Publications

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    ABSTRACT: During social bargain, one has to both figure out the others' intentions and behave strategically in such a way that the others' behaviors will be consistent with one's expectations. To understand the neurobiological mechanisms underlying these behaviors, we used electroencephalography while subjects played as proposers in a repeated Ultimatum Game. We found that subjects adapted their offers in order to obtain more acceptances in the last round and that this adaptation correlated negatively with prefrontal theta oscillations. People with higher prefrontal theta activity related to a rejection did not adapt their offers along the game to maximize their earning. Moreover, between-subject variation in posterior theta oscillations correlated positively with how individual theta activity influenced the change of offer after a rejection, reflecting a process of behavioral adaptation to the others' demands. Interestingly, people adapted better their offers when they knew that they where playing against a computer, although the behavioral adaptation did not correlate with prefrontal theta oscillation. Behavioral changes between human and computer games correlated with prefrontal theta activity, suggesting that low adaptation in human games could be a strategy. Taken together, these results provide evidence for specific roles of prefrontal and posterior theta oscillations in social bargaining.
    Social Cognitive and Affective Neuroscience 02/2014; · 5.04 Impact Factor
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    ABSTRACT: The capacity to inhibit prepotent and automatic responses is crucial for proper cognitive and social development, and inhibitory impairments have been considered to be key for some neuropsychiatric conditions. One of the most used paradigms to analyze inhibitory processes is the Go-Nogo task (GNG). This task has been widely used in psychophysical and cognitive EEG studies, and more recently in paradigms using fMRI. However, a technical limitation is that the time resolution of fMRI is poorer than that of the EEG technique. In order to compensate for these temporal constraints, it has become common practice in the fMRI field to use longer inter-stimulus intervals (ISI) than those used in EEG protocols. Despite the noticeable temporal differences between these two techniques, it is currently assumed that both approaches assess similar inhibitory processes. We performed an EEG study using a GNG task with both short ISI (fast-condition, FC, as in EEG protocols) and long ISI (slow-condition, SC, as in fMRI protocols). We found that in the FC there was a stronger Nogo-N2 effect than in the SC. Moreover, in the FC, but not in the SC, the number of preceding Go trials correlated positively with the Nogo-P3 amplitude and with the Go trial reaction time; and negatively with commission errors. In addition, we found significant topographical differences for the Go-P3 elicited in FC and SC, which is interpreted in terms of different neurotransmitter dynamics. Taken together, our results provide evidence that frequency of stimulus presentation in the GNG task strongly modulates the behavioral response and the evoked EEG activity. Therefore, it is likely that short-ISI EEG protocols and long-ISI fMRI protocols do not assess equivalent inhibitory processes.
    PLoS ONE 01/2014; 9(1):e87232. · 3.73 Impact Factor
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    ABSTRACT: A cardinal symptom of attention deficit and hyperactivity disorder (ADHD) is a general distractibility where children and adults shift their attentional focus to stimuli that are irrelevant to the ongoing behavior. This has been attributed to a deficit in dopaminergic signaling in cortico-striatal networks that regulate goal-directed behavior. Furthermore, recent imaging evidence points to an impairment of large scale, antagonistic brain networks that normally contribute to attentional engagement and disengagement, such as the task-positive networks and the default mode network (DMN). Related networks are the ventral attentional network (VAN) involved in attentional shifting, and the salience network (SN) related to task expectancy. Here we discuss the tonic-phasic dynamics of catecholaminergic signaling in the brain, and attempt to provide a link between this and the activities of the large-scale cortical networks that regulate behavior. More specifically, we propose that a disbalance of tonic catecholamine levels during task performance produces an emphasis of phasic signaling and increased excitability of the VAN, yielding distractibility symptoms. Likewise, immaturity of the SN may relate to abnormal tonic signaling and an incapacity to build up a proper executive system during task performance. We discuss different lines of evidence including pharmacology, brain imaging and electrophysiology, that are consistent with our proposal. Finally, restoring the pharmacodynamics of catecholaminergic signaling seems crucial to alleviate ADHD symptoms; however, the possibility is open to explore cognitive rehabilitation strategies to top-down modulate network dynamics compensating the pharmacological deficits.
