This article investigates the emergence of the concept of stress in the 1930s and outlines its changing disciplinary and conceptual frames up until 1960. Originally stress was a physiological concept applied to the hormonal regulation of the body under stressful conditions. Correlated closely with chemical research into corticosteroids for more than a decade, the stress concept finally became a topic in cognitive psychology. One reason for this shift of the concept to another discipline was the fact that the hormones (...) previously linked to the stress concept were successfully transferred from laboratory to medical practice and adopted by disciplines such as rheumatology and dermatology. Thus the stress concept was dissociated from its hormonal context and became a handy formula that allowed postindustrial society to conceive of stress as a matter of individual concern. From a physiological phenomenon stress turned into an object of psychological discourse and individual coping strategies. (shrink)

A large number of previous reports described an effect of the pituitary hormone prolactin (PRL) on steroid hormone production by the adrenal cortex. However, those studies remained anecdotal and were never converted into a conceptual and mechanistic framework, let alone being translated into clinical care. In the light of our recently published landmark study where we described PRL signalling as a pivotal regulator of the sexually dimorphic adrenal phenotype in mouse and of adrenal androgen production in (...) humans, we present here the overarching hypothesis that PRL signalling increases the activity of Steroidogenic Factor‐1 (SF‐1/NR5A1), a transcription factor that has an essential role in adrenal gland development and function, to regulate adrenal cortex growth and hormonal production in physiological and pathological conditions. PRL can then be considered as a bona fide adrenocorticotropic hormone synergizing with ACTH in the endocrine control of adrenal cortex function. (shrink)

Albert (von) Szent-Györgyi started his studies on biological oxidation processes - which also resulted in the discovery of vitamin C, for which he received the Nobel Price in 1937 - in the Laboratory of Physiology of the University in Groningen in 1922-1926. These studies were later continued in Cambridge (UK) and Szeged (Hungary). When he had already received the invitation as well as the financial means to come and work in Cambridge, he still did experiments in Groningen to find out (...) whether the adrenal extract, isolated by him and later found to be a major source of vitamin C, contained the hormone essential for the survival of cats whose adrenals were removed. He was rather upset by the negative results of this experiment, judging by the recollections of a former student of his. This history constitutes an interesting example of the difference between serendipitous discovery and planned invention. (shrink)

Human development has become particularly complex during the evolution. In this complexity, adolescence is an extremely important developmental stage. Adolescence is characterized by biological and social changes that create the prerequisites to psychopathological problems, including both substance and non-substance addictive behaviors. Central to the dynamics of the biological changes during adolescence are the synergy between sexual and neurophysiological development, which activates the motivational/emotional systems of Dominance/Submission. The latter are characterized by the interaction between the sexual hormones, the dopaminergic system (...) and the stress axis (HPA). The maturation of these motivational/emotional systems requires the integration with the phylogenetically more recent Attachment/CARE Systems, which primarily have governed the subject’s relationships until puberty. The integration of these systems is particularly complex in the human species, due to the evolution of the process of competition related to sexual selection: from a simple fight between two individuals (of the same genus and species) to a struggle for the acquisition of a position in rank and the competition between groups. The latter is an important evolutionary acquisition and believed to be the variable that has most contributed to enhancing the capacity for cooperation in the human species. The interaction between competition and cooperation, and between competition and attachment, characterizes the entire human relational and emotional structure and the unending work of integration to which the BrainMind is involved. The beginning of the integration of the aforementioned motivational/emotional systems is currently identified in the prepubertal period, during the juvenile stage, with the development of the Adrenarche—the so-called Adrenal Puberty. This latter stage is characterized by a low rate of release of androgens, the hormones released by the adrenal cortex, which activate the same behaviors as those observed in the PLAY system. The Adrenarche and the PLAY system are biological and functional prerequisites of adolescence, a period devoted to learning the difficult task of integrating the phylogenetically ancient Dominance/Submission Systems with the newer Attachment/CARE Systems. These systems accompany very different adaptive goals which can easily give rise to mutual conflict and can in turn make the balance of the BrainMind precarious and vulnerable to mental suffering. (shrink)

