This study investigated auditory attentional processes associated with schizophrenic thought diso... more This study investigated auditory attentional processes associated with schizophrenic thought disorder. Thirty-®ve chronically schizophrenic, state hospital inpatients were assessed for thought disorder using the Thought, Language, and Communication Disorders Scale (TLC) and tested in an attentional task. Two measures of attention were derived from the Digit Span Distraction Test (DSDT) (Oltmannns, T.F., Neale, J.M., 1975. Schizophrenic performance when distractors are present: attentional de®cit or differential task dif®culty. J. Abnorm. Psychol. 84, 205±209), a digit recall task in which distractor digits were interspersed with target digits. The two measures were Distractibility Ð the overall inaccuracy of recall Ð which measured attentional incapacity, and Distractible Intrusion Ð the number of irrelevant digits recalled Ð which was developed in this study to separately measure the inability to allocate attentional resources. These two measures predicted thought disorder strongly and independently. Distractibility did not signi®cantly correlate with any TLC subscale. In contrast, Distractible Intrusions correlated with the TLC subscales Distractible Speech, Incoherence, Loss of Goal, and Word Approximations. The present ®ndings suggest that these subtypes may comprise a distinct subsyndrome of thought disorder, characterized by a dysfunctionally low threshold for selecting appropriate speech information, and that an attentional allocation de®cit is related to this language dysfunction. q
Background: Patients with schizophrenia show deficits in early-stage visual processing, potential... more Background: Patients with schizophrenia show deficits in early-stage visual processing, potentially reflecting dysfunction of the magnocellular visual pathway. The magnocellular system operates normally in a nonlinear amplification mode mediated by glutamatergic (N-methyl-D-aspartate) receptors. Investigating magnocellular dysfunction in schizophrenia therefore permits evaluation of underlying etiologic hypotheses.
Patients with schizophrenia show deficits in several neurocognitive domains. However, the relatio... more Patients with schizophrenia show deficits in several neurocognitive domains. However, the relationship between white matter integrity and performance in these domains is poorly understood. The authors conducted neurocognitive testing and diffusion tensor imaging in 25 patients with schizophrenia. Performance was examined for tests of verbal declarative memory, attention, and executive function. Relationships between fractional anisotropy and cognitive performance were examined by using voxelwise correlational analyses. In each case, better performance on these tasks was associated with higher levels of fractional anisotropy in task-relevant regions.
Recently, a great deal of interest has arisen in resting state fMRI as a measure of tonic brain f... more Recently, a great deal of interest has arisen in resting state fMRI as a measure of tonic brain function in clinical populations. Most studies have focused on the examination of temporal correlation between resting state fMRI low-frequency oscillations (LFOs). Studies on the amplitudes of these low-frequency oscillations are rarely reported. Here, we used amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF; the relative amplitude that resides in the low frequencies) to examine the amplitude of LFO in schizophrenia. Twenty-six healthy controls and 29 patients with schizophrenia or schizoaffective disorder participated. Our findings show that patients showed reduced low-frequency amplitude in proportion to the total frequency band investigated (i.e., fALFF) in the lingual gyrus, left cuneus, left insula/superior temporal gyrus, and right caudate and increased fALFF in the medial prefrontal cortex and the right parahippocampal gyrus. ALFF was reduced in patients in the lingual gyrus, cuneus, and precuneus and increased in the left parahippocampal gyrus. These results suggest LFO abnormalities in schizophrenia. The implication of these abnormalities for schizophrenic symptomatology is further discussed.
The International Journal of Neuropsychopharmacology, 1999
Schizophrenia is associated with cognitive deficits for which treatments remain elusive. The effe... more Schizophrenia is associated with cognitive deficits for which treatments remain elusive. The effects of risperidone (an antipsychotic differing in some of its pharmacological properties from typical agents) on cognitive deficits have not been extensively investigated. Mismatch negativity (MMN), N2 and P3 are cognitive event-related potentials that index preattentive (MMN) and attention-dependent information processing (N2, P3) and provide a measure of cognitive deficits in schizophrenia. The effects of risperidone treatment on MMN, N2 and P3 generation in chronic schizophrenic patients were investigated in an open- label, uncontrolled study. Risperidone treatment significantly reduced psychotic symptoms. It was associated with a decrease of peak latencies, particularly pronounced for P3. However, it did not significantly affect abnormal MMNor P3 amplitudes. The results suggest an effect of risperidone on processing speed, particularly in attention-dependent tasks. These results are in agreement with findings in recent studies on the cognitive effects of risperidone.
