A multimodal interface for speech perception: the role of the left superior temporal sulcus in social cognition and autism.

Multimodal integration is crucial for human interaction, in particular for social communication, which relies on integrating information from various sensory modalities. Recently a third visual pathway specialized in social perception was proposed, which includes the right superior temporal sulcus (STS) playing a key role in processing socially relevant cues and high-level social perception. Importantly, it has also recently been proposed that the left STS contributes to audiovisual integration of speech processing. In this article, we propose that brain areas along the right STS that support multimodal integration for social perception and cognition can be considered homologs to those in the left, language-dominant hemisphere, sustaining multimodal integration of speech and semantic concepts fundamental for social communication. Emphasizing the significance of the left STS in multimodal integration and associated processes such as multimodal attention to socially relevant stimuli, we underscore its potential relevance in comprehending neurodevelopmental conditions characterized by challenges in social communication such as autism spectrum disorder (ASD). Further research into this left lateral processing stream holds the promise of enhancing our understanding of social communication in both typical development and ASD, which may lead to more effective interventions that could improve the quality of life for individuals with atypical neurodevelopment.

A healthcare approach to mental integrity.

The current human rights framework can shield people from many of the risks associated with neurotechnological applications. However, it has been argued that we need either to articulate new rights or reconceptualise existing ones in order to prevent some of these risks. In this paper, we would like to address the recent discussion about whether current reconceptualisations of the right to mental integrity identify an ethical dimension that is not covered by existing moral and/or legal rights. The main challenge of these proposals is that they make mental integrity indistinguishable from autonomy. They define mental integrity in terms of the control we can have over our mental states, which seems to be part of the authenticity condition for autonomous action. Based on a fairly comprehensive notion of mental health (ie, a notion that is not limited to the mere absence of illness), we propose an alternative view according to which mental integrity can be characterised both as a positive right to (medical and non-medical) interventions that restore and sustain mental and neural function, and promote its development and a negative right protecting people from interventions that threaten or undermine these functions or their development. We will argue that this notion is dissociated from cognitive control and therefore can be adequately distinguished from autonomy.

Mutations in trpγ, the homologue of TRPC6 autism candidate gene, causes autism-like behavioral deficits in Drosophila.

Autism Spectrum Disorder (ASD) is characterized by impaired social communication, restricted interests, and repetitive and stereotyped behaviors. The TRPC6 (transient receptor potential channel 6) represents an ASD candidate gene under an oligogenic/multifactorial model based on the initial description and cellular characterization of an individual with ASD bearing a de novo heterozygous mutation disrupting TRPC6, together with the enrichment of disruptive TRPC6 variants in ASD cases as compared to controls. Here, we perform a clinical re-evaluation of the initial non-verbal patient, and also present eight newly reported individuals ascertained for ASD and bearing predicted loss-of-function mutations in TRPC6. In order to understand the consequences of mutations in TRPC6 on nervous system function, we used the fruit fly, Drosophila melanogaster, to show that null mutations in transient receptor gamma (trpγ; the fly gene most similar to TRPC6), cause a number of behavioral defects that mirror features seen in ASD patients, including deficits in social interactions (based on courtship behavior), impaired sleep homeostasis (without affecting the circadian control of sleep), hyperactivity in both young and old flies, and defects in learning and memory. Some defects, most notably in sleep, differed in severity between males and females and became normal with age. Interestingly, hyperforin, a TRPC6 agonist and the primary active component of the St. John's wort antidepressant, attenuated many of the deficits expressed by trpγ mutant flies. In summary, our results provide further evidence that the TRPC6 gene is a risk factor for ASD. In addition, they show that the behavioral defects caused by mutations in TRPC6 can be modeled in Drosophila, thereby establishing a paradigm to examine the impact of mutations in other candidate genes.

Neural responses to sensory novelty with and without conscious access.

Detection of novel stimuli that violate statistical regularities in the sensory scene is of paramount importance for the survival of biological organisms. Event-related potentials, phasic increases in pupil size, and evoked changes in oscillatory power have been proposed as markers of sensory novelty detection. However, how conscious access to novelty modulates these different brain responses is not well understood. Here, we studied the neural responses to sensory novelty in the auditory modality with and without conscious access. We identified individual thresholds for conscious auditory discrimination and presented to our participants sequences of tones, where the last stimulus could be another standard, a subthreshold target or a suprathreshold target. Participants were instructed to report whether the last tone of each sequence was the same or different from those preceding it. Results indicate that attentional orientation to behaviorally relevant stimuli and overt decision-making mechanisms, indexed by the P3 event-related response and reaction times, best predict whether a novel stimulus will be consciously accessed. Theta power and pupil size do not predict conscious access to novelty, but instead reflect information maintenance and unexpected sensory uncertainty. These results highlight the interplay between bottom-up and top-down mechanisms and how the brain weights neural responses to novelty and uncertainty during perception and goal-directed behavior.

