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Word and Tone Working Memory Deficits in Schizophrenia
Abstract
Verbal memory deficits have been reported in many studies of patients with schizophrenia. We evaluated the specificity of these deficits by comparing patients and control subjects on several verbal and nonverbal auditory memory tests.
Performance of stable, medicated outpatients with DSM-III-R diagnoses of schizophrenia (N = 38) was compared with that of healthy subjects (N = 39) on a word list immediate recall task, tone delayed discrimination tasks, and word and tone serial position tasks. Before memory testing, patients were divided into 2 groups based on their ability to perform normally on a screening test requiring pitch discrimination and sustained attention.
The nonverbal tests were more difficult for control subjects than the verbal tests. Despite this, patients who performed normally on the screening test of perception and attention performed normally on both nonverbal tests but had highly significant deficits on both verbal tests (P<.001 and P = .02). Patients who performed poorly on the screening test had highly significant performance deficits on all the memory tests.
One subgroup of patients with schizophrenia has a selective deficit in verbal memory despite normal motivation, attention, and general perceptual function. Another group has deficits in multiple aspects of cognitive function suggestive of failure in early stages of information processing.
... Dans la 2 e condition, des chiffres prononcés par une voix masculine sont intercalés entre les chiffres cibles constituant une distraction. Word serial position test [124] Chaque essai commence par une présentation vocale de quatre mots. Après un délai de neuf secondes, un des mots précédemment présentés est répété. ...
... D'autres tests ont été également utilisés. Ainsi, les patients atteints de schizophrénie présentent des performances altérées au digit span distractibility test [53], au word serial position test [14,124] et à la tâche de réponse verbale différée [64]. ...
... Un screening urinaire des produits toxiques est fréquemment demandé afin d'éliminer l'effet d'une substance [27,50,55,119]. L'évaluation des compétences perceptuelles et attentionnelles des patients est fortement recommandée afin de ne pas négliger leur contribution dans les performances obtenues lors des tests évaluant la mémoire de travail [14,50,55,70,119,124]. ...
La mémoire de travail se réfère à un système à capacité limitée pour le maintien temporaire et le traitement de l’information. Son exploration chez les patients atteints de schizophrénie a fait l’objet de très nombreux travaux portant sur différents types de populations et utilisant une large gamme de tests cognitifs. Malgré la diversité des méthodologies, la majorité des études récentes met en évidence des déficits affectant toutes les composantes de la mémoire de travail chez les patients atteints de schizophrénie. Ces déficits ne semblent pas être liés à l’âge, au sexe, au QI prémorbide, à la durée d’évolution des troubles et aux symptômes positifs de la maladie, mais apparaissent corrélés à un bas niveau d’instruction et aux symptômes négatifs et de désorganisation. Ils seraient présents dès le début des troubles et sont également retrouvés parmi les parents des patients et chez les sujets présentant une personnalité schizotypique pouvant ainsi constituer des marqueurs de vulnérabilité de cette affection. L’effet spécifique des médications antipsychotiques sur la mémoire de travail a été peu exploré. Quelques études rapportent un effet bénéfique de certains neuroleptiques atypiques, notamment la rispéridone. Son niveau de fonctionnement a été trouvé fortement prédictif du degré d’acquisition d’habiletés psychosociales contribuant ainsi dans le pronostic fonctionnel des patients. Son déficit a fait l’objet d’une remédiation cognitive spécifique avec comme résultat une amélioration mesurable et durable.
... Thus, the analysis of tests showed that 'Reading the Mind in the Eyes' is the most sensitive to detecting ToM deficit in patients with the first psychotic episode. Wexler et al. 1998). However, it is this non-verbal test that poses the greatest challenge for the healthy subjects compared to the other tasks (Wexler et al. 1998), which, perhaps, results in comparable scores in the above-mentioned studies. ...
... Wexler et al. 1998). However, it is this non-verbal test that poses the greatest challenge for the healthy subjects compared to the other tasks (Wexler et al. 1998), which, perhaps, results in comparable scores in the above-mentioned studies. ...
The research is based on comparative analysis of 'Hinting Task', 'Faux Pas', and 'Reading the Mind in the Eyes' tests sensitivity
in detection of Theory of Mind deficits. The study included 20 subjects with schizophrenia and schizophrenia spectrum disorders with
the first episode of psychosis. Every subject performed the three proposed tests. It was shown that success rate of the three tests
differed significantly. The non-verbal test 'Reading the Mind in the Eyes' caused the most difficulties. The success rate percentage of
this test performance correlated negatively with the severity of psychopathological symptoms evaluated according to the PANSS
scale. Thus, 'Reading the Mind in the Eyes' test is the most sensitive out of the three to Theory of Mind deficits detection, which may
be used for diagnostic purposes.
... Disruptions in early auditory processing (EAP) give rise to altered sensory and perceptual experiencesranging from the misrepresentation of simple sounds to complex clinical features; e.g. aberrant salience and auditory hallucinations (Iliadou et al., 2013;Javitt & Freedman, 2015;Martin et al., 2018;McKay, Headlam, & Copolov, 2000;Wexler, Stevens, Bowers, Sernyak, & Goldman-Rakic, 1998). Hence, EAP abnormalities have pervasive consequences on neurocognition, psychosocial functioning and quality of life for individuals with SZ and other central nervous system disorders (Brown & Kuperberg, 2015;Revheim et al., 2014;Thomas et al., 2017). ...
Background
Auditory system plasticity is a promising target for neuromodulation, cognitive rehabilitation and therapeutic development in schizophrenia (SZ). Auditory-based targeted cognitive training (TCT) is a ‘bottom up’ intervention designed to enhance the speed and accuracy of auditory information processing, which has been shown to improve neurocognition in certain SZ patients. However, the dynamics of TCT learning as a function of training exercises and their impact on neurocognitive functioning and therapeutic outcomes are unknown.
Methods
Forty subjects (SZ, n = 21; healthy subjects (HS), n = 19) underwent comprehensive clinical, cognitive, and auditory assessments, including measurements of auditory processing speed (APS) at baseline and after 1-h of TCT. SZ patients additionally completed 30-hours of TCT and repeated assessments ~10–12 weeks later.
Results
SZ patients were deficient in APS at baseline ( d = 0.96, p < 0.005) relative to HS. After 1-h of TCT, analyses revealed significant main effects of diagnosis ( d = 1.75, p = 0.002) and time ( d = 1.04, p < 0.001), and a diagnosis × time interaction ( d = 0.85, p = 0.02) on APS. APS learning effects were robust after 1-h in SZ patients ( d = 1.47, p < 0.001) and persisted throughout the 30-h of training. Baseline APS was associated with verbal learning gains after 30-h of TCT ( r = 0.51, p = 0.02) in SZ.
Conclusions
TCT learning metrics may have prognostic utility and aid in the prospective identification of individuals likely to benefit from TCT. Future experimental medicine studies may advance predictive algorithms that enhance TCT-related clinical, cognitive and functional outcomes.
... Three studies showed that BAP deficits were bimodally distributed in patients. Two subgroups of patients could be defined depending on their pitch discrimination deficits: a group of 'discriminators' able to correctly perceive differences between easy tones and a group of 'nondiscriminators' who are not (Dondé et al., 2019b;Holcomb et al., 2000;Wexler et al., 1998). However, the two subgroups did not differ in their symptomatology, except in Dondé et al. (2019b) where patients with pitch discrimination deficits scored higher on cognitive items in a five-factor Positive and Negative Syndrome Scale (PANSS) model (e.g., abstract thinking, disorientation, poor attention) compared to patients without discrimination deficits, even if they presented a similar PANSS total score to patients without deficits. ...
Processing of basic auditory features, one of the earliest stages of auditory perception, has been the focus of considerable investigations in schizophrenia. Although numerous studies have shown abnormalities in pitch perception in schizophrenia, other basic auditory features such as intensity, duration, and sound localization have been less explored. Additionally, the relationship between basic auditory features and symptom severity shows inconsistent results, preventing concrete conclusions. Our aim was to present a comprehensive overview of basic auditory processing in schizophrenia and its relationship with symptoms. We conducted a systematic review according to the PRISMA guidelines. PubMed, Embase, and PsycINFO databases were searched for studies exploring auditory perception in schizophrenia compared to controls, with at least one behavioral task investigating basic auditory processing using pure tones. Forty-one studies were included. The majority investigated pitch processing while the others investigated intensity, duration and sound localization. The results revealed that patients have a significant deficit in the processing of all basic auditory features. Although the search for a relationship with symptoms was limited, auditory hallucinations experience appears to have an impact on basic auditory processing. Further research may examine correlations with clinical symptoms to explore the performance of patient subgroups and possibly implement remediation strategies.
... Since one of the variables we examined in the sentence production test is grammatical tone, two tone-discrimination tests were administered. First, in the online Tone Screening Test (Kayser, 2011;Wexler, Stevens, Bowers, Sernyak, & Goldman-Rakic, 1998), we played two non-linguistic tones for the participant who had to indicate whether the tones s/he heard were the "same" or "different". Second, we tested lexical tone discrimination using Akan words, for which the agrammatic speakers heard two words that were identical or only differed in tone: they had to indicate whether the words they heard were the "same" or "different". ...
