Eyeblink conditioning deficits indicate timing and cerebellar abnormalities in schizophrenia

Accumulating evidence indicates that individuals with schizophrenia manifest abnormalities in structures (cerebellum and basal ganglia) and neurotransmitter systems (dopamine) linked to internal-timing processes. A single-cue tone delay eyeblink conditioning paradigm comprised of 100 learning and 50 extinction trials was used to examine cerebellar timing circuits in 13 medicated patients with schizophrenia and 13 age- and sex-matched controls. Patients with schizophrenia showed impaired learning of the conditioned response compared to controls and also greater within-subject variability in the timing of their responses. These findings are consistent with models of schizophrenia in which timing deficits underlie information-processing abnormalities and clinical features of the disorder.     

The contribution of metamemory deficits to schizophrenia

A number of recent studies have demonstrated that individuals with schizophrenia display knowledge corruption; that is, they hold false information with strong conviction. This aberration in metamemory is thought to stem from poor memory accuracy in conjunction with impaired discrimination of correct and incorrect judgments in terms of confidence. Thirty-one participants with schizophrenia, along with 61 healthy control participants and 48 control participants with other psychiatric conditions, participated in a computerized source memory task. Whereas no differences in memory accuracy were observed between the group with schizophrenia and the group with other psychiatric diagnoses, knowledge corruption was specifically impaired in those with schizophrenia. Schizophrenia participants showed a significantly decreased confidence gap: They were more confident in errors and less confident in correct responses relative to those in the control groups. Knowledge corruption is theorized to be a potential risk factor for the emergence of delusions.     

Word production deficits in schizophrenia

Fronto-cerebellar circuitry is implicated in word production. Data suggest that the cerebellum is involved in word search, whereas the prefrontal cortex underlies the selection of words from among competing alternatives. We explored the role of search and selection processes in word production deficits in schizophrenia patients. In Experiment 1, patients were impaired in a verb generation task under both high and low selection conditions but were more impaired in the high selection condition. In Experiment 2, when the difficulty level of search and selection conditions was equated in a word stem completion task, patients were only impaired in the search condition. Word search deficits underlie word production problems in schizophrenia, and may involve fronto-cerebellar dysfunction.     

Verbal processing deficits in schizophrenia

The authors reported that a subgroup of schizophrenic patients performed well on a tone serial position task but was impaired on an auditory word serial position task (Wexler, Stevens, Bowers, Cerniak, & Goldman-Rakic, 1998). This study assessed 30 schizophrenic and 32 controls (matched for comparable tone discrimination) on 4 versions of the verbal serial position tasks and 2 tone serial position tasks. Patients performed poorly on all verbal tasks but performed comparably to controls when tones served as stimuli. Proactive interference and visual presentation further compounded the verbal deficits. Deficits persisted with pronounceable nonword stimuli. These findings provide evidence of specific deficits in language-related processing, although the authors could not rule out the possibility that the differential effects that were observed between the tone and word tasks, and particularly among the verbal tasks, may result from differing discriminating power of the different tests.     

Autobiographical memory deficits in schizophrenia

This study investigated autobiographical memory processes in a group of individuals diagnosed with schizophrenia and matched controls. The schizophrenia group displayed an overgeneral style of autobiographical memory retrieval on two widely used measures, and displayed problems retrieving both autobiographical facts and events. They showed a specific impairment in the recall of autobiographical events and facts in early adulthood, around the time of onset of their illness. Retrieval deficits were independent of mood state and premorbid intellectual functioning. The magnitude of the deficits in autobiographical memory retrieval specificity were considerably greater than any general impairments in episodic and working memory.     

Emotion deficits in schizophrenia: timing matters

The past two decades of research on emotional response in schizophrenia has demonstrated that people with schizophrenia do not have a marked deficit in reported emotional experience in the presence of emotionally evocative stimuli. However, the extent to which people with schizophrenia maintain their emotional state to guide future behavior remains a largely unexplored area of investigation. In the present study, we tested hypotheses about whether people with schizophrenia maintained their emotional state in the absence of emotionally evocative stimuli. In addition to reported emotional experience, we measured startle response magnitude both during the viewing and after the offset of emotional pictures to assess whether people with schizophrenia (n = 31) and without schizophrenia (n = 28) differ in their patterns of immediate response to emotional pictures and in their patterns of maintenance of these responses. Our findings indicated that people with and without schizophrenia did not differ in their self-report or startle response magnitude during presentation of emotional pictures. However, healthy controls maintained these responses after the stimuli were removed from view, but people with schizophrenia did not.     

