Auditory recognition memory, conscious recollection, and executive function in patients with schizophrenia

BACKGROUND: Dual-process models propose that recognition memory (RM) involves two processes: conscious recollection and familiarity-aware memory. Studies investigating RM in schizophrenia report a selective deficit in conscious recollection and intact levels of familiarity-driven RM for stimuli presented in the visual and olfactory domains. It has been suggested that abnormalities in conscious recollection result from a breakdown in frontal strategic memory processes involved in encoding and retrieval and executive functions linked to reality monitoring and decision making. We investigated three predictions arising from these proposals. Firstly, if conscious recollection abnormalities arise from a central impairment, then these abnormalities should not be domain specific. Secondly, if the deficits in conscious recollection arise from a breakdown in executive processes, deficiencies should be correlated with executive dysfunction. Finally, the conscious recollection deficiencies are likely to be more severe in schizophrenia, a condition associated with marked executive dysfunction relative to Major Depressive Disorder, Recurrent (MDDR), in which executive dysfunction is less marked. METHODS: The remember/know paradigm was used to investigate RM for voices in three groups: patients with schizophrenia (n = 14), patients with MDDR (n = 16), and normal controls (n = 16). Executive function was assessed using the Wisconsin Card Sorting Task. RESULTS: Patients with schizophrenia made significantly fewer remember responses than normal controls (p < 0.01), despite normal levels of discrimination and familiarity-driven auditory RM. Patients with MDDR did not differ significantly from either normal controls or patients with schizophrenia. Executive dysfunction was limited to the schizophrenia group and was not correlated with conscious recollection deficiencies. CONCLUSIONS: Patients with schizophrenia exhibit a deficit in conscious recollection for auditory RM of voices. These findings, when considered alongside remember/know data collected from the same set of patients for olfactory and visual RM, support proposals that abnormalities in conscious recollection stem from a breakdown in central rather than domain-specific processes.     

Functional mechanisms of episodic memory impairment in schizophrenia.

OBJECTIVE: To achieve a better understanding of the functional mechanisms underlying episodic memory dysfunction in schizophrenia, which is a prerequisite for unravelling schizophrenia's neural correlates in neuroimaging studies and, more generally, for developing an integrated approach to the pathophysiology of schizophrenia. It is also crucial for developing cognitive remediation. METHOD: This paper reviews empirical evidence of episodic memory dysfunction in schizophrenia obtained with reference to various theoretical models of episodic memory. RESULTS: All the studies converge to show a significant impairment of the critical feature of episodic memory: conscious recollection. Schizophrenia is also associated with a defect of autobiographical memory. The episodic memory dysfunction results from a predominant failure of strategic processing at encoding, although an impairment of strategic processing at retrieval cannot be ruled out. The possibility that it is not the execution of the encoding strategies that is defective but, rather, their self-initiation by the patients is plausible. CONCLUSIONS: These findings may explain some behavioural abnormalities associated with schizophrenia, notably, inadequate functional outcomes in everyday life. They may also have implications for cognitive remediation and better social and work functioning of patients with schizophrenia.     

Preserved memory monitoring but impaired memory control during episodic encoding in patients with schizophrenia.

Metamemory awareness refers to the ability to monitor and control how well information is processed depending on the loads and needs of the task at hand. There is some evidence that metamemory functions are impaired in schizophrenia at the time of memory retrieval. This study investigated whether patients with schizophrenia exhibit metamemory abnormalities during the encoding of new information. The frequency of item presentation was varied. Both memory control and memory monitoring were assessed using study-time allocation and Judgments of Learning (JOL), respectively. Repeated items were recalled better by both groups, but memory performance was lower in patients than controls. Patients' behavior patterns were abnormal in terms of the study-time allocated for each item according to presentation frequency. Patients' JOLs were lower than those of controls but remained sensitive to item repetition. Patients' predictive values on memory accuracy were no different to those measured in controls. In addition, none of the patients reported using efficient strategies to help memorize target items. The results show a dissociation between memory control, which was impaired, and memory monitoring, which was spared, in patients with schizophrenia during encoding of new information.     

