An integration of 40 Hz Gamma and phasic arousal: novelty and routinization processing in schizophrenia.

OBJECTIVES: Frontal and lateralized schizophrenia disturbances were examined in terms of arousal-modulated changes in 40 Hz Gamma activity. METHODS: Forty patients with schizophrenia and 40 age- and gender-matched controls were studied in a conventional auditory ERP oddball paradigm. We investigated sub-averaged Gamma activity based upon a simultaneous measure of electrodemal skin conductance response (phasic arousal) to differentiate novelty (large responses) from routinization (small or no responses). Both early Gamma (Gamma 1) and later induced Gamma (Gamma 2) activities were examined. RESULTS: Patients with schizophrenia (compared with controls) had significantly reduced Gamma 1 amplitude in the right hemisphere for novelty processing and delayed Gamma 2 latency in the left hemisphere for both novelty and routinization. Overall, reduced Gamma 1 amplitude in patients with schizophrenia was also evident. CONCLUSIONS: These findings indicate that the normal laterality of Gamma activity is specifically disturbed in schizophrenia in response to novel, but not routine (familiar) stimuli. The distinct pattern of findings suggests a dysregulation of activation across left and right hemispheres during initial attention and preparatory phases of information processing, in particular, in patients with schizophrenia.     

Apathy in schizophrenia: reduced frontal lobe volume and neuropsychological deficits

OBJECTIVE: Apathy is a common negative symptom in schizophrenia. The authors investigated neuropsychological performance and regional brain volumes in schizophrenia patients with high versus low levels of apathy. METHOD: Schizophrenia patients with low apathy levels (N=18) and high apathy levels (N=20) and 12 healthy comparison subjects completed neuropsychological testing as well as magnetic resonance imaging scanning to obtain lobar volumes after total intracranial volume was controlled. RESULTS: The high apathy group scored lower than comparison subjects on rapid visuomotor sequencing and verbal learning/recall. The high apathy group had lower performance IQ scores than the low apathy and comparison groups. Only the high apathy group showed significantly reduced bilateral frontal lobe volumes relative to comparison subjects; both schizophrenia patient groups showed bilateral temporal lobe volume reductions. CONCLUSIONS: The present findings are consistent with studies in other disorders showing frontal lobe involvement in apathy.     

Apathy in schizophrenia: clinical correlates and association with functional outcome

Apathy is considered one of the negative symptoms of schizophrenia, but its natural history and relationship to other clinical characteristics have not been systematically studied. The purpose of this cross-sectional study was to measure the level of apathy in schizophrenia and its relation to other symptoms and functional outcome. Twenty-eight patients with schizophrenia, and receiving antipsychotic treatment, were assessed with the Apathy Evaluation Scale (AES). The mean level of apathy of patients with schizophrenia, as rated by the AES, was significantly higher than that of matched healthy control subjects. In the patients, apathy was not significantly correlated with positive symptoms or depressive symptoms. It was significantly correlated with the item "emotional withdrawal" on the negative subscale of the Positive and Negative Syndrome Scale (PANSS), but was not correlated with the overall negative subscale score. Apathy was more highly associated with functional outcome than were other symptom measures, and it was independently associated with functional outcome above and beyond other negative symptoms. It was not associated with observed interest in playing a video game or performance on a simulated clerical task.     

Hippocampal novelty activations in schizophrenia: disease and medication effects

We examined hippocampal activation in schizophrenia (SZ) with fMRI BOLD in response to the presentation of novel and familiar scenes. Voxel-wise analysis showed no group differences. However, anatomical region-of-interest analyses contrasting normal (NL), SZ-on-medication (SZ-ON), SZ-off-medication (SZ-OFF) showed substantial differences in MTL-based novelty responding, accounted for by the reduction in novelty responses in the SZ-OFF predominantly in the anterior hippocampus and parahippocampal cortex. These differences in novelty-based activation in the SZ-OFF group represent disease characteristics of schizophrenia without confounding effects of antipsychotic medication and illustrate the tendency of antipsychotic drug treatment to improve memory functions in schizophrenia.     