Affective deficits and pain insensitivity in schizophrenia

Affective deficits have long been considered a prominent feature of schizophrenia and play a central role in recent theory and research on the pathophysiology of this disorder. However, it has recently been argued that current approaches to the conceptualization and assessment of affective flattening in schizophrenia are confounded by the social and neuromotor deficits that are also prevalent in this disorder. Insensitivity to pain in individuals with schizophrenia — a phenomenon that has been reported frequently but never systematically investigated — provides one approach to examining affective flattening unconfounded by social and neuromotor deficits. Two studies are described in which signal detection theory measures of thermal pain sensitivity were examined in patients with schizophrenia, mood disorder, and normal controls; in addition, in the patients with schizophrenia, the relationships between these measures and measures of affective deficits were examined. Patients with schizophrenia had significantly poorer sensory discrimination of painful thermal stimuli than control subjects, but did not differ from controls with respect to their response criterion for reports of pain; patients with mood disorder had a significantly higher (i.e., more stoical) criterion for reports of pain than controls. As predicted, among the patients with schizophrenia, higher response criterion was significantly correlated with greater affective flattening and less intense affective experience (as well as with fewer positive symptoms and poorer premorbid adjustment). The results of these studies suggest that pain insensitivity in schizophrenia may reflect affective as well as sensory abnormalities, and that pain insensitivity in schizophrenia may provide a method for studying affective flattening in this disorder that is relatively independent of the social and neuromotor deficits that confound existing measures of this symptom. Continued examination of the relationship between pain insensitivity and affective deficits in schizophrenia is also important because numerous clinical reports have suggested that pain insensitivity is detrimental to health and can have life-threatening consequences in individuals with this disorder.This research was supported, in part, by research grants from the National Institute of Neurological Disorders and Stroke to Robert H. Dworkin (NS-30714) and W. Crawford Clark (NS-09263, NS-20248).     

Common and specific cognitive deficits in schizophrenia: relationships to function

The goals of the present study were to assess the interrelationships among tasks from the MATRICS and CNTRACS batteries, to determine the degree to which tasks from each battery capture unique variance in cognitive dysfunction in schizophrenia, and to determine the ability of tasks from each battery to predict functional outcome. Subjects were 104 schizophrenia patients and 132 healthy control subjects recruited as part of the CNTRACS initiative. All subjects completed four CNTRACS tasks and two tasks from the MATRICS battery: Brief Assessment of Cognition in Schizophrenia Symbol Coding and the Hopkins Verbal Learning Test. Functional outcome was also assessed in the schizophrenia subjects. In both the patient and control groups, we found significant intercorrelations between all higher order cognitive tasks (episodic memory, goal maintenance, processing speed, verbal learning) but minimal relationships with the visual task. For almost all tasks, scores were significantly related to measures of functional outcome, with higher associations between CNTRACS tasks and performance-based measures of function and between one of the MATRICS tasks and self-reported functioning, relative to the other functioning measures. After regressing out variance shared by other tasks, we continued to observe group differences in performance among task residuals, particularly for measures of episodic memory from both batteries, although these residuals did not correlate as robustly with functional outcome as raw test scores. These findings suggest that there exists both shared and specific variance across cognitive tasks related to cognitive and functional impairments in schizophrenia and that measures derived from cognitive neuroscience can predict functional capacity and status in schizophrenia.     

Reading deficits in learning disabled children

The purpose of this study was to determine whether LD children exhibited problems in the processes of attention, memory, or syntactical awareness when decoding written prose. Eighteen LD children and 18 normal controls were matched for initial word recognition skills. Subjects were then trained to read a list of individual words to criterion. Subsequently, they were tested on their ability to decode the same words in paragraph form, presented both immediately after training, and then again one week later. Half the children read paragraphs following standard English syntax, while the other half read a syntactically scrambled version of the same paragraph. The results indicated that a major contributing factor in the reading (decoding) difficulties demonstrated by the LD children derived from problems of acquisition and retrieval from long-term memory storage. The results were discussed in terms of their implications for the developmental lag theory of learning disabilities.     

Hemispheric processing deficits in patients with paranoid schizophrenia

The purpose of the present study was to investigate hemispheric deficits in individuals with paranoid schizophrenia on four kinds of tasks: dichoptic viewing tasks involving verbal and nonverbal visual stimuli, and dichotic listening tasks involving verbal and nonverbal auditory stimuli. As dependent measures, both accuracy and speed of (correct) responding were measured. The sample recruited for this study consisted of 18 patients with paranoid schizophrenia, 15 outpatients with anxiety disorders, and 20 controls with no history of psychiatric disorders. Results indicated that, relative to the controls, the paranoid schizophrenic patients were less accurate and less efficient on auditory-verbal tasks requiring right hemisphere processing. Unlike the controls the paranoid schizophrenic patients manifested a lateralized left hemisphere advantage.     

Metamemory knowledge and beliefs in patients with schizophrenia and how these relate to objective cognitive abilities

Subjective reports and theories about memory may have an influence on other beliefs and behaviours. Patients with schizophrenia suffer a wide range of deficits affecting their awareness of daily life, including memory. With the Metamemory Inventory in Adulthood (MIA) we ascertained patients’ memory knowledge and thoughts about their own cognitive capacities and about several aspects of cognitive functioning: personal capacities, knowledge of processes, use of strategies, perceived change with ageing, anxiety, motivation and mastery. The participants’ ratings were correlated with their intellectual, cognitive and psychiatric data. Patients felt they had a lower capacity and marginally lower mastery over their memory than comparison subjects. They reported less recourse to strategies, and higher levels of memory-related anxiety. However, their knowledge of basic memory processes, motivation to succeed, and perception of ageing effects were similar. So patients with schizophrenia do not suffer a general and non specific impairment of their metacognitive knowledge.     

