Diffusion tensor imaging of frontal lobe white matter tracts in schizophrenia

The hypothesis that schizophrenia is an illness arising from disconnection or misconnections of circuits connecting prefrontal cortex with the thalamus and striatum has received support from studies of post-mortem brains [1,2], imaging [3-5], and electrophysiology[6]. The thalamus has been viewed as a key element in potential schizophrenia-related deficits in this circuit because of the reciprocal circuitry between the prefrontal lobe and the medial dorsal nucleus [7-9]. The thalamus comprises multiple nuclei that relay and filter sensory and higher order inputs to and from the cerebral cortex and limbic structures; thus, deficits are consistent with behavioral abnormalities in schizophrenia [10]. The medial dorsal nucleus (MDN) of the thalamus, important in attention as reviewed elsewhere [11], has interconnections with the dorsolateral prefrontal cortex [12]. The connections of the MDN have been used to define the prefrontal cortex [13], a key area of functional and structural alteration in schizophrenia (reviewed by: [14]. Since deficits in the frontal lobes, the thalamus, and the striatum have been found in schizophrenia with both structural and functional imaging as reviewed elsewhere [14,15], the white matter connections between the thalamus and prefrontal cortex are of special interest.The anterior limb of the internal capsule contains fronto-thalamic and thalamo-frontal pathways, the cortico-pontine pathways, and a lesser number of caudate/pallidum fibers, while the posterior section of the anterior limb of the internal capsule has primarily corticopontine fibers [16] Reduction in the size of the internal capsules in patients with schizophrenia [17-20] would be consistent with diminished corticothalamic and corticostriatal connectivity and with previous reports of schizophrenia-associated abnormalities in the striatum [21,22] and thalamus [4,5,23,24].To investigate white matter circuitry of these frontal-thalamic connections, we applied diffusion tensor magn