[Show abstract][Hide abstract] ABSTRACT: Background: Schizophrenia patients exhibit deficient processing of perceptual and cognitive information. However, it is not well-understood how basic perceptual deficits contribute to higher level cognitive problems in this mental disorder. Perception of biological motion, a motion-based cognitive recognition task, relies on both basic visual motion processing and social cognitive processing, thus providing a useful paradigm to evaluate the potentially hierarchical relationship between these two levels of information processing. Methods: In this study, we designed a biological motion paradigm in which basic visual motion signals were manipulated systematically by incorporating different levels of motion noise. We measured the performances of schizophrenia patients (n = 21) and healthy controls (n = 22) in this biological motion perception task, as well as in coherent motion detection, theory of mind, and a widely used biological motion recognition task. Results: Schizophrenia patients performed the biological motion perception task with significantly lower accuracy than healthy controls when perceptual signals were moderately degraded by noise. A more substantial degradation of perceptual signals, through using additional noise, impaired biological motion perception in both groups. Performance levels on biological motion recognition, coherent motion detection and theory of mind tasks were also reduced in patients. Conclusion: The results from the motion-noise biological motion paradigm indicate that in the presence of visual motion noise, the processing of biological motion information in schizophrenia is deficient. Combined with the results of poor basic visual motion perception (coherent motion task) and biological motion recognition, the association between basic motion signals and biological motion perception suggests a need to incorporate the improvement of visual motion perception in social cognitive remediation.
Frontiers in Psychology 01/2013; 4:391. · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although schizophrenia and schizoaffective disorders have both similar and differing clinical features, it is not well understood whether similar or differing pathophysiological processes mediate patients' cognitive functions. Using psychophysical methods, this study compared the performances of schizophrenia (SZ) patients, patients with schizoaffective disorder (SA), and a healthy control group in two face-related cognitive tasks: emotion discrimination, which tested perception of facial affect, and identity discrimination, which tested perception of non-affective facial features. Compared to healthy controls, SZ patients, but not SA patients, exhibited deficient performance in both fear and happiness discrimination, as well as identity discrimination. SZ patients, but not SA patients, also showed impaired performance in a theory-of-mind task for which emotional expressions are identified based upon the eye regions of face images. This pattern of results suggests distinct processing of face information in schizophrenia and schizoaffective disorders.
Schizophrenia Research 08/2011; 134(1):95-100. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neurocognitive dysfunction in schizophrenia (SZ), bipolar (BD) and related disorders represents a core feature of these illnesses, possibly a marker of underlying pathophysiology. Substantial overlap in domains of neuropsychological deficits has been reported among these disorders after illness onset. However, it is unclear whether deficits follow the same longitudinal pre- and post-morbid course across diagnoses. We examine evidence for neurocognitive dysfunction as a core feature of all idiopathic psychotic illnesses, and trace its evolution from pre-morbid and prodromal states through the emergence of overt psychosis and into chronic illness in patients with SZ, BD and related disorders.
Articles reporting on neuropsychological functioning in patients with SZ, BD and related disorders before and after illness onset were reviewed. Given the vast literature on these topics and the present focus on cross-diagnostic comparisons, priority was given to primary data papers that assessed cross-diagnostic samples and recent meta-analyses.
Patients with SZ exhibit dysfunction preceding the onset of illness, which becomes more pronounced in the prodrome and early years following diagnosis, then settles into a stable pattern. Patients with BD generally exhibit typical cognitive development pre-morbidly, but demonstrate deficits by first episode that are amplified with worsening symptoms and exacerbations.
Neuropsychological deficits represent a core feature of SZ and BD; however, their onset and progression differ between diagnostic groups. A lifetime perspective on the evolution of neurocognitive deficits in SZ and BD reveals distinct patterns, and may provide a useful guide to the examination of the pathophysiological processes underpinning these functions across disorders.
Psychological Medicine 02/2011; 41(2):225-41. · 5.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Early invasive electrical stimulation studies suggested that enhancement of cerebellar vermal activity might prove valuable in symptomatic treatment of refractory neuropsychiatric diseases via modulation of emotion and affect. This proof of principle study aimed to test this hypothesis using noninvasive brain stimulation, and to explore the safety of this protocol in schizophrenia.