    Frontiers in Psychology 01/2014; 5:183.
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    Pablo Billeke, Francisco Aboitiz
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    ABSTRACT: Social cognition consists of several skills which allow us to interact with other humans. These skills include social stimuli processing, drawing inferences about others' mental states, and engaging in social interactions. In recent years, there has been growing evidence of social cognitive impairments in patients with schizophrenia. Apparently, these impairments are separable from general neurocognitive impairments, such as attention, memory, and executive functioning. Moreover, social cognition seems to be a main determinant of functional outcome and could be used as a guide to elaborate new pharmacological and psychological treatments. However, most of these studies focus on individual mechanisms and observational perspectives; only few of them study schizophrenic patients during interactive situations. We first review evidences of social cognitive impairments both in social stimuli processing and in mental state attribution. We focus on the relationship between these functions and both general cognitive impairments and functional outcome. We next review recent game theory approaches to the study of how social engagement occurs in schizophrenic patients. The advantage of using game theory is that game-oriented tasks can assess social decision making in an interactive everyday situation model. Finally, we review proposed theoretical models used to explain social alterations and their underlying biological mechanisms. Based on interactive studies, we propose a framework which takes into account the dynamic nature of social processes. Thus, understanding social skills as a result of dynamical systems could facilitate the development of both basic research and clinical applications oriented to psychiatric populations.
    Frontiers in Psychiatry 01/2013; 4:4.
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    Enzo Brunetti, Pedro E Maldonado, Francisco Aboitiz
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    ABSTRACT: During monitoring of the discourse, the detection of the relevance of incoming lexical information could be critical for its incorporation to update mental representations in memory. Because, in these situations, the relevance for lexical information is defined by abstract rules that are maintained in memory, a central aspect to elucidate is how an abstract level of knowledge maintained in mind mediates the detection of the lower-level semantic information. In the present study, we propose that neuronal oscillations participate in the detection of relevant lexical information, based on "kept in mind" rules deriving from more abstract semantic information. We tested our hypothesis using an experimental paradigm that restricted the detection of relevance to inferences based on explicit information, thus controlling for ambiguities derived from implicit aspects. We used a categorization task, in which the semantic relevance was previously defined based on the congruency between a kept in mind category (abstract knowledge), and the lexical semantic information presented. Our results show that during the detection of the relevant lexical information, phase synchronization of neuronal oscillations selectively increases in delta and theta frequency bands during the interval of semantic analysis. These increments occurred irrespective of the semantic category maintained in memory, had a temporal profile specific for each subject, and were mainly induced, as they had no effect on the evoked mean global field power. Also, recruitment of an increased number of pairs of electrodes was a robust observation during the detection of semantic contingent words. These results are consistent with the notion that the detection of relevant lexical information based on a particular semantic rule, could be mediated by increasing the global phase synchronization of neuronal oscillations, which may contribute to the recruitment of an extended number of cortical regions.
    Frontiers in Psychology 01/2013; 4:308.
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    Francisco Aboitiz, Francisco Zamorano
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    ABSTRACT: The anatomical organization of the mammalian neocortex stands out among vertebrates for its laminar and columnar arrangement, featuring vertically oriented, excitatory pyramidal neurons. The evolutionary origin of this structure is discussed here in relation to the brain organization of other amniotes, i.e., the sauropsids (reptiles and birds). Specifically, we address the developmental modifications that had to take place to generate the neocortex, and to what extent these modifications were shared by other amniote lineages or can be considered unique to mammals. In this article, we propose a hypothesis that combines the control of proliferation in neural progenitor pools with the specification of regional morphogenetic gradients, yielding different anatomical results by virtue of the differential modulation of these processes in each lineage. Thus, there is a highly conserved genetic and developmental battery that becomes modulated in different directions according to specific selective pressures. In the case of early mammals, ecological conditions like nocturnal habits and reproductive strategies are considered to have played a key role in the selection of the particular brain patterning mechanisms that led to the origin of the neocortex.