Auditory and visual novelty processing in normally-developing Kenyan children

ObjectiveThe aim of this study was to describe the normative development of the electrophysiological response to auditory and visual novelty in children living in rural Kenya.MethodsWe examined event-related potentials (ERPs) elicited by novel auditory and visual stimuli in 178 normally-developing children aged 4–12 years (86 boys, mean 6.7 years, SD 1.8 years and 92 girls, mean 6.6 years, SD 1.5 years) who were living in rural Kenya.ResultsThe latency of early components (auditory P1 and visual N170) decreased with age and their amplitudes also tended to decrease with age. The changes in longer-latency components (Auditory N2, P3a and visual Nc, P3a) were more modality-specific; the N2 amplitude to novel stimuli decreased with age and the auditory P3a increased in both latency and amplitude with age. The Nc amplitude decreased with age while visual P3a amplitude tended to increase, though not linearly.ConclusionsThe changes in the timing and magnitude of early-latency ERPs likely reflect brain maturational processes. The age-related changes to auditory stimuli generally occurred later than those to visual stimuli suggesting that visual processing matures faster than auditory processing.SignificanceERPs may be used to assess children’s cognitive development in rural areas of Africa.     

Auditory novelty processing is enhanced in obsessive-compulsive disorder

Background: Cognitive models propose that anxiety disorders are associated with an attentional bias toward potentially threatening stimuli. In this study, it was analyzed whether patients with obsessive–compulsive disorder (OCD) show enhanced responses of their event‐related brain potentials to novel stimuli, either in a context of potential threat or in a neutral context. Methods: In this study, 20 OCD patients and 20 matched healthy control subjects performed a visual recognition task during which irrelevant repeated standard sounds and unitary novel sounds were interspersed. Results: As expected, OCD patients showed an increase in the novelty‐P3 amplitude elicited by unitary novel sounds. However, no effect of emotional context conditions was observed. Conclusion: It is suggested that the novelty P3 amplitude increase in OCD patients represents a physiological indicator of an enhanced cortical orienting response implicating stronger involuntary shifts of attention. This characteristic is driven by novelty per se and not moderated by potential threat of upcoming events. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

Negative emotional context enhances auditory novelty processing

We used an auditory-visual distraction task to investigate the functional relationship between distraction elicited by auditory novel events and a context of negative emotional processing, both at behavioural and electrophysiological (event-related brain potentials) levels in humans. Participants performed a decision task on pictures disclosing sceneries with a task-irrelevant emotional load or neutral, whereas ignoring sounds presented concomitantly. Our data showed that novel sounds yielded stronger behavioural disruption on participants' visual task performance in negative context compared to the neutral one. Accordingly, late novelty P3 responses to novel sounds were enhanced. These results demonstrate that the negative emotional context enhances the activation of neural networks in the auditory novelty system, enhancing auditory novelty processing under potentially threatening conditions.     

Contextual interaction between novelty and reward processing within the mesolimbic system

Medial temporal lobe (MTL) dependent long-term memory for novel events is modulated by a circuitry that also responds to reward and includes the ventral striatum, dopaminergic midbrain, and medial orbitofrontal cortex (mOFC). This common neural network may reflect a functional link between novelty and reward whereby novelty motivates exploration in the search for rewards; a link also termed novelty "exploration bonus." We used fMRI in a scene encoding paradigm to investigate the interaction between novelty and reward with a focus on neural signals akin to an exploration bonus. As expected, reward related long-term memory for the scenes (after 24 hours) strongly correlated with activity of MTL, ventral striatum, and substantia nigra/ventral tegmental area (SN/VTA). Furthermore, the hippocampus showed a main effect of novelty, the striatum showed a main effect of reward, and the mOFC signalled both novelty and reward. An interaction between novelty and reward akin to an exploration bonus was found in the hippocampus. These data suggest that MTL novelty signals are interpreted in terms of their reward-predicting properties in the mOFC, which biases striatal reward responses. The striatum together with the SN/VTA then regulates MTL-dependent long-term memory formation and contextual exploration bonus signals in the hippocampus.     

