To understand the endogenous components of the event-related brain potential (ERP), we must use data about the components' antecedent conditions to form hypotheses about the information-processing function of the underlying brain activity These hypotheses, in turn, generate testable predictions about the consequences of the component We review the application of this approach to the analysis of the P300 component The amplitude of the P300 is controlled multiplicatively by the subjective probability and the task relevance of the eliciting events, whereas its latency depends on the duration of stimulus evaluation These and other factors suggest that the P300 is a manifestation of activity occurring whenever one's model of the environment must be revised Tests of three predictions based on this “context updating” model are reviewed Verleger's critique is based on a misconstrual of the model as well as a partial and misleading reading of the relevant literature

Is the P300 component a manifestation of context updating

A review of MRI findings in schizophrenia

Basal ganglia and cerebellar loops: motor and cognitive circuits.

Despite a hundred years' research, the neuropathology of schizophrenia remains obscure. However, neither can the null hypothesis be sustained--that it is a 'functional' psychosis, a disorder with no structural basis. A number of abnormalities have been identified and confirmed by meta-analysis, including ventricular enlargement and decreased cerebral (cortical and hippocampal) volume. These are characteristic of schizophrenia as a whole, rather than being restricted to a subtype, and are present in first-episode, unmedicated patients. There is considerable evidence for preferential involvement of the temporal lobe and moderate evidence for an alteration in normal cerebral asymmetries. There are several candidates for the histological and molecular correlates of the macroscopic features. The probable proximal explanation for decreased cortical volume is reduced neuropil and neuronal size, rather than a loss of neurons. These morphometric changes are in turn suggestive of alterations in synaptic, dendritic and axonal organization, a view supported by immunocytochemical and ultrastructural findings. Pathology in subcortical structures is not well established, apart from dorsal thalamic nuclei, which are smaller and contain fewer neurons. Other cytoarchitectural features of schizophrenia which are often discussed, notably entorhinal cortex heterotopias and hippocampal neuronal disarray, remain to be confirmed. The phenotype of the affected neuronal and synaptic populations is uncertain. A case can be made for impairment of hippocampal and corticocortical excitatory pathways, but in general the relationship between neurochemical findings (which centre upon dopamine, 5-hydroxytryptamine, glutamate and GABA systems) and the neuropathology of schizophrenia is unclear. Gliosis is not an intrinsic feature; its absence supports, but does not prove, the prevailing hypothesis that schizophrenia is a disorder of prenatal neurodevelopment. The cognitive impairment which frequently accompanies schizophrenia is not due to Alzheimer's disease or any other recognized neurodegenerative disorder. Its basis is unknown. Functional imaging data indicate that the pathophysiology of schizophrenia reflects aberrant activity in, and integration of, the components of distributed circuits involving the prefrontal cortex, hippocampus and certain subcortical structures. It is hypothesized that the neuropathological features represent the anatomical substrate of these functional abnormalities in neural connectivity. Investigation of this proposal is a goal of current neuropathological studies, which must also seek (i) to establish which of the recent histological findings are robust and cardinal, and (ii) to define the relationship of the pathological phenotype with the clinical syndrome, its neurochemistry and its pathogenesis.

/pdf/the-neuropathology-of-schizophrenia-a-critical-review-of-the-1zxk39qd1v.pdf

The neuropathology of schizophrenia. A critical review of the data and their interpretation.

Objective: The authors’ goal was to determine whether patients with schizophrenia differ from comparison subjects in regional brain volumes and whether these differences are similar in male and female subjects. Method: They conducted a systematic search for structural magnetic resonance imaging (MRI) studies of patients with schizophrenia that reported volume measurements of selected cortical, subcortical, and ventricular regions in relation to comparison groups. They carried out a meta-analysis of the volumes of these regions in the patients with schizophrenia and the comparison subjects using a random effects model; they also used random effects regression analysis to examine the influence of gender on effect sizes. Results: Fifty-eight studies were identified as suitable for analysis; these studies included 1,588 independent patients with schizophrenia. Assuming a volume of 100% in the comparison group, they found that the mean cerebral volume of the subjects with schizophrenia was smaller (98%), but the mean total ventricular volume of the subjects with schizophrenia was greater (126%). Relative to the cerebral volume differences, the regional volumes of the subjects with schizophrenia were 94% in the left and right amygdala, 94% in the left and 95% in the right hippocampus/amygdala, and 93% in the left and 95% in the right parahippocampus. Relative to the global ventricular system differences, the largest differences in ventricular subdivisions were in the right and left body of the lateral ventricle, where the volumes of schizophrenic subjects were 116% and 116%, respectively. For most regions, effect size was not significantly related to gender. Conclusions: Regional structural differences in patients with schizophrenia include bilaterally reduced volume of medial temporal lobe structures. There is a need for greater integration of results from structural MRI studies to avoid redundant research activity. (Am J Psychiatry 2000; 157:16‐25)

https://ajp.psychiatryonline.org/doi/pdf/10.1176/ajp.157.1.16

Meta-Analysis of Regional Brain Volumes in Schizophrenia

• We used magnetic resonance imaging to examine the morphologic characteristics of the amygdala/hippocampus, prefrontal cortex, and caudate nucleus in 29 healthy volunteers matched for age, gender, and head of household socioeconomic status and 44 patients with chronic schizophrenia. Total volumes of these structures were determined from 3-mm contiguous coronal sections. Schizophrenic patients, compared with healthy controls, had significantly smaller right and left amygdala/hippocampal complex volumes, smaller right and left prefrontal volumes, and larger left caudate volumes. A secondary analysis revealed reductions in the right and left amygdala and the left hippocampus. In addition, prefrontal white matter, but not gray matter, was reduced in the schizophrenic patients. Moreover, the right white matter volume in schizophrenic patients was significantly related to right amygdala/hippocampal volume ( r =.39), data that provide preliminary support for a hypothesis of abnormal limbic-cortical connection in schizophrenia. We studied the implications of these data for the pathophysiology of schizophrenia.

