No abstract

The detailed anatomical distribution of iron in the post-mortem human brain has been studied using Perl’s and Turnbull’s methods with the diaminobenzidine intensification procedure for the demonstration of non-haem Fe³⁺ and Fe²⁺ respectively. Attention to methodological procedures has revealed that even brief immersion of tissue in routinely used fixatives causes a reduction of staining intensity in areas of high iron content and, often, loss of staining in areas of low iron content. Optimal staining is obtained using frozen section briefly fixed for 5 min in 4% formalin and Perl’s stain (Fe³⁺) with diaminobenzidine intensification. Highest levels of stainable iron were found in the extrapyramidal system with the globus pallidus, substantia nigra zona reticulata, red nucleus and myelinated fibres of the putamen showing highest staining reactivity. Moderate staining intensity with Perl’s technique was found in the majority of forebrain, midbrain and cerebellar structures with the striatum, thalamus, cortex and deep white matter, substantia nigra zona compacta, and cerebellar cortex showing consistent staining patterns with intensification of Perl’s stain. The brain-stem and spinal cord generally only showed staining with the intensification procedure and even this was of low intensity. Microscopically the non-heam iron appears to be found predominantly in glial cells as fine cytoplasmic granules which in heavily stained areas coalesce to fill the entire cell. Iron-positive granules appear to be free in the neuropil and also around blood vessels in the globus pallidus, striatum and substantia nigra. The neuropil shows a fibrous impregnation when stained for iron which is, in part, derived from glial processes, myelinated fibres and fibre bundles. Neurones, in general, show only very low reactivity for iron, and this is difficult to discern due, often, to the higher reactivity of the surrounding neuropil. In the globus pallidus and substantia nigra zona reticulata, neurones with highly stainable iron content are found with granular cytoplasmic iron reactivity similar to that seen in the local glial cells. Our results are comparable with those of early workers, but with the use of intensification extend the distribution of non-haem iron to areas previously reported as negative. No apparent correlation of iron staining with known neurotransmitter systems is seen and the predilection for the extrapyramidal system is not easily explained, though the non-haem iron in the brain appears to be as a storage form in the iron storage protein ferritin. The localization of iron in the brain provides a foundation for the study of iron in certain neurodegenerative diseases such as Parkinson’s disease, where iron has been implicated in the pathogenesis.

Nine patients with Parkinson's disease were compared with aged-matched normal controls on a tracking and a reaction time task. In the tracking task, subjects had to follow a target moving either predictably or unpredictably at various frequencies. There were no differences between the groups on this task. Both groups were able to use the predictable target movements to eliminate the lag between the target movements and their own movements, indicating that they could emit preprogrammed responses which did not depend on visual feedback. The reaction time task also contrasted predictable and unpredictable movements since the subjects were sometimes told in advance which finger they would have to lift in response to the imperative signal. The patients were significantly less able than controls to use this predictability to reduce their reaction times. It is concluded that parkinsonian patients can use prior information to control the form of a preprogrammed movement, but cannot use this information to help initiate such a movement.

SUMMARY Twelve patients with Parkinson's disease learned two novel skills in which they had to track a target by moving a joystick. In task 1 they had to learn to anticipate the movements of a semi predictable target. In task 2 they had to learn a novel control system in which the movements of the joystick were mirror reversed in relation to the computer screen.On each task they performed two sessions of three minutes continuous practice separated by a 10 minute rest. In both tasks the patients performed much worse than the controls, but showed clear evidence of learning, particularly after the ten minute rest. Detailed examination of their performance suggested that the skill was becoming automatic, releasing attention for aspects of the task that could not be learned. The major difference from the controls appeared during the first minute of each practice session when the controls showed a marked improvement in performance while the patients did not. We suggest that this rapid but temporary improvement in performance reflects the acquisition of a motor "set" whereby existing motor programs or skills are modified to suit the task currently in hand. We concluded that patients with Parkinson's disease have difficulty in maintaining such sets.

SUMMARY Ten patients with Parkinson's disease performed a simple reaction time task in which, on hearing a tone, they pressed a button with the left thumb. In the first experiment tones sometimes occurred unannounced and at other times were preceded (by between 0 and 3200 ms) by a warning signal. The second experiment was identical to the first except that the subject had simultaneously to perform a simple continuous task with his right hand. Patients had slower reaction times than controls under all circumstances. In general, however, the effect of a warning signal and the effect of a second task were the same for both groups. In the control group the effect of a warning signal depended on whether or not a second task was being performed. Specifically, the advantage of a warning signal for reaction time was lost after long intervals (> 200 ms) when a second task was being performed. Parkinson's disease patients lost this advantage even when they were not performing a second task. Animal studies have suggested that dopamine deficiency results in an increase in neural "noise" in the basal ganglia. The behavioural consequences of this may be that Parkinson's disease patients always perform as if they were carrying out another task at the same time. In contrast, their ability to benefit from a warning signal and to allocate attentional resources are unimpaired.