Letter to the Editor

Molecular Psychiatry (2012) 17, 568–569; doi:10.1038/mp.2011.141; published online 1 November 2011

Communication breakdown: delta-9 tetrahydrocannabinol effects on pre-speech neural coherence

J M Stone1,2, P D Morrison1, S Brugger1,3, J Nottage1, S Bhattacharyya1, A Sumich1,4, D Wilson1,4, N Tunstall1, A Feilding5, R Brenneisen6, P McGuire1, R M Murray1 and D H ffytche1

  1. 1King's College London Institute of Psychiatry, De Crespigny Park, London, UK
  2. 2Imperial College London, London, UK
  3. 3St George's University of London, London, UK
  4. 4Division of Psychology, School of Social Sciences, Nottingham Trent University, Nottingham, UK
  5. 5The Beckley Foundation, Oxford, UK
  6. 6Department of Clinical Research, University of Bern, Bern, Switzerland

Correspondence: JM Stone, E-mail: james.m.stone@imperial.ac.uk

Synchronised neural oscillations preceding speech generation are reduced in patients with schizophrenia, this deficit being implicated in symptom formation. We measured synchronisation of neural oscillations preceding vocalisation in the presence of delta-9 tetrahydrocannabinol (THC) and found they were significantly disrupted. Furthermore, the degree of disruption was related to THC-induced symptoms, suggesting THC may modulate a similar neural substrate to schizophrenia.

Self-generated actions are preceded by synchronised neural oscillations thought to be associated with preparation for movement.1, 2 These oscillations may be involved in forming an internal representation (efference copy) of the actions, allowing subsequent sensory inputs to be correctly identified as originating from the self.2, 3 This process may be impaired in patients with schizophrenia, leading to a failure to generate a sense of agency, and giving rise to delusions and hallucinations.3, 4 For example, patients with schizophrenia do not display the normal pattern of frontal neural oscillatory synchronisation (intertrial coherence; ITC) in the 150ms preceding the onset of self-generated speech as measured by electroencephalography.2 This disruption of ITC is related to auditory hallucinations.2

Acute intravenous administration of delta-9 THC—the main psychoactive component of cannabis—may induce perceptual disturbances some of which resemble positive symptoms of schizophrenia.5, 6, 7 Here, we test the hypothesis that intravenous THC administration disrupts ITC in the 150ms before the onset of self-generated vocalisation, over the same region of frontal cortex previously studied in patients with schizophrenia (electroencephalography lead FCz)2 and that the level of disruption is associated with the degree of THC-induced psychopathology.

Methods are fully described in Supplementary materials. We administered 1.25mg THC or placebo to 16 healthy volunteers before a self-generated vocalisation task during electroencephalography acquisition. Volunteers completed a self-rated 24-item questionnaire on cannabis effects before and 30minutes after the infusion (see Supplementary materials). THC led to a significant increase in self-rated measures of salience (t=2.69, df=15, P=0.01), ipseity disturbance (t=2.73, df=15, P=0.015), anxiety (t=2.50, df=15, P=0.02), paranoid persecutory ideation (t=2.97, df=15, P=0.01) and perceptual abnormalities (t=4.16, df=15, P=0.0008).

THC administration attenuated pre-speech ITC in the 150ms before the onset of self-generated speech, primarily at 3.9Hz, but also at 7.8Hz (3.9Hz: t=4.78, df=15, P=0.0002; 7.8Hz: t=2.63, df=15, P=0.02, Figure 1). The ITC reduction was specific to speech generation, as there was no difference in ITC between THC and placebo conditions before the onset of the visual cue used in the task at frontal or occipital electrode sites. At 11.7Hz, THC led to a modest increase in ITC (t=2.29, df=15, P=0.04), and there was a trend for increase in ITC at 15.6Hz (t=1.96, df=15, P=0.07).

Figure 1.
Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

Time-frequency analysis of ITC electroencephalography data acquired from FCz before the onset of vocalisation (time 0) following intravenous injection of placebo (a) or delta-9 THC (b).

Full figure and legend (119K)Download PowerPoint slide (246 KB)

The degree of reduction in 3.9Hz ITC 150–0ms before onset of vocalisation was related to increasing self-rated measures of salience, simplifying to a single term—‘my thoughts are more special or significant than usual’ (F1,14=4.69, P=0.048). It was also related to increasing self-rated measures of ipseity disturbance, simplifying to a single term—‘I believe my mind is being read’ (F1,14=7.871, P=0.014). There was no relationship between ITC changes in any other frequency band with self-rated measures of cannabis effects.

These results provide the first evidence that THC disrupts ITC before the onset of self-generated vocalisation, and that the degree of disruption is related to THC-induced psychological effects. The findings show considerable overlap with previously reported data in patients with schizophrenia,2 although the frequency changes reported here are in a lower frequency band. This may reflect the lower frequency resolution used in the schizophrenia study, where changes in theta- and alpha-range ITC would have contributed to the lowest resolvable frequency at 15.6Hz. However, it is also possible the ITC pre-vocalisation changes in schizophrenia have a different frequency composition to those found under THC, pointing to a difference in efference processing dysfunction in the two conditions. Whether the effect of THC is the same or closely related to that found in schizophrenia, our findings indicate modulation of ITC by THC may be a useful biomarker for the development of novel antipsychotic drugs.

Top

Conflict of interest

The authors declare no conflict of interest.

Top

References

  1. Nicolelis MA, Baccala LA, Lin RC, Chapin JK. Science 1995; 268: 1353–1358. | Article | PubMed | ISI | CAS |
  2. Ford JM, Roach BJ, Faustman WO, Mathalon DH. Am J Psychiat 2007; 164: 458–466. | Article | PubMed | ISI |
  3. Feinberg I. Schizophrenia bull 1978; 4: 636–640.
  4. Frith CD, Done DJ. Br J Psychiatry 1988; 153: 437–443. | Article | PubMed | ISI |
  5. DSouza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT et al. Neuropsychopharmacol 2004; 29: 1558–1572. | Article |
  6. Morrison PD, Zois V, McKeown DA, Lee TD, Holt DW, Powell JF et al. Psychol Med 2009; 39: 1607–1616. | Article | PubMed | ISI | CAS |
  7. Bhattacharyya S, Fusar-Poli P, Borgwardt S, Martin-Santos R, Nosarti C, O'Carroll C et al. Arch Gen Psychiatry 2009; 66: 442–451. | Article | PubMed | ISI | CAS |

Supplementary Information accompanies the paper on the Molecular Psychiatry website