Academic Appointments

Research & Scholarship

Current Research and Scholarly Interests

I work with event-related brain potentials (ERPs), a functional brain imaging tool, giving millisecond to millisecond temporal information about sensory and cognitive processes. Recently, I have been combining functional Magnetic Resonance Imaging (fMRI) techniques with ERP data to provide high spatial resolution information about cortical sources of the various components of the ERP. ERPs enable assessment of cognition even in the absence of overt behavior, making them an ideal tool for understanding clinical groups in whom responses are unreliable or difficult to acquire. To understand how patients with schizophrenia experience auditory hallucinations, we are using fMRI and ERPs to probe the brain during periods with and without hallucinations. To understand the role of self-monitoring deficits in symptoms of schizophrenia, we are using ERP paradigms that elicit a negative wave in normal subjects when they realize they have made a mistake.


Journal Articles

  • Function biomedical informatics research network recommendations for prospective multicenter functional MRI studies JOURNAL OF MAGNETIC RESONANCE IMAGING Glover, G. H., Mueller, B. A., Turner, J. A., van Erp, T. G., Liu, T. T., Greve, D. N., Voyvodic, J. T., Rasmussen, J., Brown, G. G., Keator, D. B., Calhoun, V. D., Lee, H. J., Ford, J. M., Mathalon, D. H., Diaz, M., O'Leary, D. S., Gadde, S., Preda, A., Lim, K. O., Wible, C. G., Stern, H. S., Belger, A., McCarthy, G., Ozyurt, B., Potkin, S. G. 2012; 36 (1): 39-54


    This report provides practical recommendations for the design and execution of multicenter functional MRI (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The study was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multisite aspects include: (i) establishing and verifying scan parameters including scanner types and magnetic fields, (ii) establishing and monitoring of a scanner quality program, (iii) developing task paradigms and scan session documentation, (iv) establishing clinical and scanner training to ensure consistency over time, (v) developing means for uploading, storing, and monitoring of imaging and other data, (vi) the use of a traveling fMRI expert, and (vii) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery.

    View details for DOI 10.1002/jmri.23572

    View details for Web of Science ID 000305185700003

    View details for PubMedID 22314879

  • Out-of-synch and out-of-sorts: Dysfunction of motor-sensory communication in schizophrenia BIOLOGICAL PSYCHIATRY Ford, J. M., Roach, B. J., Faustman, W. O., Mathalon, D. H. 2008; 63 (8): 736-743


    Phase synchronization of neural activity preceding a motor act may reflect an efference copy of the motor plan and its expected sensory consequences (corollary discharge), which is sent to sensory cortex to herald the arrival of self-generated sensations and dampen the resulting sensory experience. We performed time-frequency decomposition of response-locked electroencephalogram (EEG) to examine phase synchronization of oscillations across trials (phase-locking factor [PLF]) to self-paced button presses. If prepress PLF reflects the activity in motor cortex, it should be contralateralized. If it reflects the action of the efference copy, it should be related to subsequent sensory suppression. If efference copy/corollary discharge mechanisms are abnormal in schizophrenia, it should be reduced in patients with schizophrenia.Electroencephalogram was collected while 23 patients (20 schizophrenia; 3 schizoaffective) and 25 age-matched control subjects pressed a button, at will, every 1 to 2 sec. Phase-locking factor preceding and following button presses was calculated from single-trial EEG; averaging single trials yielded response-locked event-related potentials (ERPs) to the tactile response associated with button pressing.Consistent with its hypothesized reflection of efference copy/corollary discharge signals, prepress gamma band neural synchrony was 1) maximal over the contralateral sensory-motor cortex in healthy subjects, 2) correlated with the ipsilateralized somatosensory ERP amplitude evoked by the press, and 3) reduced in patients. Prepress neural synchrony in the beta band was also reduced in patients, especially those with avolition/apathy.These data are consistent with dysfunction of forward model circuitry in schizophrenia and suggest that the specific motor-sensory system affected is selectively linked to symptoms involving that system.

    View details for DOI 10.1016/j.biopsych.2007.09.013

    View details for Web of Science ID 000254817100004

    View details for PubMedID 17981264

  • Fine-tuning of auditory cortex during speech production PSYCHOPHYSIOLOGY Heinks-Maldonado, T. H., Mathalon, D. H., Gray, M., Ford, J. M. 2005; 42 (2): 180-190


    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.