Background: The distribution of pronouns varies cross-linguistically. This distribution has led to conflicting results in studies that investigated pronoun resolution in agrammatic indviduals. In the investigation of pronominal resolution, the linguistic phenomenon of "resumption" is understudied in agrammatism. The construction of pronominal resolution in Akan presents the opportunity to thoroughly examine resumption. Aims: To start, the present study examines the production of (pronominal) resumption in Akan focus constructions (who-questions and focused declaratives). Second, we explore the effect of grammatical tone on the processing of pronominal (resumption) since Akan is a tonal language. Methods & Procedures: First, we tested the ability to distinguish linguistic and non-linguistic tone in Akan agrammatic speakers. Then, we administered an elicitation task to five Akan agrammatic individuals, controlling for the structural variations in the realization of resumption: focused who-questions and declaratives with (i) only a resumptive pronoun, (ii) only a clause determiner, (iii) a resumptive pronoun and a clause determiner co-occurring, and (iv) neither a resumptive pronoun nor a clause determiner. Outcomes & Results: Tone discrimination .both for pitch and for lexical tone was unimpaired. The production task demonstrated that the production of resumptive pronouns and clause determiners was intact. However, the production of declarative sentences in derived word order was impaired; wh-object questions were relatively well-preserved. Conclusions: We argue that the problems with sentence production are highly selective: linguistic tones and resumption are intact but word order is impaired in non-canonical declarative sentences.
... SZ patients demonstrate a broad range of central auditory processing (CAP) deficits, including impairment in auditory discrimination (e.g., speech perception and recognition), sound localization and lateralization, and auditory temporal processing (Iliadou et al., 2013;Martin et al., 2018;Perrin et al., 2010;Wexler et al., 1998). This constellation of abnormalities in behavioral and electrophysiological tests of auditory function has led clinical investigators to suspect the presence of a comorbid Central Auditory Processing Disorder in certain SZ patients (Iliadou et al., 2013;McKay et al., 2000). ...
Background
Sensory processing abnormalities are common in schizophrenia (SZ) and impact everyday functions, such as speech perception in noisy environments. Auditory-based targeted cognitive training (TCT) is a “bottom up” cognitive remediation intervention designed to enhance the speed and accuracy of low-level auditory information processing. However, the effects of TCT on behavioral measures of central auditory processing (CAP) and the role of CAP function on verbal learning outcomes in SZ are unknown.
Methods
SZ (n = 42) and healthy subjects (CTL; n = 18) underwent comprehensive clinical, neurocognitive, and auditory assessments, including tests of hearing sensitivity and speech recognition (Words-in-Noise (WIN), Quick Speech-in-Noise (SIN)). SZ patients were randomized to receive either treatment-as-usual (TAU); or 30-h of TCT + TAU using a stratified, parallel design. SZ patients repeated assessments ~10–12 weeks later.
Results
Patients exhibited deficits in both WIN (p < 0.05, d = 0.50) and SIN (p < 0.01, d = 0.63). A treatment × time interaction on WIN (p < 0.05, d = 0.74), but not SIN discriminability, was seen in the TCT group relative to TAU. Specific enhancements in the 4-dB over background range drove gains in WIN performance. Moreover, SZ patients with greater CAP deficits experienced robust gains in verbal learning after 30-h of TCT relative to SZ patients without CAP impairment (p < 0.01, d = 1.28).
Conclusion
Findings demonstrate that intensive auditory training enhances the fidelity of auditory processing and perception, such that specific CAP deficits were ‘normalized’ and were predictive of gains in verbal learning after TCT. It is conceivable that patients with deficiencies in CAP measures may benefit most from TCT and other interventions targeting auditory dysfunction in SZ.
... Pretests for tone discrimination abilities Because grammatical tone perception is crucial in distinguishing between Akan past and present habitual, five 3 of the agrammatic speakers performed a Tonal Screening Test (TST: Bruder et al., 2011;Bruder, Wexler, Sage, Gil, & Gorman, 2004;Kayser, 2011;Stevens, Donegan, Anderson, Goldman-Rakic, & Wexler, 2000;Wexler, Stevens, Bowers, Sernyak, & Goldman-Rakic, 1998), in which a pair of non-linguistic tones is judged to be either the same or different. The tones were made up of 300-ms sine waves with frequencies between 325 and 1994 Hz. ...
Background: Languages of the world have several ways of expressing time reference. Many languages such as those in the Indo-European group express time reference through tense. Languages such as Chinese and Standard Indonesian express time reference through aspectual adverbs, while Akan does so through grammatical tone. Previous studies have found that time reference is selectively impaired, with reference to the past being more impaired than reference to the non-past. The PAst DIscourse LInking Hypothesis (PADILIH) posits that pastime reference is difficult because it requires discourse linking.
Aims: The goal of this study was first to examine whether pastime reference is impaired also in languages that do not use grammatical affixes but rather tone, to make time reference. Second, this study aims to decouple the effect of tone from the effect of temporal reference on Akan verbs.
Method and Procedures: Ten Akan agrammatic speakers and 10 non-brain-damaged speakers (NBDs) participated in this study. An Akan adapted version of the Test for Assessing Reference of Time (African TART), for both production and comprehension was used. The TART focuses on the future, present (habitual) and the pastime frames. Additionally, five of the agrammatic speakers performed two tonal discrimination tasks: a non-linguistic and a linguistic (lexical) one.
Outcomes and Results: While the NBDs scored at ceiling, the agrammatic speakers made errors, and these affected past more than present and the future time references, in both comprehension and production tasks. However, the comprehension data showed a dissociation between the present habitual and the future. The substitution error analysis revealed a preference for the present. The five agrammatic speakers showed an intact performance on non-linguistic tonal discrimination task.
Conclusion: The conclusion is that regardless of how time reference is expressed, whether through inflectional morphology or grammatical tone, reference to the past is problematic for individuals with agrammatic aphasia. The fact that the agrammatic speakers could perceive the non-linguistic tonal differences demonstrates that it is not tone in general that is disrupted, but rather time reference, particularly reference to the past, as predicted by the PADILIH.
... Since one of the variables we examined in the sentence production test is grammatical tone, two tone-discrimination tests were administered. First, in the online Tone Screening Test (Kayser, 2011;Wexler, Stevens, Bowers, Sernyak, & Goldman-Rakic, 1998), we played two non-linguistic tones for the participant who had to indicate whether the tones s/he heard were the "same" or "different". Second, we tested lexical tone discrimination using Akan words, for which the agrammatic speakers heard two words that were identical or only differed in tone: they had to indicate whether the words they heard were the "same" or "different". ...
Background: The distribution of pronouns varies cross-linguistically. This distribution has led to conflicting results in studies that investigated pronoun resolution in agrammatic indviduals. In the investigation of pronominal resolution, the linguistic phenomenon of “resumption” is understudied in agrammatism. The construction of pronominal resolution in Akan presents the opportunity to thoroughly examine resumption.
Aims: To start, the present study examines the production of (pronominal) resumption in Akan focus constructions (who-questions and focused declaratives). Second, we explore the effect of grammatical tone on the processing of pronominal (resumption) since Akan is a tonal language.
Methods & Procedures: First, we tested the ability to distinguish linguistic and non-linguistic tone in Akan agrammatic speakers. Then, we administered an elicitation task to five Akan agrammatic individuals, controlling for the structural variations in the realization of resumption: focused who-questions and declaratives with (i) only a resumptive pronoun, (ii) only a clause determiner, (iii) a resumptive pronoun and a clause determiner co-occurring, and (iv) neither a resumptive pronoun nor a clause determiner.
Outcomes & Results: Tone discrimination .both for pitch and for lexical tone was unimpaired. The production task demonstrated that the production of resumptive pronouns and clause determiners was intact. However, the production of declarative sentences in derived word order was impaired; wh-object questions were relatively well-preserved.
Conclusions: We argue that the problems with sentence production are highly selective: linguistic tones and resumption are intact but word order is impaired in non-canonical declarative sentences.
... D'autres épreuves permettent d'estimer la mémoire de travail verbale des individus et usent du même procédé de rappel immédiat. Il peut s'agir des quatre phases de rappel immédiat (A1, A5, A6, B1) de la Rey Auditory Verbal Learning Test (Fitzgerald et al., 2004;Manglam & Das, 2013;, où les sujets énoncent le plus de mots dont ils se souviennent, mais aussi le Word serial position test (Wexler et al., 1998) où les sujets estiment l'ordre dans lequel les mots ont été présentés. D'après ces études, l'efficience de la mémoire de travail verbale des sujets qui ont une schizophrénie est inférieure à celle des sujets non cliniques (Addington & Addington, 2002;Brébion et al., 2011Brébion et al., , 2015aBrébion et al., , 2015bCzepielewski et al., 2015;Fitzgerald et al., 2004;Gisselgard et al., 2014;Gold et al., 2000;Lo et al., 2016;Manglam & Das, 2013;Massuda et al., 2013;Pukrop et al., 2003;Sanchez-Torres et al., 2015;Silver et al., 2003). ...
