Transcranial magnetic stimulation (TMS) is a non-invasive, save method to stimulate the cerebral cortex and thereby alter neuronal function. In TMS a coil, which delivers brief magnetic pulses is placed adjacent to the scalp. The magnetic field…
ID
Source
Brief title
Condition
- Schizophrenia and other psychotic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome of the study is a significant decline of negative symptoms
and cognitive dysfunctioning after bilateral high frequency rTMS treatment of
the DLPFC.
Secondary outcome
The secondary outcome of the study is increased cortical activation in the
DLPFC after rTMS treatment, measured through a fMRI study. The relationships
between rTMS treatment, improvement in cognitive functioning, decrease of
negative symptoms and changes in the measurement of the Blood Oxygenation Level
Dependent (BOLD) signal through fMRI will be studied. In addition, we aim to
investigate any possible improvement in cognitive functioning, as cognitive
dysfunction in schizophrenia has also been related to frontal brain impairment.
Background summary
Schizophrenia is a mental illness that frequently causes long term disability.
In most cases the disease manifests itself between the ages of 16 and 30 years.
Symptoms can be categorized in three types: positive symptoms, cognitive
impairment and negative symptoms. Positive symptoms include false beliefs
(delusions) and perceptual experiences not shared by others (hallucinations).
Cognitive impairment includes deficits in attention, learning, memory and
executive functions. Negative symptoms are manifested by diminishing or loss of
function in the behavioural and/or emotional domain including anhedonia,
avolition, alogia and apathy. Negative symptoms and cognitive impairments
predict a worse clinical outcome and are often indicative of poorer social,
occupational and global outcomes. Currently, treatment options to improve
negative symptoms and cognitive functioning yield disappointing results.
Antipsychotic medication has limited efficacy to improve cognitive functioning
and negative symptoms.
Brain activity in people with schizophrenia differs when compared to brain
activity of people who do not have this condition. There is evidence that the
negative symptoms of schizophrenia are related to reduced cortical activation
involving the prefrontal cortex, in particular the activation in the
dorsolateral prefrontal cortex (DLPFC) seems to be reduced. The reduced
activity in the frontal cortex correlates with the severity of negative
symptoms. Furthermore, several publications on functional neuroimaging
literature suggest that hypofrontality in schizophrenia may be related to both
negative symptoms and cognitive deficits. A possible treatment approach would
therefore be to increase the brain activation within this region.
Study objective
Transcranial magnetic stimulation (TMS) is a non-invasive, save method to
stimulate the cerebral cortex and thereby alter neuronal function. In TMS a
coil, which delivers brief magnetic pulses is placed adjacent to the scalp. The
magnetic field passes the skull without hindrance and induces an electric
current in certain brain regions. The neuronal pathways may be excited or
inhibited, depending on the intensity and frequency of stimulation. Low
frequency TMS (1 Hz) decreases brain activity and high frequency TMS (>5 Hz)
increases brain activity.
As mentioned earlier the activation in de DLPFC is reduced in people suffering
from schizophrenia, and this reduction correlates with the severity of negative
symptoms. Therefore, increasing brain activity in the DLPFC by using bilateral
high frequency rTMS might prove an effective treatment of negative symptoms and
cognitive disfunctioning in schizophrenia.
Study design
Double-blind sham controlled study.
Intervention
The rTMS group of 16 patients will receive bilateral rTMS stimulation during 15
days, sessions being given twice daily. The sham group of 16 patients will
constitute the placebo group and receive 15 days of bilateral sham stimulation
twice daily.
Study burden and risks
The estimated burden for participating in this study is approximately 31 hours.
The risk's in both treatment arms include the risks surrounding fMRI research,
such as claustrophobia or hearing damage. Any indication of claustrophobia or
anxiety is a cause for immediate cessation of the experiment and further
exclusion from the study. Furthermore, in order to protect the subjects*
hearing, protective headphones will be provided.
In addition, high frequency rTMS does have a small risk of inducing epileptic
seizures.
Hanzeplein 1
9700 RB Groningen
NL
Hanzeplein 1
9700 RB Groningen
NL
Listed location countries
Age
Inclusion criteria
Patients included must have prominent negative symptoms and patients must have a negative subscore >= 15 on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Only patients who are fully capable of making their own decision regarding participation in the research will be included.
Exclusion criteria
Exclusion criteria include rTMS and MRI contraindications (e.g. a personal or family history of epileptic seizures, history of brain surgery, intracerebral or pacemaker implants, inner ear prosthesis or other metal prosthetics/implants), neurological disorders, a head injury with loss of consciousness in the past, substance dependency within the previous 6 months, previous treatment with rTMS, severe behavioural disorders, inability to provide informed consent and claustrophobia. Female patients who are pregnant will be excluded.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL21420.042.08 |