The recognition potential and conscious awareness

The idea that conscious awareness of a recognizable image is necessary for it to evoke the recognition potential (RP) was tested by asking bilingual subjects to selectively attend to superimposed English and Chinese word images. The subjects detected most of the words in the attended language, but were largely oblivious of words in the non-attended language. Attended word images evoked the RP. Non-attended words did not. RP latency was less for Chinese than for English words. This provided a basis for inferring which language a subject was trying to read when valid English and Chinese words were both present. A subject was looking for Chinese if the latency was short and for English if it was long. The results showed that selective attention had a powerful effect on the RP. They supported the idea that conscious awareness is necessary for evoking it, though they did not rule out the theoretical possibility that some method not yet tested could be found that would block conscious awareness without blocking the RP. The sensitivity of the RP to what a subject is trying to see and its low variance seem to provide advantages for studying visual perception. It provides a short latency indicator of image processing that merits further investigation. Use of it may lead to a better understanding of visual perceptual processes.     

Schizophrenic patients are impaired in memory reinstatement underlying mismatch negativity system.

OBJECTIVE: We modified the paradigm used in the report of Cowan et al. [J Exp Psychol Learn Mem Cogn 19 (1993) 909] to investigate how the silent intervals influence the memory trace underlying mismatch negativity (MMN) generation in schizophrenic patients. METHODS: Experiment 1 was designed to explore how long an inter-train interval would be needed for the memory to become dormant. Experiment 2 was designed to elucidate how many standard stimuli would be needed to reinstate the memory. RESULTS: In Experiment 1, schizophrenic patients showed a significant reduction in MMN amplitude after the longer inter-train intervals compared to the shorter ones, although little difference was observed in controls. Specifically, the memory trace underlying the MMN system in the schizophrenic patients easily became dormant after the extended silent intervals. In Experiment 2, we could not conclude that schizophrenic patients needed more reminders than did controls in order to reinstate the memory once the memory trace became dormant. The patients might be little impaired with respect to forming the memory trace. CONCLUSIONS: In schizophrenic patients, the memory trace in MMN generation might easily become out of context after silent intervals. Patients could not effectively reinstate the memory that was put out of context by the extended silent interval. SIGNIFICANCE: This article provides some suggestions in terms of patients' difficulty encoding episodes and retrieving them within distinct contexts in preconscious processes.     

Preserved subliminal processing and impaired conscious access in schizophrenia

BACKGROUND: Studies of visual backward masking have frequently revealed an elevated masking threshold in schizophrenia. This finding has frequently been interpreted as indicating a low-level visual deficit. However, more recent models suggest that masking may also involve late and higher-level integrative processes, while leaving intact early bottom-up visual processing. OBJECTIVE: To test the hypothesis that the backward-masking deficit in schizophrenia corresponds to a deficit in the late stages of conscious perception, whereas the subliminal processing of masked stimuli is fully preserved. DESIGN: Twenty-eight patients with schizophrenia and 28 normal control subjects performed 2 backward-masking experiments. We used Arabic digits as stimuli and varied quasi-continuously the interval with a subsequent mask, thus allowing us to progressively unmask the stimuli. We finely quantified their degree of visibility using objective and subjective measures to evaluate the threshold duration for access to consciousness. We also studied the priming effect caused by the variably masked numbers in a comparison task performed on a subsequently presented and highly visible target number. RESULTS: The threshold delay between the digit and mask necessary for the conscious perception of the masked stimulus was longer in patients compared with controls. This higher consciousness threshold in patients was confirmed by an objective and a subjective measure, and both measures were highly correlated for the patients and controls. However, subliminal priming of masked numbers was effective and identical in patients and controls. CONCLUSIONS: Access to conscious report of masked stimuli is impaired in schizophrenia, whereas fast bottom-up processing of the same stimuli, as assessed by subliminal priming, is preserved. These findings suggest a high-level origin of the masking deficit in schizophrenia, although they leave open for further research its exact relation to previously identified bottom-up visual processing abnormalities.     

Investigation of conscious recollection, false recognition and delusional misidentification in patients with schizophrenia

BACKGROUND: Recognition memory (RM) is impaired in patients with schizophrenia, as they rely largely on feelings of familiarity rather than conscious recollection. It has been suggested that this abnormality may reflect a breakdown in strategic memory processes involved in both encoding and retrieval. By studying 2 patients with false recognition (FR; patient C.T.) and delusional misidentification (DM; patient B.C.), and a group of psychotic control patients, we examined proposals that FR and DM exist on a continuum of increasingly severe impairment in strategic memory function. METHODS: Executive function, autobiographical memory and verbal and facial RM were assessed using standard neuropsychological tests and the remember/know paradigm. RESULTS: The psychotic control group displayed a significantly reduced reliance on remember judgements and compensatory elevation in know judgements on both RM tasks compared with the normal control group. Patient B.C. also followed this trend, but in a much more pronounced manner. In contrast, patient C.T. displayed a qualitatively different performance profile, which was marked by an increased dependence on remember responses. CONCLUSIONS: We have presented evidence which support proposals that a breakdown in strategic memory and executive dysfunction are more pronounced in DM than FR. However, the small sample size precludes any firm conclusions being drawn.     