D’après les modélisations cognitives contemporaines, les pensées répétitives négatives (PRN) favorisent le déclenchement et le maintien des Hallucinations Acoustico-Verbales (HAVs). Toutefois, les études empiriques qui font le parallèle entre ces deux phénomènes verbaux sont rares. Notre étude est composée de deux expériences où les sujets sont répartis en trois groupes. Le premier groupe correspond à des sujets qui ont des HAVs (HAV1), le second groupe à des sujets qui n’en ont plus depuis plus d’un an (HAV2) et le troisième groupe à des sujets qui n’en ont jamais eu (HAV3). Les deux expériences (n = 38, n = 42) analysent la sévérité de l’intrusion de PRN, l’efficience cognitive et les performances en situation de double tâche. A la seconde expérience, certaines caractéristiques phénoménologiques des HAVs, la sévérité des symptômes dépressifs, anxieux et de l’activité hallucinatoire sont étudiées. Une tâche d’induction de PRN est également utilisée. D’après nos résultats, les sujets qui ont des HAVs tendent à avoir davantage de PRN et un trait de caractère anxieux plus important par rapport aux sujets des deux autres groupes. De plus, la sévérité des symptômes anxieux est liée positivement à la sévérité de l’activité hallucinatoire et de l’intrusion de PRN. Le temps de réalisation de la partie B du TMT est lié positivement à la sévérité des HAVs, de l’anxiété état et des symptômes dépressifs. La sévérité de l’intrusion de PRN n’est pas liée au fonctionnement cognitif. La survenue et le maintien des HAVs peut être expliqué par l’augmentation de la sévérité de l’intrusion de PRN, de la symptomatologie anxieuse et dépressive, mais également par la diminution de l’efficience de la flexibilité réactive.
... Phonological loop is a sub-component of working memory system responsible for sequence retention and onlinemanipulation of auditory-verbal items without any extrinsic facilitation [151,152]. Several studies investigated the possible impairment of verbal/auditory working memory and its potential involvement in determining linguistic dysfunctions in psychotic syndromes [153][154][155][156][157][158][159]. Menon et al. [160] administered to schizophrenic patients and healthy participants the auditory 2-back task, in order to properly assess WM skills. ...
Background: Schizophrenia is a severe and debilitating mental disorder whose cause is still unclear. It is accompanied by cognitive deficits that are commonly attributed to a dysfunction of the frontal and temporal lobes. Recently, compelling experimental evidence has been collected suggesting a role also for the parietal lobe. Parietal lobe integrates sensory information among various modalities and is engaged in a number of cognitive operations.
Objective: To review the existent literature on cognitive deficits present in schizophrenia that show suggestive analogies with deficits that follow lesions of the parietal lobe.
Results: Analogies between cognitive disorders related to lesions of the parietal region and those related to schizophrenia were found for visuospatial attention, space representation, motor imagery, sense of agency, praxis abilities, and language.
Conclusion: Some specific cognitive deficits present in schizophrenia can be attributed to parietal lobe impairment. This view is also supported by neuroimaging studies showing both structural and functional disorders of the parietal lobe in schizophrenia. Furthermore, being parietal areas functionally interconnected with other brain regions, parietal impairment may also contribute to deficits usually attributed to the dysfunction of other brain regions.
... Auditory sensory processing deficits typically emerge in schizophrenia around the time of the first psychotic episode and persist over the course of the illness (McCarley et al., 1991;Holcomb et al., 1995;Strous et al., 1995;Javitt et al., 1997;Wexler et al., 1998;Leitman et al., 2005Leitman et al., , 2010Kantrowitz et al., 2011;Gold et al., 2012;Jahshan et al., 2013). Electroencephalography studies reveal that individuals with schizophrenia exhibit reduced auditory mismatch negativity (MMN) responses (Shelley et al., 1991;Javitt, 1993;Catts et al., 1995;Michie et al., 2000;Kasai et al., 2002). ...
It has long been known that auditory processing is disrupted in schizophrenia. More recently, postmortem studies have provided direct evidence that morphological alterations to neurons in auditory cortex are implicated in the pathophysiology of this illness, confirming previous predictions. Potential neural substrates for auditory impairment and gray matter loss in auditory cortex in schizophrenia have been identified, described, and are the focus of this review article. Pyramidal cell somal volume is reduced in auditory cortex, as are dendritic spine density and number in schizophrenia. Pyramidal cells are not lost in this region in schizophrenia, indicating that dendritic spine reductions reflect fewer spines per pyramidal cell, consistent with the reduced neuropil hypothesis of schizophrenia. Stereological methods have aided in the proper collection, reporting and interpretation of this data. Mechanistic studies exploring relationships between genetic risk for schizophrenia and altered dendrite morphology represent an important avenue for future research in order to further elucidate cellular pathology in auditory cortex in schizophrenia.
... Indeed, some of these clinical language disturbances are evident in individuals at high risk for developing the disorder (Klosterkötter et al., 2001;Solomon et al., 2011;Thompson et al., 2011). Second, language dysfunction is one of the core cognitive sequelae of schizophrenia, with verbal abilities often compromised relative to other cognitive domains in both patients with schizophrenia (e.g., Wexler et al., 1998;Wood et al., 2007), and in people at risk for developing the disorder (Fuller et al., 2002;Lencz et al., 2006;Pukrop et al., 2007;Simon et al., 2007;Fusar-Poli et al., 2012;Koutsouleris et al., 2012). Third, patients' difficulties with encoding, representing, and categorizing auditory stimuli also extend to the perceptual processing of speech (e.g., Cienfuegos et al., 1999;Kasai et al., 2002;Fisher et al., 2008). ...
Language and thought dysfunction are central to the schizophrenia syndrome. They are evident in the major symptoms of psychosis itself, particularly as disorganized language output (positive thought disorder) and auditory verbal hallucinations (AVHs), and they also manifest as abnormalities in both high-level semantic and contextual processing and low-level perception. However, the literatures characterizing these abnormalities have largely been separate and have sometimes provided mutually exclusive accounts of aberrant language in schizophrenia. In this review, we propose that recent generative probabilistic frameworks of language processing can provide crucial insights that link these four lines of research. We first outline neural and cognitive evidence that real-time language comprehension and production normally involve internal generative circuits that propagate probabilistic predictions to perceptual cortices - predictions that are incrementally updated based on prediction error signals as new inputs are encountered. We then explain how disruptions to these circuits may compromise communicative abilities in schizophrenia by reducing the efficiency and robustness of both high-level language processing and low-level speech perception. We also argue that such disruptions may contribute to the phenomenology of thought-disordered speech and false perceptual inferences in the language system (i.e., AVHs). This perspective suggests a number of productive avenues for future research that may elucidate not only the mechanisms of language abnormalities in schizophrenia, but also promising directions for cognitive rehabilitation.
... Arbeitsgedächtnisses (Carter et al. 1996;Keefe et al. 1995;Weickert et al. 2000;Wexler et al. 1998) und exekutiver Funktionen (Catafau et al. 1994;Weinberger et al. 1986). Insgesamt scheinen verschiedene Funktionsbereiche relativ gleichmäßig betroffen zu sein, so dass eher von einem generellen neuropsychologischen Defizit mit Akzentuierung in bestimmten Funktionsbereichen auszugehen ist als von mehreren isolierten Problemen (Frith 1992;Lautenbacher und Möser 2004). ...
... Wexler et al. noted a general deficit in verbal memory despite normal motivation, attention and general perceptual function in a group of patients with schizophrenia. In the same study verbal working memory tasks were more impaired than nonverbal working memory tasks in patients with schizophrenia (29). This study, however, found greater deficits in nonverbal (visual) working memory. ...
Background Significant cognitive impairment has been considered a core characteristic of schizophrenia. Though many studies have reviewed the phenomenon, only a few Indian studies have investigated this aspect. Aims To compare the functioning of six cognitive domains of patients with chronic schizophrenia with an age, sex and education matched control group and to assess the association of socio-demographic and clinical correlates with cognitive functioning. Methods Nine different neuropsychological tests were administered to assess the different cognitive domains. These were administered to 47 patients with chronic schizophrenia and 29 healthy controls.Results Patients with schizophrenia performed poorly in the areas of processing speed, verbal learning, verbal working memory and visual working memory. We also found that negative symptoms predict poor performance in speed of processing and verbal working memory. Increased age was a predictor of better verbal fluency. Family history of schizophrenia in first degree relatives is a predictor of poor verbal working memory. Conclusions The findings suggest that patients with chronic schizophrenia show selective cognitive impairment. The study failed to show any impairment in the area of concentration and executive function, though patients needed more time and intermittent verbal prompts to reach a level of performance equivalent to controls. Negative symptoms were found to affect cognitive performance while age was associated with better verbal fluency performance.DOI: http://dx.doi.org/10.4038/sljpsyc.v3i1.3836 SL J Psychiatry 2012; 3 (1):21-27
... Schizophrenia patients show working memory deficits across different modalities including spatial (e.g., Badcock et al., 2008;Choi et al., 2012;Haenschel et al., 2009;Holzman, 1992, 1993;Park et al., 1999;Reilly et al., 2007), verbal/auditory (e.g. Barch et al., 2002;Bell et al., 2001;Conklin et al., 2000;Gold et al., 1997;Huguelet et al., 2000;Kim et al., 2010;Wexler et al., 1998), object (e.g. Coleman et al., 2002;Gooding and Tallent, 2004;Park and Lee, 2002;Spindler et al., 1997) and haptic (Park and Holzman, 1992). ...