Eight treatment-refractory patients with schizophrenia underwent ten sessions of intermittent theta burst stimulation (TBS) to the cerebellar vermis using MRI-guided transcranial magnetic stimulation (TMS). Assessments included side effect questionnaires, cardiovascular monitoring, psychiatric evaluations and comprehensive neuropsychological testing before and after TBS and at one-week follow-up.
Overall, TBS was tolerated well with mild side effects primarily comprising neck pain and headache. No serious adverse events occurred. Diastolic blood pressure (BP) showed mild decreases for five minutes post-TBS; no significant changes were detected for systolic BP or pulse. PANSS negative subscale showed significant improvements following TBS and during the follow-up. Calgary Depression Scale and self-report visual analog scales for Happiness and Sadness pointed to significant mood elevation. Neuropsychological testing revealed significantly fewer omissions in working memory and interference conditions of a Continuous Performance Test, a longer spatial span and better delay organization on the Rey-Osterrieth Complex Figure during follow-up. No significant worsening in psychiatric or neuropsychological measures was detected.
Theta burst stimulation of the cerebellar vermis is safe and well-tolerated, while offering the potential to modulate affect, emotion and cognition in schizophrenia. Future randomized, sham-stimulation controlled studies are warranted to support the clinical efficacy of this technique.
Schizophrenia Research 12/2010; 124(1-3):91-100. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous research has identified several key processes of visual perception and visually guided action that are implicated in schizophrenia. Yet, it is not well understood whether similar or different brain mechanisms mediate the abnormalities in these two processes. To explore this issue, we examined visual and visuomotor processing in schizophrenia, utilizing an illusion known as the Roelofs effect. This illusion refers to the spatial mislocalization of an object within an off-centered frame, with the object appearing to be shifted towards the opposite direction of the frame offset. In this study, localization of the object was measured either by a direct visual response or by an immediate or delayed visuomotor (reaching-to-touch) response. Patients demonstrated significantly greater magnitudes of the Roelofs effect in all response modes, indicating the existence of excessive spatial contextual effects of the frame during the processing of visual and visuomotor information, and when the two types of information are integrated over a delayed visuomotor response condition. These results provide evidence for a hypothesis of improper inhibitory control as a common mechanism underpinning abnormal visual and visuomotor processes in this mental disorder.
[Show abstract][Hide abstract] ABSTRACT: Oral high-dose glycine administration has been used as an adjuvant treatment for schizophrenia to enhance glutamate neurotransmission and mitigate glutamate system hypofunction thought to contribute to the disorder. Prior studies in schizophrenia subjects documented clinical improvements after 2 weeks of oral glycine administration, suggesting that brain glycine levels are sufficiently elevated to evoke a clinical response within that time frame. However, no human study has reported on brain glycine changes induced by its administration. We utilized a noninvasive proton magnetic resonance spectroscopy ((1)H-MRS) technique termed echo time-averaged (TEAV) (1)H-MRS, which permits noninvasive quantification of brain glycine in vivo, to determine whether 2 weeks of oral glycine administration (peak dose of 0.8 g/kg/day) increased brain glycine/creatine (Gly/Cr) ratios in 11 healthy adult men. In scans obtained 17 h after the last glycine dose, brain (Gly/Cr) ratios were significantly increased. The data indicate that it is possible to measure brain glycine changes with proton spectroscopy. Developing a more comprehensive understanding of human brain glycine dynamics may lead to optimized use of glycine site agonists and glycine transporter inhibitors to treat schizophrenia, and possibly to treat other disorders associated with glutamate system dysfunction.
Psychiatry Research 07/2009; 173(2):143-9. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Impaired emotion recognition has been reported in schizophrenia, yet the nature of this impairment is not completely understood. Recognition of facial emotion depends on processing affective and nonaffective facial signals, as well as basic visual attributes. We examined whether and how poor facial emotion recognition in schizophrenia is related to basic visual processing and nonaffective face recognition.
Schizophrenia patients (n = 32) and healthy control subjects (n = 29) performed emotion discrimination, identity discrimination, and visual contrast detection tasks, where the emotionality, distinctiveness of identity, or visual contrast was systematically manipulated. Subjects determined which of two presentations in a trial contained the target: the emotional face for emotion discrimination, a specific individual for identity discrimination, and a sinusoidal grating for contrast detection.