    View details for DOI 10.1111/j.1469-8986.2005.00272.x

    View details for Web of Science ID 000228198100006

    View details for PubMedID 15787855

  • Acquiring and inhibiting prepotent responses in schizophrenia - Event-related brain potentials and functional magnetic resonance imaging ARCHIVES OF GENERAL PSYCHIATRY Ford, J. M., Gray, M., Whitfield, S. L., Turken, A. U., Glover, G., Faustman, W. O., Mathalon, D. H. 2004; 61 (2): 119-129


    Schizophrenia is associated with deficits in using context to establish prepotent responses in complex paradigms and failures to inhibit prepotent responses once established.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.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.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.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.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.

    View details for Web of Science ID 000188652800002

    View details for PubMedID 14757588

  • Electrophysiological evidence of corollary discharge dysfunction in schizophrenia during talking and thinking JOURNAL OF PSYCHIATRIC RESEARCH Ford, J. M., Mathalon, D. H. 2004; 38 (1): 37-46


    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.

    View details for DOI 10.1016/S0022-3956(03)00095-5

    View details for Web of Science ID 000220190700005

    View details for PubMedID 14690769

  • Are impairments of action monitoring and executive control true dissociative dysfunctions in patients with schizophrenia? AMERICAN JOURNAL OF PSYCHIATRY Turken, U., Vuilleumier, P., Mathalon, D. H., Swick, D., Ford, J. M. 2003; 160 (10): 1881-1883


    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.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.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.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.

    View details for Web of Science ID 000185880300027

    View details for PubMedID 14514505

  • Reduced communication between frontal and temporal lobes during talking in schizophrenia BIOLOGICAL PSYCHIATRY Ford, J. M., Mathalon, D. H., Whitfield, S., Faustman, W. O., Roth, W. T. 2002; 51 (6): 485-492


    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.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.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.Reduced fronto-temporal functional connectivity may contribute to the misattribution of inner thoughts to external voices in schizophrenia.

    View details for Web of Science ID 000174739000008

    View details for PubMedID 11922884

  • Neurophysiological evidence of corollary discharge dysfunction in schizophrenia AMERICAN JOURNAL OF PSYCHIATRY Ford, J. M., Mathalon, D. H., Heinks, T., Kalba, S., Faustman, W. O., Roth, W. T. 2001; 158 (12): 2069-2071


    Speaking is hypothesized to generate a corollary discharge of motor speech commands transmitted to the auditory cortex, dampening its response to self-generated speech sounds. Event-related potentials were used to test whether failures of corollary discharge during speech contribute to the pathophysiology of schizophrenia.The N1 component of the event-related potential elicited by vowels was recorded while the vowels were spoken by seven patients with schizophrenia and seven healthy comparison subjects and while the same vowels were played back.In the healthy subjects, the N1 elicited by spoken vowels was smaller than the N1 elicited by played-back vowels. This reduction in N1 elicited by spoken vowels was not observed in the patients with schizophrenia.These findings provide direct neurophysiological evidence for a corollary discharge that dampens sensory responses to self-generated, relative to externally presented, percepts in healthy comparison subjects and its failure in patients with schizophrenia.

    View details for Web of Science ID 000172452100023

    View details for PubMedID 11729029

  • Cortical responsiveness during inner speech in schizophrenia: An event-related potential study AMERICAN JOURNAL OF PSYCHIATRY Ford, J. M., Mathalon, D. H., Kalba, S., Whitfield, S., Faustman, W. O., Roth, W. T. 2001; 158 (11): 1914-1916


    The study assessed the effects of inner speech on auditory cortical responsiveness in schizophrenia.Comparison subjects (N=15) and patients with schizophrenia (N=15) were presented with acoustic and visual stimuli during three conditions: while subjects were silent, when spontaneous inner speech might occur; during directed inner speech, while subjects repeated a statement silently to themselves; and while subjects listened to recorded speech. N1 event-related potentials were recorded during the three conditions.N1 event-related potentials elicited by acoustic stimuli, but not by visual stimuli, were lower during directed inner speech than during the silent baseline condition in the comparison subjects but not in the patients.Abnormal auditory cortical responsiveness to inner speech in patients with schizophrenia may be a sign of corollary discharge dysfunction, which may potentially cause misattribution of inner speech to external voices.