    Frontiers in Neuroanatomy 01/2013; 7:38. · 4.06 Impact Factor
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    ABSTRACT: Visual spatial orienting of attention towards exogenous cues has been one of the attentional functions considered to be spared in ADHD. Here we present a design in which 60 (30 ADHD) children, age: 10.9±1.4, were asked to covertly orient their attention to one or two (out of four) cued locations, and search for a target stimulus in one of these locations, while recording behavioral responses and EEG/ERP. In all conditions, ADHD children showed delayed reaction times and poorer behavioral performance. They also exhibited larger cue-elicited P2 but reduced CNV in the preparation stage. Larger amplitude of CNV predicted better performance in the task. Target-elicited N1 and selection negativity were also reduced in the ADHD group compared to non-ADHD. Groups also differed in the early and late P3 time-windows. The present results suggest that exogenous orienting of attention could be dysfunctional in ADHD under certain conditions. This limitation is not necessarily caused by an impairment of the orienting process itself, but instead by a difficulty in maintaining the relevant information acquired during the early preparation stage through the target processing stage, when it is really needed.
    Brain research 11/2012; · 2.46 Impact Factor
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    ABSTRACT: Background: The assessment of Attentional Deficit Hyperactivity Disorder (ADHD) among ethnic groups may reveal environmental or cultural variables that influence the appearance of this disorder. Aim: To assess the presence and characteristics of ADHD in two communities of the inland Arica valleys (Azapa and Lluta), where the Aymara population predominates. Material and Methods: Startingfrom a screening based on the Conner's test, we evaluated 79 children aged 8 to 13 years. Sixty children were of Aymara origin and 19 children were of non-Aymara origin. Twenty Aymara and 9 non-Aymara children had ADHD. They were compared with a group of patients from Santiago, Chile (110 children) that were previously assessed. Results: Patientsfrom Azapa/Lluta displayed similar characteristics to those from Santiago. However the former had significantly less psychiatric comorbidities than the latter. On the other hand, the non-Aymara subgroup of Azapa/ Lluta displayed an increased rate of comorbidities and was exclusively of the combined subtype, although their sample size is too small to draw strong conclusions. Conclusions: Although we cannot dismiss biological variables, the importance of family values and the respect to authorities may be protective factors for ADHD, associated to Aymara culture. Our findings suggest that the clinical characteristics of ADHD are not uniform among ethnic groups and cultures. The relative contribution of environmental and genetic factors in this variability remain to be determined.
    Revista medica de Chile 11/2012; 140(11):1409-16. · 0.36 Impact Factor
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    ABSTRACT: Background: Worldwide diversity of alleles of D4 receptor gene (DRD4), linked to attention deficit hyperactivity disorder (ADHD), is mostly the result of length and single nucleotide polymorphisms in a 48-bp tandem repeat (VNTR). Alleles containing from two (2R) to eleven (11R) repeats have been identified. The most common are 4R, 7R and 2R. Aim: To study the association of ADHD risk with DRD4 genotypes in Chilean students. Subjects and Methods: ADHD risk data were obtained through the abbreviated Conner's Scale for School Teachers in 66 Aymara children (11 cases and 55 controls), 91 Rapa-Nui children (60 cases ad 31 controls) and 96 children from a mixed urban population from Santiago (51 cases and 45 controls). DNA extracted from saliva was amplified by polymerase chain reaction (PCR) to genotype the DRD4 VNTR. Results: The distribution of DRD4 alleles reveals that, beneath the 4R allele, 7R exhibits the second highest frequencies in Aymara and Santiago children. In Polynesian children, 2R ranks after 4R. A statistically significant association between ADHD risk and 2R/4R genotype was identified in Polynesian children (p < 0.05; odds ratio = 3.7). Conclusions: Different DRD4 genotypes are associated with ADHDphenotype in Chilean populations, probably as a consequence of their initial colonization history.