Various explanations have been proposed to account for complex differentiation and development in humans, despite the human genome containing only two to three times the number of genes in invertebrates. Ignored are the actions of adrenal and sex steroids—androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins—which act through receptors that arose from an ancestral nuclear receptor in a protochordate. This ligand‐based mechanism is unique to vertebrates and was integrated into the already robust network of transcription factors in invertebrates. Adrenal and (...) sex steroids influence almost all aspects of vertebrate differentiation and development. I propose that evolution of this ligand‐based mechanism in a primitive vertebrate was an important contribution to vertebrate complexity. Sequencing of genomes from a cephalochordate, such as amphioxus, and from hagfish and lamprey will establish early events in the evolution of steroid hormone signaling, and also allow genetic studies to elucidate how vertebrate complexity depends on steroid hormones. BioEssays 25:396–400, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Hormonal changes across the menstrual cycle have been shown to influence reward-related motivation and impulsive behaviors. Here, to compare neural mechanisms of cognitive impulse control during the mid-luteal phase (LP) versus during the late follicular phase (FP), we employed functional magnetic resonance imaging (fMRI) with an event-related monetary delay discounting (EMDD) behavioral task (study 1) and then employed resting state (RS)-fMRI (study 2). The imaging data were analyzed and related to behavior-associated neural activation. In study 1, women in the late (...) FP showed a preference for sooner rewards while exhibiting enhanced activity in the dorsal striatum (DS), whereas women in the mid-LP showed a preference for delayed, higher-value rewards with enhanced activity in the dorsolateral prefrontal cortex (dlPFC). Discount rate (transformed k) in the EMDD task correlated with functional connectivity (FC) of the DS-dlPFC circuitry, consistent with the possibility that DS-dlPFC circuitry may regulate impulsivity. In study 2, the right dlPFC was significantly more active in mid-LP than in late FP, and this effect was sensitive to estradiol (E2) and relative E2 levels during mid-LP. The magnitude of DS-dlPFC FC correlated negatively with psychometric impulsivity scores during the late FP. These results replicated findings from study 1 and further indicated that relative E2 levels may play an important role in increasing cognitive control during the mid-LP, which provides new insight into the treatment of conditions characterized by hyper-impulsivity, such as obsessive-compulsive disorder, Parkinson disease, and attention deficit hyperactivity disorder. In conclusion, our results suggest that cyclical gonadal hormones affect cognitive control on impulsive behavior periodically, possibility via DS-dlPFC circuitry. (shrink)

We propose a theoretical model of the cerebral cortex which is based on its cellular components and integrates its different levels of organization: (1) cells have general adaptive and memorization properties; (2) cortical columns are repetitive interneuronal circuits which determine an adaptive processing specific to the cerebral cortex; (3) cortical maps effect selective combinations which are very efficient to learn basic behaviourial adaptations such as invariant recognition of forms, visually-guided hand movements, or execution of structured motor programs; (4) (...) the network between cortical areas has a global architecture which integrates successive learning experiences into coherent functions such as the human language. (shrink)

This target article considers the relation of fluid cognitive functioning to general intelligence. A neurobiological model differentiating working memory/executive function cognitive processes of the prefrontal cortex from aspects of psychometrically defined general intelligence is presented. Work examining the rise in mean intelligence-test performance between normative cohorts, the neuropsychology and neuroscience of cognitive function in typically and atypically developing human populations, and stress, brain development, and corticolimbic connectivity in human and nonhuman animal models is reviewed and found to provide evidence (...) of mechanisms through which early experience affects the development of an aspect of cognition closely related to, but distinct from, general intelligence. Particular emphasis is placed on the role of emotion in fluid cognition and on research indicating fluid cognitive deficits associated with early hippocampal pathology and with dysregulation of the hypothalamic-pituitary-adrenal axis stress-response system. Findings are seen to be consistent with the idea of an independent fluid cognitive construct and to assist with the interpretation of findings from the study of early compensatory education for children facing psychosocial adversity and from behavior genetic research on intelligence. It is concluded that ongoing development of neurobiologically grounded measures of fluid cognitive skills appropriate for young children will play a key role in understanding early mental development and the adaptive success to which it is related, particularly for young children facing social and economic disadvantage. Specifically, in the evaluation of the efficacy of compensatory education efforts such as Head Start and the readiness for school of children from diverse backgrounds, it is important to distinguish fluid cognition from psychometrically defined general intelligence. (Published Online April 5 2006) Key Words: cognition; cognition-emotion reciprocity; developmental disorders; emotion; fluid cognition; Flynn effect; general intelligence; limbic system; neuroscience; phenylketonuria; prefrontal cortex; psychometrics; schizophrenia. (shrink)

