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Daniel H Mathalon

Publications and source records attributed to Daniel H Mathalon.

At least 19 recordsLinked to original sources
PubMed2006

A functional magnetic resonance imaging study of working memory abnormalities in schizophrenia.

BACKGROUND: Previous neuroimaging studies of working memory (WM) in schizophrenia, typically focusing on dorsolateral prefrontal cortex, yield conflicting results, possibly because of varied choice of tasks and analysis techniques. We examined neural function changes at several WM loads to derive a more complete picture of WM dysfunction in schizophrenia. METHODS: We used a version of the Sternberg Item Recognition Paradigm to test WM function at five distinct loads. Eighteen schizophrenia patients and 18 matched healthy controls were scanned with functional magnetic resonance imaging at 3 Tesla. RESULTS: Patterns of both overactivation and underactivation in patients were observed depending on WM load. Patients' activation was generally less responsive to load changes than control subjects', and different patterns of between-group differences were observed for memory encoding and retrieval. In the specific case of successful retrieval, patients recruited additional neural circuits unused by control subjects. Behavioral effects were generally consistent with these imaging results. CONCLUSIONS: Differential findings of overactivation and underactivation may be attributable to patients' decreased ability to focus and allocate neural resources at task-appropriate levels. Additionally, differences between encoding and retrieval suggest that WM dysfunction may be manifested differently during the distinct phases of encoding, maintenance, and retrieval.

Adult↗
PubMed2005

Fore-period effect and stop-signal reaction time.

The effect of response readiness on the stop-signal reaction time (SSRT) in a stop-signal task was examined, with the stop-signal delay updated following a staircase procedure. We computed SSRT on the basis of a horse race model. A fore-period effect was computed, which described subjects' readiness to respond to the GO signal. The results showed that the fore-period effect correlated positively with SSRT, providing evidence of the effect of response prepotency on stop signal processing. This finding suggests that response readiness needs to be accounted for in examining response inhibition in a stop-signal task.

Attention↗
PubMed2005

Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial.

BACKGROUND: Most patients with obsessive-compulsive disorder (OCD) show only partial reduction of symptoms with standard therapy. Recent imaging data suggests glutamatergic dysfunction in the corticostriatal pathway in OCD. We investigated the efficacy of augmentation therapy with riluzole, a glutamate-modulating agent, in treatment-resistant OCD. METHODS: Thirteen patients aged between 18 and 65 years with a primary diagnosis of OCD that had proven resistant to standard treatment were treated with the addition of riluzole to their existing pharmacotherapy. Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Depression Inventory (HAM-D), and Hamilton Anxiety Inventory (HAM-A) scores were obtained weekly. RESULTS: Thirteen treatment-resistant OCD patients received riluzole 50 mg twice a day. Y-BOCS scores improved significantly over time. Of 13 patients, 7 (54%) demonstrated a >35% reduction in Y-BOCS scores, and 5 (39%) were categorized as treatment responders. HAM-D and HAM-A scores for the group also significantly improved over time. Riluzole was well tolerated with no serious adverse effects noted. CONCLUSIONS: Riluzole appears to have significant antiobsessional, antidepressant, and antianxiety properties. The addition of this agent may be of practical clinical benefit in patients with OCD.

Adult↗
PubMed2005

Corollary discharge dysfunction in schizophrenia: can it explain auditory hallucinations?

Failure of corollary discharge, a mechanism for distinguishing self-generated from externally generated percepts, has been posited to underlie certain positive symptoms of schizophrenia, including auditory hallucinations. Although originally described in the visual system, corollary discharge may exist in the auditory system, whereby signals from motor speech commands prepare auditory cortex for self-generated speech. While associated with sensorimotor systems, it might also apply to inner speech or thought, regarded as our most complex motor act. In this paper, we describe the results of a series of studies in which we have shown that: (1) event-related brain potentials (ERPs) can be used to demonstrate the corollary discharge phenomenon during talking, (2) corollary discharge is abnormal in patients with schizophrenia, (3) EEG gamma band coherence between frontal and temporal lobes is greater during talking than listening and is disrupted by distorted feedback during talking in normals, and (4) patients with schizophrenia do not show this pattern for EEG gamma coherence. While these studies have identified ERPs and EEG gamma coherence indices of the efference copy/corollary discharge system and documented abnormalities in these systems in patients with schizophrenia, we have so far had limited success in establishing a relationship between these neurobiologic indicators of corollary discharge abnormality and reports of hallucinations in patients.

