Trial of Stimulus-response Potentiation in Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      This clinical trial aims at examining the effects of auditory high-frequency stimulation in
      schizophrenia patient, aiming to increase their AEPs, which are known to be attenuated from
      previous literature
    

Detailed description: 
      Schizophrenia is a chronic psychiatric disorder with a lifetime prevalence of 4.0 per 1,000.
      The introduction of antipsychotic medications in the 1950s resulted in marked clinical
      improvement in the symptom profile of schizophrenia, nevertheless the disease still
      contributes to a significant proportion of global disease burden in terms of both morbidity
      and mortality. In this regard, cognitive deficits and residual negative symptoms are
      considered major contributing factors to psychosocial disability and poor functional outcome
      associated with the disorder.

      Higher-order cognitive functions; e.g. working memory and executive functions; show variable
      deficits and are considered a core clinical symptom of schizophrenia. On the other hand, the
      disorder is also characterized by abnormalities at the basic level of primary sensory
      processing, i.e. auditory, visual and somatosensory processing. Such abnormalities in the
      primary process of sensory perception could change the sensory experiences of schizophrenia
      patients and thus contribute to the psychopathology.

      Event-related potentials (ERPs) are the neurophysiological correlates of sensory processing.
      ERP abnormalities have been widely described in schizophrenia literature: Pre-pulse
      inhibition of startle (PPI) in which a weaker pre-stimulus (pre-pulse) inhibits the reaction
      to a subsequent strong startling stimulus (pulse) is impaired in schizophrenia. P50
      suppression, a measure of sensory gating, is also often absent or reduced in the disorder.
      N100; a measure of basic auditory sensory perception; shows significant amplitude reduction
      in patients compared to controls. Mismatch negativity (MMN), a measure of automatic deviance
      detection and shows characteristic attenuation in schizophrenia. P300, which is involved in
      higher-level stimulus evaluation and categorization, also shows abnormalities along the
      disease course.

      In the study by Clapp et al., 2005, auditory high frequency stimulation (tetanizing
      stimulation) resulted in an increase in auditory-evoked potentials (AEPs) in healthy
      individuals; i.e. an increase in N1 amplitude that persisted even after stimulation. This
      augmentation of N1 amplitude was regarded as a result of plastic synaptic potentiation
      similar to long-term potentiation (LTP) described after electrical tetanic stimulation in
      cellular studies. Similar findings were later replicated by Lei et al., 2017, where they used
      pure tones, narrow band noises and white noise to induce stable potentiation and augmentation
      of N1 amplitude.
    

Intervention name(s): Auditory High Frequency Tetanizing Stimulation; Sham Comparator
Intervention type(s): Diagnostic Test; Diagnostic Test
Intervention description(s): 50 ms tone pips presented at high frequency for 120 seconds; auditory tone pips with interstimulus interval (ISI) 1 sec
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment