Processing Deficits In Schizophrenia Research Articles

Verbal declarative memory dysfunction in schizophrenia: from clinical assessment to genetics and brain mechanisms.

The recent literature on the neuropsychology of schizophrenia has emphasized memory deficits as a key area of impairment. Abnormalities in the medial temporal lobe, a brain region crucial for long-term memory formation, have also consistently been reported. We conducted a comprehensive review of verbal declarative memory (VDM) in schizophrenia with the aim of systematically addressing the nature of this impairment. We conclude that verbal declarative memory is significantly impaired in schizophrenia and is largely accounted for by deficits in the encoding stage. Subtle impairments in increased rates of forgetting are present, but are mild compared with those in amnestic disorders. Impairment in other cognitive domains studied thus far (e.g., attention), medication effects, or fluctuations in symptoms do not completely account for the deficit. VDM is among the most impaired neurocognitive domains in schizophrenia (along with attention and executive functions). Milder encoding deficits are present in high-risk subjects and non-psychotic relatives of individuals with schizophrenia suggesting that components of the deficit are associated with a genetic vulnerability to the illness, and are independent of the frank psychotic illness. Furthermore, VDM is observed in individuals experiencing their first-psychotic episode and it remains fairly consistent over time. Preliminary imaging studies and other work suggest abnormalities in prefrontal-hippocampal processing networks. Future work should emphasize delineating specific information processing components contributing to the deficit. This would allow imaging studies to determine which brain regions contribute to specific information processing deficits in schizophrenia.

Auditory temporal processing in schizophrenia: High level rather than low level deficits?

Introduction: Patients with schizophrenia demonstrate a wide range of information processing deficits. Most recent studies argue in favour of high level deficits, including attention and context processing, whereas fewer studies have demonstrated deficits at earlier stages of processing, such as perceptual discrimination and organisation. This is the first study to investigate both high and low level processing, within a single paradigm, in the case of auditory temporal processing in schizophrenia. Methods: Patients with schizophrenia were compared to controls on a series of tasks involving three auditory temporal processes varying from low to higher level: (1) segregation of a complex sequence into component auditory streams; (2) detection of local temporal irregularities within a stream; (3) attentional focusing on one stream by the use of a cue preceding the complex sequence. Results: The lowest level of processing examined here--stream segregation--appeared to function equally well in patients as in controls. However, the higher level processes--irregularity detection and attentional focus--functioned in both groups, but less efficiently in patients with schizophrenia. Conclusions: Results demonstrate abnormal auditory temporal processing in schizophrenia. Abnormal performances only in Processes 2 and 3 support and hypothesis of higher level rather than lower level processing deficits in schizophrenia.

Deficits in auditory and visual temporal perception in schizophrenia

Introduction. Characteristics of time perception have not been well documented in patients with schizophrenia. The current study investigated time estimation to (1) test whether visual and auditory time perception varied between patients and controls, (2) assess the degree to which patients and controls can differentiate changes in experimental intervals, and (3) explore whether the temporal deficits suggest a general time perception deficit versus modality-specific differences. Methods. Participants were asked to decide whether temporal intervals were shorter or longer than standard intervals on computer-based auditory and visual temporal perception tasks. Data are presented for a sample of 10 patients with schizophrenia and 10 normal controls. Results. Data suggest that patients with schizophrenia exhibit deficits in differentiating subtle differences in intervals in the tens of milliseconds range, compared to their normal control peers on both auditory (p <.01) and visual perception tasks (p <.01). Conclusions. Preliminary data suggest that there is a general temporal processing deficit in schizophrenia. However, future research using complementary techniques may provide useful information regarding the specific types of temporal deficits that affect patients with schizophrenia and the physiology of the dysfunction.

Prepulse inhibition of the startle response in risperidone-treated patients: comparison with typical antipsychotics

Individuals with schizophrenia are known to show deficits in prepulse inhibition (PPI) of the startle response. PPI refers to a response suppression in reaction to a strong startling stimulus, if preceded briefly by a weak non-startling stimulus and represents a well-established animal model to investigate information processing deficits in schizophrenia. This study examined PPI of the startle acoustic response in schizophrenic patients given typical antipsychotics or a second generation atypical antipsychotic, risperidone, using a naturalistic between-subjects design. Two groups of male schizophrenic patients: (i) stable on a range of typical antipsychotics ( n=20), and (ii) stable on risperidone ( n=10) were tested for PPI (prepulse-to-pulse intervals: 30, 60, and 120 ms, prepulses 15 dB above the background) of the acoustic startle response, and compared with a group of healthy male subjects ( n=20). Patients on typical antipsychotics showed significantly less PPI with 30 and 60 ms prepulse trials than healthy subjects. Risperidone-treated patients did not differ from healthy subjects for PPI with any prepulse trials. Further longitudinal within-subject studies are now required to examine whether risperidone is superior to typical antipsychotics in improving information processing functions, as assessed by PPI of the acoustic startle response, in treatment-responsive male patients with schizophrenia.

Early visual processing deficits in schizophrenia: impaired P1 generation revealed by high-density electrical mapping.

Integrity of early visual sensory processing in schizophrenia was assessed using the well characterized P1 and N1 components of the visual evoked potential (VEP) as our dependent measures. VEPs were recorded in response to successively less fragmented line drawings of common objects. P1 amplitudes were significantly reduced across all stimulus conditions for patients versus controls. Further, this decrement was relatively greater at parieto-occipital than occipito-temporal electrode sites. No differences in N1 amplitude were found. The finding of P1 deficits in patients, particularly over dorsal scalp, supports the view that schizophrenia is associated with impairment of early dorsal visual stream processing. On the other hand, the finding of normal N1 amplitudes in patients suggests that early stages of ventral stream processing may be relatively more intact. These results imply that the cognitive impairment seen in schizophrenia is not just due to deficits in higher order aspects of cognition but also encompasses significant deficits in early sensory processing.

Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia

Schizophrenia patients have prominent deficits in information processing that can be detected by measures of prepulse inhibition (PPI) of the startle response. Deficient PPI in schizophrenia is thought to reflect a failure of brain-based information ‘protective’ mechanisms that normally inhibit responsivity for 30–500 ms after a weak prepulse stimulus. The relationship between specific prepulse stimulus characteristics and PPI deficits in this study was examined in 31 schizophrenia patients and 34 normal comparison subjects. Schizophrenia patients had overall deficits in PPI across four conditions where the prepulse was either discrete (abrupt) or continuous (sustained) and consisted of either white noise or a pure tone. On inspection and analysis of the data, it appears that the white noise conditions, rather than tone conditions, account for the group differences. Thus, the discrete white noise prepulse was most effective in eliciting PPI deficits, resulting in a large effect size between groups ( d=0.85; P<0.01). Deficits in information-protective mechanisms in schizophrenia may be differentially sensitive to specific stimulus characteristics; this observation may be relevant both to the neurobiology of information processing deficits in schizophrenia and to the methodologies for studying these deficits experimentally.

Effects of methylphenidate on functional MRI blood oxygen level dependent (BOLD) contrast

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171. Information processing deficits in schizophrenia: effects of risperidone as compared to typical antipsychotics

171. Information processing deficits in schizophrenia: effects of risperidone as compared to typical antipsychotics

173. Age of onset of psychotic symptoms predicts information processing deficits in schizophrenia

Prepulse inhibition (PPI) of the startle reflex, a cross species measure, has been extensively used to index abnormalities in processing of rapidly presented information in schizophrenia. PPI refers to a reduction in response to an intense startling stimulus, the pulse, if this is preceded shortly (30–100 milliseconds) by a weak nonstartling prestimulus, the prepulse. This effect is found to be reduced in people with schizophrenia, as compared to healthy people. This study investigated whether age of onset of psychotic symptoms predicts disruption of PPI in schizophrenia. We measured PPI (expressed as percent reduction of non-prepulse trials) of the acoustic startle response (indexed electromyographically as the eyeblink) in 40 male individuals with schizophrenia and 20 healthy male volunteers. We observed that patients with an early onset of psychotic symptoms (at 20 years or younger; range 10–20 years) showed markedly reduced PPI, as compared to patients with a relatively later onset of psychotic symptoms and healthy volunteers. These data indicate that onset of psychotic symptoms during adolescence is associated with remarkably impaired information processing functions, as indexed by PPI of the acoustic startle response, in males with schizophrenia. It is concluded that PPI may provide an important objective experimental tool to investigate heterogeneity in schizophrenia.

