuits, nor with the central cholinergic activity. We propose that the hyperexcitability of the motor cortex is caused by an abnormality of intracortical excitatory circuits.
authors.affiliation: Institute of Neurology, Università Cattolica, Largo A. Gemelli 8, 00168 Rome, Italy. vdilazzaro@rm.unicatt.it
authors.forename: V
authors.initials: V
authors.lastname: Di Lazzaro
authors.forename: A
authors.initials: A
authors.lastname: Oliviero
authors.forename: F
authors.initials: F
authors.lastname: Pilato
authors.forename: E
authors.initials: E
authors.lastname: Saturno
authors.forename: M
authors.initials: M
authors.lastname: Dileone
authors.forename: C
authors.initials: C
authors.lastname: Marra
authors.forename: A
authors.initials: A
authors.lastname: Daniele
authors.forename: S
authors.initials: S
authors.lastname: Ghirlanda
authors.forename: G
authors.initials: G
authors.lastname: Gainotti
authors.forename: P A
authors.initials: PA
authors.lastname: Tonali
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology*; D002219:Carbamates; D002540:Cerebral Cortex / Q000503:physiopathology*; D002799:Cholinergic Fibers / Q000502:physiology; D002800:Cholinesterase Inhibitors; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000294:innervation; D016202:N-Methylaspartate / Q000502:physiology; D009415:Nerve Net / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology*; D048448:Phenylcarbamates; D011930:Reaction Time / Q000502:physiology; D000068836:Rivastigmine; D012684:Sensory Thresholds / Q000502:physiology; D012815:Signal Processing, Computer-Assisted; D050781:Transcranial Magnetic Stimulation; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D000068836:Rivastigmine