    Revista medica de Chile 10/2012; 140(10):1276-81. · 0.36 Impact Factor
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    ABSTRACT: En este artículo discutimos investigaciones recientes relacionadas a los mecanismos neurobiológicos subyacientes al Trastorno por Déficit Atencional e Hiperactividad, (TDAH) en particular la dinámica de señalización dopaminérgica y la llamada red por defecto, que consiste en patrones de actividad que se generan durante el reposo. Ambos tipos de fenómenos han sido asociados al TDAH, y aquí proponemos una relación entre ambas dinámicas, y cómo ésta puede estar afectada enel TDAH. Palabras clave: TDAH, Dopamina, Red por Defecto. SUMMARY In this article we discuss recent findings on the neurobiological mechanisms underlying Attentional Deficit Hyperactivity Disorder (ADHD); specifically the dynamics of dopaminergic signaling and the default mode network, consisting of activity patterns generated during the resting state. Both phenomena have been related to ADHD, and we propose here a relationship between both dynamics, and how this can be affected in ADHD.
    Revista Medica Clínica las Condes. 09/2012; 23(5-23):559-565.
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    ABSTRACT: Behavioral variability may be an ADHD key feature. Currently used ex-Gaussian/Fast Fourier Transform analyses characterize general distribution and oscillatory/rhythmic components of performance but are unable to demonstrate slow cumulative changes over entire tasks. Objective: To explore how performance of ADHD children and unaffected sibs gradually evolves in relation to genetic variants linked to ADHD. Method: A total of 40 kids (20 ADHD-discordant sib pairs) between 8 and 13 years resolved a visual Go/NoGo with 10% NoGo probability. Variable number tandem repeats (VNTRs) at DRD4 and SLC6A3 were identified following standard protocols. Performance changes were assessed by linear/logistic mixed-effect models. Results: Models exploring SLC6A3 effects demonstrated less accentuated increments of response time (RT) (p = .046) and cumulative increments in the correct responses to NoGo (p = .00027) in 10R/10R participants. Models for DRD4 showed faster decline of correct responses to Go (p = .0078) in 2R/7R carriers. Conclusion: Dynamical analysis of attention/inhibition measures may unravel new correlates to DRD4 and SLC6A3 variants.
    Journal of Attention Disorders 08/2012; · 2.16 Impact Factor
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    Francisco Aboitiz, Juan F Montiel
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    ABSTRACT: Primates are endowed with a brain about twice the size that of a mammal with the same body size, and humans have the largest brain relative to body size of all animals. This increase in brain size may be related to the acquisition of higher cognitive skills that permitted more complex social interactions, the evolution of culture, and the eventual ability to manipulate the environment. Nevertheless, in its internal structure, the primate brain shares a very conserved design with other mammals, being covered by a six-layered neocortex that, although expands disproportionately to other brain components, it does so following relatively well-defined allometric trends. Thus, the most fundamental events generating the basic design of the primate and human brain took place before the appearance of the first primate-like animal. Presumably, the earliest mammals already displayed a brain morphology radically different from that of their ancestors and that of their sister group, the reptiles, being characterized by the presence of an incipient neocortex that underwent an explosive growth in subsequent mammal evolution. In this chapter, we propose an integrative hypothesis for the origin of the mammalian neocortex, by considering the developmental modifications, functional networks, and ecological adaptations involved in the generation of this structure during the cretaceous period. Subsequently, the expansion of the primate brain is proposed to have relied on the amplification of the same, or very similar, developmental mechanisms as those involved in its primary origins, even in different ecological settings.