Coordinated prefrontal-hippocampal activity and navigation strategy-related prefrontal firing during spatial memory formation.

Learning the location of relevant places in the environment is crucial for survival. Such capacity is supported by a distributed network comprising the prefrontal cortex and hippocampus, yet it is not fully understood how these structures cooperate during spatial reference memory formation. Hence, we examined neural activity in the prefrontal-hippocampal circuit in mice during acquisition of spatial reference memory. We found that interregional oscillatory coupling increased with learning, specifically in the slow-gamma frequency (20 to 40 Hz) band during spatial navigation. In addition, mice used both spatial and nonspatial strategies to navigate and solve the task, yet prefrontal neuronal spiking and oscillatory phase coupling were selectively enhanced in the spatial navigation strategy. Lastly, a representation of the behavioral goal emerged in prefrontal spiking patterns exclusively in the spatial navigation strategy. These results suggest that reference memory formation is supported by enhanced cortical connectivity and evolving prefrontal spiking representations of behavioral goals.

Morphological evolution of the vertebrate forebrain: From mechanical to cellular processes.

Although the cerebral hemispheres are among the defining characters of vertebrates, each vertebrate class is characterized by a different anatomical organization of this structure, which has become highly problematic for comparative neurobiology. In this article, we discuss some mechanisms involved in the generation of this morphological divergence, based on simple spatial constraints for neurogenesis and mechanical forces generated by increasing neuronal numbers during development, and the different cellular strategies used by each group to overcome these limitations. We expect this view to contribute to unify the diverging vertebrate brain morphologies into general, simple mechanisms that help to establish homologies across groups.

Imitation of novel conspecific and human speech sounds in the killer whale (Orcinus orca).

Vocal imitation is a hallmark of human spoken language, which, along with other advanced cognitive skills, has fuelled the evolution of human culture. Comparative evidence has revealed that although the ability to copy sounds from conspecifics is mostly uniquely human among primates, a few distantly related taxa of birds and mammals have also independently evolved this capacity. Remarkably, field observations of killer whales have documented the existence of group-differentiated vocal dialects that are often referred to as traditions or cultures and are hypothesized to be acquired non-genetically. Here we use a do-as-I-do paradigm to study the abilities of a killer whale to imitate novel sounds uttered by conspecific (vocal imitative learning) and human models (vocal mimicry). We found that the subject made recognizable copies of all familiar and novel conspecific and human sounds tested and did so relatively quickly (most during the first 10 trials and three in the first attempt). Our results lend support to the hypothesis that the vocal variants observed in natural populations of this species can be socially learned by imitation. The capacity for vocal imitation shown in this study may scaffold the natural vocal traditions of killer whales in the wild.

[Heritability and genetic comorbidity of attention deficit disorder with hyperactivity]. / Déficit atencional con hiperactividad: trastorno multicausal de la conducta, con heredabilidad y comorbilidad genética moderadas.

This review aims to summarize information about the genetic etiology of attention deficit disorder with hyperactivity (ADHD), with particular reference to the contributions of our research group. We also discuss the genetic comorbidity estimated from genome-wide single nucleotide polymorphisms (SNP´s) between ADHD and major psychiatric disorders such as schizophrenia (E), major depressive disorder (MDD), bipolar disorder (BD) and autism spectrum disorders (ASD). A high genetic comorbidity was found between E and BD (46%), a moderate comorbidity between MDD and E, MDD and BD and MDD and ADHD (18%, 22% and 10% respectively) and a low comorbidity between E and ASD (2.5%). Furthermore, we show evidence concerning the genetic determination of psychiatric diseases, which is significantly lower when it is estimated from genome-wide SNP´s rather than using traditional quantitative genetic methodology (ADHD = E = 23%, BD = 25%, MDD = 21% and ASD = 17%). From an evolutionary perspective, we suggest that behavioral traits such as hyperactivity, inattention and impulsivity, which play a role in ADHD and perhaps also other hereditary traits which are part of major psychiatric disorders, could have had a high adaptive value during the early stages of the evolution of Homo sapiens. However, they became progressively less adaptive and definitively disadvantageous, to the extreme that they are involved in frequently diagnosed major psychiatric disorders.

Prenatal Stress Produces Persistence of Remote Memory and Disrupts Functional Connectivity in the Hippocampal-Prefrontal Cortex Axis.