Auditory Cortex↗
PubMed2005

Delayed hemodynamic responses in schizophrenia.

While there are many reports of reduced amplitude of hemodynamic responses in schizophrenia, there are no reports of delayed hemodynamic responses, in spite of event-related brain potential (ERP) evidence of slowed neural responses. Recently, Henson et al. (2002) [Henson, R., Price, C., Rugg, M., Turner, R., Friston, K., 2002. Detecting latency differences in event-related BOLD responses: application to words versus nonwords and initial versus repeated face presentations. NeuroImage, 15:83-97] proposed a new method for testing small latency effects (<2 s) in hemodynamic responses. fMRI data were collected during a visual oddball task with infrequent (12%) targets (K) and frequent (88%) standards (X), presented every 1-3 s pseudorandomly, with 7-24 s between targets. SPM99 yielded parameter estimates for the hemodynamic response and its temporal derivative (TD). Beta images reflecting hemodynamic response magnitude to target stimuli were minimally thresholded (P < 0.05, uncorrected), and latencies were estimated for surviving voxels using TD and hemodynamic response beta values. DSM-IV schizophrenia patients (n = 12) and sex- and age-matched healthy control subjects (n = 12) were recruited from the community. Although groups differed only minimally in activation height, hemodynamic responses were significantly delayed in basal ganglia, thalamus, and anterior cingulate in patients with schizophrenia. Psychomotor slowing reflected in reaction times to targets recorded outside the magnet was related to hemodynamic slowing in basal ganglia, anterior cingulate, thalamus, as well as left cerebellum in controls. Delays in the hemodynamic response have far-reaching implications for understanding the pathophysiology of schizophrenia from slowed neural responses to slowed substrate delivery, and depending of the degree of delay, may raise methodological issues regarding modeling hemodynamic responses in patients and controls.

Adult↗
PubMed2005

Reduced gamma-band coherence to distorted feedback during speech when what you say is not what you hear.

BACKGROUND: Communication between the frontal lobes, where speech is generated, and the temporal lobes, where it is perceived, may occur through the action of an efference copy/corollary discharge mechanism that prepares the temporal lobes for the expected sound. We suggest that coherence of EEG in gamma-band between frontal and temporal lobes may reflect the successful action of such a mechanism. We tested the hypothesis that there would be a disruption of gamma-band coherence when the expected auditory consequence of speech does not match the auditory experience. METHOD: EEG was recorded from 21 healthy adult subjects as they uttered the sound [a:] (Talking condition) and as they heard these recorded sounds played back (Listening condition). As they spoke, subjects heard real-time feedback of the sounds that were: (1) pitch-shifted down one semi-tone, (2) pitch-shifted down one-half of a semi-tone, or (3) not pitch-shifted (veridical), each in separate runs. Event-related gamma coherence between frontal and temporal sites was calculated relative to the onset of the sound, as it was being spoken during Talking, and as it was being played back during Listening. RESULTS: Frontal-temporal gamma-band coherence spanning 33-43 Hz was greater during Talking than Listening and greater when speech was veridical than when it was distorted a whole semi-tone. CONCLUSIONS: Gamma-band fronto-temporal synchrony may reflect a "binding of expectation with experience." Disruption of this synchrony may provide feedback to the frontal lobes, particularly regions subserving vocalization, to implement sensorimotor adaptations to either adjust motor programs for speech production in the short run, or to reorganize expectations in the long run.

Adult↗
PubMed2005

Fine-tuning of auditory cortex during speech production.

The cortex suppresses sensory information when it is the result of a self-produced motor act, including the motor act of speaking. The specificity of the auditory cortical suppression to self-produced speech, a prediction derived from the posited operation of a precise forward model system, has not been established. We examined the auditory N100 component of the event-related brain potential elicited during speech production. While subjects uttered a vowel, they heard real-time feedback of their unaltered voice, their pitch-shifted voice, or an alien voice substituted for their own. The subjects' own unaltered voice feedback elicited a dampened auditory N100 response relative to the N100 elicited by altered or alien auditory feedback. This is consistent with the operation of a precise forward model modulating the auditory cortical response to self-generated speech and allowing immediate distinction of self and externally generated auditory stimuli.

Adult↗
PubMed2004

Acquiring and inhibiting prepotent responses in schizophrenia: event-related brain potentials and functional magnetic resonance imaging.