    View details for Web of Science ID 000171946300022

    View details for PubMedID 11691701

  • Cortical responsiveness during talking and listening in schizophrenia: An event-related brain potential study BIOLOGICAL PSYCHIATRY Ford, J. M., Mathalon, D. H., Kalba, S., Whitfield, S., Faustman, W. O., Roth, W. T. 2001; 50 (7): 540-549


    Failures to recognize inner speech as self-generated may underlie positive symptoms of schizophrenia-like auditory hallucinations. This could result from a faulty comparison in auditory cortex between speech-related corollary discharge and reafferent discharges from thinking or speaking, with misattribution of internal thoughts to external sources. Although compelling, failures to monitor covert speech (thoughts) are not as amenable to investigation as failures to monitor overt speech (talking).Effects of talking on auditory cortex responsiveness were assessed in 10 healthy adults and 12 patients with schizophrenia (DSM-IV) using N1 event-related potentials (ERPs) to acoustic and visual probes during talking aloud, listening to one's speech played back, and silent baseline. Trials contaminated by muscle artifact while talking were excluded.Talking and listening affected N1 to acoustic but not to visual probes, reflecting modality specificity of effects. Patterns of responses to acoustic probes differed between control subjects and patients. N1 to acoustic probes was reduced during talking compared with baseline in control subjects, but not in patients. Listening reduced N1 equivalently in both groups.Although the failure of N1 to be reduced during talking was not related to current hallucinations in patients, it may be related to the potential to hallucinate.

    View details for Web of Science ID 000171582200008

    View details for PubMedID 11600107

  • Event-related brain potential evidence of spared knowledge in Alzheimer's disease PSYCHOLOGY AND AGING Ford, J. M., Askari, N., Gabrieli, J. D., Mathalon, D. H., Tinklenberg, J. R., Menon, V., Yesavage, J. 2001; 16 (1): 161-176


    The authors recorded event-related brain potentials (ERPs) to picture primes and word targets (picture-name verification task) in patients with Alzheimer's disease (AD) and in elderly and young participants. N400 was more negative to words that did not match pictures than to words that did match pictures in all groups: In the young, this effect was significant at all scalp sites; in the elderly, it was only at central-parietal sites; and in AD patients, it was limited to right central-parietal sites. Among AD patients pretested with a confrontation-naming task to identify pictures they could not name, neither the N400 priming effect nor its scalp distribution was affected by ability to name pictures correctly. This ERP evidence of spared knowledge of these items was complemented by 80% performance accuracy. Thus, although the name of an item may be inaccessible in confrontation naming, N400 shows that knowledge is intact enough to prime cortical responses.

    View details for DOI 10.1037//0882-7974.16.1.161

    View details for Web of Science ID 000171004800014

    View details for PubMedID 11302364

  • Left temporal deficit of P300 in patients with schizophrenia: effects of task INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY Ford, J. M., Mathalon, D. H., White, P. M., Pfefferbaum, A. 2000; 38 (1): 71-79


    P300 is often, but not always, observed to be more reduced over left than right temporal lobes in patients with schizophrenia. The possibility that task differences contribute to the inconsistency in the literature was explored in this study. ERPs were collected from 17 right-handed men with schizophrenia (DSM-IIIR) and 11 right-handed healthy male community controls, performing three auditory oddball tasks - respond to a target tone by: (1) counting; (2) pressing a response button with the right index finger; or (3) pressing a response button with the left index finger. Although patients with schizophrenia had smaller and later P300 amplitudes than controls, they did not have smaller P300s over the left temporal scalp (T3) than over the right (T4). P300 recorded over the left (C3) and right (C4) motor cortices indicated sensitivity to responding hand, with greater negativity being associated with contralateral button pressing. Failure to find P300 asymmetry is not related to the presence or absence of a button pressing task, or the hand used for button pressing. Rather, P300 asymmetry may be related to structural neuroanatomical asymmetries.