    Progress in brain research 01/2012; 195:3-24. · 4.19 Impact Factor
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    Francisco Aboitiz
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    ABSTRACT: THIS ARTICLE DISCUSSES THE POSSIBLE HOMOLOGIES BETWEEN THE HUMAN LANGUAGE NETWORKS AND COMPARABLE AUDITORY PROJECTION SYSTEMS IN THE MACAQUE BRAIN, IN AN ATTEMPT TO RECONCILE TWO EXISTING VIEWS ON LANGUAGE EVOLUTION: one that emphasizes hand control and gestures, and the other that emphasizes auditory-vocal mechanisms. The capacity for language is based on relatively well defined neural substrates whose rudiments have been traced in the non-human primate brain. At its core, this circuit constitutes an auditory-vocal sensorimotor circuit with two main components, a "ventral pathway" connecting anterior auditory regions with anterior ventrolateral prefrontal areas, and a "dorsal pathway" connecting auditory areas with parietal areas and with posterior ventrolateral prefrontal areas via the arcuate fasciculus and the superior longitudinal fasciculus. In humans, the dorsal circuit is especially important for phonological processing and phonological working memory, capacities that are critical for language acquisition and for complex syntax processing. In the macaque, the homolog of the dorsal circuit overlaps with an inferior parietal-premotor network for hand and gesture selection that is under voluntary control, while vocalizations are largely fixed and involuntary. The recruitment of the dorsal component for vocalization behavior in the human lineage, together with a direct cortical control of the subcortical vocalizing system, are proposed to represent a fundamental innovation in human evolution, generating an inflection point that permitted the explosion of vocal language and human communication. In this context, vocal communication and gesturing have a common history in primate communication.
    Frontiers in Evolutionary Neuroscience 01/2012; 4:2.
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    ABSTRACT: In social interactions, the perception of how risky our decisions are depends on how we anticipate other people's behaviors. We used electroencephalography to study the neurobiology of perception of social risk, in subjects playing the role of proposers in an iterated ultimatum game in pairs. Based on statistical modeling, we used the previous behaviors of both players to separate high-risk [HR] offers from low-risk [LR] offers. The HR offers present higher rejec-tion probability and higher entropy (variability of possible outcome) than the LR offers. Rejections of LR offers elicited both a stronger mediofrontal negativity and a higher prefrontal theta activity than rejections of HR offers. Moreover, prior to feedback, HR offers gen-erated a drop in alpha activity in an extended network. Interestingly, trial-by-trial variation in alpha activity in the medial prefrontal, pos-terior temporal, and inferior pariental cortex was specifically modu-lated by risk and, together with theta activity in the prefrontal and posterior cingulate cortex, predicted the proposer's subsequent be-havior. Our results provide evidence that alpha and theta oscil-lations are sensitive to social risk and underlie a fine-tuning regulation of social decisions.
    Cerebral Cortex 01/2012; · 6.83 Impact Factor
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    Schizophrenia Research 09/2011; 131(1-3):268-9. · 4.59 Impact Factor
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    ABSTRACT: Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness or inattentiveness. To search for differences in risk for ADHD and its components among Chilean native and mixed populations and to look forpossible associations with dopamine receptor D4 (DRD4) and dopamine transporter 1 (DAT1) polymorphisms. School teachers were requested to complete the Conners test, which uses DSM-IV criteria, to screen for ADHD risk among Aymara and Rapa-Nui students. Rapa-Nui children from Easter Island had the highest risk of hyperactivity/impulsiveness. Aymara children from the Arica-Parinacota Region had lower scores. Although inattentiveness scores had lower differences between groups, overall ADHD score differences among studied populations were highly significant. DRD4 and DAT1 alleles had a heterogeneous distribution. Easter islanders had more divergent frequencies, mostprobably as a result of separate migration routes utilized at different timeperiods during the colonization of America and Polynesia. The comparison of ADHD risk parameters between Rapa-Nui and Aymara children showed marked differences. Allele distri-bution of dopamine polymorphisms in Easter Island was also significantly different from northern Chile, due probably to different colonization histories. These findings suggest that higher ADHD risk scores in Easter Island children may be linked to the presence of different DRD4 alleles.