BACKGROUND: Schizophrenia is associated with deficits in using context to establish prepotent responses in complex paradigms and failures to inhibit prepotent responses once established. OBJECTIVE: To assess prepotent response establishment and inhibition in patients with schizophrenia using event-related brain potential (ERP) and functional magnetic resonance imaging (fMRI) in a simple NoGo task. To combine fMRI and ERP data to focus on fMRI activations associated with the brief (approximately 200 ms) moment of context updating reflected in the NoGo P300 ERP component. DESIGN AND SETTING: We collected ERP and fMRI data while subjects performed a NoGo task requiring a speedy button press to X stimuli (P=.88) but not to K stimuli (P=.12). The ERPs were collected at the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif; fMRIs were collected at Stanford University, Stanford, Calif. PARTICIPANTS: We recruited patients with DSM-IV schizophrenia (n=11) from the community and the VA hospital and sex- and age-matched healthy control subjects (n=11) from the community. MAIN OUTCOME MEASURES: Behavioral accuracy, P300 amplitudes and latencies, and fMRI activations suggested that patients with schizophrenia did not establish as strong a prepotent tendency to respond to the Go stimulus as healthy subjects. In healthy subjects, NoGo P300 was related to activations in the anterior cingulate cortex, dorsal lateral prefrontal cortex, and right inferior parietal lobule and caudate nucleus, perhaps reflecting conflict experienced when withholding a response, control needed to inhibit a response, and stopping a response in action, respectively. In patients with schizophrenia, NoGo P300 was modestly related to activations in the anterior cingulate cortex, which is consistent with experiencing conflict. CONCLUSIONS: The difference in ERP and fMRI responses to Go and NoGo stimuli suggested that inhibiting a response was easier for patients with schizophrenia than for healthy subjects. Correlations of P300 and fMRI data suggested that patients with schizophrenia and healthy subjects used different neural structures to inhibit responses, with healthy subjects using a more complex system.

Adult↗
PubMed2004

Electrophysiological evidence of corollary discharge dysfunction in schizophrenia during talking and thinking.

Failure of corollary discharge, a mechanism for distinguishing self-generated from externally-generated percepts, has been posited to underlie certain positive symptoms of schizophrenia, including auditory hallucinations. Although originally described in the visual system, corollary discharge may exist in the auditory system, whereby signals from motor speech commands prepare auditory cortex for self-generated speech. While associated with sensorimotor systems, it might also apply to inner speech or thought, regarded as our most complex motor act. We had four aims in the studies summarized in this paper: (1) to demonstrate the corollary discharge phenomenon during talking and inner speech in human volunteers using event-related brain potentials (ERPs), (2) to demonstrate that the corollary discharge is abnormal in patients with schizophrenia, (3) to demonstrate the role of frontal speech areas in the corollary discharge during talking, and (4) to relate the dysfunction of the corollary discharge in schizophrenia to auditory hallucinations. Using EEG and ERP measures, we addressed each aim in patients with schizophrenia (DSM IV) and healthy control subjects. The N1 component of the ERP reflected dampening of auditory cortex responsivity during talking and inner speech in control subjects but not in patients. EEG measures of coherence indicated inter-dependence of activity in the frontal speech production and temporal speech reception areas during talking in control subjects, but not in patients, especially those who hallucinated. These data suggest that a corollary discharge from frontal areas where thoughts are generated fails to alert auditory cortex that they are self-generated, leading to the misattribution of inner speech to external sources and producing the experience of auditory hallucinations.

Adult↗
PubMed2004

Selective attention in schizophrenia: sparing and loss of executive control.

OBJECTIVE: Auditory selective attention involves top-down modulation of sensory processing to selectively filter relevant from irrelevant information. Patients with schizophrenia have deficits in auditory selective attention, but whether these attention deficits are evident at the earliest stages of auditory processing or emerge later in the processing stream is unknown. METHOD: Event-related potentials were used to assess the integrity and time course of auditory attention in schizophrenia during a cross-modal selective attention task. A random sequence of equiprobable loud and soft speech sounds and bright and dim checkerboard patterns occurred every 800 to 1200 msec. A button press was required in response to soft speech sounds in the auditory attention task and to dim checkerboards in the visual attention task. Event-related potentials were recorded from 15 patients with DSM-IV schizophrenia and 16 age- and gender-matched healthy comparison subjects. RESULTS: As early as 50 msec, both patients and comparison subjects showed evidence of cross-modal selective attention. These attention effects were sustained until 300 msec in comparison subjects but were no longer evident in patients by 100 msec. CONCLUSIONS: Schizophrenia patients implemented an early attentional filter but failed to sustain selective attention later in the processing stream. This suggests that initially intact executive control of auditory attention cannot be sustained in schizophrenia, perhaps implicating dysfunction in frontotemporal pathways.