567. NMDA-mediated neurophysiologic deficits in schizophrenia

Deficits in auditory event-related potential (aERP) generation are among the most consistent and robust indices of impaired cortical information processing in schizophrenia. Deficits in P300 generation were first demonstrated over 30 years ago. More recently, deficits have been demonstrated as well in earlier aERP components, including mismatch negativity (MMN) and N1. Both MMN and N1 are obtained under passive attention conditions. Nevertheless, deficits in MMN and N1 generation are as robust as those observed in attentionally demanding paradigms, and reflect impaired ERP generation at the level of auditory sensory cortex. MMN is elicited to deviant stimuli in an auditory oddball paradigm and reflects integrity of auditory sensory (echoic) memory system. N1, in contrast, is observed even to repetitive standard stimuli and reflects stimulus registration within auditory cortex. N1 normally increases with increasing interstimulus interval. In schizophrenia, N1 generation is significantly reduced in amplitude at long, but not short, ISI, reflecting a failure of normal augmentation. Monkeys generate MMN- and N1-like ERP components and can thus be used to evaluate mechanisms underlying cortical information processing. In monkeys, phencyclidine (PCP) and other N-methyl-D-aspartate (NMDA) antagonists induce aERP deficits closely resembling those of schizophrenia. Deficits are associated with decreased NMDA-dependent current flow within supragranular layers of auditory cortex, whereas input to auditory cortex remains intact. These findings indicate that NMDA receptors play a crucial role in cortical response amplification and that deficits in NDMA receptor-mediated neurotransmission may contribute significantly to cortical information processing deficits in schizophrenia.

Emotional processing in schizophrenia across cultures: standardized measures of discrimination and experience

Schizophrenia appears quite similar across a range of cultures. However, variability has been noted, and understanding the variant and invariant features of the disorder is necessary for elucidating its biological and environmental basis. Evidence of prominent emotion processing deficits in schizophrenia, including perceptual and experiential aspects, led us to extend the paradigm of standardized measures cross-culturally. We assessed performance of American, German, and Indian patients with schizophrenia and healthy controls on standardized emotion discrimination and experience (mood induction) procedures using happy, sad, and neutral facial expressions of Caucasian actors. Participants were 80 Americans (40 patients; 40 controls), 48 Germans (24 patients; 24 controls), and 58 Indians (29 patients; 29 controls). Face discrimination performance was impaired across patient groups, but was most impaired in those of Indian origin. Lower performance was also found in Indian controls, relative to their American and German counterparts. Mood induction produced weaker effects in all patient groups relative to their respective controls. The results supported the feasibility of cross-cultural comparisons and also emphasized the importance of poser ethnic background for facial affect identification, while poser ethnicity was less consequential for mood induction effects. Emotion processing deficits in schizophrenia may add to the clinical burden, and merit further examination.

Information processing deficits in schizophrenia: Effects of risperidone as compared to typical antipsychotics

Information processing deficits in schizophrenia: Effects of risperidone as compared to typical antipsychotics

Investigations into the neurobiology of information processing deficits in schizophrenia

Investigations into the neurobiology of information processing deficits in schizophrenia

Effects of procyclidine on prepulse inhibition of the acoustic startle response in healthy human volunteers

Individuals with schizophrenia are known to show deficits in prepulse inhibition (PPI) of the startle response. PPI refers to a response suppression in reaction to a strong startling stimulus, if preceded briefly by a weak non-startling stimulus and represents a well-established animal model to investigate information processing deficits in schizophrenia. This study examined PPI of the startle acoustic response in schizophrenic patients given typical antipsychotics or a second generation atypical antipsychotic, risperidone, using a naturalistic between-subjects design. Two groups of male schizophrenic patients: (i) stable on a range of typical antipsychotics (n=20), and (ii) stable on risperidone (n=10) were tested for PPI (prepulse-to-pulse intervals: 30, 60, and 120 ms, prepulses 15 dB above the background) of the acoustic startle response, and compared with a group of healthy male subjects (n=20). Patients on typical antipsychotics showed significantly less PPI with 30 and 60 ms prepulse trials than healthy subjects. Risperidone-treated patients did not differ from healthy subjects for PPI with any prepulse trials. Further longitudinal within-subject studies are now required to examine whether risperidone is superior to typical antipsychotics in improving information processing functions, as assessed by PPI of the acoustic startle response, in treatment-responsive male patients with schizophrenia.

Normalization of information processing deficits in schizophrenia with clozapine.

The authors tested the hypothesis that the use of an atypical drug, clozapine, for patients with schizophrenia is related to less impairment in information processing deficits (assessed by prepulse inhibition of the startle response) than is the use of typical antipsychotics. Two groups of schizophrenic patients--receiving either clozapine or a range of typical antipsychotics--were tested for prepulse inhibition (a reduction in response to a starting stimulus, if preceded briefly by a weak, nonstartling stimulus; measured at prepulse-to-pulse intervals of 30 msec, 60 msec, and 120 msec) of the acoustic startle response and compared with a group of healthy volunteers. Patients receiving typical antipsychotics showed less prepulse inhibition with 30-msec and 60-msec prepulse trials than did comparison subjects. Clozapine-treated patients showed normal levels of prepulse inhibition. Clozapine is superior to typical antipsychotics in normalizing prepulse inhibition, presumably because of its pharmacological effects on prefrontal regions of the brain or its effects on a broader range of neuroreceptors.

