Steven F. Faux

The auditory N2 component in schizophrenia: Relationship to MRI temporal lobe gray matter and to other ERP abnormalities

The N2 component of the auditory event-related potential (ERP) indexes cognitive processes involved in the categorization of deviant stimuli. Although N2 amplitude and latency abnormalities have been reported in schizophrenia, their relationship to MRI structural changes, clinical status, and P3 abnormalities has not been defined. We therefore studied the auditory N2 and P3 components elicited by an oddball paradigm in 15 right-handed male subjects with schizophrenia and 14 control subjects who had quantitative MRI measures of temporal lobe gray-matter structures. To provide a methodological comparison, we measured the auditory N2 from both the target ERP (N2t) and the target-minus-frequent ERP difference (N2d) waveforms. Both N2t and N2d amplitude were bilaterally reduced in schizophrenics, with N2d showing a more pronounced reduction. Within the schizophrenic group, N2 amplitude reduction was associated with reduction in gray-matter volume of the left superior temporal gyrus (STG) and of medial temporal lobe structures bilaterally, and clinically, with greater chronicity. P3 amplitude, in contrast, correlated only with left posterior STG volume, and was more prominently associated with delusions and thought disorder. These findings suggest that the N2 and P3 components, though occurring sequentially in the ERP, tap separable anatomic and behavioral abnormalities in schizophrenia.

Correlations between abnormal auditory P300 topography and positive symptoms in schizophrenia: A preliminary report

P300 component amplitude in the left temporal scalp region, shown in three previous studies to differentiate normals from schizophrenics, was found to be significantly correlated with the Thought Disorder Index (TDI) and the Scale for the Assessment of Positive Symptoms (SAPS). These correlations occurred primarily in the P300 waveform derived from the Goodin paradigm. These findings suggest a brain processing disturbance in positive symptom schizophrenia that may be reflected by electrophysiological abnormalities detectable in the temporal scalp region.

Attentional Cues in Chronic Schizophrenia: Abnormal Disengagement of Attention

Posners (1980) reaction time (RT) paradigm was used to examine the engagement and disengagement operations of visual selective attention in patients with schizophrenia. In the 1st experiment, 14 medicated, chronic schizophrenic subjects (diagnosed by criteria of the Diagnostic and Statistical Manual of Mental Disorders; American Psychiatric Association, 1987) and 15 age-matched normal control subjects made a speeded response to a target preceded by a valid, an invalid, or no cue. Control subjects showed the expected advantage and disadvantage in RT for valid and invalid cues, which suggests intact engagement and disengagement operations. For schizophrenic patients, valid cues also enhanced RT, but invalid cues did not slow RT. Similar results were found in the 2nd experiment. The failure of unpredictable, invalid cues to inhibit RT in chronic schizophrenia may be related to an abnormality in the disengagement operation of selective attention.

Preservation of P300 event-related potential topographic asymmetries in schizophrenia with use of either linked-ear or nose reference sites

Previous studies of the auditory P300 event-related potential (ERP) from our laboratory have reported a left- greater than right-sided attenuation in medicated chronic schizophrenics compared with normal controls. A possible confound in these studies has been the use of the linked-ear reference (LER), which has been criticized on the grounds that it might either induce or suppress topographic asymmetries. To test the effects of LER on P300 asymmetries in schizophrenia, we recorded ERPs with both LER and a nose reference (NR) in a group of 20 chronic medicated schizophrenics and in group of 20 age-matched normal controls. We here report: (1) confirmation of our previous P300 findings of left temporal scalp region deficit using both LER and NR with a 28-electrode montage; this feature was prominent in the wave form associated with the target stimulus, without the use of the wave form subtractions of our previous studies; (2) no statistically significant topographic differences between the LER and NR for either the schizophrenic or normal subjects; and (3) better performance of the LER in differentiating schizophrenics versus normal controls, due to lower wave form variability. We conclude that the LER is preferable for studies using subject groups and methodology similar to the present study.

Reversed temporal region asymmetries of P300 topography in left- and right-handed schizophrenic subjects

The auditory P300 evoked potential was recorded in 36 subjects: left- (LH) and right-handed (RH) schizophrenic males and LH and RH normal controls. LH and RH normals showed no asymmetry in P300 scalp topography. LH and RH schizophrenics, however, showed lateralized asymmetries in temporal scalp regions: left < right P300 voltage asymmetry in RH schizophrenics and left > right P300 voltage asymmetry in LH schizophrenics. These data suggest that the schizophrenic pathology of P300 neural generators is lateralized according to handedness and provide the first evidence that LH and RH schizophrenics can be dissociated based on left-right voltage asymmetries in P300 topography. These findings further emphasize the need for control of handedness in P300 studies of schizophrenia.

Cognitive neuroscience from a behavioral perspective: A critique of chasing ghosts with geiger counters.

Cognitive neuroscience is a growing new discipline concerned with relating complex behavior to neuroanatomy. Relatively new advances in the imaging of brain function, such as positron emission tomography (PET), have generated hundreds of studies that have demonstrated a number of interesting but also potentially problematic brain–behavior relations. For example, cognitive neuroscientists largely favor interpretations of their data that rely on unobserved hypothetical mechanisms. Their reports often contain phraseology such as central executive, willed action, and mental imagery. As B. F. Skinner argued for decades, cognitive constructs of neurological data may yield nothing more than a conceptual nervous system.

Temporal lobe abnormalities in a patient with schizophrenia who has word-finding difficulty: Use of high-resolution magnetic resonance imaging and auditory p300 event-related potentials

&NA; Postmortem, magnetic resonance, and event‐related potential studies suggest the presence of temporal lobe abnormalities in schizophrenia. Analyses using convergent measurements of brain structure and function, however, have rarely been done in the same patients. We recently developed a protocol using high‐spatial‐resolution magnetic resonance scans, auditory P300 event‐related potentials, and thought disorder scales to examine temporal lobe structure and function in the same patients. We report a case of schizophrenia that showed left‐lateralized volume reduction in the superior temporal gyrus, hippocampus, and parahippocampal gyrus (also on right), with associated P300 amplitude reduction and thought disorder marked by word‐finding difficulties and perseverations.

Two syndromes of schizophrenic psychopathology associated with left vs. right temporal deficits in P300 amplitude. Four case reports.

In four schizophrenic patients, we examined the relationship between clinical course, including neuroleptic response, and the following biological and psychological measures: topography of the auditory P300 event-related potential, computerized tomography (CT), Andreasens positive and negative symptom scales, the Thought Disorder Index, and a neuropsychological test battery. Two previous studies in our laboratory had shown that schizophrenic patients were differentiated from a matched normal control group by a left temporal scalp region deficit in P300 topography. This present report compares two schizophrenic patients with the typical left temporal P300 topography deficit with two schizophrenic patients with a right temporal P300 topography deficit. The two right temporal deficit patients had more positive symptoms, more thought disorder, more severely impaired functioning, earlier age of onset, poorer response to neuroleptic medications, more diffuse cognitive deficits on a neuropsychological testing battery, and poorer premorbid history than the two left temporal deficit patients. There was some evidence for the presence of more CT abnormalities suggestive of frontal lobe pathology in the right temporal deficit patients.