Acoustic Stimulation↗
PubMed2003

Compounded brain volume deficits in schizophrenia-alcoholism comorbidity.

BACKGROUND: Schizophrenia and alcoholism are characterized by brain volume abnormalities. Despite the frequent comorbidity of these conditions, the potentially compounded effects of comorbidity on brain structure have seldom been rigorously assessed. METHODS: To determine the compounding effect of schizophrenia and alcoholism on regional brain volumes, we performed retrospective quantitative analysis of magnetic resonance images from men who participated in research protocols at the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif. Participants were selected on the basis of diagnostic criteria, yielding 4 comparison groups: 35 men comorbid for DSM-III-R schizophrenia or schizoaffective disorder and lifetime alcohol abuse or dependence; 64 men with DSM-III-R schizophrenia or schizoaffective disorder; 62 men with Research Diagnostic Criteria alcoholism; and 62 healthy men screened to exclude any Axis I diagnosis or heavy alcohol use. The comorbid group matched the schizophrenia group on age and illness severity but was younger and drank 5 times less alcohol in their lifetimes than the alcoholism group. Gray and white matter volumes from 6 cortical regions were expressed as age- and head size-corrected z scores and were subjected to multivariate profile analyses. RESULTS: Gray matter volume deficits were present in all 3 patient groups but were greatest in the comorbid group. In the comorbid group, the most prominent volume deficits were in the prefrontal and anterior superior temporal regions. CONCLUSIONS: Despite lower alcohol exposure than in pure alcoholism, the comorbidity of schizophrenia with alcoholism has a particularly profound effect on prefrontal gray matter volume, compounding the prominent prefrontal deficits present independently in schizophrenia and alcoholism.

Adult↗
PubMed2003

Response-monitoring dysfunction in aging and Alzheimer's disease: an event-related potential study.

Executive control is a broad-reaching function that includes response monitoring and is likely implemented in the frontal lobes. Age- and dementia-related changes in response-monitoring were assessed during a Picture-Name Verification Task, using response-synchronized event-related potential (ERP) markers of response monitoring: the centrally oriented error-related negativity (ERN); the smaller and more frontally-oriented correct-response negativity (CRN); and the positivity associated with errors (Pe), a marker of error awareness. These were recorded from 10 younger and 10 older healthy controls, as well as 12 Alzheimer's disease (AD) patients. Although the older and younger controls showed equivalent accuracy, error awareness (Pe), and relative ERN>CRN amplitude, aging was associated with slower behavioral responses and decreased ERN amplitude. Although dementia was associated with decreased accuracy, decreased ERN, and a loss of relative ERN>CRN amplitude, error awareness (Pe) remained somewhat intact in AD patients. In AD patients, CRN amplitude was affected by item certainty (assessed a week earlier), being larger to items that were idiosyncratically difficult for patients to name.

Adult↗
PubMed2003

Anatomy of an error: ERP and fMRI.

Successful inhibition of pre-potent responses involves conflict; failed inhibition involves both conflict and errors, complicating the study of errors. Event-related potential (ERP) and functional magnetic resonance imaging (fMRI) data were collected while ten subjects (26-55 years old) performed a Go/NoGo task, with pre-potent responses (88% Go) and inhibition of responses (12% NoGo). We measured error-related negativity (ERN) to false alarms (FA), correct-related negativity (CRN) to hits, NoGo N2 to correct rejections (CR) and Go N2 to hits. ERP difference scores were derived (ERN-CRN; NoGoN2-GoN2) for correlating with fMRI contrasts (FA-hits; CR-hits). Age effects were removed from ERN and N2 difference scores, and conflict effects, reflected in N2 difference scores, were removed from ERN. The resulting ERN correlated with fMRI activations in both caudal and rostral anterior cingulate cortex (ACC), while N2 correlated with fMRI activations in caudal ACC and in executive control regions including dorsolateral prefrontal cortex. Thus, error and conflict monitoring may be dissociable, subserved by both overlapping and distinct ACC regions.

Adult↗
PubMed2003

Are impairments of action monitoring and executive control true dissociative dysfunctions in patients with schizophrenia?

