Pejman Sehatpour

A human intracranial study of long-range oscillatory coherence across a frontal-occipital-hippocampal brain network during visual object processing.

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 object-recognition 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.

Oscillatory Sensory Selection Mechanisms during Intersensory Attention to Rhythmic Auditory and Visual Inputs: A Human Electrocorticographic Investigation

Oscillatory entrainment mechanisms are invoked during attentional processing of rhythmically occurring stimuli, whereby their phase alignment regulates the excitability state of neurons coding for anticipated inputs. These mechanisms have been examined in the delta band (1–3 Hz), where entrainment frequency matches the stimulation rate. Here, we investigated entrainment for subdelta rhythmic stimulation, recording from intracranial electrodes over human auditory cortex during an intersensory audiovisual task. Audiovisual stimuli were presented at 0.67 Hz while participants detected targets within one sensory stream and ignored the other. It was found that entrainment operated at twice the stimulation rate (1.33 Hz), and this was reflected by higher amplitude values in the FFT spectrum, cyclic modulation of alpha-amplitude, and phase–amplitude coupling between delta phase and alpha power. In addition, we found that alpha-amplitude was relatively increased in auditory cortex coincident with to-be-ignored auditory stimuli during attention to vision. Thus, the data suggest that entrainment mechanisms operate within a delimited passband such that for subdelta task rhythms, oscillatory harmonics are invoked. The phase of these delta-entrained oscillations modulates alpha-band power. This may in turn increase or decrease responsiveness to relevant and irrelevant stimuli, respectively.

Impaired visual object processing across an occipital-frontal-hippocampal brain network in schizophrenia: an integrated neuroimaging study.

CONTEXT Perceptual closure is the ability to identify objects based on partial information and depends on the function of a distributed network of brain regions that include the dorsal and the ventral visual streams, prefrontal cortex (PFC), and hippocampus. OBJECTIVE To evaluate network-level interactions during perceptual closure in schizophrenia using parallel event-related potential (ERP), functional magnetic resonance imaging (fMRI), and neuropsychological assessment. DESIGN Case-control study. SETTING Inpatient and outpatient facilities associated with the Nathan Kline Institute for Psychiatric Research. Patients Twenty-seven patients with schizophrenia or schizoaffective disorder and 23 healthy controls. Intervention Event-related potentials were obtained from 24 patients and 20 healthy volunteers in response to fragmented (closeable) and control-scrambled (noncloseable) line drawings. Functional MRI was performed in 11 patients and 12 controls. Main Outcome Measure Patterns of between-group differences for predefined ERP components and fMRI regions of interest were determined using both analysis of variance and structural equation modeling. Global neuropsychological performance was assessed using standard neuropsychological batteries. RESULTS Patients showed impaired generation of event-related components reflecting early sensory and later closure-related activity. In fMRI, patients showed impaired activation of the dorsal and ventral visual regions, PFC, and hippocampus. Impaired activation of dorsal stream visual regions contributed significantly to impaired PFC activation, which contributed significantly to impaired activation of the hippocampus and ventral visual stream. Impaired ventral stream and hippocampal activation contributed significantly to deficits on neuropsychological measures of perceptual organization. CONCLUSIONS Schizophrenia is associated with severe activation deficits across a distributed network of sensory and higher order cognitive regions. Deficit in early visual processing within the dorsal visual stream contributes significantly to impaired frontal activation, which, in turn, leads to dysregulation of the hippocampus and ventral visual stream. Dysfunction within this network underlies deficits in more traditional neurocognitive measures, supporting distributed models of brain dysfunction in schizophrenia.