This review focuses on the viability of working memory impairment as an endophenotypic marker of a schizophrenia diathesis. It begins with an introduction of the construct of working memory. It follows with a consideration of the operational criteria for defining an endophenotype. Research findings regarding the working memory performance of schizophrenia and schizophrenia-spectrum patients, first-degree relatives of schizophrenia patients and healthy controls, are reviewed in terms of the criteria for being considered an endophenotypic marker. Special attention is paid to specific components of the working memory deficit (namely, encoding, maintenance, and manipulation), in terms of which aspects are likely to be the best candidates for endophenotypes. We examine the extant literature regarding working memory performance in bipolar disorder and major depression in order to address the issue of relative specificity to schizophrenia. Despite some unresolved issues, it appears that working memory impairment is a very promising candidate for an endophenotypic marker of a schizophrenia diathesis but not for mood disorders. Throughout this review, we identify future directions for research in this exciting and dynamic area of research and evaluate the contribution of working memory research to our understanding of schizophrenia.
... Schizophrenia patients exhibit cognitive deficits in working memory and attention related to changes in the dorsolateral prefrontal cortex [199], which are thought to be stable over time [159]. Studies have shown that NAA ratios with respect to Cho and/or Cr are reduced in schizophrenia patients specifically in the prefrontal cortex [8][9][10]7,25,50] and the hippocampus [8 -10,7,51,148,205], even without structural abnormalities [26,52]. ...
... Before reducing the number of tone pairs within a difficulty level, we investigated the similarity between performance of the first 13 and second 13 items and whether it differed by diagnostic group. First, we estimated the intra-class correlation coefficients (ICCs) between the total percent correct over pairs 1-13 and over pairs [14][15][16][17][18][19][20][21][22][23][24][25][26]. The overall ICC is 0.92, suggesting a high level of similarity between performance on the first and second sets of tone pairs. ...
Schizophrenia patients exhibit impairments in auditory-based social cognition, indicated by deficits in detection of prosody, such as affective prosody and basic pitch perception. However, little is known about the psychometric properties of behavioral tests used to assess these functions. The goal of this paper is to characterize the properties of prosody and pitch perception tasks and to investigate whether they can be shortened. The pitch perception test evaluated is a tone-matching task developed by Javitt and colleagues (J-TMT). The prosody test evaluated is the auditory emotion recognition task developed by Juslin and Laukka (JL-AER). The sample includes 124 schizophrenia patients (SZ) and 131 healthy controls (HC). Properties, including facility and discrimination, of each item were assessed. Effects of item characteristics (e.g., emotion) were also evaluated. Shortened versions of the tests are proposed based on facility, discrimination, and/or ability of item characteristics to discriminate between patients and controls. Test-retest reliability is high for patients and controls for both the original and short forms of the J-TMT and JL-AER. Thus, the original as well as short forms of the J-TMT and JL-AER are suggested for inclusion in clinical trials of social cognitive and perceptual treatments. The development of short forms further increases the utility of these auditory tasks in clinical trials and clinical practice. The large SZ vs. HC differences reported here also highlight the profound nature of auditory deficits and a need for remediation.
... Wexler et al. noted a general deficit in verbal memory despite normal motivation, attention and general perceptual function in a group of patients with schizophrenia. In the same study verbal working memory tasks were more impaired than nonverbal working memory tasks in patients with schizophrenia (29). This study, however, found greater deficits in nonverbal (visual) working memory. ...
Background
Significant cognitive impairment has been considered
a core characteristic of schizophrenia. Though many
studies have reviewed the phenomenon, only a few
Indian studies have investigated this aspect.
Aims
To compare the functioning of six cognitive domains
of patients with chronic schizophrenia with an age,
sex and education matched control group and to
assess the association of socio-demographic and
clinical correlates with cognitive functioning.
Methods
Nine different neuropsychological tests were
administered to assess the different cognitive
domains. These were administered to 47 patients
with chronic schizophrenia and 29 healthy controls.
Results
Patients with schizophrenia performed poorly in the
areas of processing speed, verbal learning, verbal
working memory and visual working memory. We
also found that negative symptoms predict poor
performance in speed of processing and verbal
working memory. Increased age was a predictor of
better verbal fluency. Family history of schizophrenia
in first degree relatives is a predictor of poor verbal
working memory.
Conclusions
The findings suggest that patients with chronic
schizophrenia show selective cognitive impairment.
The study failed to show any impairment in the area
of concentration and executive function, though
patients needed more time and intermittent verbal
prompts to reach a level of performance equivalent
to controls. Negative symptoms were found to affect
cognitive performance while age was associated with
better verbal fluency performance
... Wexler et al(22) stellen vast dat de meeste gestabiliseerde, ambulante, schizofrene patiënten auditief verbale geheugenstoornissen vertonen. Ze gaan dit na aan de hand van de WLRT (Word List Recall Test, cf. ...
... The importance of the prefrontal cortex in cognition and the cognitive deficits observed in schizophrenia is supported by neuropsychological and neurophysiological studies (Goldberg et al. 1993;Levin 1984;Merriam et al. 1990; Morihisa et al. 1983;Weinberger et al. 1986Weinberger et al. , 1988Wolkin et al. 1988). Schizophrenic patients perform poorly on prefrontal cortex-mediated tasks that involve working memory (Park and Holzman 1992;Wexler et al. 1999). These tasks require that the subject retains knowledge of the information provided by an environmental cue in order to perform the appropriate behavioral response some time after the cue has been removed (Goldman-Rakic 1987). ...
An understanding of the role of the prefrontal cortex in normal cognitive processes has advanced our comprehension of the pathophysiology underlying the cognitive deficits in schizophrenia. Studies of single-neuron activity in monkeys during performance of delayed-response tasks have confirmed the involvement of the prefrontal cortex in working memory. The “memory fields” of prefrontal neurons are analogous to the receptive fields of visual neurons and the cellular expression of a working memory process that allows mnemonic information to guide behavior. D1-dopamine antagonists produce a dose-dependent effect (U-shaped) on the firing rate of cells with memory fields during delayed-response tasks. Disordered cognitive processes in schizophrenia can be attributed to impairment of function in the prefrontal cortex, as evidenced by hypometabolic activity in the prefrontal cortex and selective impairment in working memory tasks. Advances in our understanding of the role of D1 receptors in the cognitive deficits observed in schizophrenia should provide us with a rational basis for developing alternative antipsychotic treatments and may provide insight into the cellular basis of the disorder.
... (2) R In order to study the behavior of different physiological bands, the ERSlERD was computed for a band range 1-48 Hz with a frequency resolution of 4 Hz increments for 1-16 Hz range and 8 Hz increments for 16-48 Hz. Since the theta and alpha rhythms have narrow band widths compared to higher rhythms such as beta (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) and gamma bands (32-48 Hz), we used 4 Hz bin in lower frequencies and 8 Hz bin in higher frequencies. The final analysis was done with a time resolution of 250 ms with time windows overlapping by 125 ms. ...
... The evidence that prefrontal cortex is a site of abnormal brain function in schizophrenia is overwhelming. This includes data from many studies of neuropsychological and cognitive function (Barch and Carter, 1998;Gold et al 1997;Goldberg et al 1987Keefe et al 1995;Mahurin et al 1998;Park and Holzman 1992;Stone et al 1998;Weickert et al 2000;Wexler et al 1998), neuroimaging (Andreasen et al 1996(Andreasen et al , 1997Berman et al 1992;Callicott et al 1998aCallicott et al , 2000aCarter et al 1998b;Catafu et al 1994;Curtis et al 1998;Ingvar and Franzen, 1974;Kawasaki et al 1993;Manoach et al 1999Manoach et al , 2000Stevens et al 1998;Volz et al 1997;Weinberger et al 1986Weinberger et al , 1988aWeinberger et al , 1992, studies of eye movements (Cegalis and Sweeney 1979;Holzman et al 1974;Jacobsen et al 1996;Lieberman et al 1992;Litman et al 1997;Shagass et al 1974), and electrophysiologic studies (Abrams and Taylor, 1979;Guenther et al 1988;Hoffmann et al 1996;Karson et al 1987;Tauscher et al 1998). Results of this body of research have been summarized in several recent reviews (Bunney and Bunney, 2000;Callicott and Weinberger, 1999;Goldman-Rakic, 1999). ...
