Testing cerebral function: will it help the understanding or diagnosis of central nervous system disease?

The recent introduction of non-invasive tools for the quantitative mapping of cerebral function in humans (e.g. cerebral blood flow measurement and positron emission tomography) in conjunction with detailed in vivo tomographic morphology (computed tomography and magnetic resonance imaging) has led to a fruitful interaction between clinicians and fundamental neuroscientists. This has led to the development of a productive, scientifically sound human neuroscience whose aim is to explore brain function directly in the human subject. With respect to the physiological state, this research has resulted in major findings especially in the fields of visual function, attention, anticipatory anxiety, language, motion and somaesthesia. The study of disease states has resulted in less impressive findings. The investigation of patients with focal brain lesions has revealed time-dependent alterations of cerebral blood flow and energy metabolism in widespread grey matter structures, as a result of disconnection; however, these functional alterations apparently reflect a variety of processes, from Wallerian or retrograde degeneration to reversible or irreversible transsynaptic or transneuronal effects, which makes their interpretation uncertain. Likewise the cellular and neurochemical basis for the recovery of energy metabolism in deafferented brain areas remains speculative. Although several types of metabolic effects due to disconnection are correlated to well-defined neuropsychological/behavioural impairment (and recovery therefrom) unexplained discrepancies exist and their role in individual patients remains obscure. The study of the brain's 'functional reserve' by activation paradigms would presumably shed more light on the clinical/functional brain relationships in disease but such investigations are hampered by unresolved methodological issues such as the choice criteria for the control population (?healthy controls, ?asymptomatic brain-lesioned patients) and task (?pseudo-impaired). There are also complex statistical issues because of the requirement to study single cases as a result of the inter-subject variability in lesion topography, size or duration, as well as in the pattern and degree of behavioural impairment. The design of controlled experimental paradigms in non-human primates, involving controlled lesions and sequential behavioural and PET assessment, may help to resolve some of these issues.