Sensory Deficits and Distributed Hierarchical Dysfunction in Schizophrenia

OBJECTIVE Schizophrenia is characterized by widespread cognitive deficits that reflect distributed dysfunction across multiple cortical regions. Here the authors examined the relationship between lower- and higher-level dysfunction within the auditory domain using the event-related brain potentials mismatch negativity (MMN) and P300. METHOD Event-related brain potentials were obtained from 50 schizophrenia patients and 21 healthy subjects in two conditions: a standard condition employing fixed differences between standard tones and pitch deviants and a novel individualized condition employing tones matched to each individuals tone-discrimination threshold. The relationship among measures was assessed by multiple regression analysis and structural equation modeling. RESULTS In the standard fixed-deviance condition, schizophrenia patients showed deficits of large effect size in generation of MMN (d>1.26) and P300 (d=1.08) relative to comparison subjects. Assessment of deviance-detection thresholds showed that patients required significantly elevated tone-matching thresholds relative to comparison subjects (d=0.97). When tone differences were individually adjusted to equate tone-matching performance across groups, the groups no longer differed significantly in MMN amplitude during deviant pitch tones, and the degree of deficit in P300 generation was significantly reduced. In both multiple regression analysis and structural equation modeling, MMN and diagnostic group were significant independent predictors of reduced P300 amplitude. MMN generation was well explained (>90% variance) by dipoles seeded within the bilateral auditory cortex. CONCLUSIONS These findings confirm and extend previous reports of impaired basic sensory processing in schizophrenia and demonstrate significant contributions of early sensory processing dysfunction to higher-order cognitive impairments. Overall, the findings support distributed, hierarchical models of cognitive impairment in schizophrenia, consistent with glutamatergic and other widespread neurochemical models of the disorder.

The neurophysiology of human biological motion processing: A high-density electrical mapping study

The neural processing of biological motion (BM) is of profound experimental interest since it is often through the movement of another that we interpret their immediate intentions. Neuroimaging points to a specialized cortical network for processing biological motion. Here, high-density electrical mapping and source-analysis techniques were employed to interrogate the timing of information processing across this network. Participants viewed point-light-displays depicting standard body movements (e.g. jumping), while event-related potentials (ERPs) were recorded and compared to ERPs to scrambled motion control stimuli. In a pair of experiments, three major phases of BM-specific processing were identified: 1) The earliest phase of BM-sensitive modulation was characterized by a positive shift of the ERP between 100 and 200 ms after stimulus onset. This modulation was observed exclusively over the right hemisphere and source-analysis suggested a likely generator in close proximity to regions associated with general motion processing (KO/hMT). 2) The second phase of BM-sensitivity occurred from 200 to 350 ms, characterized by a robust negative-going ERP modulation over posterior middle temporal regions bilaterally. Source-analysis pointed to bilateral generators at or near the posterior superior temporal sulcus (STS). 3) A third phase of processing was evident only in our second experiment, where participants actively attended the BM aspect of the stimuli, and was manifest as a centro-parietal positive ERP deflection, likely related to later cognitive processes. These results point to very early sensory registration of biological motion, and highlight the interactive role of the posterior STS in analyzing the movements of other living organisms.

Enhanced and bilateralized visual sensory processing in the ventral stream may be a feature of normal aging

Evidence has emerged for age-related amplification of basic sensory processing indexed by early components of the visual evoked potential (VEP). However, since these age-related effects have been incidental to the main focus of these studies, it is unclear whether they are performance dependent or alternately, represent intrinsic sensory processing changes. High-density VEPs were acquired from 19 healthy elderly and 15 young control participants who viewed alphanumeric stimuli in the absence of any active task. The data show both enhanced and delayed neural responses within structures of the ventral visual stream, with reduced hemispheric asymmetry in the elderly that may be indicative of a decline in hemispheric specialization. Additionally, considerably enhanced early frontal cortical activation was observed in the elderly, suggesting frontal hyper-activation. These age-related differences in early sensory processing are discussed in terms of recent proposals that normal aging involves large-scale compensatory reorganization. Our results suggest that such compensatory mechanisms are not restricted to later higher-order cognitive processes but may also be a feature of early sensory-perceptual processes.

Differential Relationships of Mismatch Negativity and Visual P1 Deficits to Premorbid Characteristics and Functional Outcome in Schizophrenia

BACKGROUND Mismatch negativity (MMN) and visual P1 are established event-related potential (ERP) markers of impaired auditory and visual sensory function in schizophrenia. Differential relationships of these measures with premorbid and present function and with clinical course have been noted previously in independent cohorts, but measures have not yet been compared within the same patient group. METHODS Twenty-six schizophrenia patients and 19 control subjects participated in a simultaneous visual and auditory ERPs experiment. Attended visual ERPs were obtained to low- and high-spatial frequency stimuli. Simultaneously, MMN was obtained to unattended pitch, duration, and intensity deviant stimuli. Premorbid function, symptom, and global outcome measures were obtained as correlational measures. RESULTS Patients showed substantial P1 reductions to low- but not high-spatial frequency stimuli, unrelated to visual acuity. Patients also exhibited reduced MMN to all deviant types. No significant correlations were observed between visual ERPs and premorbid or global outcome measures or illness duration. In contrast, MMN amplitude correlated significantly and independently with premorbid educational achievement, cognitive symptoms, global function, and illness duration. The MMN to duration versus other deviants was differentially reduced in individuals with poor premorbid function. CONCLUSIONS Visual and auditory ERP measures are differentially related to the pathophysiology of schizophrenia. Visual deficits correlate poorly with functional measures and illness duration and serve primarily as trait vulnerability markers. The MMN deficits are independently related to premorbid function and illness duration, suggesting independent neurodevelopmental and neurodegenerative contributions. The lack of correlation between auditory and visual ERPs in schizophrenia suggests contributions from divergent underlying neurophysiological processes.