This article reviews prefrontal cortical biology as it relates to pathophysiology and genetic risk for schizophre- nia. Studies of prefrontal neurocognition and functional neuroimaging of prefrontal information processing con- sistently reveal abnormalities in patients with schizophre- nia. Abnormalities of prefrontal information processing also are found in unaffected individuals who are geneti- cally at risk for schizophrenia, suggesting that genetic polymorphisms affecting prefrontal function may be sus- ceptibility alleles for schizophrenia. One such candidate is a functional polymorphism in the catechol-o-methyl trans- ferase (COMT) gene that markedly affects enzyme activity and that appears to uniquely impact prefrontal dopamine. The COMT genotype predicts performance on prefrontal executive cognition and working memory tasks. Func- tional magnetic resonance imaging confirms that COMT genotype affects prefrontal physiology during working memory. Family-based association studies have revealed excessive transmission to schizophrenic offspring of the allele (val) related to poorer prefrontal function. These various data provide convergent evidence that the COMT val allele increases risk for schizophrenia by virtue of its effect on dopamine-mediated prefrontal information pro- cessing—the first plausible mechanism for a genetic effect on normal human cognition and risk for mental illness. Biol Psychiatry 2001;50:825- 844 © 2001 Society of Bi- ological Psychiatry
... Although AHs were not formally assessed during the testing sessions, it is possible that NMDAR antagonism induced an abnormality in auditory signaling and increased hallucinating activity, which may have impacted MMN generation. In support of this argument, patients in general exhibit reduced sensory-level processing of auditory input (e.g., diminished auditory acuity, elevated thresholds for tone dis- crimination; Mathew et al., 1993; Holcomb et al., 1995; Strous et al., 1995; Wexler et al., 1998; Rabinowicz et al., 2000); patients with (vs. without) AHs have greater difficulty in sound (speech) discrimination (Hugdahl et al., 2008), and the temporal cortex evidences both high glutamate levels in patients (Marsman et al., 2011) and hypofunctional activation in controls during ketamine infusion (Hugdahl et al., 2008). ...
Background: The procognitive actions of the nicotinic acetylcholine receptor (nAChR) agonist nicotine are believed, in part, to motivate the excessive cigarette smoking in schizophrenia, a disorder associated with deficits in multiple cognitive domains, including low-level auditory sensory processes and higher-order attention-dependent operations. Objectives: As N-methyl-d-aspartate receptor (NMDAR) hypofunction has been shown to contribute to these cognitive impairments, the primary aims of this healthy volunteer study were to: (a) to shed light on the separate and interactive roles of nAChR and NMDAR systems in the modulation of auditory sensory memory (and sustained attention), as indexed by the auditory event-related brain potential – mismatch negativity (MMN), and (b) to examine how these effects are moderated by a predisposition to auditory hallucinations/delusions (HD). Methods: In a randomized, double-blind, placebo-controlled design involving a low intravenous dose of ketamine (0.04 mg/kg) and a 4 mg dose of nicotine gum, MMN, and performance on a rapid visual information processing (RVIP) task of sustained attention were examined in 24 healthy controls psychometrically stratified as being lower (L-HD, n = 12) or higher (H-HD) for HD propensity. Results: Ketamine significantly slowed MMN, and reduced MMN in H-HD, with amplitude attenuation being blocked by the co-administration of nicotine. Nicotine significantly enhanced response speed [reaction time (RT)] and accuracy (increased % hits and d′ and reduced false alarms) on the RVIP, with improved performance accuracy being prevented when nicotine was administered with ketamine. Both % hits and d′, as well as RT were poorer in H-HD (vs. L-HD) and while hit rate and d′ was increased by nicotine in H-HD, RT was slowed by ketamine in L-HD. Conclusions: Nicotine alleviated ketamine-induced sensory memory impairment and improved attention, particularly in individuals prone to HD.
... The central executive is devoted to the manipulation and reorganization of maintained information in order to accomplish goal-directed planning and problem solving. Several studies have provided compelling evidence that virtually all aspects of working memory are impaired in schizophrenia, depending on the task used and the clinical characteristics of patients included (Goldberg et al. 1987;Park and Holzman 1992;Fleming et al. 1995Fleming et al. , 1997; Morice and Delahunty 1996; Gold et al. 1997;Spindler et al. 1997;Wexler et al. 1998;Salamé et al. 1998; Kéri et al. 1999; Glahn et al. 2000). The biological substrate of working memory includes a large-scale neuronal network in which the prefrontal cortex plays a central role (Smith and Jonides 1999). ...
Working memory and information processing abnormalities are often reported in schizophrenia. The aim of this study was to
examine visual backward masking (BM) functions in remitted schizophrenia-spectrum patients with spared working memory functions.
Seventy-two patients with DSM-IV schizophrenia-spectrum disorders were screened using the Wisconsin Card Sorting Test (WCST)
and the digit span forward/backward tasks. Patients with spared WCST and digit span performances were selected and administered
a spatial working memory test and two BM procedures (target identification and location). The schizophrenia-spectrum group
with spared WCST and digit span performances included individuals with schizophreniform disorder (N=11), schizophrenia (N=2),
and schizoaffective disorder (N=2). These patients were clinically remitted and demonstrated spared IQ, normal spatial working
memory, and relatively high psychosocial functioning. However, there was a significant impairment in the BM procedure, most
prominently in the target location task and at short interstimulus intervals. These results suggest that the BM dysfunction
is a trait marker of schizophrenia-spectrum disorders and may be present in the absence of working memory abnormalities.
It remains a matter of debate what roles the left and right hemispheres play in processing speech prosody. Brain lesion studies have demonstrated that lexical tone perception among native speakers of tonal languages is more disrupted in left hemisphere damaged (LHD) individuals than right hemisphere damaged (RHD) individuals. This has been taken to suggest that linguistically-relevant prosodic cues are predominantly left-lateralised, whereas non-linguistic stimuli are predominantly right-lateralised. However, this phenomenon has only been examined in lexical tone, leaving grammatical tone perception unexplored. The aim of this study was twofold: Firstly, to examine how individuals with LHD and RHD perceive grammatical tone, and secondly to compare grammatical tone to non-linguistic tone perception. Therefore, native Akan speakers with LHD, RHD and no-brain damage (NBD) controls were tested in two discrimination tasks that examined linguistic and non-linguistic tone perception. The results showed that while both the individuals with LHD and RHD show impairment in grammatical tone perception, there was a trend of a better performance for the RHD group. Nonetheless, for non-linguistic tone perception, individuals with LHD outperformed the RHD individuals, although both had reduced performance compared to the NBD individuals. A further analysis revealed that the reduced perceptual abilities of both the LHD and RHD groups in grammatical tone perception can be attributed to grammatical problems rather than tone per se. We conclude that there is potentially a bilateral involvement of the two hemispheres in grammatical tone processing, with the left being the dominant hemisphere.
Although schizophrenia and developmental dyslexia are considered distinct disorders in terms of clinical presentation and functional outcome, they both involve disruption in the processes that support skilled reading, including language, auditory perception, visual perception, oculomotor control, and executive function. Further, recent work has proposed a common neurodevelopmental basis for the two disorders, as suggested by genetic and pathophysiological overlap. Thus, these lines of research suggest that reading may be similarly impacted in schizophrenia and dyslexia. In this review, we survey research on reading abilities in individuals with schizophrenia, and review the potential mechanisms underlying reading deficits in schizophrenia that may be shared with those implicated in dyslexia. Elucidating the relationship between reading impairment in schizophrenia and dyslexia could allow for a better understanding of the pathophysiological underpinnings of schizophrenia, and could facilitate remediation of cognitive deficits that impact day-to-day functioning.
Attentional disturbances occurring among people with four psychiatric conditions will be considered: (1) affective disorders, (2) schizophrenia, (3) attention deficit hyperactivity disorder (ADHD), and (4) anxiety/stress disorders. For each of these disorders, the nature and the underlying pathophysiological mechanisms that account for disturbances of attention will be considered. We will also discuss evidence from the field of behavioral medicine that implicates attention as contributing to particular health risk factors, including pain, obesity, physical activity, and substance dependence, particularly smoking and heavy alcohol and drug use.
Background:
Deficits in verbal working memory (VWM) have consistently been observed in schizophrenia, ranging from impairments in capacity, encoding, to irregular semantic organisation. However, syntactic deficits are less well-characterised, despite its crucial role in language construction. This study examines the role of simple syntactic structure (basis of the "sentence superiority effect") in VWM of patients with psychotic disorders.
Methods:
Patients with schizophrenia-spectrum disorders (n=40) and healthy controls matched on age, sex and education (n=40) were administered an auditory serial recall task containing word lists with low semantic coherence and either syntactically familiar structure (noun-verb-noun sequence) or syntactically unfamiliar structure. Other neurocognitive measures, symptoms and social functioning of patients were also assessed.
Results:
A 4-way analysis of variance (group×version×list type×serial position) indicated that patients had significantly worse performance overall, suggesting a generalised verbal memory impairment. In addition, a significant interaction was found for list type and Group, demonstrating that healthy controls, but not patients, had superior performance in syntactically familiar word lists. A subgroup analysis of high-performing patients revealed that the interaction was not an artefact of poor verbal memory, but a selective deficit in syntactic facilitation.
Conclusions:
Our findings may suggest segregated mechanisms for maintenance and computational aspects of VWM, and show that even simple syntactic structure facilitates recall of syntactically unfamiliar words lists. Additionally, schizophrenic patients show difficulty utilising syntactic information, which highlights the need to understand the neuropsychological basis of working memory and linguistic impairments in psychosis.