Patients had significantly higher thresholds (worse performance) than control subjects for discriminating both fearful and happy faces. Furthermore, patients' poor performance in fear discrimination was predicted by performance in visual detection and face identity discrimination.
Schizophrenia patients require greater emotional signal strength to discriminate fearful or happy face images from neutral ones. Deficient emotion recognition in schizophrenia does not appear to be determined solely by affective processing but is also linked to the processing of basic visual and facial information.
[Show abstract][Hide abstract] ABSTRACT: Face recognition involves several physiological and psychological processes, including those in visual, cognitive and affective domains. Studies have found that schizophrenia patients are deficient at recognizing facial emotions, yet visual and cognitive processing of facial information in this population has not been systematically examined. In this study, we examined visual detection, perceptual discrimination and working memory of faces as well as non-face visual objects in patients. Visual detection was measured by accuracy when detecting the presence of a briefly displayed face, image which contained only the basic configural information of a face. Perceptual discrimination was measured by discriminability scores for individual facial identity images, in which the degree of similarity between images was systematically varied via morphing. Working memory was measured by the discriminability scores when two comparison face images were separated by 3 or 10 s. All measurements were acquired using a psychophysical method (two-alternative forced choice). Relative to controls, patients showed significantly reduced accuracy in visual detection of faces (p=0.003), moderately degraded performance in perceptual discrimination of faces (p=0.065), and significantly impaired performance in working memory of faces (p<0.001 for both 3 and 10 sec conditions). Patients' performance on non-face versions of these tasks, while degraded, was not correlated with performance on face recognition. This pattern of results indicates that greater signal strength is required for visual and cognitive processing of facial information in schizophrenia.
Schizophrenia Research 10/2008; 107(1):92-8. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transmission of reward signals is a function of dopamine, a neurotransmitter known to be involved in the mechanism of psychosis. Using functional magnetic resonance imaging (fMRI), we investigated how expectation and receipt of monetary rewards modulate brain activation in patients with bipolar mania and schizophrenia. We studied 12 acutely manic patients with a history of bipolar disorder, 12 patients with a current episode of schizoaffective disorder or schizophrenia and 12 healthy subjects. All patients were treated with dopamine antagonists at the time of the study. Subjects performed a delayed incentive paradigm with monetary reward in the scanner that allowed for investigating effects of expectation, receipt, and omission of rewards. Patients with schizophrenia and healthy control subjects showed the expected activation of dopaminergic brain areas, that is, ventral tegmentum activation upon expectation of monetary rewards and nucleus accumbens activation during receipt vs omission of rewards. In manic patients, however, we did not find a similar pattern of brain activation and the differential signal in the nucleus accumbens upon receipt vs omission of rewards was significantly lower compared to the healthy control subjects. Our findings provide evidence for abnormal function of the dopamine system during receipt or omission of expected rewards in bipolar disorder. These deficits in prediction error processing in acute mania may help to explain symptoms of disinhibition and abnormal goal pursuit regulation.
[Show abstract][Hide abstract] ABSTRACT: Disorganization is a core dysfunction in schizophrenia. Coherent thought and behavior rely on the interactive neural responses to temporally discrete external events. Previous studies have demonstrated that a single visual stimulus (event) is abnormally affected by another (as in backward masking), but the integration (or 'synthesis') of temporally discrete events remains largely unexplored in schizophrenia. We examined the perceived interaction of two elementary visual events in schizophrenia patients, using a psychophysical approach.
Two brief, spatially-coincident foveal light pulses (5 ms) were presented with different inter-stimulus intervals (ISIs). At ISIs around 100 ms, a substantial proportion of the light pulse pairs was paradoxically perceived as three flashes, a known phenomenon in normal subjects. The subjects reported the number of flashes perceived ('one', 'two' or 'three').
Schizophrenia patients (n=28) reported fewer 'three flashes' than normal controls (n=26) at the ISIs where 'three flash' reports were greatest in normal subjects (90 to 110 ms). On the other hand, at longer ISIs (130-310 ms) patients reported 'three flashes' in more trials than did normal subjects. The perception of three flashes in patients was correlated with certain aspects of clinical status, including the positive and general subscales of the PANSS.