Prenatal stress is a risk factor for the development of neuropsychiatric disorders, many of which are commonly characterized by an increased persistence of aversive remote memory. Here, we addressed the effect of prenatal stress on both memory consolidation and functional connectivity in the hippocampal-prefrontal cortex axis, a dynamical interplay that is critical for mnemonic processing. Pregnant mice of the C57BL6 strain were subjected to restraint stressed during the last week of pregnancy, and male offspring were behaviorally tested at adulthood for recent and remote spatial memory performance in the Barnes Maze test under an aversive context. Prenatal stress did not affect the acquisition or recall of recent memory. In contrast, it produced the persistence of remote spatial memory. Memory persistence was not associated with alterations in major network rhythms, such as hippocampal sharp-wave ripples (SWRs) or neocortical spindles. Instead, it was associated with a large decrease in the basal discharge activity of identified principal neurons in the medial prefrontal cortex (mPFC) as measured in urethane anesthetized mice. Furthermore, functional connectivity was disrupted, as the temporal coupling between neuronal discharge in the mPFC and hippocampal SWRs was decreased by prenatal stress. These results could be relevant to understand the biological basis of the persistence of aversive remote memories in stress-related disorders.

Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior.

Schizophrenia is a severe psychiatric disorder that results in a significant disability for the patient. The disorder is characterized by impairment of the adaptive orchestration of actions, a cognitive function that is mainly dependent on the prefrontal cortex. This behavioral deficit, together with cellular and neurophysiological alterations in the prefrontal cortex, as well as reduced density of GABAergic cells and aberrant oscillatory activity, all indicate structural and functional deficits of the prefrontal cortex in schizophrenia. Among the several risk factors for the development of schizophrenia, stress during the prenatal period has been identified as crucial. Thus, it is proposed that prenatal stress induces neurodevelopmental alterations in the prefrontal cortex that are expressed as cognitive impairment observed in schizophrenia. However, the precise mechanisms that link prenatal stress with the impairment of prefrontal cortex function is largely unknown. Reelin is an extracellular matrix protein involved in the development of cortical neural connectivity at embryonic stages, and in synaptic plasticity at postnatal stages. Interestingly, down-regulation of reelin expression has been associated with epigenetic changes in the reelin gene of the prefrontal cortex of schizophrenic patients. We recently showed that, similar to schizophrenic patients, prenatal stress induces down-expression of reelin associated with the methylation of its promoter in the rodent prefrontal cortex. These alterations were paralleled with altered prefrontal cortex functional connectivity and impairment in prefrontal cortex-dependent behavioral tasks. Therefore, considering molecular, cellular, physiological and behavioral evidence, we propose a unifying framework that links prenatal stress and prefrontal malfunction through epigenetic alterations of the reelin gene.

Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders.

Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.

Oscillatory brain activity correlates with risk perception and predicts social decisions.

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 rejection 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 generated a drop in alpha activity in an extended network. Interestingly, trial-by-trial variation in alpha activity in the medial prefrontal, posterior temporal, and inferior pariental cortex was specifically modulated by risk and, together with theta activity in the prefrontal and posterior cingulate cortex, predicted the proposer's subsequent behavior. Our results provide evidence that alpha and theta oscillations are sensitive to social risk and underlie a fine-tuning regulation of social decisions.

Multimodal imitative learning and synchrony in cetaceans: A model for speech and singing evolution.

Multimodal imitation of actions, gestures and vocal production is a hallmark of the evolution of human communication, as both, vocal learning and visual-gestural imitation, were crucial factors that facilitated the evolution of speech and singing. Comparative evidence has revealed that humans are an odd case in this respect, as the case for multimodal imitation is barely documented in non-human animals. While there is evidence of vocal learning in birds and in mammals like bats, elephants and marine mammals, evidence in both domains, vocal and gestural, exists for two Psittacine birds (budgerigars and grey parrots) and cetaceans only. Moreover, it draws attention to the apparent absence of vocal imitation (with just a few cases reported for vocal fold control in an orangutan and a gorilla and a prolonged development of vocal plasticity in marmosets) and even for imitation of intransitive actions (not object related) in monkeys and apes in the wild. Even after training, the evidence for productive or "true imitation" (copy of a novel behavior, i.e., not pre-existent in the observer's behavioral repertoire) in both domains is scarce. Here we review the evidence of multimodal imitation in cetaceans, one of the few living mammalian species that have been reported to display multimodal imitative learning besides humans, and their role in sociality, communication and group cultures. We propose that cetacean multimodal imitation was acquired in parallel with the evolution and development of behavioral synchrony and multimodal organization of sensorimotor information, supporting volitional motor control of their vocal system and audio-echoic-visual voices, body posture and movement integration.

Anatomy of corpus callosum in prenatally malnourished rats.