Objective:
Small-scale studies of auditory processing cognitive remediation programs have demonstrated efficacy in schizophrenia. We describe a multicenter, rater-blinded, randomized, controlled study of auditory-focused cognitive remediation, conducted from June 24, 2010, to June 14, 2013, and approved by the local institutional review board at all sites.
Method:
Prior to randomization, participants with schizophrenia (DSM-IV-TR) were stabilized on a standardized antipsychotic regimen (lurasidone [40-160 mg/d]), followed by randomization to adjunctive cognitive remediation: auditory focused (Brain Fitness) versus control (nonspecific video games), administered 1-2 times weekly for 30 sessions. Coprimary outcome measures included MATRICS Consensus Cognitive Battery (MCCB) and the University of California, San Diego, Performance-Based Skills Assessment-Brief scale.
Results:
120 participants were randomized and completed at least 1 auditory-focused cognitive remediation (n = 56) or video game control session (n = 64). 74 participants completed ≥ 25 sessions and postrandomization assessments. At study completion, the change from prestabilization was statistically significant for MCCB composite score (d = 0.42, P < .0001) across groups. Participants randomized to auditory-focused cognitive remediation had a trend-level higher mean MCCB composite score compared to participants randomized to control cognitive remediation (P = .08). After controlling for scores at the time of randomization, there were no significant between-treatment group differences at study completion.
Conclusions:
Auditory processing cognitive remediation combined with lurasidone did not lead to differential improvement over nonspecific video games. Across-group improvement from prestabilization baseline to study completion was observed, but since all participants were receiving lurasidone open label, it is difficult to interpret the source of these effects. Future studies comparing both pharmacologic and behavioral cognitive enhancers should consider a 2 × 2 design, using a control for both the medication and the cognitive remediation.
Trial registration:
ClinicalTrials.gov identifier: NCT01173874.
Introduction The success with which preclinical models of mental illness can appropriately represent the complexities of disorders of higher cognitive function is limited. There are also confounds which often limit the insights which can be gained from directly studying patients with these disorders, such as the effects of the chronicity of disease and treatment, for example. Human psychopharmacological models of psychiatric illness, involving drug manipulations resulting in the reproduction of key features of the syndrome, therefore provide an important contribution in understanding the pathophysiology underlying neuropsychological impairments in psychiatry. However, as with any model, the fundamental aspects in which the model departs from the real-world situation one attempts to approximate must be acknowledged and appreciated, in order to evaluate the ways in which this impacts on the interpretation of important findings which can be gained from this approach. Modeling cognitive impairment Human pharmacological models of disease involve the administration of psychoactive compounds to healthy individuals in order to reproduce symptoms which are qualitatively similar to those experienced by people with mental illness. The assumption is that if symptoms of a disease process are convincingly replicated by the drug model, then the mechanisms mediating the effects of both drug and disease may share important commonalities.
It has been 15 years since the original publication of Neuropsychology of Attention. At the time of its publication, attention was a construct that had long been of theoretical interest in the field of psychology and was receiving increased research by cognitive scientists. Yet, attention was typically viewed as a nuisance variable; a factor that needed to be accounted for when assessing brain function, but of limited importance in its own right. There is a need for a new edition of this book within Neuropsychology to present an updated and integrated review of what is know about attention, the disorders that affect it, and approaches to its clinical assessment and treatment. Such a book will provide perspectives for experimental neuropsychological study of attention and also provide clinicians with insights on how to approach this neuropsychological domain. © Springer Science+Business Media New York 2014. All rights reserved.
Functional Magnetic Resonance (fMRI) is an imaging technique with high spatial and temporal resolution that allows investigation of in vivo information about the functionality of discrete neuronal groups during their activity utilizing the magnetic properties of oxy- and deoxy-hemoglobin. fMRI permits the study of normal and pathological brain during performance of various neuropsychological functions. Several research groups have investigated prefrontal cognitive abilities (including working memory) in schizophrenia using functional imaging. Even if with some contradictions, large part of these studies have reported relative decrease of prefrontal cortex activity during working memory, defined as hypofrontality. However, hypofrontality is still one of the most debated aspects of the patophysiology of schizophrenia because the results can be influenced by pharmacotherapy, performance and chronicity. The first fMRI studies in patients with schizophrenia seemed to confirm hypofrontality. However, more recent studies during a range of working memory loads showed that patients are hypofrontal at some segments of this range, while they are hyperfrontal at others. These studies seem to suggest that the alterations of prefrontal functionality are not only due to reduction of neuronal activity, but they probably are the result of complex interactions among various neuronal systems.
Working memory (WM) deficits are core symptoms of cognitive impairment in schizophrenia. WM-models serve as theoretical and empirical framework for the investigation of cognitive dysfunction as well as of schizophrenic phenomenology. Behavioral and functional neuroimaging data support the concept of a supramodal WM-deficit in schizophrenia, associated with the functional integrity of prefrontal regions. This review provides a short overview of WM-dysfunction in schizophrenia as well as its impact on psychopathology. Furthermore, the relationship of WM-associated cerebral activation and psychopathological symptoms is illustrated. Currently available studies on WM-function and psychopathology in schizophrenia obtained rather heterogeneous results, although disorganisation and negative symptoms may be closely linked to prefrontal regions. The investigation of WM-function in schizophrenic subsyndromes with functional neuroimaging techniques still remains a clinical and scientific desideratum.
Working memory (WM) deficits are core symptoms of cognitive impairment in schizophrenia. The psychological concept of WM offers a theoretical and empirical framework for the investigation of perceptual and attentional dysfunction as well as of deficits of higher cognitive functions in schizophrenia. From a theoretical perspective, schizophrenic psychopathology and cognitive dysfunction can be both integrated and experimentally validated within the concept of WM-impairment. In the last years investigation of WM has been a major issue in neuropsychiatric research, not least because of the association of prefrontal cortex and WM-function. The advent of functional imaging techniques, e. g. functional magnetic resonance imaging (fmri) has additionally contributed in generating neurobiological WM-models. Regarding the neuronal basis of WM-deficits in schizophrenia, prefrontal cortex dysfunction has been of major interest. This review provides a short overview on the concept of WM and its relevance for cognitive psychology, discussing both recent behavioral and functional neuroimaging evidence on WM-dysfunction in schizophrenia.
The scope of this study was to trace of central auditory processing issues in patients with first episode psychosis using a psychoacoustic test battery approach.
Patients were included in the study on the basis of normal hearing sensitivity. A central auditory processing battery was implemented consisting of monaural and binaural tests with verbal and non-verbal stimuli.
Seventeen control subjects were volunteers with no personal or family history of schizophrenia. Seventeen (17) patients were tested to evaluate central auditory processing abilities.
Perceptual deficits in both non-verbal and verbal auditory stimuli are reported in this study with temporal central auditory processing deficits and a mean left ear left ear advantage (LEA) being documented in the patient group.
This study points to the possibility of existence of central auditory processing deficits in first episode psychosis leading to schizophrenia. Audiologists should be aware of the psychiatric research pointing to enhanced verbal memory as a result of auditory training; linking bottom-up remediation with top-down improvement.
Az elmult evekben a szkizofreniaval kapcsolatos kognitiv deficit szamos jellegzetessege feltarasra kerult. A neuropszichologiai jellemzők meghatarozasaval lehetőseg nyilik a heterogen betegcsoport diszkret alpopulaciokra tortenő felosztasara, amely a biologiai mechanizmusok felterkepezesenel kovetkezetesebb eredmenyekhez vezethet. Masreszt olyan pszichofiziologiai jellegzetessegek is is-mertte valtak, amelyek szkizofren betegek tunetmentes rokonaiban is kimutathatok (peldaul P50 diszhabituacio, a szemmozgasok zavara, vizualis backward masking deficit). Ezek a "trait" markerek fontos segitseget nyujthatnak a molekularis genetikai vizsgalatokban. A funkcionalis kepalkoto elja-rasok segitsegevel a kognitiv zavarok idegrendszeri alapjaiba is betekintes nyerhető. Az ide vago tanulmanyok egy kiterjedt neuronalis halozat dezintegralt műkodeset mutattak ki (diszkonnekcios szindroma). Az alabbi osszefoglalas a munkamemoria, a figyelem, a szenzoros kapuzas es a szeman-tikus memoria teruleten feltart eredmenyeket te...
THE NEUROPSYCHOLOGICAL STUDY OF HYPOFRONTLITY IN SCHIZOPHRENIC PATIENTS
The clinical observations according to which the negative symptoms of schizophrenia are similar to those that appear in the case of lesions of the frontal lobe, especially the prefrontal region drew attention to the role of the frontal lobe is the patomechanism of schizophrenia. The findings of the studies using structural and functional neuroimaging techniques and neuropsychological tests gave support to this idea.
The study presented in this paper aims at investigating the symptoms of hypofrontality in schizophrenia using neuropsychological methods. Tests of attention, verbal and visual memory, visuopreception, visuoconstruction and simple motor tasks were administered to schizophrenic patients and healthy control subjects. According to our hypothesis, the performabce of the schizophrenic group is expected to be poorer than that of the control group concerning both quantitative measures and qualitative variables, that is types of errors. The results support the hypothesis; the poor performance of schizophrenic patients were mostly due to preseveration errors, lack of organization and planning, and severe attentional deficit. The purpose of this paper is to point out that neuropsychological tests can be useful tools in diagnostic work, therapy and rehabilitation of psychiatric patients.
