Different types of motor learning in patients with early psychosis

Schizophrenia is the psychiatric disorder with the worst prognosis. Its
lifetime prevalence is about 1% and the disorder starts at an early lifetime,
often with a chronic course.
Although a lot of research has focused on the pathophysiology of schizophrenia,
today it still remains unclear which neurobiological foundations cause the
disorder. Focusing on the symptom level, it is well documented that besides the
positive and negative symptoms neurological hard and soft signs are more
prominent in patients with schizophrenia.
There is clear evidence from a broad field of research that patients suffering
from schizophrenia demonstrate impairments in a lot of neuropsychological
functions such as working memory, selected attention, verbal memory, explicit
learning etc. Based on these impairments a number of theories about the
underlying pathophysiology have been developed, most of them stating that
schizophrenia is a brain disorder affecting mostly the frontal and temporal
regions of the brain. There is a lot of support for these theories from
neuroimaging studies which find different brain activation patterns in patients
with schizophrenia compared to healthy controls during task performance.
Less attention has been given to motor learning, although the dopamine
hypothesis strongly refers to the basal ganglia, a part of the motor system
involved in motor skill acquisition. One recent theory, proposed by Andreasen
states that the observed phenomenology of schizophrenia is based on disturbance
of the cortico-cerebellar-thalamo-cortical circuit (CCTCC), resulting in a
neurodevelopmentally derived *misconnection* syndrome. Very rapid on-line
feedback between cortex and cerebellum via the thalamus is stated to be
responsible for fluidly coordinating sequences of motor activity and thinking.
This circuit is stated to be responsible for the synchronized coordination of
sequences of motor activity and thinking. In patients suffering from
schizophrenia this would cause a *cognitive dysmetria*.

The aim of this study is to examine three types of motor learning reflecting
the function of different brain regions: brain stem, cerebellum and the basal
ganglia. Besides the basal ganglia which are one region with a high presence of
dopaminergic neurons, all these regions are stated to be involved in the
pathophysiology of schizophrenia as stated by the model of Andreasen.

The paradigm comprises three motor learning tasks:
1. Motor sequence learning: Subjects have to perform finger tapping sequence on
a computer keyboard 12 times for 30 seconds each. Each trial is followed by a
rest period of 30 seconds. Two hours later, subjects are asked to perform the
finger tapping sequence again twice for 30 seconds separated by a rest period
of 30 seconds. 24 hours later, this will be repeated again twice for 30
seconds. Outcome is the increase in performance measured in speed and accuracy
2. Eye-blink conditioning: Subjects will see a film on a computer screen. At
the same time equipment to measure the eye-blink will be mounted on the head of
subjects and a headphone will be put on. In a random order little air puffs
will be delivered to the eye, which will be followed by a reflective eye-blink.
In a certain percentage the air puff will be preceded by a tone delivered via
the headphone. Outcome is how many trials have to be performed until subjects
will make an eye- blink due to the tone before the air puff will be delivered.
3. Adaptation of saccadic eye movements: Subjects have to fixate a red dot on a
computer screen which will be moved repeatedly. The reflective saccadic eye
movements will be observed. After a short baseline measurement in which the
saccade properties such as accuracy and latency are characterized, the saccade
adaptation paradigm will start. The red dot that first jumped to the right 25
degrees, will be moved 5 degrees back to the left at the very moment of the
reflective saccade. The consequence is that the subject perceives the first
saccade as having been hypermetric. When this stimulus is repeated, subjects
gradually and subconsciously decrease their initial saccadic eye movement.
Outcome is how quickly the subject decreases the saccade amplitude.

Non invasive psychophysiological examination lasting about 3 hours (breaks
included). In a separate session, for patients only, actual psychopathology and
extrapyramidal symptoms will be assessed.

For these non-invasive psychophysiological examination procedures no risks are
known.