The alteration of the 'three-flash' illusion in schizophrenia suggests that the synthesis of discrete visual events is temporally 'dilated' or distorted, which might contribute to disorganized thought and behavior.
Schizophrenia Research 09/2008; 103(1-3):275-82. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Schizophrenia is a brain disorder that spans across biological and behavioral levels. The links between altered neural circuitry and abnormal behaviors are yet to be understood. Visual motion perception has been established in basic neuroscience and may provide an opportunity to link different levels of brain functions in schizophrenia. Center-surround interaction is a ubiquitous neural mechanism underlying the organization of visual information over different spatial locations.
We applied a psychophysical paradigm to examine center-surround interaction in schizophrenia. Patients (n = 24) and control subjects (n = 33) judged the direction of a moving random dot pattern (RDP, center) with and without the presence of another concentric surrounding RDP (surround).
The presence of a moving surround shifted the perceptual judgments of center motion in the opposite direction from the surround in both subject groups but the magnitude of the perceptual shift was significantly larger in patients. The increased perceptual shift was not correlated with psychotic symptoms, which were mild in this patient sample, or antipsychotic medication.
The increased perceptual shift suggests that the putative surround suppression on visual motion perception is abnormally increased in schizophrenia. This result provides perceptual evidence for altered basic inhibitory control of visual motion context in schizophrenia.
[Show abstract][Hide abstract] ABSTRACT: Higher levels of facial processing, such as recognition of the individuality and emotional expression of faces, are abnormal in schizophrenia. It is unknown, however, whether the visual detection of a face as face is impaired as well.
We examined the performance of schizophrenia patients (n=29) and normal controls (n=28) in locating a line-drawn face on the left or the right side of a larger line drawing. To prevent the normal formation of general facial impressions, stimulus presentations were brief (13-104 ms). The face stimuli were either displayed upright or inverted in order to study the face inversion effect, ie, the specific effect of stimulus inversion on face processing.
Schizophrenia patients showed a significantly reduced face inversion effect, resulting primarily from significantly lower accuracy in detecting upright faces than normal controls. In tree detection, a comparison task that was also administered, the stimulus inversion effect was similarly small in both groups.
Given the primitive nature and brief duration of the stimuli, and the simplicity of the task, these results indicate that at the initial visual detection stage, facial processing is inefficient in schizophrenia. By isolating face detection from other aspects of face recognition, this study identifies a face-specific visual deficit in schizophrenia, which may ultimately contribute to impaired face-related cognitive and emotional processing and social interaction.
[Show abstract][Hide abstract] ABSTRACT: Bipolar disorder (BPD) is among the top 10 causes of disability worldwide. Recent findings on the etiology of the disease point to a disturbed mitochondrial energy metabolism in the brain of subjects with BPD.
To test whether gene transcripts for proteins of the mitochondrial respiratory chain have altered levels in glucose-deprived lymphocytes from patients with BPD.
Microarrays were used to measure gene expression levels in fresh lymphocytes and in lymphocytes cultured for 5 days in regular or low-glucose medium.
Subjects with BPD were recruited through the Schizophrenia and Bipolar Disorders Program, McLean Hospital, Belmont, Mass. Controls were recruited through advertising. Patients A total of 21 patients with BPD (inpatients and outpatients) and 21 control subjects. Main Outcome Measure Expression levels for genes of proteins involved in mitochondrial respiration.
We found an opposite molecular response of control and BPD lymphocytes to glucose deprivation. Whereas lymphocytes of normal controls responded to glucose deprivation with an up-regulation of nuclear transcripts for proteins of the electron transfer chain, subjects with BPD had a tendency to down-regulate these transcripts.
The results suggest that the normal molecular adaptation to energy stress is deficient in lymphocytes from patients with BPD.
