Frontal and temporal dysfunction of auditory stimulus processing in schizophrenia

Attentiondeficits have been consistently described in schizophrenia. Functional neuroimaging and electrophysiological studies have focused on anterior cingulate cortex (ACC) dysfunction as a possible mediator. However, recent basic research has suggested that the effect of attention is also observed as a relative amplification of activity in modality-associated cortical areas. In the present study, the question was addressed whether an amplification deficit is seen in the auditory cortex of schizophrenic patients during an attention-requiring choice reaction task. Twenty-one drug-free schizophrenic patients and 21 age- and sex-matched healthy controls were studied (32-channel EEG). The underlying generators of the event-related N1 component were separated in neuroanatomic space using a minimum-norm (LORETA) and a multiple dipole (BESA) approach. Both methods revealed activation in the primary auditory cortex (peak latency ≈ 100 ms) and in the area of the ACC (peak latency ≈ 130 ms). In addition, the adapted multiple dipole model also showed a temporal-radial source activation in nonprimary auditory areas (peak latency ≈ 140 ms). In schizophrenic patients, significant activation deficits were found in the ACC as well as in the left nonprimary auditory areas that differentially correlated with negative and positive symptoms. The results suggest that (1) the source in the nonprimary auditory cortex is detected only with a multiple dipole approach and (2) that the N1 generators in the ACC and in the nonprimary auditory cortex are dysfunctional in schizophrenia. This would be in line with the notion that attention deficits in schizophrenia involve an extended cortical network

High-frequency neural oscillations and visual processing deficits in schizophrenia

Visual information is fundamental to how we understand our environment, make predictions, and interact with others. Recent research has underscored the importance of visuo-perceptual dysfunctions for cognitive deficits and pathophysiological processes in schizophrenia. In the current paper, we review evidence for the relevance of high frequency (beta/gamma) oscillations towards visuo-perceptual dysfunctions in schizophrenia. In the first part of the paper, we examine the relationship between beta/gamma band oscillations and visual processing during normal brain functioning. We then summarize EEG/MEG-studies which demonstrate reduced amplitude and synchrony of high-frequency activity during visual stimulation in schizophrenia. In the final part of the paper, we identify neurobiological correlates as well as offer perspectives for future research to stimulate further inquiry into the role of high-frequency oscillations in visual processing impairments in the disorder

Event-related brain potential correlates of human auditory sensory memory-trace formation

The event-related potential (ERP) component mismatch negativity (MMN) is a neural marker of human echoic memory. MMN is elicited by deviant sounds embedded in a stream of frequent standards, reflecting the deviation from an inferred memory trace of the standard stimulus. The strength of this memory trace is thought to be proportional to the number of repetitions of the standard tone, visible as the progressive enhancement of MMN with number of repetitions (MMN memory-trace effect). However, no direct ERP correlates of the formation of echoic memory traces are currently known. This study set out to investigate changes in ERPs to different numbers of repetitions of standards, delivered in a roving-stimulus paradigm in which the frequency of the standard stimulus changed randomly between stimulus trains. Normal healthy volunteers (n = 40) were engaged in two experimental conditions: during passive listening and while actively discriminating changes in tone frequency. As predicted, MMN increased with increasing number of standards. However, this MMN memory-trace effect was caused mainly by enhancement with stimulus repetition of a slow positive wave from 50 to 250 ms poststimulus in the standard ERP, which is termed here "repetition positivity" (RP). This RP was recorded from frontocentral electrodes when participants were passively listening to or actively discriminating changes in tone frequency. RP may represent a human ERP correlate of rapid and stimulus-specific adaptation, a candidate neuronal mechanism underlying sensory memory formation in the auditory cortex

Impairment in predictive processes during auditory mismatch negativity in ScZ: evidence from event-related fields

Patients with schizophrenia (ScZ) show pronounced dysfunctions in auditory perception but the underlying mechanisms as well as the localization of the deficit remain unclear. To examine these questions, the current study examined whether alterations in the neuromagnetic mismatch negativity (MMNm) in ScZ-patients could involve an impairment in sensory predictions in local sensory and higher auditory areas. Using a whole-head MEG-approach, we investigated the MMNm as well as P300m and N100m amplitudes during a hierarchical auditory novelty paradigm in 16 medicated ScZ-patients and 16 controls. In addition, responses to omitted sounds were investigated, allowing for a critical test of the predictive coding hypothesis. Source-localization was performed to identify the generators of the MMNm, omission responses as well as the P300m. Clinical symptoms were examined with the positive and negative syndrome scale. Event-related fields (ERFs) to standard sounds were intact in ScZ-patients. However, the ScZ-group showed a reduction in the amplitude of the MMNm during both local (within trials) and global (across trials) conditions as well as an absent P300m at the global level. Importantly, responses to sound omissions were reduced in ScZ-patients which overlapped both in latency and generators with the MMNm sources. Thus, our data suggest that auditory dysfunctions in ScZ involve impaired predictive processes that involve deficits in both automatic and conscious detection of auditory regularities