https://jamanetwork.com/journals/PSYCH/articlepdf/495963/archpsyc_49_12_003.pdf

Brain morphology and schizophrenia. A magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures.

Objective: Previous studies have suggested the involvement of the frontal and parietal cortices and thalamus in a neural circuit underlying the production ofprimary enduring negative or deficit symptoms of schizophrenia. The purpose of this study was to examine whether structural changes in the proposed circuit are associated with the production ofdeficit symptoms. Method: Magnetic resonance imaging was used to measure the volume ofselected circuit brain regions (i.e., the prefrontal region and caudate) and noncircuit brain regions (i.e., the amygdala/hippocampus complex) in 1 7 deficit and 24 nondeficit schizophrenic outpatients and 30 normal comparison subjects. Results: Right and left total prefrontal volumes discriminated deficit from nondeficit patients, with prefrontal volumes being smaller in nondeficit patients. There were no differences between the two schizophrenic subgroups in left caudate or right and left amygdala/hippocampus complex volumes. The right caudate was larger in deficit patients, but the difference between the two schizophrenic subgroups was not significant. There were no differences between deficit and normal subjects on any prefrontal region measure. Nondeficit patients had smaller total right and left prefrontal volumes than normal subjects. Both schizophrenic subgroups had larger left caudate volumes and smaller right and left amygdala/hippocampus complex volumes than the normal subjects. There was a trend for deficit patients to have larger right caudate volumes. Conclusions: These results suggest that structural changes in the prefrontal region are not responsible for deficit symptoms. The caudate, particularly the right caudate, may be associated with the production ofthese symptoms. (Am J Psychiatry 1993; 150:59-65)

Structural Abnormalities in Deficit and Nondeficit Schizophrenia

This experiment is concerned with the issue of functional equivalence of emitted (in response to ahsence of a stimulus) and evoked (in response to presentation of a stimulus) P300s. Subjects attempted to estimate a 600-msec time interval hy the method of reproduction. Subjects were informed whether the time interval was under- or overestimated and whether the estimation error magnitude was within a limit (“correct” estimate, positive feedback) or exceeded the limit (“incorrect,” negative feedback). This feedback was presented by means of either a single event or a combination of two events. Each event consisted of a pair of stimuli.



Emitted, as well as evoked, early fronto-central and late parietal P3OOs were elicited by the feedback event regardless of whether positive or negative feedback was delivered, and regardless of whether feedback was delivered by a single event or by the combination of two events. In addition, what appears to be a positive Slow Wave was found following the first stimulus ofthe feedback event when this stimulus was low intensity indicating an underestimation. The other condition (high intensity, overestimation) was followed by a CNV. Since these slow wave findings were serendipitous, counterbalancing was not available to determine whether intensity (low vs high) or information (underestimation vs overestimation) was responsible for the difference.

P300 and feedback provided by absence of the stimulus.

Magnetic resonance imaging was used to measure the volumes of the caudate, putamen, and globus pallidus of 25 schizophrenic patients (17 men and eight women) and 26 age- and sex-matched comparison subjects (18 men and eight women). Schizophrenic patients had significantly larger right and left globus pallidus and right putamen volumes than comparison subjects. There were no significant differences between schizophrenic patients with and without persistent tardive dyskinesia in the volume of any of the three structures.

Basal ganglia pathology in schizophrenia and tardive dyskinesia: an MRI quantitative study.

This study is concerned with P300 and Slow Wave in an experimental paradigm in which information is transmitted by a combination of two successive events (a ‘message’). Each event delivered essential information for understanding the message, but the meaning of the message could not be determined until occurrence of the second event. The amount of information in each event was varied by varying its perceptual difficulty. Increasing perceptual difficulty causes an information loss, termed equivocation.



A positive Slow Wave was elicited by both events. Slow wave was clearly increased in amplitude by equivocation in the eliciting event, and less clearly increased in amplitude by equivocation in the other event. The first event elicited a small P290 component. It could not be determined whether this component corresponded to P300. The second event elicited a large P300. This component was much reduced in amplitude by equivocation in the second event, but was only moderately reduced in amplitude by equivocation in the first event.

Robert C. Munson

Papers

Brain morphology and schizophrenia. A magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures.

Structural Abnormalities in Deficit and Nondeficit Schizophrenia

P300 and feedback provided by absence of the stimulus.

Basal ganglia pathology in schizophrenia and tardive dyskinesia: an MRI quantitative study.

P300 and Slow Wave in a Message Consisting of Two Events