Key words: hypofrontality, cognitive deficit, attentional deficit, perseveration, deficit of planning
Eine 40-jährige Patientin mit wiederholten Rezidiven einer paranoiden Schizophrenie beabsichtigt, nach 10-jährigem erfolglosem
Studium endlich eine neue Berufsausbildung anzustreben. Selbst leidet sie subjektiv unter Konzentrations- und Gedächtnisstörungen
und fühlt sich den kommenden Anforderungen nicht gewachsen. In dieser Situation wird eine neuropsychologische Untersuchung
mit folgendem Ergebnis durchgeführt: Fünf Tests zur Aufmerksamkeit, die verschiedene Aspekte wie selektive Aufmerksamkeit,
Daueraufmerksamkeit, geteilte Aufmerksamkeit, Aufmerksamkeitswechsel und Informationsverarbeitungsgeschwindigkeit messen,
lassen ein massives Aufmerksamkeitsdefizit erkennen. Die Gedächtnisleistungen sind demgegenüber relativ wenig betroffen. Bei
der Untersuchung der Exekutivfunktionen zeigt sich, dass die Patientin schlecht einmal gefundene Lösungen wieder aufgeben
kann, selbst wenn sie nicht mehr korrekt sind, sie „perseveriert“.
Although all current treatments for schizophrenia mediate their effects via blockade of the dopamine (D2) receptor, limitations of the dopamine hypothesis have become increasingly apparent, as has the need for alternative neurochemical
conceptualizations of schizophrenia.
Over the past 20 years, attention has turned increasingly to dysfunction of the brain glutamate system as a fundamental mechanism
underlying brain dysfunction in schizophrenia. As opposed to dopamine which is present only in circumscribed brainstem nuclei
- from which it projects widely in cortex and subcortical structures – glutamate is a widespread neurotransmitter in both
cortex and subcortical systems and accounts for as many as 60% of brain synapses. Attention first turned to glutamatergic
systems with the observation that phencyclidine (PCP) and similarly acting psychotomimetic compounds induced their unique
behavioral effects by blocking neurotransmission at N-methyl-D-aspartate (NMDA)-type glutamate receptors. The ability of
these compounds to transiently reproduce key symptoms of schizophrenia by blocking NMDA receptors led to the concept that
symptoms in schizophrenia may reflect underlying dysfunction or dysregulation of NMDA receptor-mediated neurotransmission.
Since the original promulgation of the glutamate/NMDA hypothesis of schizophrenia in the late 1980’s, significant progress
has been made in delineating the potential role of NMDA dysfunction in the etiology of schizophrenia. Many of the most mystifying
aspects of schizophrenia - such as why positive and negative symptoms fluctuate in severity in parallel rather than in opposition
or why specific neurocognitive processes are impaired but others are paradoxically spared – become much more obvious when
the disease is viewed from a glutamate/NMDA, rather than dopaminergic, perspective. Further, many of the findings from etiological
investigations, such as genetic association studies, synergize much more with glutamatergic than dopaminergic models of the
disorders.
Finally, viewing the disorder from a glutamatergic, rather than dopaminergic, perspective has opened new potential avenues
for treatment that are only now making their way from preclinical to clinical investigation. These include interventions
targeted at specific types of glutamate receptors, and include NMDA receptor modulators, glycine transport inhibitors and
metabotropic agonists. To the extent that glutamatergic models of schizophrenia are correct, glutamate-based treatments should
offer new opportunities for prevention and reversal of persistent symptoms and neurocognitive deficits of schizophrenia.
This article briefly reviews some methodological limitations of functional neuroimaging studies in psychiatric patients. We argue that the investigation of the neural substrates of cognitive deficits in psychiatric disorders requires a combination of functional neuroimaging studies in healthy subjects with corresponding behavioral experiments in patients. In order to exemplify this methodological approach we review recent findings regarding the functional neuroanatomy of distinct components of human working memory and provide evidence for selective dysfunctions of cortical networks that underlie specific working memory deficits in schizophrenia. This identification of subgroups of schizophrenic patients according to neurocognitive parameters may facilitate the establishment of behavioral and neurophysiological endophenotypes and the development of a neurobiological classification of psychiatric disorders.
Arbeitsgedächtnisstörungen treten bei verschiedenen psychiatrischen Erkrankungen auf und spielen eine wichtige Rolle für die
kognitive Leistungsfähigkeit im Alltag und damit auch für die soziale Integration von Patienten. Für die Schizophrenie und
die bipolaren Störungen besteht gute Evidenz für eine Assoziation von Arbeitsgedächtnisdefiziten mit der Erkrankung und für
eine Verbindung zu dem genetisch vermittelten Krankheitsrisiko. Neuere Studien legen zudem nahe, dass die Heterogenität der
traditionellen diagnostischen Kategorien durch eine exakte Charakterisierung von Patienten anhand entsprechender neurokognitiver
Funktionsparameter reduziert und die Differenzialdiagnose zwischen Störungsbildern verbessert werden kann. Das Wissen über
selektive Störungen von Subkomponenten des Arbeitsgedächtnisses könnte somit in der klinischen Praxis als zusätzliche Informationsquelle
für diagnostische und therapeutische Entscheidungen dienen.
Working memory disturbances occur in various psychiatric disorders and play a major role for general cognitive ability in
everyday life and thus social integration of the patients. In schizophrenia and bipolar disorder, working memory deficits
have been found to be associated with certain genotypes and clinical symptoms. This makes them promising endophenotypes, i.e.,
mediators between genotype and phenotype. Furthermore recent studies indicate that the identification of selective deficits
in working memory may be useful in order to define patient subgroups that are more homogenous with respect to the functional
integrity or dysfunction of neural systems underlying working memory subcomponents. This scientific approach may ultimately
lead to better understanding of the pathophysiologic mechanisms underlying working memory dysfunctions in psychiatric disorders
and may provide clinicians with additional information for diagnostic and therapeutic decisions.
Describes 2 experiments with 18-27 yr old nonpsychotic schizophrenics (n = 32), nonschizophrenic psychiatric patients (n = 112), and nonhospitalized normals (n = 32). In Exp. I, Ss were given repeated free-recall trials of 20 "unrelated" words and of 20 categorized words. The schizophrenics' recall and mnemonic organization, as indexed by measures of subjective organization, categorical clustering, and hierarchical clustering schemes, were both inferior to those of the normals and, to some extent, to those of the nonschizophrenics. While the normals and nonschizophrenics tended to build up higher-order mnemonic units with trials, this trend was weak in the schizophrenics. In Exp. II, nonpsychotic schizophrenics and normals engaged in repeated recognition tasks of 40 words and 40 consonant-vowel-consonant trigrams. The recognition memory of the schizophrenics was the same as that of the normals, in spite of contextual variations of the study and test lists. Results are interpreted on the basis of the 2-process theory of recall as supporting the view that the basic deficit of schizophrenia in mnemonic processing is a difficulty in unitizing the material. (36 ref.)
Recognition of the pitch of a tone was severely disrupted by the incorporation of six other tones during a 5-second retention
interval, even though the intervening tones could be ignored. However, the requirement to recall six numbers spoken at equal
loudness during the identical retention interval produced only a minimum decrement in the same pitch-recognition task. Further,
the requirement to remember the tone produced no decrement in recall of the numbers. It is concluded that immediate memory
for pitch is subject to a large interference effect which is highly specific in nature and which is not due to some limitation
in general short-term memory capacity or to a distraction of attention.
Eight schizophrenics (mean age 27.3 yrs), 8 depressed patients (mean age 33.1 yrs), and 8 normal controls (mean age 27 yrs) completed the MMPI and were asked to recall short word strings in both the presence and absence of distraction. Results show a differential cognitive deficit among schizophrenics both before and after a general improvement in their level of adjustment. That is, despite an overall improvement in their accuracy of recall prior to discharge, their performance continued to be impaired relative to depressed and normal Ss on the words presented in the 1st serial position. A tendency toward greater distractibility among schizophrenics failed to reach statistical significance at both points of assessment. Further substantiation of such stable forms of cognitive impairment may facilitate the identification of individuals who are vulnerable to the development of schizophrenia and may shed light on the adjustment problems that many chronic patients continue to experience after discharge from the hospital. (18 ref)
Working memory is the type of memory that allows one to hold information in mind while working on a task or problem. The present study investigated attention-independent auditory sensory ("echoic") memory in 18 schizophrenic participants and 17 controls. Schizophrenic participants showed impaired delayed tone matching performance in comparison with controls. However, when groups were matched for performance at 1 s by varying the difficulty of the task across groups, schizophrenic participants showed normal retention of information as reflected in normal tone matching performance. These findings demonstrate that schizophrenic may be in the sensitivity of the system rather than the duration for which memory traces were retained.