Abstract: Mismatch negativity (MMN) is an early cognitive auditory event-related potential that i... more Abstract: Mismatch negativity (MMN) is an early cognitive auditory event-related potential that indexes preattentive auditory information processing and reflects the functioning of an automatic mismatch detector and of an acoustic working memory. P300 is attention-dependent, elicited by a response to a deviant in an'oddball'paradigm and believed to reflect memory updating. Schizophrenic patients show reduced MMN and P300 amplitudes. In 32 chronic schizophrenic patients (25 m/7 f; mean age 36 y) we have been investigating ...
Proceedings of the National Academy of Sciences, 2008
Visual object-recognition is thought to involve activation of a distributed network of cortical r... more Visual object-recognition is thought to involve activation of a distributed network of cortical regions, nodes of which include the lateral prefrontal cortex, the so-called lateral occipital complex (LOC), and the hippocampal formation. It has been proposed that long-range oscillatory synchronization is a major mode of coordinating such a distributed network. Here, intracranial recordings were made from three humans as they performed a challenging visual objectrecognition task that required them to identify barely recognizable fragmented line-drawings of common objects. Subdural electrodes were placed over the prefrontal cortex and LOC, and depth electrodes were placed within the hippocampal formation. Robust beta-band coherence was evident in all subjects during processing of recognizable fragmented images. Significantly lower coherence was evident during processing of unrecognizable scrambled versions of the same. The results indicate that transient beta-band oscillatory coupling between these three distributed cortical regions may reflect a mechanism for effective communication during visual object processing.
Refractoriness of the generators of the mismatch negativity (MMN) was examined in two experiments... more Refractoriness of the generators of the mismatch negativity (MMN) was examined in two experiments in which two deviant tones occurred in a row. In Experiment 1, the size of the MMN elicited by the first deviant was manipulated by using deviants that were close to or far from the standard in frequency. In Experiment 2, the time between two identical deviants was varied. It was found that neither the size of the MMN elicited by the first deviant, nor the time between two deviants, affected the amplitude of the MMN elicited by the second deviant. It was concluded that refractoriness played no role in the amplitude of the MMN for the parameters used.
Patients with schizophrenia frequently present with negative symptoms and cognitive impairments f... more Patients with schizophrenia frequently present with negative symptoms and cognitive impairments for which no effective treatments are known. Agents that act at the glycine site of the N-methyl-D-aspartic acid (NMDA) glutamatergic receptor have been suggested as promising treatments for moderate to severe negative symptoms and cognitive impairments. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST) was a 16-week double-blind, double-dummy, parallel group, randomized clinical trial of adjunctive glycine, D-cycloserine, or placebo conducted at four sites in the United States and one site in Israel. The participants were 157 inpatients and outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder and retrospective and prospective criteria for moderate to severe negative symptoms without marked positive, depressive, or extrapyramidal symptoms. The primary outcome measures were the average "rate of change" of Scale for the Assessment of Negative Symptoms (SANS) total scores and change in the average cognitive domain z scores. There were no significant differences in change in the SANS total score between glycine and placebo subjects or D-cycloserine and placebo subjects. A prespecified test for the site-by-treatment-by-time interaction was significant in post hoc tests. One site had greater reduction in the SANS total score for patients receiving D-cycloserine relative to patients receiving placebo. A second site had greater reduction in the SANS total score for placebo patients compared with glycine patients. There were no significant differences between glycine and placebo or D-cycloserine and placebo subjects on the average cognition z score. The study results suggest that neither glycine nor D-cycloserine is a generally effective therapeutic option for treating negative symptoms or cognitive impairments.