    View details for Web of Science ID 000090143800006

    View details for PubMedID 11027795

  • Trait and state aspects of P300 amplitude reduction in schizophrenia: A retrospective longitudinal study BIOLOGICAL PSYCHIATRY Mathalon, D. H., Ford, J. M., Pfefferbaum, A. 2000; 47 (5): 434-449


    The P300 component of the auditory event-related brain potential (ERP) is consistently reduced in schizophrenia. Longitudinal data are examined to determine whether P300 amplitude is a trait marker of schizophrenia or a state marker tracking clinical fluctuations over time.Schizophrenic men (DSM-III-R) (n = 36) received ERP and the Brief Psychiatric Rating Scale (BPRS) assessments on multiple occasions, at varying intervals, under varying medication states. Automatically elicited auditory P3a and effortfully elicited auditory and visual P3b amplitudes were assessed. Brief Psychiatric Rating Scale scores were regressed on P300 amplitude within patients using both multiple regression models and nonparametric analyses of individual patient slopes. Event related brain potentials in patients were compared to ERPs from 34 age-matched control men, and stability of P300 over time was estimated with intraclass correlations.P300 amplitude, regardless of elicitation method or sensory modality, tracked BPRS Total and positive symptom scores over time, decreasing with symptom exacerbations and increasing with improvements. In addition, effortful auditory and visual P3b amplitudes tracked negative symptoms, and automatic auditory P3a tracked depression-anxiety symptoms. When analyses were limited to unmedicated occasions, auditory P3a and P3b persisted in tracking BPRS Total scores, with additional tracking of positive symptoms by P3b and mood symptoms by P3a. Mean auditory and visual P3bs, averaged over all measurement occasions for each individual, were inversely related to mean negative symptoms. Auditory P3a and P3b, but not visual P3b, amplitudes were smaller in patients than control subjects, even when patients were least symptomatic. P300 amplitudes showed high test-retest reliability in control subjects and patients and moderate stability over time in patients.Auditory, and possibly visual, P300 amplitudes track fluctuations in clinical state, but only auditory P300 amplitude is a trait marker of schizophrenia.

    View details for Web of Science ID 000085721400008

    View details for PubMedID 10704955

  • Schizophrenia: The broken P300 and beyond PSYCHOPHYSIOLOGY Ford, J. M. 1999; 36 (6): 667-682


    Many of the social, economic, and political problems facing people with schizophrenia are due to a misconception in the community that schizophrenia is not a biologically based disease but a myth. Because the diagnosis is based on self-reported symptoms, it is difficult for many people to acknowledge that schizophrenia is real. One goal of psychophysiological research has been to anchor both diagnosis and symptoms in biological reality. Reduction of the amplitude of the P300 component of the event-related potential (ERP) is the most replicable biological marker of the disease. Data are presented suggesting that P300 is both a state and a trait marker of the disease and may be sensitive to the progressive/degenerative course of the disease. Although the P300 tracks changes in clinical symptoms, it remains reduced even in patients in relative remission. P300 amplitude reduction is related to enduring negative symptoms, waning of attention, and gray matter volume deficits. ERP components other than P300 can also manifest the biological reality of various symptoms of the disease.

    View details for Web of Science ID 000083311300001

    View details for PubMedID 10554581

  • Failures of automatic and strategic processing in schizophrenia: comparisons of event-related brain potential and startle blink modification SCHIZOPHRENIA RESEARCH Ford, J. M., Roth, W. T., Menon, V., Pfefferbaum, A. 1999; 37 (2): 149-163


    Noises elicit startle blinks that are inhibited when immediately (approximately 100 ms) preceded by non-startling prepulses, perhaps reflecting automatic sensory gating. Startle blinks are facilitated when preceded by prepulses at longer lead intervals, perhaps reflecting strategic processes. Event-related brain potentials (ERPs) and startle blinks were used to investigate the well-documented prepulse inhibition failure in schizophrenia. Blinks and ERPs were recorded from 15 schizophrenic men and 20 age-matched controls to noises alone and to noises preceded by prepulses at 120 (PP120), 500 (PP500) and 4000 ms (PP4000) lead intervals. Neither blinks nor any of the ERP components elicited by the noise alone differentiated schizophrenics from controls, although responses to noises were modified by prepulses differently in the two groups. With the N1 component of the ERP, patients showed normal inhibition but lacked facilitation, and with P2, patients lacked inhibition, but showed normal facilitation. With reflex blinks and P300, inhibition was seen in both groups, but no facilitation. These results suggest that different neural circuits are involved in blink and cortical reflections of startle modification in schizophrenics and controls, with both automatic and strategic processes being impaired in schizophrenia.

