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.     

精神分裂症患者的情绪调节

日常生活中, 个体通常有不同的理想与目标, 当个体被特定的目标驱动, 试图去影响自身将要体验到的情绪类别、将要体验到的情绪感受发生的时间, 以及如何体验、表达此种情绪时, 情绪调节就发生了。精神分裂症是一种复杂的精神疾病, 该类疾病患者普遍存在情绪方面的缺陷, 通过操控各种内外因素, 可以帮助精神分裂症患者进行有效的情绪调节, 有利于帮助他们构建健全的情绪体验, 对促进其身心健康发展具有现实临床意义。     

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.     

Social information processing in strategic decision-making: Why timing matters

In strategic decision situations, as modeled in games, the outcome depends on all decision-makers involved. In such situations, people make different decisions when they move simultaneously as compared to when they move sequentially without knowledge of prior moves. This is called the timing effect, which is not predicted by classic game theory. We hypothesize that pseudo-sequential game structures activate concepts of social interactions, which in turn increase individual’s interpersonal trust and decreases cautiousness in situations of interdependence. Simultaneous game structures are more likely to activate concepts of games of chances, as a consequence of which the possibility of an actual total loss is more salient. In four experiments, participants played a coordination game either simultaneously or pseudo-sequentially. We manipulated processing time (Experiment 1), assessed participants’ perception of game features (Experiment 2), manipulated activation of concepts such as social interaction (Experiment 3), and asked participants what decision they make being in a social interaction or a game of a chance (Experiment 4). The results support our hypothesis that different cognitive processes, which either intensify or diminish the focus on the other person, mediate the timing effect. In Experiment 5 we reversed the timing effect by embedding the game in a competitive context.     

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.     

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.     

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.     

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).     

Declarative memory deficits and schizophrenia: problems and prospects

Cognitive deficits are among the most important factors leading to poor functional outcomes in schizophrenia, with deficits in declarative memory among the largest and most robust of these. Thus far, attempts to enhance cognition in schizophrenia have shown only modest success, which underlies increasing efforts to develop effective treatment strategies. This review is divided into three main parts. The first section delineates the nature and extent of the deficits in both patients with schizophrenia and in their adult, non-psychotic relatives. The second part focuses on structural and functional abnormalities in the hippocampus, both in people with schizophrenia and in animal studies that model relevant features of the illness. The third section views problems in declarative memory and hippocampal function from the perspective of elevated rates of common medical disorders in schizophrenia, with a focus on insulin insensitivity/diabetes. The likelihood that poor glucose regulation/availability contribute to declarative memory deficits and hippocampal abnormalities is considered, along with the possibility that schizophrenia and poor glucose regulation share common etiologic elements, and with clinical implications of this perspective for enhancing declarative memory.     

Identification of tone duration, line length, and letter position: an experimental approach to timing and working memory deficits in schizophrenia

Patients with schizophrenia display numerous cognitive deficits, including problems in working memory, time estimation, and absolute identification of stimuli. Research in these fields has traditionally been conducted independently. We examined these cognitive processes using tasks that are structurally similar and that yield rich error data. Relative to healthy control participants (n = 20), patients with schizophrenia (n = 20) were impaired on a duration identification task and a probed-recall memory task but not on a line-length identification task. These findings do not support the notion of a global impairment in absolute identification in schizophrenia. However, the authors suggest that some aspect of temporal information processing is indeed disturbed in schizophrenia.     

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.     

Emotion processing deficits in the different dimensions of psychometric schizotypy

Schizotypy refers to a personality structure indicating “proneness” to schizophrenia. Around 10% of the general population has increased schizotypal traits, they also share other core features with schizophrenia and are thus at heightened risk for developing schizophrenia and spectrum disorders. A key aspect in schizophrenia‐spectrum pathology is the impairment observed in emotion‐related processes. This review summarizes findings on impairments related to central aspects of emotional processes, such as emotional disposition, alexithymia, facial affect recognition and speech prosody, in high schizotypal individuals in the general population. Although the studies in the field are not numerous, the current findings indicate that all these aspects of emotional processing are deficient in psychometric schizotypy, in accordance to the schizophrenia‐spectrum literature. A disturbed frontotemporal neural network seems to be the critical link between these impairments, schizotypy and schizophrenia. The limitations of the current studies and suggestions for future research are discussed.     

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.     

Motor timing deficits in community and clinical boys with hyperactive behavior: the effect of methylphenidate on motor timing

In a previous paper we showed that community children with hyperactive behavior were more inconsistent than controls in the temporal organization of their motor output. In this study we investigated: (1) various aspects of motor timing processes in 13 clinically diagnosed boys with attention deficit hyperactivity disorder (ADHD) who were compared to 11 community boys with hyperactive behavior and to a control group and (2) the effect of methylphenidate on the motor timing processes in the clinical group with ADHD in a double blind, cross-over, medication-placebo design, including 4 weeks of medication. The clinical group with ADHD, like the community group with hyperactivity, showed greater variability in sensorimotor synchronization and in sensorimotor anticipation relative to controls. The clinical group was also impaired in time perception, which was spared in the community group with hyperactivity. The persistent, but not the acute dose, of methylphenidate reduced the variability of sensorimotor synchronization and anticipation, but had no effect on time perception. This study shows that motor timing functions are impaired in both clinical and community children with hyperactivity. It is the first study to show the effectiveness of persistent administration of methylphenidate on deficits in motor timing in ADHD children and extends the use of methylphenidate from the domain of attentional and inhibitory functions to the domain of executive motor timing.     

Motor timing deficits in children with Attention-Deficit/Hyperactivity disorder

Children with Attention-Deficit/Hyperactivity Disorder (ADHD) are thought to have fundamental deficits in the allocation of attention for information processing. Furthermore, it is believed that these children possess a fundamental difficulty in motoric timing, an assertion that has been explored recently in adults and children. In the present study we extend this recent work by fully exploring the classic Wing and Kristofferson (1973) analysis of timing with typically developing children (n=24) and children with ADHD (n=27). We provide clear evidence that not only do children with ADHD have an overall timing deficit, they also time less consistently when using a similar strategy to typically developing children. The use of the Wing and Kristofferson approach to timing, we argue, will result in the discovery of robust ADHD-related timing differences across a variety of situations.     

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.     

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.