The effect of prenatal malnutrition on the anatomy of the corpus callosum was assessed in adult rats (45-52 days old). In the prenatally malnourished animals we observed a significant reduction of the corpus callosum total area, partial areas, and perimeter, as compared with normal animals. In addition, the splenium of corpus callosum (posterior fifth) showed a significant decrease of fiber diameters in the myelinated fibers without changing density. There was also a significant decrease in diameter and a significant increase in density of unmyelinated fibers. Measurements of perimeter's fractal dimensions from sagittal sections of the brain and corpus callosum did not show significant differences between malnourished and control animals. These findings indicate that cortico-cortical connections are vulnerable to the prenatal malnutrition, and suggest this may affect interhemispheric conduction velocity, particularly in visual connections (splenium).

[DRD4 dopamine receptor alleles in Chilean students of different ethnic origin and its relation with the risk for attention deficit/hyperactivity disorder]. / Variación de alelos del gen receptor de dopamina DRD4 en escolares chilenos de diferente origen étnico y su relación con riesgo de déficit atencional/hiperactividad.

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 ADHD phenotype in Chilean populations, probably as a consequence of their initial colonization history.

[Attention deficit hyperactivity disorder in Aymara children]. / Trastorno por déficit de atención e hiperactividad en niños aymara: primera aproximación clínica.

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: Starting from 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: Patients from 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.

Faces and Voices Processing in Human and Primate Brains: Rhythmic and Multimodal Mechanisms Underlying the Evolution and Development of Speech.

While influential works since the 1970s have widely assumed that imitation is an innate skill in both human and non-human primate neonates, recent empirical studies and meta-analyses have challenged this view, indicating other forms of reward-based learning as relevant factors in the development of social behavior. The visual input translation into matching motor output that underlies imitation abilities instead seems to develop along with social interactions and sensorimotor experience during infancy and childhood. Recently, a new visual stream has been identified in both human and non-human primate brains, updating the dual visual stream model. This third pathway is thought to be specialized for dynamics aspects of social perceptions such as eye-gaze, facial expression and crucially for audio-visual integration of speech. Here, we review empirical studies addressing an understudied but crucial aspect of speech and communication, namely the processing of visual orofacial cues (i.e., the perception of a speaker's lips and tongue movements) and its integration with vocal auditory cues. Along this review, we offer new insights from our understanding of speech as the product of evolution and development of a rhythmic and multimodal organization of sensorimotor brain networks, supporting volitional motor control of the upper vocal tract and audio-visual voices-faces integration.

Differences in cortical processing of facial emotions in broader autism phenotype.

Autism Spectrum Disorder (ASD) is a heterogeneous condition that affects face perception. Evidence shows that there are differences in face perception associated with the processing of low spatial frequency (LSF) and high spatial frequency (HSF) of visual stimuli between non-symptomatic relatives of individuals with autism (broader autism phenotype, BAP) and typically developing individuals. However, the neural mechanisms involved in these differences are not fully understood. Here we tested whether face-sensitive event related potentials could serve as neuronal markers of differential spatial frequency processing, and whether these potentials could differentiate non-symptomatic parents of children with autism (pASD) from parents of typically developing children (pTD). To this end, we performed electroencephalographic recordings of both groups of parents while they had to recognize emotions of face pictures composed of the same or different emotions (happiness or anger) presented in different spatial frequencies. We found no significant differences in the accuracy between groups but lower amplitude modulation in the Late Positive Potential activity in pASD. Source analysis showed a difference in the right posterior part of the superior temporal region that correlated with ASD symptomatology of the child. These results reveal differences in brain processing of recognition of facial emotion in BAP that could be a precursor of ASD.

Voluntary self-initiation of the stimuli onset improves working memory and accelerates visual and attentional processing.

The ability of an organism to voluntarily control the stimuli onset modulates perceptual and attentional functions. Since stimulus encoding is an essential component of working memory (WM), we conjectured that controlling the initiation of the perceptual process would positively modulate WM. To corroborate this proposition, we tested twenty-five healthy subjects in a modified-Sternberg WM task under three stimuli presentation conditions: an automatic presentation of the stimuli, a self-initiated presentation of the stimuli (through a button press), and a self-initiated presentation with random-delay stimuli onset. Concurrently, we recorded the subjects' electroencephalographic signals during WM encoding. We found that the self-initiated condition was associated with better WM accuracy, and earlier latencies of N1, P2 and P3 evoked potential components representing visual, attentional and mental review of the stimuli processes, respectively. Our work demonstrates that self-initiated stimuli enhance WM performance and accelerate early visual and attentional processes deployed during WM encoding. We also found that self-initiated stimuli correlate with an increased attentional state compared to the other two conditions, suggesting a role for temporal stimuli predictability. Our study remarks on the relevance of self-control of the stimuli onset in sensory, attentional and memory updating processing for WM.