Meaningfulness and global-local processing in schizophrenia

The present work aimed to study the influence of the meaningfulness of stimuli during global-local processing in schizophrenia. Study participants were asked to determine whether pairs of compound stimuli (global forms composed of local forms) were identical or not. Both global and local forms represented either objects or non-objects. Results indicated that when identification processes were useful for performing the task, similar global-local response patterns were observed in patients and controls. However, patients were more affected than controls when an object was present at a distractor level, particularly when this information came from the local level. These results are discussed in terms of the conjunction of executive and visuospatial deficits and underscore the importance of meaningful identification in the visual perception of schizophrenia patients, given its central role in day-to-day situations.     

Alterations in theta activity associated with novelty and routinization processing in ADHD

ObjectiveNovelty and routinization-related information processing disturbances were examined in adolescent males with ADHD using an oddball paradigm and electrophysiological measurement of theta (4–7 Hz) activity.MethodsFifty-four unmedicated adolescent males (12–18 years) with Attention Deficit Hyperactivity Disorder (ADHD) and matched controls performed an auditory oddball task. Theta activity was sub-averaged, and Fourier Integrals with simultaneous measurement of electrodermal activity (EDA) was used to index response to stimulus novelty and routinization.ResultsADHD participants showed an overall increase in theta activity to both novel and routine stimuli relative to controls. While controls showed increased theta activity in response to novel compared to routine targets across the brain, ADHD participants did not show this novelty-related increase in theta activity in the right anterior/frontal brain.ConclusionsThe findings of this study are consistent with disturbances in theta activity and the brain substrates of novelty relative to routinization-related processing in ADHD.SignificanceThese findings show that there are distinct alterations in theta activity related to stimulus novelty and routinization during an auditory oddball task in ADHD, and they highlight the value of using an event-related approach to elucidate the neural substrates of stimulus processing in ADHD.     

Human hippocampal processing of environmental novelty during spatial navigation

The detection and processing of novel information encountered as we explore our environment is crucial for learning and adaptive behavior. The human hippocampus has been strongly implicated in laboratory tests of novelty detection and episodic memory, but has been less well studied during more ethological tasks such as spatial navigation, typically used in animals. We examined fMRI BOLD activity as a function of environmental and object novelty as humans performed an object‐location virtual navigation task. We found greater BOLD response to novel relative to familiar environments in the hippocampus and adjacent parahippocampal gyrus. Object novelty was associated with increased activity in the posterior parahippocampal/fusiform gyrus and anterior hippocampus extending into the amygdala and superior temporal sulcus. Importantly, whilst mid‐posterior hippocampus was more sensitive to environmental novelty than object novelty, the anterior hippocampus responded similarly to both forms of novelty. Amygdala activity showed an increase for novel objects that decreased linearly over the learning phase. By investigating how participants learn and use different forms of information during spatial navigation, we found that medial temporal lobe (MTL) activity reflects both the novelty of the environment and of the objects located within it. This novelty processing is likely supported by distinct, but partially overlapping, sets of regions within the MTL. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

Early information processing in schizophrenia

In summary, approaches from various sensory modalities indicate a similar processing deficit for various schizophrenics occurring at approximately 100 milliseconds during or post-stimulus presentation. This deficit occurs during the time period that has been associated with a dysfunctional inhibitory mechanism that is maximally activated during the 100 millisecond time period (e.g., during the period of temporal integration). The inhibitory mechanism is presently conceptualized as being a "transient" or "fast" system involved in the serial/sequential processing of information. The inability of certain schizophrenics to serially process may suggest a dysfunctional inhibitory mechanism for which GABA is a potential candidate.     