Habit and skill learning in schizophrenia: evidence of normal striatal processing with abnormal cortical input

Different forms of nondeclarative learning involve regionally specific striatal circuits. The motor circuit (involving the putamen) has been associated with motor–skill learning and the dorsolateral prefrontal cortex (DLPFC) circuit (involving the caudate) has been associated with cognitive–habit learning. Efforts to differentiate functional striatal circuits within patient samples have been limited. Previous studies have provided mixed results regarding striatal-dependent nondeclarative learning deficits in patients with schizophrenia. In this study, a cognitive–habit learning task (probabilistic weather prediction) was used to assess the DLPFC circuit and a motor–skill learning task (pursuit rotor) was used to assess the motor circuit in 35 patients with schizophrenia and 35 normal controls. Patients with schizophrenia displayed significant performance differences from controls on both nondeclarative tasks; however, cognitive–habit learning rate in patients did not differ from controls. There were performance and learning-rate differences on the motor–skill learning task between the whole sample of patients and controls, however, analysis of a subset of patients and controls matched on general intellectual level eliminated learning rate differences between groups. The abnormal performance offset between patients with schizophrenia and controls in the absence of learning rate differences suggests that abnormal cortical processing provides altered input to normal striatal circuitry.     

Visuospatial attention in schizophrenia: deficits in broad monitoring

Although selective attention is thought to be impaired in people with schizophrenia (PSZ), prior research has found no deficit in the ability to select one location and withdraw attention from another. PSZ and healthy control subjects (HCS) performed a stimulus detection task in which one, two, or all four peripheral target locations were cued. When one or two locations were cued, both PSZ and HCS responded faster when the target appeared at a cued than uncued location. However, increases in the number of validly cued locations had much more deleterious effects on performance for PSZ than HCS, especially for targets of low contrast whose detection was more dependent on attention. PSZ also responded more slowly in trials with four cued locations relative to trials with one or two invalidly cued locations. Thus, visuospatial attention deficits in schizophrenia arise when broad monitoring is required rather than when attention must be focused narrowly.     

Interval-timing deficits in individuals at high risk for schizophrenia

A duration-bisection procedure was used to study the effects of signal modality and divided attention on duration classification in participants at high genetic risk for schizophrenia (HrSz), major affective disorder (HrAff), and normal controls (NC). Participants learned short and long target durations during training and classified probe durations during test. All groups classified visual signals as shorter than equivalent duration auditory signals. However, the difference between auditory and visual signal classification was significantly larger for the HrSz group than for the NC group. We posit a model in which there is a clock rate difference between auditory and visual signals due to an attentional effect at the level of a mode switch that gates pulses into an accumulator. This attentionally mediated clock rate difference was larger for the HrSz participants than for the NC participants, resulting in a larger auditory/visual difference for the HrSz group.     

Motor fluency deficits in the sequencing of actions in schizophrenia

Many everyday activities depend on the capacity to organize and smoothly execute motor sequences. The authors tested the hypothesis that a sequencing deficit is associated with schizophrenia. They used a new method to distinguish between lower and higher order mechanisms for the impairment. The 1st task involved triggered sequences in which sensory information from 1 movement was the cue for initiation of the following movement. Results showed that the motor sequences were performed as fluently in patients as in controls. The 2nd and 3rd tasks involved sequences in which the entire movement sequence could be preplanned. Patients executed the sequences less fluently than controls but only under the condition where action sequences were required. Furthermore, the patients' fluency deficit increased with sequence complexity. The high discrimination power of Task 3 gave the authors a means to control for a potential psychometric confound involving differential discriminating power and to argue in favor of a specific higher order motor fluency deficit in patients with schizophrenia. It is suggested that basic lower order mechanisms that integrate sensory information with outgoing motor commands are preserved in schizophrenia, whereas higher order integrative mechanisms that are required for the smooth coordination of motor sequences are impaired.     

An abbreviated review of immune abnormalities in schizophrenia

Initial investigations of the possible interaction between schizophrenia and the immune system began in the early 1900s and have proceeded in a rather halting fashion because of the methodological challenges faced by investigators. However, a confluence of recent data suggests that activation of the inflammatory response system, the cellular immune system, and the humoral immune system may be present in some patients with schizophrenia. Some of the most compelling data support the hypothesis that minor levels of immune activation may be associated with acute psychotic exacerbations. However, a second body of evidence suggests that some individuals with schizophrenia may have chronic, evolving autoimmune processes. This article is an overview of the history, rationale, and some of the recent findings on the interaction between schizophrenia and the immune system.