Archives of General Psychiatry 06/2007; 64(5):555-64. · 13.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neural models of schizophrenia have implicated the thalamus in deficits of early sensory processing and multimodal integration. We have reviewed the existing neuroimaging literature for evidence in support of models that propose abnormalities of thalamic relay nuclei, the mediodorsal thalamic nucleus, and large-scale cortico-thalamic networks. Thalamic volume reduction was found in some but not all studies. Studies of the early stages of schizophrenia suggest that thalamic volume reduction is present early in the course of the illness. Functional imaging studies have revealed task related abnormalities in several cortical and subcortical areas including the thalamus, suggesting a disruption of distributed thalamocortical networks. Chemical imaging studies have provided evidence for a loss of thalamic neuronal integrity in schizophrenia. There is, at present, inadequate data to support the hypothesis that schizophrenia is associated with abnormalities of sensory relay or association nuclei. There is evidence for a perturbation of cortico-thalamic networks, but further research is needed to elucidate the underlying mechanisms at the cellular and systems levels. The challenges ahead include better delineation of thalamic structure and function in vivo, the combination of genetic and imaging techniques to elucidate the genetic contributions to a thalamic phenotype of schizophrenia, and longitudinal studies of thalamic structure and function.
Journal of Neural Transmission 08/2006; 113(7):907-28. · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assessed the potential relationship between personality disorder (PD) clusters, as assessed by the SCID-II, and temperamental traits assessed by the Tridimensional Personality Questionnaire (TPQ) among a well-characterized, unmedicated cohort of outpatients with major depressive disorder (MDD). The TPQ and SCID-II were administered to 263 depressed outpatients (mean age = 39.9 +/- 10.5 years; women = 139, 53%; initial 17-item Hamilton Rating Scale for Depression = 19.6 +/- 3.4) who currently met criteria for MDD and who were enrolled in an 8-week treatment trial. The multiple linear regression method was used to evaluate the relationship between TPQ factors and personality disorder clusters, controlling for age, gender, and initial 17-item Hamilton Rating Scale for Depression score as necessary. Among outpatients with MDD, meeting criteria for a Cluster A PD diagnosis was related to high harm avoidance (HA) scores, as well as low reward dependence and novelty seeking (NS) scores. Additionally, high HA scores were associated with meeting criteria for a Cluster C PD diagnosis, while high NS scores were associated with meeting criteria for a Cluster B PD diagnosis. Certain temperament traits, especially HA and NS, appear to be associated with specific patterns of personality clusters among depressed patients.
[Show abstract][Hide abstract] ABSTRACT: We used the Tridimensional Personality Questionnaire (TPQ) to study the relationship between temperamental traits and comorbid anxiety disorders as well as age of onset of major depressive disorder (MDD) in 263 patients with MDD.
Patients recruited for a large clinical study on MDD underwent a Structured Clinical Interview for DSM-III-R assessment and were administered the self-rated TPQ [mean age = 39.5 +/- 10.5 years, women = 138 (53%), initial 17-item Hamilton Rating Scale for Depression (HAM-D-17) score = 19.6 +/- 3.4]. The TPQ was scored for three previously identified factors -- harm avoidance (HA), novelty seeking (NS), and reward dependence (RD). Multiple linear regression methods were used to evaluate the relationship between TPQ factors and each comorbid anxiety disorder as well as between early-- vs. late-onset MDD, after controlling for age, gender and initial HAM-D-17 score (when these were related to the dependent variable in simple regressions).
Social anxiety disorder in MDD was strongly associated with higher scores on HA and lower scores on NS and RD (t = 5.4, p < 0.0001; t = 2.6, p = 0.009; t = 2.2, p = 0.028, respectively). A diagnosis of generalized anxiety disorder in MDD was significantly related to higher HA scores (t = 2.8, p = 0.006). The presence of comorbid obsessive-compulsive disorder was associated with lower NS scores (t = 2.3, p = 0.023) as was that of comorbid panic disorder (t = 2.0, p = 0.051). Finally, the presence of simple phobias was associated with lower scores on RD (t = 2.4, p = 0.016). HA scores were higher in patients with early onset of MDD (adjusted p = 0.05). Early versus late onset of MDD was not significantly related to NS or RD scores.
Since our sample consisted of moderately depressed outpatients, our ability to generalize our findings to other populations is limited.
Features of temperament are related to patterns of anxiety disorder comorbidity and age of onset among patients with MDD. Higher levels of HA and lower levels of RD and NS were associated with an increased risk of anxiety disorder comorbidity in our sample. HA may also be related to early onset of depression.
Psychotherapy and Psychosomatics 01/2005; 74(3):173-8. · 9.38 Impact Factor