    View details for Web of Science ID 000080583700003

    View details for PubMedID 10374650

  • P300 amplitude is related to clinical state in severely and moderately ill schizophrenics. Biological Psychiatry Ford, J., Mathalon, D, Marsh, L, Faustman, WO, Harris, D, Hoff, AL, Beal, DM, Pfefferbaum, A 1999: 46: 94-101
  • Combined event-related fMRI and EEG evidence for temporal-parietal cortex activation during target detection NEUROREPORT Menon, V., Ford, J. M., Lim, K. O., Glover, G. H., Pfefferbaum, A. 1997; 8 (14): 3029-3037


    Target detection is the process of bringing a salient stimulus into conscious awareness. Target detection evokes a prominent event-related potential (ERP) component (P3) in the electroencephalogram (EEG). We combined the high spatial resolution of functional magnetic resonance imaging (fMRI) with the high temporal resolution of EEG to investigate the neural generators of the P3. Event-related brain activation (ERBA) and ERPs were computed by time-locked averaging of fMRI and EEG, respectively, recorded using the same paradigm in the same subjects. Target detection elicited significantly greater ERBAs bilaterally in the temporal-parietal cortex, thalamus and anterior cingulate. Spatio-temporal modelling of ERPs based on dipole locations derived from the ERBAs indicated that bilateral sources in the temporal-parietal cortex are the main generators of the P3. The findings provide convergent fMRI and EEG evidence for significant activation of the temporal-parietal cortex 285-610 ms after stimulus onset during target detection. The methods developed here provide a novel multimodal neuroimaging technique to investigate the spatio-temporal aspects of processes underlying brain function.

    View details for Web of Science ID A1997XX91000009

    View details for PubMedID 9331910

  • Automatic and effortful processing in aging and dementia: Event-related brain potentials NEUROBIOLOGY OF AGING Ford, J. M., Roth, W. T., Isaacks, B. G., Tinklenberg, J. R., Yesavage, J., Pfefferbaum, A. 1997; 18 (2): 169-180


    Automatic and effortful processes were investigated using event-related brain potentials (ERPs) recorded from moderately impaired subjects with probable Alzheimer's Disease (AD), normal elderly, and normal young controls. The effects of effortful attention on ERPs to loud noises and the effects of stimulus intrusiveness on effortfully elicited ERPs were studied. First, ERPs to task relevant and irrelevant startling noises were compared. Second, ERPs to startling noises and moderate tones were compared when both were targets. The effects of age (young vs. elderly controls) and effects of dementing disease (AD subjects vs. elderly controls) were also assessed. Effortful attention augmented noise-elicited P300 amplitude in elderly subjects, but not in young. Intrusiveness augmented task-relevant P300 amplitude in young subjects, but not in elderly. Neither variable affected P300 amplitude in AD subjects. Thus, effects of age and disease depended on how P300 was elicited: when effortfully elicited, P300 amplitude was affected by disease but not age; when automatically elicited, P300 amplitude was affected by age but not disease. N1 effects differed from P300 effects.

    View details for Web of Science ID A1997XP01300006

    View details for PubMedID 9258894



    Event-related potentials (ERPs) and brain magnetic resonance images (MRIs) were acquired from 28 normal men, age 21-60 years. ERPs were recorded during 3 paradigms designed to elicit automatic or effortful attention, and a combination of both. MRI-derived measures of brain gray matter, white matter and cerebral spinal fluid (CSF) volumes were computed from frontal, parietal and temporal lobes. P300 amplitude correlated significantly with gray matter volumes but not with white matter or CSF volumes. Furthermore, the relationships between P300 amplitude and gray matter volumes reflected functional rather than direct topographical relationships: P300 recorded at Pz during automatically elicited attention correlated significantly with frontal but not parietal lobe gray matter volumes, P300 recorded during effortful attention correlated significantly with parietal but not frontal lobe gray matter volumes, and P300 recorded when both types of attention were invoked correlated significantly with both frontal and parietal gray matter volumes. Startle blinks, also elicited during automatic attention-engaging paradigms, were significantly correlated with frontal but not parietal lobe gray matter volumes. There was no evidence for a direct spatial relationship between P300 amplitude and the gray matter volumes underlying the recording electrode.