Effects of sustained cocaine exposure on sensorimotor gating of startle in rats.

Deficient sensorimotor gating, as measured by a relative loss of prepulse inhibition (PPI) of the startle reflex, has been reported in schizophrenia patients and in rats treated acutely with dopamine (DA) agonists or other psychotomimetic agents. For this reason, PPI has been used as a cross-species measure for studying the neurochemistry of specific information processing deficits in schizophrenia. Cocaine is a DA reuptake inhibitor which can precipitate psychosis after sustained use in humans. In rats, sustained exposure to cocaine results in neuropathological and neurochemical changes in several brain regions, and is also associated with specific prolonged behavioral abnormalities. In the present study, we examined the effects of both acute and sustained cocaine administration on PPI and other measures of the startle reflex in rats. Cocaine produced a significant, dose-dependent reduction in PPI, both after acute administration, and after 3 days of sustained administration via implanted subcutaneous pellets. PPI returned to control levels when rats were tested 10 days after sustained (5 day) cocaine administration. The effects of acute cocaine administration on PPI are consistent with those of other DA agonists and psychotomimetics, but PPI does not appear to be sensitive to lasting effects of a method of prolonged cocaine administration associated with neuropathological and neurochemical changes in several brain regions.

Hemispheric asymmetry in schizophrenia: a “dual deficits” model

Background: The aim was 1) to investigate left hemisphere functional integrity for auditory language processing in schizophrenic patients; and 2) to investigate the interaction between brain laterality and attentional processing by having subjects shift attention to the left or right ear. Methods: The subjects were 33 schizophrenic inpatients, and 33 healthy comparison subjects with the same age, handedness, and gender distribution as the patient subjects. All subjects were tested with dichotic listening (DL) to consonant–vowel syllables, which is a measure of lateralized temporal lobe language processing. The subjects were tested under three different attentional conditions: a non–forced attention condition, attention focused to the right ear stimulus, and attention focused to the left ear stimulus. Results: The main findings were 1) an absence of the expected right ear advantage in the schizophrenic group during the non–forced attention condition; and 2) a failure to modify DL performance through shifting of attention to either the right or left ear. The comparison group showed a right ear advantage during the non-forced and forced-right attention conditions (increased right ear advantage during the forced-right condition), and a left ear advantage during the forced-left attention condition. There were no significant effects of handedness. Conclusions: This pattern of results may indicate a “dual deficit” involving both automatic and controlled processing deficits in schizophrenia.

The time course of visuospatial processing deficits in schizophrenia: An event-related brain potential study.

The time course of visuospatial processing deficits in schizophrenia: An event-related brain potential study.

Cognitive processing efficiency in schizophrenia: generalized vs domain specific deficits

The issue of generalized vs specific cognitive deficits in schizophrenia was explored by examining reaction time data from 40 published studies with 196 reaction time conditions. Using a regression-based approach, the proportional relationship between the response times of groups with schizophrenia was compared with those of age-matched, healthy comparison groups. Through this method, the extent to which deficits in processing efficiency are explained by a single factor, general processing speed, was compared with possible domain specific or task specific deficits. The results suggest that, overall, the data conforms well to a general linear slowing model which accounts for 87% of the variance in reaction time performance. Some additional variance, however, is accounted for by different degrees of linear slowing for three types of tasks: tasks involving selective attention/inhibition showed the most slowing (2.3-times slower for schiziphrenia), followed by lexical tasks (1.8-times slower for schizophrenia), and finally, non-lexical tasks showed the least slowing (1.4-times slower for schizophrenia). This pattern is distinct from other groups showing generalized slowing, such as older adults, and suggests a unique pattern of information processing deficits in schizophrenia.

The time course of visuospatial processing deficits in schizophrenia: an event-related brain potential study.

Event-related brain potentials (ERPs) were recorded during a dot enumeration task so as to investigate electrophysiologic correlates of early visuospatial processing in schizophrenia. Twenty-eight patients having a diagnosis of schizophrenia (n = 19) or schizoaffective disorder (n = 9) and 28 controls were tested. Patients showed poorer dot enumeration than did controls and also had markedly reduced early negative ERPs, which began about 150 ms after stimulus onset at the peak of the N1 potential and reached its maximum about 275 ms at the N2 peak. The N1 reduction in patients was greatest over left parietal sites for stimuli in the right visual field. The marked N1 and N2 reductions in patients are supportive of models postulating deficits in early visuospatial attention and allocation of conceptual resources in schizophrenia.