Preserved executive function in high-performing elderly is driven by large-scale recruitment of prefrontal cortical mechanisms

High‐density electrical mapping of event‐related potentials was used to investigate the neural processes that permit some elderly subjects to preserve high levels of executive functioning. Two possibilities pertain: (1) high‐performance in elderly subjects is underpinned by similar processing mechanisms to those seen in young adults; that is, these individuals display minimal functional decay across the lifespan, or (2) preserved function relies on successfully recruiting and amplifying control processes to compensate for normal sensory‐perceptual decline with age. Fifteen young and nineteen elderly participants, the latter split into groups of high and low performers, regularly alternated between a letter and a number categorization task, switching between tasks every third trial (AAA‐BBB‐AAA…). This allowed for interrogation of performance during switch, repeat, and preparatory pre‐switch trials. Robust effects of age were observed in both frontal and parietal components of the task‐switching network. Greatest differences originated over prefrontal regions, with elderly subjects generating amplified, earlier, and more differentiated patterns of activity. This prefrontal amplification was evident only in high‐performing (HP) elderly, and was strongest on pre‐switch trials when participants prepared for an upcoming task‐switch. Analysis of the early transient and late sustained activity using topographic analyses and source localization collectively supported a unique and elaborated pattern of activity across frontal and parietal scalp in HP‐elderly, wholly different to that seen in both young and low‐performing elderly. On this basis, we propose that preserved executive function in HP‐elderly is driven by large‐scale recruitment and enhancement of prefrontal cortical mechanisms. Hum Brain Mapp, 2009.

Preliminary Evidence of Pre-Attentive Distinctions of Frequency-Modulated Tones that Convey Affect

Recognizing emotion is an evolutionary imperative. An early stage of auditory scene analysis involves the perceptual grouping of acoustic features, which can be based on both temporal coincidence and spectral features such as perceived pitch. Perceived pitch, or fundamental frequency (F0), is an especially salient cue for differentiating affective intent through speech intonation (prosody). We hypothesized that: (1) simple frequency-modulated tone abstractions, based on the parameters of actual prosodic stimuli, would be reliably classified as representing differing emotional categories; and (2) that such differences would yield significant mismatch negativities (MMNs) – an index of pre-attentive deviance detection within the auditory environment. We constructed a set of FM tones that approximated the F0 mean and variation of reliably recognized happy and neutral prosodic stimuli. These stimuli were presented to 13 subjects using a passive listening oddball paradigm. We additionally included stimuli with no frequency modulation (FM) and FM tones with identical carrier frequencies but differing modulation depths as control conditions. Following electrophysiological recording, subjects were asked to identify the sounds they heard as happy, sad, angry, or neutral. We observed that FM tones abstracted from happy and no-expression speech stimuli elicited MMNs. Post hoc behavioral testing revealed that subjects reliably identified the FM tones in a consistent manner. Finally, we also observed that FM tones and no-FM tones elicited equivalent MMNs. MMNs to FM tones that differentiate affect suggests that these abstractions may be sufficient to characterize prosodic distinctions, and that these distinctions can be represented in pre-attentive auditory sensory memory.

Mismatch Negativity to Tonal Contours Suggests Preattentive Perception of Prosodic Content

Modulation of speech conveys information that is decoded within audio-sensory structures. For example, the termination of an utterance with a rise in pitch distinguishes statements and questions. This study evaluated the sensitivity of early auditory structures to such linguistic prosodic distinctions using mismatch negativity (MMN). MMN is a preattentive auditory event-related potential (ERP) sensitive to stimulus deviance. High-density ERP to pitch contour stimuli were collected in a passive listening oddball paradigm from 11 healthy subjects. Voltage analysis revealed significant MMN responses to declarative and interrogative oddball stimuli. Further, MMN was significantly larger to interrogative, than declarative, deviants, indicating non-symmetric brain processing. These MMNs demonstrate that pitch contour abstractions reflecting interrogative/ declarative distinctions can be represented in preattentive auditory sensory memory.