Spatiotemporal visual processing in schizophrenia

Studies examining visual processing in schizophrenia have provided inconsistent results. In this study, the authors measured static and dynamic visual contrast sensitivity (CS) in patients with schizophrenia (n=20) and control subjects (n=15). Extrapyramidal symptoms were evaluated with the Simpson-Angus scale. In the static condition, the patients with schizophrenia showed reduced CS in the spatial frequency range of 2.9-14.4 cycles per degree of visual angle (c/d). In the dynamic condition, CS loss was present over the whole range tested (0.5-14.4 c/d). Higher Simpson-Angus scores and higher doses of antipsychotic medication were associated with more severe CS deficits. These results suggest that the hypodopaminergic state induced by antipsychotic medication may produce parkinsonian visual impairments in schizophrenia patients.     

Evolution of a sensory novelty: tympanic ears and the associated neural processing

Tympanic hearing is a true evolutionary novelty that appears to have developed independently in at least five major tetrapod groups-the anurans, turtles, lepidosaurs, archosaurs and mammals. The emergence of a tympanic ear would have increased the frequency range and sensitivity of hearing. Furthermore, tympana were acoustically coupled through the mouth cavity and therefore inherently directional in a certain frequency range, acting as pressure difference receivers. In some lizard species, this acoustical coupling generates a 50-fold directional difference, usually at relatively high frequencies (2-4kHz). In ancestral atympanate tetrapods, we hypothesize that low-frequency sound may have been processed by non-tympanic mechanisms like those in extant amphibians. The subsequent emergence of tympanic hearing would have led to changes in the central auditory processing of both high-frequency sound and directional hearing. These changes should reflect the independent origin of the tympanic ears in the major tetrapod groups. The processing of low-frequency sound, however, may have been more conserved, since the acoustical coupling of the ancestral tympanate ear probably produced little sensitivity and directionality at low frequencies. Therefore, tetrapod auditory processing may originally have been organized into low- and high-frequency streams, where only the high-frequency processing was mediated by tympanic input. The closure of the middle ear cavity in mammals and some birds is a derived condition, and may have profoundly changed the operation of the ear by decoupling the tympana, improving the low-frequency response of the tympanum, and leading to a requirement for additional neural computation of directionality in the central nervous system. We propose that these specializations transformed the low- and high-frequency streams into time and intensity pathways, respectively.     

Cognitive and emotional processing in high novelty seeking associated with the L-DRD4 genotype

The personality trait of novelty seeking (NS) has been associated with the long variant of the dopamine D4 receptor (L-DRD4) VNTR polymorphism. This is the first study to examine the influence of L-DRD4 polymorphism on some of the cognitive (i.e. decision making) and emotional underpinnings of the NS phenotype. One hundred and eighteen healthy males grouped in a L-DRD4 (n = 24) and a S-DRD4 (n = 94) group, completed multimodal assessment for personality, planning for problem solving and decision making. Two age-matched L-DRD4 and S-DRD4 sub-samples (n = 17 each) entered and completed emotional processing using startle modulation by affective pictures. ANOVAs showed that L-DRD4 individuals had higher NS, made more risky choices and won less money in the decision making task, but had intact planning for problem solving. They also had reduced startle reactivity and late startle modulation by both pleasant and unpleasant pictures. Early, attentional startle modulation by the affective pictures was intact. NS correlated negatively with startle reactivity and performance in the emotional decision task. These results suggest that the L-DRD4 polymorphism is associated with high NS and risk taking, under-reactivity to unconditioned aversive stimuli, constricted emotional responses but preserved attentional processing of emotional stimuli and efficient problem solving. These results extend animal evidence on DRD4-mediated control of decision making and emotional processing to humans. The proposed role of the NS phenotype in human evolution and in disorders of impulsivity is discussed under the light of the present findings.