A pet study of monozygotic twins discordant for frontal lobe injury: neurophysiological and cognitive sequelae

Abstract

Because the frontal lobes are extremely susceptible to traumatic brain insuit, closed head injury patients may serve as a useful model of frontal lobe damage. We had the opportunity to study with positron emission tomography (PET) a 28-year-old pair of male, college-educated monozygntic twins who had been involved in a motor vehicle accident, one of whom sustained a severe closed head injury. A CT scan conducted early during his 2-week coma revealed bilateral frontal lobe damage, more severe on the right side. These circumstances afforded a unique opportunity to view with PET the long-term cognitive sequelae of his frontal lobe injury and their neumphysiological concomitants against a geneticallyequated control subject. Six years after the accident, an MR! scan showed some resolution of these pathological changes but cognitive deficits remaine& At that time, we measured regional cerebral blood flow (tCBF) in both twins using the oxygen-15 water method during the Wisconsin Card Sorting Test (WCS) and during a sensorimotor control task. Data were normalized on a pixel-by-pixel basis as a percentage of the whole brain mean. To examine patterns of rCBF activation specific to higher cognitive functions, rCBF values for the sensorimotor control task were subtracted from those for the abstract reasoning task. Regions were drawn on the twins' coplanar MRi's and applied to their respective PET data. Consistent with the pattern of tCBF activation during the WCS identified in several cohorts of normal subjects in previous studies by our lab, the uninjured twin showed activation of Brodman's areas 46 and 9 in the left and right inferior frontal gyri with relative deactivation of the left hippocampus. Like his uninjm~l co-twin, the injured twin activated the left inferior frontal gyms. However, the injured twin failed to activate the right inferior frontal gyms and, instead, activated the left hippocampus, it is interesting to note that this pattern of prefrontal hypoactivity and hippocampal hyperactivity during the WCS has been shown to be associated with poor task performance in normal subjects and to be a characteristic of patients with schizophrenia. These data may help to clarify the relative contributions of the dorsolateral prefrontal cortex and the hippocampus in higher order human cognition.