    View details for Web of Science ID A1994ND22100006

    View details for PubMedID 7511503



    Because P300 is typically measured from an average of single trials, variations among individual trials may account for P300 amplitude reduction so often seen in patients with schizophrenia. We tested three hypotheses regarding single-trial contribution to small average P300s in schizophrenics: normal P300s are elicited on some trials and no P300s on others, all trials have consistently small P300s, or P300 latency varies over trials. Nineteen schizophrenics and 35 controls were tested on a two-tone auditory oddball event-related potential (ERP) paradigm. ERPs recorded from the parietal electrode (Pz) were subjected to a P300-screening procedure in which a 2 Hz half-sine wave template was moved across the electroencephalogram (EEG) to find the point of best fit. If, for the point of best fit, the EEG:Template covariance was greater in the signal epoch (280-600 msec) than in the noise epoch (610-930 msec), and if the EEG:Template correlation was statistically significant, the trial passed the P300-screen and was deemed to have a P300. Three types of average ERPs were constructed: Traditional Average from all good (artifact-free, correct response) trials, P300-Screen Average from all good trials that also passed the P300-screen, and Latency Adjusted Average by aligning the P300-screen trials at the latency of maximum covariance. Traditional average ERPs were significantly smaller in schizophrenics than in controls. The results of the P300-screen confirmed all three hypotheses: schizophrenics had fewer trials passing the P300-screen, smaller P300s on each trial, and P300s that were more variable in latency across trials.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1994MW69800003

    View details for PubMedID 8167215



    Multilead event-related potentials (ERPs), elicited by auditory and visual stimuli requiring a button press response and by a startling noise requiring no response, were recorded from male alcoholics and age-matched male controls (26-60 years old). Single-trial analyses of blink responses to the startling stimuli indicated that alcoholics startle less frequently but with equivalent amplitude as the controls. In contrast, single-trial analyses of P3 indicated that alcoholics generate a P3 as often as controls, but that their individual P3s are smaller. Alcoholics who reported a positive family history of problem drinking had larger startle blink amplitudes and smaller auditory and visual P3s than did alcoholics who reported a negative family history. Hierarchical regression analysis was used to demonstrate that smaller P3s in family history positive alcoholics were independent of lifetime alcohol consumption.

    View details for Web of Science ID A1991GL40900018

    View details for PubMedID 1755518



    Seventeen young (mean age = 20.2 years old) and 16 elderly (mean age = 72.6 years old) women were tested with event-related potential (ERP) paradigms designed to elicit responses in reaction time tasks and to a startling noise burst. EEG was analyzed from 17 standard 10-20 electrode sites. Reaction time and performance data suggested that the elderly did not perform worse than the young. Nevertheless, the physiological responses of the elderly differed significantly from those of the young. While the task-dependent P3s at Pz were smaller in the elderly than in the young, the automatic P3 was smaller yet. The distribution of both types of P3 across the scalp was more uniform in the elderly than in the young. Single-trial analyses revealed that the P3 amplitude differences at Pz were not due to latency dispersal of single trials. Single-trial startle eye blink responses to intense noise bursts during the automatic paradigm were considerably less frequent in the elderly, although their individual startle blinks were actually larger. The data demonstrate that the electrophysiological responses of the elderly are different from the young both in tasks eliciting automatic responses and in tasks requiring controlled processing.

    View details for Web of Science ID A1991FL58200005

    View details for PubMedID 1711455

Conference Proceedings

  • N1 and P300 abnormalities in patients with schizophrenia epilepsy, and epilepsy with schizophrenialike features Ford, J. M., Mathalon, D. H., Kalba, S., Marsh, L., Pfefferbaum, A. ELSEVIER SCIENCE INC. 2001: 848-860