Levels of processing effects on recognition memory in patients with schizophrenia

This study sought to characterize the performance of patients with schizophrenia, as compared with healthy participants, on a memory task that required encoding of items to different depths. Participants included 21 individuals with schizophrenia and 26 healthy controls. During the encoding phase of the study, participants processed successively presented words in two ways: perceptually (by making a decision as to whether the letter "a" was present in the word) or semantically (by making a living/nonliving decision for each word). During the recognition phase of the study, participants were presented with a list of words containing items that had been presented during the encoding phase (during either the letter decision task or the semantic decision task), as well as items that had not been seen before (foils). Though patients with schizophrenia performed more poorly overall on the recognition task, recognition was facilitated by semantic encoding to an equivalent degree in both groups. In other words, while significant main effects were present for group and encoding, no groupxencoding condition was present. This result is consistent with previous findings of a lack of qualitative differences in performance on learning and memory tasks between patients with schizophrenia and healthy controls. It also suggests that strategies that place constraints on the encoding processes used by patients may help improve the efficiency with which they learn and remember information.     

Verbal memory processes in schizophrenia patients and biological relatives of schizophrenia patients: intact implicit memory, impaired explicit recollection

Verbal memory deficits are arguably the most common cognitive abnormalities in biological relatives of schizophrenia patients. Because verbal memory is a complex cognitive function, it is necessary to differentiate its intact and compromised aspects in order to reveal aberrant neural systems that reflect genetic risk in relatives of schizophrenia patients. Using an experimental verbal memory task, we examined encoding, free-recall, repetition priming, and recognition of verbal material in 22 schizophrenia patients, 22 first-degree biological relatives of schizophrenia patients, and 23 nonpsychiatric control participants. Schizophrenia patients exhibited intact repetition priming, but worse size judgment task performance (encoding), recall, and recognition than the control participants. Biological relatives of schizophrenia patients exhibited intact size judgment task performance, repetition priming, and recognition, but a free-recall deficit. Although size judgment task performance at encoding was associated with recall of verbal material in schizophrenia and control groups, in the relative group encoding performance was associated with the degree of repetition priming. Findings are consistent with impaired explicit recollection of verbal material, but intact implicit verbal memory in schizophrenia patients and biological relatives of schizophrenia patients.     

Face recognition memory deficits and visual object memory performance in patients with schizophrenia and their relatives

OBJECTIVE: Face recognition memory deficits in schizophrenia are attributed to frontotemporal dysfunction. Biological relatives of patients have similar deficits, suggesting genetic susceptibility. Because the impairment may reflect generalized object memory deficits, the authors evaluated both face and visual object recognition. METHOD: The Penn Face Memory Test and Visual Object Learning Test were given to 102 patients with schizophrenia, 60 of their biological relatives, and 135 healthy comparison subjects. RESULTS: Significant immediate and delayed face recognition deficits were observed in patients and their relatives. Although patients were more impaired in visual object memory than comparison subjects, relatives were not. CONCLUSIONS: Face recognition deficits in patients with schizophrenia and their families are not secondary to generalized object memory deficits and may be an endophenotype reflecting frontotemporal impairment.     

Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients

Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this entity can be subcategorized into MCS- (i.e., patients only showing nonreflex behavior such as visual pursuit, localization of noxious stimulation and/or contingent behavior) and MCS+ (i.e., patients showing command following).Patterns of cerebral glucose metabolism were studied using [(18)F]-fluorodeoxyglucose-PET in 39 healthy volunteers (aged 46 ± 18 years) and 27 MCS patients of whom 13 were MCS- (aged 49 ± 19 years; 4 traumatic; 21 ± 23 months post injury) and 14 MCS+ (aged 43 ± 19 years; 5 traumatic; 19 ± 26 months post injury). Results were thresholded for significance at false discovery rate corrected p < 0.05.We observed a metabolic impairment in a bilateral subcortical (thalamus and caudate) and cortical (fronto-temporo-parietal) network in nontraumatic and traumatic MCS patients. Compared to MCS-, patients in MCS+ showed higher cerebral metabolism in left-sided cortical areas encompassing the language network, premotor, presupplementary motor, and sensorimotor cortices. A functional connectivity study showed that Broca's region was disconnected from the rest of the language network, mesiofrontal and cerebellar areas in MCS- as compared to MCS+ patients.The proposed subcategorization of MCS based on the presence or absence of command following showed a different functional neuroanatomy. MCS- is characterized by preserved right hemispheric cortical metabolism interpreted as evidence of residual sensory consciousness. MCS+ patients showed preserved metabolism and functional connectivity in language networks arguably reflecting some additional higher order or extended consciousness albeit devoid of clinical verbal or nonverbal expression.     