Duration judgements in patients with schizophrenia

Background. The ability to encode time cues underlies many cognitive processes. In the light of schizophrenic patients' compromised cognitive abilities in a variety of domains, it is noteworthy that there are numerous reports of these patients displaying impaired timing abilities. However, the timing intervals that patients have been evaluated on in prior studies vary considerably in magnitude (e.g. 1 s, 1 min, 1 h etc.). Method. In order to obviate differences in abilities in chronometric counting and place minimal demands on cognitive processing, we chose tasks that involve making judgements about brief durations of time (<1 s). Results. On a temporal generalization task, patients were less accurate than controls at recognizing a standard duration. The performance of patients was also significantly different from controls on a temporal bisection task, in which participants categorized durations as short or long. Although time estimation may be closely intertwined with working memory, patients' working memory as measured by the digit span task did not correlate significantly with their performance on the duration judgement tasks. Moreover, lowered intelligence scores could not completely account for the findings. Conclusions. We take these results to suggest that patients with schizophrenia are less accurate at estimating brief time periods. These deficits may reflect dysfunction of biopsychological timing processes

Somatosensory System Deficits in Schizophrenia Revealed by MEG during a Median-Nerve Oddball Task

Although impairments related to somatosensory perception are common in schizophrenia, they have rarely been examined in functional imaging studies. In the present study, magnetoencephalography (MEG) was used to identify neural networks that support attention to somatosensory stimuli in healthy adults and abnormalities in these networks in patient with schizophrenia. A median-nerve oddball task was used to probe attention to somatosensory stimuli, and an advanced, high-resolution MEG source-imaging method was applied to assess activity throughout the brain. In nineteen healthy subjects, attention-related activation was seen in a sensorimotor network involving primary somatosensory (S1), secondary somatosensory (S2), primary motor (M1), pre-motor (PMA), and paracentral lobule (PCL) areas. A frontal–parietal–temporal “attention network”, containing dorsal- and ventral–lateral prefrontal cortex (DLPFC and VLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), superior parietal lobule (SPL), inferior parietal lobule (IPL)/supramarginal gyrus (SMG), and temporal lobe areas, was also activated. Seventeen individuals with schizophrenia showed early attention-related hyperactivations in S1 and M1 but hypo-activation in S1, S2, M1, and PMA at later latency in the sensorimotor network. Within this attention network, hypoactivation was found in SPL, DLPFC, orbitofrontal cortex, and the dorsal aspect of ACC. Hyperactivation was seen in SMG/IPL, frontal pole, and the ventral aspect of ACC in patients. These findings link attention-related somatosensory deficits to dysfunction in both sensorimotor and frontal–parietal–temporal networks in schizophrenia

Tapping in Time: Visual and Auditory Selective Attention in Schizophrenia

Attention is a complex construct involving extensive interactions with working memory and executive control systems to process and extract meaning out of large amounts of multi-sensory information. Disruption of attention is a characteristic symptom in schizophrenia, and further studies on selective attention are crucial for understanding the disease. The current study looks at how subjects with schizophrenia selectively attend to either a visual or auditory metronome in the presence of asynchronous cross-modal distractors of 3 different frequencies (0.5, 1, and 2 Hz). Results showed that across all tasks of selective attention, patients with schizophrenia demonstrated increased variability in mean group reaction times compared to healthy volunteers. In addition, across all subjects (patients and controls), response times were most variable during the attend visual condition: a task in which subjects tapped in synchrony to a visual reversing checkerboard while ignoring an auditory metronome. Results also indicated that significantly more errors occurred in the highest (2 Hz) frequency condition. These findings are consistent with previous studies on healthy subjects showing that auditory distractors are more difficult to ignore than visual distractors during synchronized tapping. They are also consistent with studies revealing deficient selective attention in patients with schizophrenia. They do not, however, reveal any significant differences in patient vs. control performances during the auditory and visual conditions