This study investigated auditory attentional processes associated with schizophrenic thought diso... more This study investigated auditory attentional processes associated with schizophrenic thought disorder. Thirty-®ve chronically schizophrenic, state hospital inpatients were assessed for thought disorder using the Thought, Language, and Communication Disorders Scale (TLC) and tested in an attentional task. Two measures of attention were derived from the Digit Span Distraction Test (DSDT) (Oltmannns, T.F., Neale, J.M., 1975. Schizophrenic performance when distractors are present: attentional de®cit or differential task dif®culty. J. Abnorm. Psychol. 84, 205±209), a digit recall task in which distractor digits were interspersed with target digits. The two measures were Distractibility Ð the overall inaccuracy of recall Ð which measured attentional incapacity, and Distractible Intrusion Ð the number of irrelevant digits recalled Ð which was developed in this study to separately measure the inability to allocate attentional resources. These two measures predicted thought disorder strongly and independently. Distractibility did not signi®cantly correlate with any TLC subscale. In contrast, Distractible Intrusions correlated with the TLC subscales Distractible Speech, Incoherence, Loss of Goal, and Word Approximations. The present ®ndings suggest that these subtypes may comprise a distinct subsyndrome of thought disorder, characterized by a dysfunctionally low threshold for selecting appropriate speech information, and that an attentional allocation de®cit is related to this language dysfunction. q
Background: Patients with schizophrenia show deficits in early-stage visual processing, potential... more Background: Patients with schizophrenia show deficits in early-stage visual processing, potentially reflecting dysfunction of the magnocellular visual pathway. The magnocellular system operates normally in a nonlinear amplification mode mediated by glutamatergic (N-methyl-D-aspartate) receptors. Investigating magnocellular dysfunction in schizophrenia therefore permits evaluation of underlying etiologic hypotheses.
Patients with schizophrenia show deficits in several neurocognitive domains. However, the relatio... more Patients with schizophrenia show deficits in several neurocognitive domains. However, the relationship between white matter integrity and performance in these domains is poorly understood. The authors conducted neurocognitive testing and diffusion tensor imaging in 25 patients with schizophrenia. Performance was examined for tests of verbal declarative memory, attention, and executive function. Relationships between fractional anisotropy and cognitive performance were examined by using voxelwise correlational analyses. In each case, better performance on these tasks was associated with higher levels of fractional anisotropy in task-relevant regions.
Recently, a great deal of interest has arisen in resting state fMRI as a measure of tonic brain f... more Recently, a great deal of interest has arisen in resting state fMRI as a measure of tonic brain function in clinical populations. Most studies have focused on the examination of temporal correlation between resting state fMRI low-frequency oscillations (LFOs). Studies on the amplitudes of these low-frequency oscillations are rarely reported. Here, we used amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF; the relative amplitude that resides in the low frequencies) to examine the amplitude of LFO in schizophrenia. Twenty-six healthy controls and 29 patients with schizophrenia or schizoaffective disorder participated. Our findings show that patients showed reduced low-frequency amplitude in proportion to the total frequency band investigated (i.e., fALFF) in the lingual gyrus, left cuneus, left insula/superior temporal gyrus, and right caudate and increased fALFF in the medial prefrontal cortex and the right parahippocampal gyrus. ALFF was reduced in patients in the lingual gyrus, cuneus, and precuneus and increased in the left parahippocampal gyrus. These results suggest LFO abnormalities in schizophrenia. The implication of these abnormalities for schizophrenic symptomatology is further discussed.
The International Journal of Neuropsychopharmacology, 1999
Schizophrenia is associated with cognitive deficits for which treatments remain elusive. The effe... more Schizophrenia is associated with cognitive deficits for which treatments remain elusive. The effects of risperidone (an antipsychotic differing in some of its pharmacological properties from typical agents) on cognitive deficits have not been extensively investigated. Mismatch negativity (MMN), N2 and P3 are cognitive event-related potentials that index preattentive (MMN) and attention-dependent information processing (N2, P3) and provide a measure of cognitive deficits in schizophrenia. The effects of risperidone treatment on MMN, N2 and P3 generation in chronic schizophrenic patients were investigated in an open- label, uncontrolled study. Risperidone treatment significantly reduced psychotic symptoms. It was associated with a decrease of peak latencies, particularly pronounced for P3. However, it did not significantly affect abnormal MMNor P3 amplitudes. The results suggest an effect of risperidone on processing speed, particularly in attention-dependent tasks. These results are in agreement with findings in recent studies on the cognitive effects of risperidone.