Functional MRI and novel picture-learning among older patients with chronic schizophrenia: abnormal correlations between recognition memory and medial temporal brain response.

The relationship between disordered brain function and learning deficits in chronic schizophrenia is unclear. The authors compared correlations of brain response to picture encoding with subsequent recognition memory between samples of clinically stable patients over age 45 with schizophrenia and demographically similar healthy individuals. Subjects were studied with functional magnetic resonance imaging during novel picture encoding and a control condition. Comparison subjects showed an inverse relationship between subsequent recognition memory and brain response in medial temporal areas. Among schizophrenia patients, brain response in these regions was positively correlated with recognition memory. Brain-behavior relationships during learning were thus found to be qualitatively different between schizophrenic patients and healthy subjects.     

Diabetes mellitus and impaired glucose tolerance in patients with schizophrenia.

OBJECTIVES: This study aimed to establish the prevalence of diabetes mellitus (DM) and impaired glucose tolerance in patients with schizophrenia and to elucidate some of the factors associated with hyperglycemia. METHODS: We studied a sample of 194 patients with schizophrenia. We determined fasting blood glucose and insulin levels at the start of the testing period; patients were given an oral glucose tolerance test after an overnight fast. RESULTS: The overall prevalence of diabetes and impaired glucose tolerance in these patients was 16.0% and 30.9%, respectively. These rates were higher than those reported in the general population. Patients with disordered glucose homeostasis were significantly older (P = 0.005, Kruskal-Wallis test). There was no significant effect of sex or ethnicity on diabetes. CONCLUSIONS: Our findings suggest that patients with schizophrenia are more vulnerable to developing DM. We caution clinicians to be mindful of the increased risk and to be vigilant for such a development.     

Prefrontal activity and impaired memory encoding strategies in schizophrenia

Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome.     

Face recognition in patients with schizophrenia

It is well known that patients with schizophrenia show severe deficiencies in social communication skills. These deficiencies are believed to be partly derived from abnormalities in face recognition. However, the exact nature of these abnormalities exhibited by schizophrenic patients with respect to face recognition has yet to be clarified. In the present paper, we review the main findings on face recognition deficiencies in patients with schizophrenia, particularly focusing on abnormalities in the recognition of facial expression and gaze direction, which are the primary sources of information of others' mental states. The existing studies reveal that the abnormal recognition of facial expression and gaze direction in schizophrenic patients is attributable to impairments in both perceptual processing of visual stimuli, and cognitive-emotional responses to social information. Furthermore, schizophrenic patients show malfunctions in distributed neural regions, ranging from the fusiform gyrus recruited in the structural encoding of facial stimuli, to the amygdala which plays a primary role in the detection of the emotional significance of stimuli. These findings were obtained from research in patient groups with heterogeneous characteristics. Because previous studies have indicated that impairments in face recognition in schizophrenic patients might vary according to the types of symptoms, it is of primary importance to compare the nature of face recognition deficiencies and the impairments of underlying neural functions across sub-groups of patients.     

Long-term memory underlying hippocampus-dependent social recognition in mice

The ability to learn and remember individuals is critical for the stability of social groups. Social recognition reflects the ability of mice to identify and remember conspecifics. Social recognition is assessed as a decrease in spontaneous investigation behaviors observed in a mouse reexposed to a familiar conspecific. Our results demonstrate that group-housed mice show social memory for a familiar juvenile when tested immediately, 30 min, 24 h, 3 days, and 7 days after a single 2-min-long interaction. Interestingly, chronic social isolation disrupts long-term, but not 30-min, social memory. Even a 24-h period of isolation disrupts long-term social memory, a result that may explain why previous investigators only observed short-term social memory in individually housed rodents. Although it has no obvious configural, relational, or spatial characteristics, here we show that social memory shares characteristics of other hippocampus-dependent memories. Ibotenic acid lesions of the hippocampus disrupt social recognition at 30 min, but not immediately after training. Furthermore, long-term, but not short-term social memory is dependent on protein synthesis and cyclic AMP responsive element binding protein (CREB) function. These results outline behavioral, systems, and molecular determinants of social recognition in mice, and they suggest that it is a powerful paradigm to investigate hippocampal learning and memory.     

