Fronto-temporal connections have long been thought to be involved in schizophrenia. Two fronto-temporal connections of interest are uncinate fasciculus (UF) and cingulum bundle (CB), which recently have been investigating using Diffusion Tensor Imaging (DTI), a new technique that affords an opportunity to evaluate white matter fiber integrity in vivo. Using this technique, we previously reported abnormalities in UF and CB in chronic patients. Additionally, we noted that schizotypal personality disordered subjects showed UF but not CB abnormalities.

Here, we sought to determine whether or not UF and CB white matter integrity are altered at initial onset of illness, and are specific to schizophrenia. We evaluated twelve first-episode schizophrenia, 12 first-episode affective psychosis and 12 controls using DTI on a 1.5T magnet. Fractional anisotropy (FA) and mean diffusivity (Dm) were used to quantify water diffusion, and cross-sectional area was defined with a directional threshold method.

Findings showed bilateral reduction of UF FA, but not Dm, in first-episode schizophrenia compared with controls and first-episode affective psychotic patients. For CB, there were no statistically significant group differences for either FA or Dm.

These findings suggested that UF white matter integrity, but not CB white matter integrity, is altered at initial onset of schizophrenia and may be specific to schizophrenia. In contrast, CB abnormalities are not present at first episode of schizophrenia and may reflect progressive changes that occur over the course of the illness. The latter will need to be investigated using a longitudinal design.

Patients with schizophrenia (SZ) characteristically exhibit supranormal levels of cortical activity to self-induced sensory stimuli, ostensibly because of abnormalities in the neural signals (corollary discharges, CDs) normatively involved in suppressing the sensory consequences of self-generated actions. The nature of these abnormalities is unknown. This study investigated whether SZ patients experience CDs that are abnormally delayed in their arrival at the sensory cortex.

Twenty-one patients with SZ and 25 matched control participants underwent electroencephalography (EEG). Participants' level of cortical suppression was calculated as the amplitude of the N1 component evoked by a button press-elicited auditory stimulus, subtracted from the N1 amplitude evoked by the same stimulus presented passively. In the three experimental conditions, the auditory stimulus was delivered 0, 50 or 100 ms subsequent to the button-press. Fifteen SZ patients and 17 healthy controls (HCs) also underwent diffusion tensor imaging (DTI), and the fractional anisotropy (FA) of participants' arcuate fasciculus was used to predict their level of cortical suppression in the three conditions.

While the SZ patients exhibited subnormal N1 suppression to undelayed, self-generated auditory stimuli, these deficits were eliminated by imposing a 50-ms, but not a 100-ms, delay between the button-press and the evoked stimulus. Furthermore, the extent to which the 50-ms delay normalized a patient's level of N1 suppression was linearly related to the FA of their arcuate fasciculus.

These data suggest that SZ patients experience temporally delayed CDs to self-generated auditory stimuli, putatively because of structural damage to the white-matter (WM) fasciculus connecting the sites of discharge initiation and destination.