    The scalp-recorded N1 and P300 components of the event-related brain potential (ERP) are commonly reduced in patients with schizophrenia but not in patients with epilepsy. Epilepsy patients with interictal chronic schizophrenialike features (EPI-SZ) provide a comparison group for determining whether the ERP amplitude abnormalities seen in schizophrenic patients are associated with shared clinical features of EPI-SZ and schizophrenic patients or overlapping pathophysiologies, or are specific to a distinct schizophrenia etiology.Patients with schizophrenia (n = 24) were compared with normal control subjects (n = 32) and patients with epilepsy syndromes on visual and auditory oddball ERP paradigms. Epilepsy patients included those with chronic interictal schizophrenialike features (n = 6) and those without (n = 16).Auditory P300 amplitude was reduced in both schizophrenic and EPI-SZ patients, whose positive or negative symptoms did not differ. In contrast, N1 amplitude was reduced only in schizophrenic patients. Delays in both N1 and P300 were associated with epilepsy patients and EPI-SZ but not schizophrenic patients.The schizophrenialike symptoms in epilepsy probably represent a phenocopy of schizophrenia with common clinical features and some common pathophysiologies but distinct etiologies. P300 amplitude appears to be sensitive to schizophrenialike features, regardless of whether they occur in the context of schizophrenia or epilepsy. N1 amplitude reduction appears to be specific to schizophrenia, suggesting its sensitivity to the distinct etiology of schizophrenia.

    View details for Web of Science ID 000168559100004

    View details for PubMedID 11343681

  • P300 amplitude is related to clinical state in severely and moderately ill patients with schizophrenia Ford, J. M., Mathalon, D. H., Marsh, L., Faustman, W. O., Harris, D., Hoff, A. L., Beal, M., Pfefferbaum, A. ELSEVIER SCIENCE INC. 1999: 94-101


    Relationships between illness severity and neurobiologic abnormalities in schizophrenia were studied in subpopulations varying in clinical severity.Auditory ERPs were collected from 28 severely ill, chronically hospitalized schizophrenic men from a state hospital; 29 moderately ill inpatient and outpatient schizophrenic men from a veterans hospital; and 30 healthy male subjects from the community as controls. Clinical symptoms were evaluated in patients using the Brief Psychiatric Rating Scale (BPRS).Both schizophrenic patient groups had smaller P300 amplitude than the control subjects. Severely ill patients had smaller P300s than moderately ill patients and scored higher on three BPRS factor scores as well as BPRS Total. Among severely ill patients, P300 amplitude was unrelated to clinical symptoms. Among moderately ill patients, P300 was related to Withdrawal/Retardation, Anxiety/Depression, and BPRS Total. After combining patients, Thinking Disturbance emerged as an additional correlate of P300. Group differences in P300 could not be accounted for by group differences in symptom severity using analysis of covariance.Reduced P300 amplitude marks the diagnosis of schizophrenia, but also reflects individual differences in severity, including positive symptoms. Previous failures to find relationships between positive symptoms and P300 may have been due to a restricted range of clinical severity.

    View details for Web of Science ID 000081103400012

    View details for PubMedID 10394478

  • ELDERLY MEN AND WOMEN ARE LESS RESPONSIVE TO STARTLING NOISES - N1, P3 AND BLINK EVIDENCE Ford, J. M., Roth, W. T., Isaacks, B. G., White, P. M., Hood, S. H., Pfefferbaum, A. ELSEVIER SCIENCE BV. 1995: 57-80


    Previously we observed that the P3 component of the event-related brain potential (ERP) elicited by startling noises, and to a lesser extent P3 to target tones, is reduced in the elderly (Ford & Pfefferbaum, 1991). In the current experiment, we tried to eliminate possible effects of age-related hearing deficits on the responses to noises by filtering them to include only frequencies heard best by the elderly (0-1000 Hz) and by setting noise intensity relative to each subject's threshold (sensation level, SL). Twelve younger (mean 22 years) and 12 older (mean 69 years) men and women listened to three sequences of tones (80%, 500 Hz, 70 dB SPL) and noises (20%). One type of noise occurred in each sequence (wide band noise set to 107 dB SPL, narrow band noise set to 107 dB SPL, or narrow band noise set to approximately 65 dB SL). The order of the three sequences was counterbalanced across age and sex. Younger subjects blinked to the noise 4-5 times more often than older subjects and had N1 and P3 amplitudes that were 2-3 times larger, regardless of the noise type. N1 amplitude to the background frequent tones and non-startle blinks did not differ between groups. Thus, even when noises were narrow band and set relative to each subject's threshold, older subjects were less responsive to startling auditory stimuli than were younger.

    View details for Web of Science ID A1995QE66900001

    View details for PubMedID 7734630


    View details for Web of Science ID A1991HB51400033

    View details for PubMedID 1915027

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