The degree of interference caused by different kinds of stimuli on memory for tonal pitch was studied. Musically trained and untrained subjects heard a sequence of two tones separated by an interval of 5 sec. The tones were either identical in pitch or differed by a semitone. Subjects had to decide whether the tones were identical or not. The interval was filled with tonal, verbal, or visual material under attended and unattended conditions. The results revealed clear group differences. Musically trained subjects' retention of the first test tone was only affected by the interposition of other tones. In contrast, the performance of musically untrained subjects was also affected by verbal and visual items. The findings are discussed in the framework of Baddeley's (1986) working-memory model.
The resolution of the heterogeneity of schizophrenics and their relatives using cognitive tasks requires measures of individual differences--usually of differential ability, which is inferred from differential performance. Tasks that are suited for establishing a group's differential ability are often unsuited for measuring individual differences. The problem is that for any group for which Tasks A and B have different mean accuracy, the (A - B) difference scores of individual subjects have an artifactual curvilinear relation to (A + B) overall accuracy, with the largest (A - B) scores occurring at about 50% (A + B) overall accuracy for a dichotomously scored free-response task. Two possible solutions are (a) to convert Task B scores to residualized scores, using the regression of Task B scores on Task A scores as determined for normal subjects; or (b) to titrate overall (A + B) accuracy of each subject to a constant level by manipulating a variable.
The Positive and Negative Syndrome Scale (PANSS) was developed out of the need for a well-operationalized method of assessing these syndromes in schizophrenia, including their relationship to one another and to global psychopathology. We surveyed 82 acute and chronic schizophrenics to analyze the psychometric properties of the four PANSS scales. The interrater reliabilities were in the 0.80's, and significant correlations emerged with corresponding criterion measures. The PANSS positive and negative scales were inversely intercorrelated once their shared association with general psychopathology had been partialed out. The results support the scales' reliability, criterion-related validity, and construct validity, while cross-validating some of our previous findings.
A dichotic test made up of monosyllabic rhymed CVC words was modified to minimize stimulus dominance and errors and then administered to 194 dextrals and 175 sinistrals in four different laboratories. The proportion of subjects with left ear advantages in both the right and left-handed groups closely approximated that expected from neurologic data. This dichotic test appears to reflect hemispheric specialization for language function more accurately than previously available tests. Further direct validation studies are needed, however, comparing direction of ear asymmetry and other indices of hemispheric specialization for language on a subject by subject basis.
Most recent studies of recall deficit in schizophrenia have varied the encoding context while the retrieval context has not been varied. Recall of an event, however, is the product of the memory trace and a retrieval cue. In the present study, nonparanoid schizophrenics, paranoid schizophrenics, depressives, and normal controls were presented categorized word lists, matched for difficulty, that were either cued or not cued at recall. Furthermore, recall was examined on a first, immediate trial and on a second, delayed trial after an intervening task. The results indicated that the interval between recall trials produced a differential deficit for both schizophrenic groups relative to depressives and normals. Two possible explanations for this deficit are deficient encoding processes or retroactive interference. The findings indicate that varying the retrieval environment can enhance the recall of schizophrenics and that future studies should manipulate both the encoding context and the retrieval context to determine whether the schizophrenic recall deficit is due primarily to encoding or retrieval dysfunction, or both.
Some research indicates that thought-disordered schizophrenics produce language utterances that are less predictable than those of non-thought-disordered schizophrenics and controls. We examined the hypothesis that thought-disordered schizophrenics would have a parallel deficiency in the ability to use the predictabilities provided by contextual constraint to improve recall of heard language passages. Subjects were seventeen schizophrenics, ten normal controls, and twelve psychiatric controls, evaluated by standardized psychiatric interview and diagnosed according to research criteria. The data obtained supported the hypothesis and non-thought-disordered schizophrenics performed similarly to controls in the experimental task.
Failure to classify schizophrenic subjects on the dimension of thought disorder may result in misleading comparisons of general samples of schizophrenics with controls on tasks requiring language perception and production.
Medication and chronicity have complicated past attempts to characterize the neuropsychological performance of patients with schizophrenia. There have been inconsistencies regarding the pattern, selectivity, and sources of observed deficits. Our objective was to comprehensively examine neuropsychological function in patients with schizophrenia who had never been exposed to neuroleptic medication, and who were experiencing their first episode (FE) of psychosis.
Subjects were consecutive recruitments that included 37 patients with FE schizophrenia who were never exposed to neuroleptics. These subjects were compared with 65 unmedicated, previously treated (PT) patients and 131 healthy controls.
The patients groups had nearly identical profiles showing generalized impairment, particularly in verbal memory and learning, attention-vigilance, and speeded visual-motor processing and attention. Verbal memory and learning accounted for most of the variance between patients and controls and removing this effect substantially attenuated all other differences. By contrast, both the FE group and PT group continued to show highly significant deficits in verbal memory and learning after controlling for attention, abstraction, and all other functions. Some functions not typically implicated in schizophrenia (spatial cognition, fine motor speed, and visual memory) were more impaired in the PT group than in the FE group.
Verbal memory, as a primary neuropsychological deficit present early in the course of schizophrenia, implicates the left temporal-hippocampal system. Neuropsychological evaluations before treatment permit differentiation of primary deficits from changes secondary to medication or chronicity. This is essential for developing a neurobehavioral perspective on schizophrenia.
Synopsis
Learning and memory were assessed in 24 monozygotic (MZ) pairs of individuals discordant for schizophrenia or delusional disorder and seven normal pairs of MZ twins. On declarative memory tasks, the affected group displayed a pattern that might best be characterized as dysmnesic in that they performed significantly worse than the discordant unaffected group on story recall, paired associated learning, and visual recall of designs, but they learned over time, had relatively preserved recognition memory, and did not show profoundly accelerated rates of forgetting. Effortful, volitional retrieval from the lexicon, measured by verbal fluency, was also compromised in the affected group. On the other hand, procedural learning of the motor skill in a pursuit rotor task was relatively intact in the affected group. Comparisons of the normal group and unaffected group indicated that the latter group had very mild impairments in some aspects of episodic memory, namely, immediate and delayed recall of stories and delayed recall of designs. It is highly unlikely that the impairments observed in the affected group can be attributed to differences in genome, family environment, socioeconomic circumstance, or educational opportunity, as all of these were controlled by the twin paradigm. Rather, the impairments appear to be related to the intercession of disease. The neuropsychological profile is consistent with frontal lobe and medial temporal lobe dysfunction, as noted in this sample as well as other samples of schizophrenic singletons. Significant correlations between many measures of memory and global level of social and vocational functioning within the discordant group were also found. Thus difficulties in rapidly acquiring new information and propitiously retrieving old information may burden patients with schizophrenia in many of the transactions of everyday life.
Verbal learning and memory deficits are among the most severe cognitive deficits observed in schizophrenia. We have demonstrated that such deficits do not extend to working memory for tones in a substantial number of patients even when verbal working memory is impaired. In this study we used functional magnetic resonance imaging to study the neural basis of this dissociation of auditory verbal and nonverbal working memory in individuals with schizophrenia.
While undergoing functional magnetic resonance imaging, 12 schizophrenic patients and 12 matched control subjects performed auditory Word Serial Position Task and Tone Serial Position Task.
Both tasks produced activation in frontal cortex and temporal and parietal lobes of the cerebrum in both groups. While robust activation was observed in the left inferior frontal gyrus (areas 6, 44, and 45) in the control group during the Word Serial Position Task, activation in the patient group was much reduced in these areas and failed to show the same task-specific activation as in controls. Reduced activation in patients was not confined to the inferior frontal gyrus, but also extended to a medial area during the Tone Serial Position Task and to premotor and anterior temporal lobe areas during both tasks.
These findings support the hypothesis that abnormalities in cortical hemodynamic response in the inferior frontal gyrus underlie the verbal working memory deficit in schizophrenia. The relationship of verbal working memory deficits to other cognitive functions suggests that abnormal functioning in the speech-related areas may reflect a critical substrate of a broad range of cognitive dysfunctions associated with schizophrenia.
Mnemonic organization in young non-psychotic schizophrenics
- Sd Koh
- L Kayton
- R Berry
Koh SD, Kayton L, Berry R. Mnemonic organization in young non-psychotic schizophrenics. J Abnorm Psychol. 1973;81:299-310.
Neuropsychological function in schizophrenia: selective impairment in memory and learning
- Aj Saykin
- Rc Gur
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- Sm Resnick
- B Kester
- P Stafiniak
Saykin AJ, Gur RC, Gur RE, Mozley PD, Mozley LH, Resnick SM, Kester B, Stafiniak P. Neuropsychological function in schizophrenia: selective impairment in
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Stafiniak P. Neuropsychological function in schizophrenia: selective impairment in memory and learning
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- S M Resnick
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Saykin AJ, Gur RC, Gur RE, Mozley PD, Mozley LH, Resnick SM, Kester B, Stafiniak P. Neuropsychological function in schizophrenia: selective impairment in
memory and learning. Arch Gen Psychiatry. 1991;48:618-624.
Interference in memory for tonal pitch: implications for a working-memory model
- T Pechinann
- G Mohr
Pechinann T, Mohr G. Interference in memory for tonal pitch: implications for a
working-memory model. Memory Cogn. 1992;20:314-320.