ABSTRACT
Monkeys with unilateral lesions of nigrostriatal dopamine projections were tested on a series of spatial tasks. One task, in which monkeys were required to use one or the other arm to retrieve food rewards from different positions, allowed separate assessment of the use of each arm in each hemi-space in order to distinguish hemi-spatial and hemi-motor impairments. The lesioned monkeys exhibited a persistent neglect of contralesional space when using either arm which could be dissociated from a motor impairment in the contralesional arm alone. Another task allowed free use of either arm across peri-personal space and demonstrated an ipsilesional bias in the monkeys' self-determined attention (orientation) to a task which they were trying to perform. It is argued that the tendency for monkeys with this lesion to rotate ipsilesionally is due to an ipsilesional deviation of the 'centre of interest' (determined by telencephalic circuitry) relative to 'straight ahead' (determined by brainstem circuitry). The dopamine projections may contribute to cortico-subcortical circuits which determine the spatial layout of mental representation, attention and intention. The results in this primate model of unilateral Parkinson's disease (PD) support the view that patients with left-sided Parkinsonian symptoms exhibit a unilateral deficit in spatial mental representation as well as their well-recognised motor symptoms. Patients with bilateral Parkinson's symptoms may exhibit bilateral deficits in mental representation.
Subject(s)
Dopamine/physiology , Functional Laterality/physiology , Neostriatum/physiology , Parkinson Disease/physiopathology , Space Perception/physiology , Substantia Nigra/physiology , Animals , Callithrix , Conditioning, Operant/physiology , Disease Models, Animal , Female , Head Movements/physiology , Image Processing, Computer-Assisted , Male , Motor Activity/physiology , Oxidopamine , Reward , Rotation , Sympathectomy, Chemical , Sympatholytics , Tyrosine 3-Monooxygenase/metabolismABSTRACT
We have examined the effects of permanent middle cerebral artery occlusion (pMCAO) in marmoset monkeys over 5 months, using behavioural and magnetic resonance imaging (MRI) techniques. Three marmosets were trained on behavioural tests before pMCAO. Shortly after surgery, these marmosets were scanned with T2-weighted (T2W) and diffusion-weighted (DW) MRI. Three, 10 and 20 weeks after surgery, these marmosets were re-tested on the behavioural tasks and had further MRI sessions to monitor lesion development. This was followed by histological analysis. All these marmosets had a persistent contralesional motor deficit and a spatial neglect which resolved over the 20 weeks of testing. Percentage infarct volume assessed by MRI on the day of surgery and at 20 weeks matched the percentage infarct volume measured histologically at 20 weeks. However, the apparent infarct size at 3 weeks was considerably less than that measured by histological analysis or that measured at the other MRI time points. Additional histological analysis of the brains of two further marmosets removed 3 weeks after pMCAO found considerable infiltration by lipid filled macrophages into the ischaemic zone which may have caused an MRI "fogging" effect leading to an apparent reduction in infarct volume.
Subject(s)
Disease Models, Animal , Infarction, Middle Cerebral Artery/pathology , Magnetic Resonance Imaging/methods , Recovery of Function/physiology , Animals , Callithrix , Stroke/pathology , TimeABSTRACT
Transient contralesional spatial neglect, in addition to motor impairment in the contralesional arm, is sometimes seen in patients following cerebral infarction in the right hemisphere and is seen following experimental occlusion of the right middle cerebral artery in primates. To test whether contralesional visuospatial neglect arises from a disruption of the forward flow of information from the striate cortex through the dorsal territory of the middle cerebral artery, we made a small strip suction ablation in the right parietal cortex from the medial edge of the dorsal cortical surface to the posterior ventral edge of the superior temporal gyrus in marmoset monkeys. These monkeys did not exhibit a motor impairment, or misreaching, with the contralesional arm. When they were unrestrained and free to use either arm, they were impaired at finding rewards in their contralesional space and in choosing the nearer of two rewards hidden in ipsilesional space (i.e. they had an ultra-ipsilesional bias in ipsilesional space). Comparison of performance under four conditions in a task in which the monkeys were constrained to reach into each hemispace with each arm separately indicated that they were impaired at reaching into contralesional, but not ipsilesional, space with either arm but they did not exhibit any impairment confined to the contralesional arm. These impairments in contralesional space were transient suggesting that the monkeys were able to re-align their egocentric spatial coordinates to obviate these deficits.