OBJECTIVE: Impaired self-monitoring is considered a critical deficit of schizophrenia. The authors asked whether this is a specific and isolable impairment or is part of a global disturbance of cognitive and attentional functions. METHOD: Internal monitoring of erroneous actions, as well as three components of attentional control (conflict resolution, set switching, and preparatory attention) were assessed during performance of a single task by eight high-functioning patients with schizophrenia and eight comparison subjects. RESULTS: The patients exhibited no significant dysfunction of attentional control during task performance. In contrast, their ability to correct errors without external feedback and, by inference, to self-monitor their actions was markedly compromised. CONCLUSIONS: This finding suggests that dysfunction of self-monitoring in schizophrenia does not necessarily reflect a general decline in cognitive function but is evidence of disproportionately pronounced impairment of action monitoring, which may be mediated by a distinct subsystem within the brain's executive attention networks.

Adult↗
PubMed2002

Reduced communication between frontal and temporal lobes during talking in schizophrenia.

BACKGROUND: Communication between the frontal lobes, where speech and verbal thoughts are generated, and the temporal lobes, where they are perceived, may occur through the action of a corollary discharge. Its dysfunction may underlie failure to recognize inner speech as self-generated and account for auditory hallucinations in schizophrenia. METHODS: Electroencephalogram was recorded from 10 healthy adults and 12 patients with schizophrenia (DSM-IV) in two conditions: talking aloud and listening to their own played-back speech. Event-related electroencephalogram coherence to acoustic stimuli presented during both conditions was calculated between frontal and temporal pairs, for delta, theta, alpha, beta, and gamma frequency bands. RESULTS: Talking produced greater coherence than listening between frontal-temporal regions in all frequency bands; however, in the lower frequencies (delta and theta), there were significant interactions of group and condition. This finding revealed that patients failed to show an increase in coherence during talking, especially over the speech production and speech reception areas of the left hemisphere, and especially in patients prone to hallucinate. CONCLUSIONS: Reduced fronto-temporal functional connectivity may contribute to the misattribution of inner thoughts to external voices in schizophrenia.

Adult↗
PubMed2002

N400 and automatic semantic processing abnormalities in patients with schizophrenia.

BACKGROUND: One factor hypothesized to underlie thinking disturbance in patients with schizophrenia is abnormal or disinhibited automatic spreading activation of semantic networks, which can be assessed using the N400 event-related potential. N400 is a negative-going component elicited at about 400 milliseconds following semantic stimuli that are not primed by the preceding context. Semantic priming refers to facilitated semantic processing gained through preexposure to semantic context, which can happen automatically or strategically. Using N400, inferences can be drawn regarding the extent to which a given context primes a word. METHODS: During a picture-word matching task, N400s to primed (exact match) and unprimed (remotely related) words were recorded from 18 healthy control subjects and 18 patients with schizophrenia performing a picture-word matching task. A short interval (325 milliseconds) between picture and word onset (stimulus-onset asynchrony) was used to optimize the role of automatic spreading semantic activation and to minimize the role of attention, expectancy, preparation, and working memory. RESULTS: Despite behavioral evidence of normal semantic priming, patients generated an abnormally small N400 (ie, less negative) to unprimed words. The N400 to primed words was neither larger nor smaller in patients than in controls, suggesting normal use of context. CONCLUSIONS: A reduced N400 to unprimed words in patients with schizophrenia suggests that there was inappropriate priming of words by remotely related semantic contexts. This is consistent with an overly broad automatic spread of activation through semantic networks in patients with schizophrenia.

Adult↗
PubMed2002

The long and the short of it: influence of interstimulus interval on auditory P300 abnormalities in schizophrenia.

Event-related brain potentials were recorded from 10 patients with DSM-IV schizophrenia (9 men) and 10 healthy control subjects (9 men) during the performance of two auditory oddball tasks, one using a 1.5 second interstimulus interval (ISI), the other using an 8 second ISI. P300 amplitude to target tones (.20 probability) and standard tones (.80 probability) were measured from midline electrodes Fz, Cz, and Pz. Results showed different effects of ISI in the two groups. Controls showed a slight decrease in P300 amplitude to targets but a marked increase in P300 to standards with the increase in ISI. In contrast, schizophrenic patients showed no change in the P300 to targets and a relatively small increase in P300 to standards with the ISI increase. Moreover, relative to the controls, P300 amplitude to targets was reduced in the schizophrenic patients at the short but not the long ISI. Implications for the cognitive significance of the P300 and its reduction in schizophrenia are discussed.

Acoustic Stimulation↗