Eye movements reflect impaired face processing in patients with schizophrenia.

BACKGROUND: Impaired processing of faces in patients with schizophrenia may underlie aspects of disturbance in their social interaction. This study examined patterns of eye fixation in subjects with schizophrenia and non-psychiatric controls, while processing a high resolution picture of a neutral face and a nonbiological complex geometric stimulus. METHODS: Ten-second sequences of eye movement were recorded video-oculographically (50 samples/sec) while subjects were "free-viewing" the stimuli. An essential element of the study was customized software that ensured stimulus presentation on a video display only after subjects were fixated upon a centre-screen cue, so that all subjects began stimulus processing from the same point. RESULTS: Compared with the control group, subjects with schizophrenia exhibited reduced scanpath lengths and a tendency toward fewer fixations for the face stimulus. They also showed an initial relative right spatial hemineglect (for the first voluntary fixation) when viewing the Rey figure, but not when viewing the face stimulus. Overall, there were no significant differences between the schizophrenia and control groups in the lateral distribution of subsequent fixations for either stimulus. CONCLUSIONS: Disturbed spatial and temporal patterns of eye movement in some people with schizophrenia may reflect sub-optimal processing of face stimuli, that may predispose these individuals to dysfunctional interpretation of facial communication cues.     

Glucose-induced increase in memory performance in patients with schizophrenia.

Previous investigations have found that increasing circulating glucose availability can increase memory performance in rodents, healthy humans, and individuals with dementia of the Alzheimer's type. In this study, patients with schizophrenia, healthy control subjects, and controls with bipolar affective disorder were tested using double-blind treatment with either 50 g anhydrous dextrose plus 4 mg sodium saccharin (for "taste") or 23.7 mg saccharin alone, followed by cognitive testing on a complex battery. At this glucose dose, verbal memory performance on a paragraph recall task was increased during the glucose condition relative to the saccharin condition in the patients with schizophrenia; this effect was not detected in either the psychiatric or normal controls. The results provide preliminary support for the hypothesis that memory performance can be improved in patients with schizophrenia by increasing circulating glucose availability and suggest the importance of further evaluation of therapeutic manipulations of glucose availability.     

Thought disorder in schizophrenia: working memory and impaired context

This research was designed to provide data on whether thought disorder in schizophrenia patients is due to difficulty in holding external stimuli or the external context online in working memory. We assessed 231 early phase acute inpatients, including 68 schizophrenic patients and 38 bipolar manic patients. Patients were administered a thought disorder test that requires holding stimuli online in working memory as they respond and another in which the stimuli is in direct view of the patients throughout the test procedure. The results indicated that patients who were thought disordered on the test requiring holding the external stimuli online in memory also were more thought disordered on the test that provides full vision of the stimuli throughout the testing (p < 0.001). Thus, schizophrenia patients vulnerable to thought disorder show thought disorder regardless of whether or not they are required to hold the stimuli online in memory. Overall, the data did not support the formulation that thought disorder is primarily a consequence of failure to hold external stimuli or contextual material online in working memory. An alternate view of thought disorder is presented.     

TMS-EEG approach unveils brain mechanisms underlying conscious and unconscious face perception

BackgroundConscious perception of external stimuli has been related to recurrent activity in distributed cortical networks, although brain mechanisms controlling unconscious processing and stimuli access to conscious report need to be clarified.ObjectiveThis study aims at investigating modulations in cortical excitability related to conscious perception and unconscious processing of face stimuli with different visibility levels.MethodsWe used TMS-EEG over the right occipital face area (rOFA), or the right premotor cortex (rPMC) as control site, to measure cortical excitability during a backward masking paradigm with individually defined stimuli visibility.ResultsEvent related potentials showed significant differences for faces compared to houses, and detected faces compared to missed ones, 200 ms post target onset. TMS over rOFA, but not over rPMC, triggered a relative positivity starting 150 ms post target when faces with high visibility were consciously reported. Moreover, rOFA TMS evoked differential responses for high versus low visible faces in conscious and unconscious processing at 290–390 and 180–240 ms, respectively.ConclusionResults unveiled a causal link between rOFA excitability and late responses related to access to conscious perception, suggesting a critical role of recurrent activity, but distinct components, for consciously perceived stimuli and unconscious face processing.