    Revista medica de Chile 05/2011; 139(5):600-5. · 0.36 Impact Factor
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    ABSTRACT: We studied brain activity during the displacement of attention in a modified visuo-spatial orienting paradigm. Using a behaviorally relevant no-shift condition as a control, we asked whether ipsi- or contralateral parietal alpha band activity is specifically related to covert shifts of attention. Cue-related event-related potentials revealed an attention directing anterior negativity (ADAN) contralateral to the shift of attention and P3 and contingent negative variation waveforms that were enhanced in both shift conditions as compared to the no-shift task. When attention was shifted away from fixation, alpha band activity over parietal regions ipsilateral to the attended hemifield was enhanced relative to the control condition, albeit with different dynamics in the upper and lower alpha subbands. Contralateral-to-attended parietal alpha band activity was indistinguishable from the no-shift task.
    Psychophysiology 03/2011; 48(3):312-22. · 3.29 Impact Factor
  • Francisco Aboitiz
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    ABSTRACT: The six-layered neocortex is both a unique and a universal character of mammals. Historically, a major concern has been to determine its phylogenetic origins by establishing which structures, if any, correspond to it in the brains of other vertebrates. Two opposing hypotheses have been debated in the last years: (i) the neocortex arises entirely from the dorsal hemisphere of ancestral reptiles, and (ii) a large portion of it originates in the lateral hemisphere, from a structure termed the dorsal ventricular ridge (DVR), which expands significantly in reptiles and especially in birds. While developmental and genetic evidence strongly favors a dorsal origin of the neocortex, there are important similarities in the sensory connectivity to the neocortex and to the DVR, and more recently, in the phenotype of late-produced elements in both structures. It is proposed that, despite originating in different embryonic domains, the proliferative expansion of both the mammalian neocortex and the sauropsidian DVR is partly based on the amplification of similar developmental programs, possibly dependent on Pax6 activity or of related cascades that promote progenitor proliferation. While Pax6 activity is already present in the amphibian pallium, I propose that at some point(s) in amniote evolution it has been upregulated yielding brain expansion in both sauropsids and mammals. However, in the latter there has been an additional dorsalizing influence contributing to the development of the neocortex and restricting the expansion of the lateral hemisphere. Finally, a significant contribution to neocortical origins by anterior signaling centers secreting FGFs is suggested, by virtue of their association to olfactory development and their cortical patterning functions. This perspective fits a dynamical view of brain homology, where instead of searching for a one-to-one correspondence between components, emphasis is placed on changes in the modulation of conserved signaling centers and their corresponding morphogen gradients across species.
    Brain research bulletin 02/2011; 84(2):125-36. · 2.18 Impact Factor
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    ABSTRACT: Working memory (WM) tasks usually elicit a P300 ERP component, whose amplitude decreases with increasing WM load. So far, this effect has not been studied in schizophrenics (SZs), a group that is considered to have an aberrant brain connectivity and impairments in WM capacity. The aim of this study was to determine the dependency of the P300 component on WM load in a sample of SZ subjects. We recorded 26 subjects (13 SZ patients and their matched controls) with an 80-channel electroencephalogram. Subjects performed an N-back task, a WM paradigm that manipulates the number of items to be stored in memory. In healthy subjects, P300 amplitude was highest in the low WM load condition, and lowest in both the attentional control condition and the high WM load condition. In contrast, SZs evidenced low P300 amplitude in all conditions. A significant between group difference in P300 amplitude was evidenced only at the low WM load condition (1 -back), being smaller in SZs. SZ subjects display a lower than normal P300 amplitude, which does not vary as a function of memory load. These results are consistent with a general impairment in WM capacity in these patients.
    BMC Psychiatry 02/2011; 11:29. · 2.23 Impact Factor

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