Abstract: Mismatch negativity (MMN) is an early cognitive auditory event-related potential that i... more Abstract: Mismatch negativity (MMN) is an early cognitive auditory event-related potential that indexes preattentive auditory information processing and reflects the functioning of an automatic mismatch detector and of an acoustic working memory. P300 is attention-dependent, elicited by a response to a deviant in an'oddball'paradigm and believed to reflect memory updating. Schizophrenic patients show reduced MMN and P300 amplitudes. In 32 chronic schizophrenic patients (25 m/7 f; mean age 36 y) we have been investigating ...
Proceedings of the National Academy of Sciences, 2008
Visual object-recognition is thought to involve activation of a distributed network of cortical r... more Visual object-recognition is thought to involve activation of a distributed network of cortical regions, nodes of which include the lateral prefrontal cortex, the so-called lateral occipital complex (LOC), and the hippocampal formation. It has been proposed that long-range oscillatory synchronization is a major mode of coordinating such a distributed network. Here, intracranial recordings were made from three humans as they performed a challenging visual objectrecognition task that required them to identify barely recognizable fragmented line-drawings of common objects. Subdural electrodes were placed over the prefrontal cortex and LOC, and depth electrodes were placed within the hippocampal formation. Robust beta-band coherence was evident in all subjects during processing of recognizable fragmented images. Significantly lower coherence was evident during processing of unrecognizable scrambled versions of the same. The results indicate that transient beta-band oscillatory coupling between these three distributed cortical regions may reflect a mechanism for effective communication during visual object processing.
Refractoriness of the generators of the mismatch negativity (MMN) was examined in two experiments... more Refractoriness of the generators of the mismatch negativity (MMN) was examined in two experiments in which two deviant tones occurred in a row. In Experiment 1, the size of the MMN elicited by the first deviant was manipulated by using deviants that were close to or far from the standard in frequency. In Experiment 2, the time between two identical deviants was varied. It was found that neither the size of the MMN elicited by the first deviant, nor the time between two deviants, affected the amplitude of the MMN elicited by the second deviant. It was concluded that refractoriness played no role in the amplitude of the MMN for the parameters used.
Patients with schizophrenia frequently present with negative symptoms and cognitive impairments f... more Patients with schizophrenia frequently present with negative symptoms and cognitive impairments for which no effective treatments are known. Agents that act at the glycine site of the N-methyl-D-aspartic acid (NMDA) glutamatergic receptor have been suggested as promising treatments for moderate to severe negative symptoms and cognitive impairments. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST) was a 16-week double-blind, double-dummy, parallel group, randomized clinical trial of adjunctive glycine, D-cycloserine, or placebo conducted at four sites in the United States and one site in Israel. The participants were 157 inpatients and outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder and retrospective and prospective criteria for moderate to severe negative symptoms without marked positive, depressive, or extrapyramidal symptoms. The primary outcome measures were the average "rate of change" of Scale for the Assessment of Negative Symptoms (SANS) total scores and change in the average cognitive domain z scores. There were no significant differences in change in the SANS total score between glycine and placebo subjects or D-cycloserine and placebo subjects. A prespecified test for the site-by-treatment-by-time interaction was significant in post hoc tests. One site had greater reduction in the SANS total score for patients receiving D-cycloserine relative to patients receiving placebo. A second site had greater reduction in the SANS total score for placebo patients compared with glycine patients. There were no significant differences between glycine and placebo or D-cycloserine and placebo subjects on the average cognition z score. The study results suggest that neither glycine nor D-cycloserine is a generally effective therapeutic option for treating negative symptoms or cognitive impairments.
Uploads
Papers by D. Javitt