Imaging brain functions during neuropsychological testing

Abstract

This thesis has dealt with the development of tools for assessing cognitive functions(attention and working memory) using functional imaging and the evaluation of the modulatory effects of performance, nicotine, alcohol, brain injury and auditory interference. Two cognitive tasks commonly used in the assessment of patients with brain injury, the externally-generated Perceptual Maze Test (PMT) and an internally-generated arithmetical task, Serial-7, were used as activation paradigms. Regional cerebral blood flow was used as an index for neuronal activity and [15 O] butanol was the flow tracer. The imaging processing and statistical analysis was performed with a method developed at the Karolinska Hospital based on the computerized brain atlas and by statistical parametric mapping (SPM).

The externally-generated PMT task is a highly visuoperceptual task which elicited cortical activations representing visuospatial decoding, attention and motor performance, with only minor involvement of the frontal cortex outside the frontal eye fields. The internally-generated Serial-7 task elicited bilateral activations in fronto-parietal regions, which reflect involvement of attention, working memory and inner speech.

The PMT and the Serial-7 elicited different activation patterns representing the recruitment of different aspects of cognition, but a similar deactivation pattern. The activations of the Serial-7 task were modulated by disturbing irrelevant speech, which may be indicative of an attention-based modulation of activity in regions attributed to task-irrelevant processing. These findings stress the importance of considering the activations as well as the deactivations elicited by a task when interpreting functional imaging data.

Differences attributed to performance in the PMT were observed in regions involved in handling different levels of perceptual complexity. Differences attributed to performance in the Serial -7 task were found in regions that regulate aspects of attention. These findings suggest an increased level of automaticity in high than in low performers, the latter relied more on a higher level of perceptual processing and willed attention.

Nicotine elicited a specific rCBF response in regions pertaining to attention and vision in both non-smokers and smokers. These findings are consistent with the well-known behavioural effects of nicotine. Alcohol elicited behavioral disturbances expressed as CBF increases in prefrontal regions and the antenor cingulate cortex and decreases in the posterior regions. Despite these effects of nicotine and alcohol, the activation patterns elicited by the PMT and Serial-7 were unaffected. The effect of nicotine and alcohol on the anterior cingulate cortex was lateralized to the right hemisphere, which is consistent with a drug interaction with the cerebral reward systems. The increases with alcohol were attributed to the euphoriant effects of the drug, whereas the effects of nicotine may represent a more subtle effect on e.g. attention mechanisms.

Patients with previous episodes of severe hypoglycaemia activated the same regions as two control groups, when solving to the PMT task. Subtle inter-group differences in the level of activation were however observed. The prefrontal cortex was more activated in patients with severe hypoglycaemia. These activations did not overlap with those attributed to performance. When studying functional recovery after brain injury with functional imaging techniques, it is of considerable importance to use tasks and analysis that differentiate between influences from performance, compensatory strategies as well as the restoration of function.