The hypothesis that foreseeable developments in interventions directed to forestall and to treat the disabilities of aging might result in the extension of the human lifespan may be further supported by the “evolutionary theory of aging.” Besides caloric restriction, several hormone supply or replacement strategies are considered to contrast the functional decline associated with aging. Hormone treatments may include growth hormone (GH), insulin‐like growth factor I (IGF‐I) signaling, dehydroepiandrosterone (DHEA), melatonin, testosterone, progesterone, and estrogen. In the 1990s, DHEA was exalted (...) as a possible candidate for the “fountain of youth.” Several experiments on animals have shown that DHEA is a multifunctional adrenal steroid with immune function enhancement, anti‐diabetic, anti‐cancer, and anti‐aging effects. The ethical questions concerning the extension of the lifespan belong to two distinct areas: the area of individual morality and the area of social morality. (shrink)

On the basis of neuroiinaging studies, Posner & Raichle summarily report that the prefrontal cortex is involved in executive functioning and attention. In contrast to that superficial view, we briefly describe a testable model of the kinds of representations that are stored in prefrontal cortex, which, when activated, are expressed via plans, actions, thematic knowledge, and schemas.

A comprehensive and stimulating study which presents the views of 71 leading theorists on the underlying mechanisms and functions of the primary visual cortex.

The neural and endocrine bases of the generation of thirst are reviewed. Based on this review, a hierarchical system of neural structures that regulate water conservation and acquisition is proposed. The system includes primary sensory-receptive areas; secondary sensory structures (circumventricular organs), which detect levels of hormones, including angiotensin II and vasopressin, which are involved in generating thirst; preoptic and hypothalamic structures; and an area within the ventrolateral quadrant of the periaqueductal gray matter. Hodological and other data are used to (...) determine the hierarchical organization of the system. Based on studies of the effects of lesions to various structures within the hierarchy of the system, it is proposed that the awareness of thirst in rodents is either entirely or predominantly due to neuronal activities in a subsection of the ventrolateral periaqueductal gray matter. It is also hypothesized that the awareness of thirst in primates is due to neuronal activities in both the ventrolateral periaqueductal gray and in a region within the medial prefrontal and anterior cingulate cortex. (shrink)

This chapter considers the functions of the orbitofrontal cortex. It shows that the orbitofrontal cortex is involved in decoding and representing some primary reinforcers such as taste and touch; in learning and reversing associations of visual and other stimuli to these primary reinforcers; in controlling and correcting reward-related and punishment-related behavior; and, thus, in emotion.

The cerebral cortex controls our most distinguishing higher cognitive functions. Human‐specific gene expression differences are abundant in the cerebral cortex, yet we have only begun to understand how these variations impact brain function. This review discusses the current evidence linking non‐coding regulatory DNA changes, including enhancers, with neocortical evolution. Functional interrogation using animal models reveals converging roles for our genome in key aspects of cortical development including progenitor cell cycle and neuronal signaling. New technologies, including iPS cells and (...) organoids, offer potential alternatives to modeling evolutionary modifications in a relevant species context. Several diseases rooted in the cerebral cortex uniquely manifest in humans compared to other primates, thus highlighting the importance of understanding human brain differences. Future studies of regulatory loci, including those implicated in disease, will collectively help elucidate key cellular and genetic mechanisms underlying our distinguishing cognitive traits. (shrink)

Training can influence behavioral performance and lead to brain reorganization. In particular, training in one modality, for example, auditory, can improve performance in another modality, for example, visual. Previous research suggests that one of the mechanisms behind this phenomenon could be the cross-modal recruitment of the sensory areas, for example, the auditory cortex. Studying expert musicians offers a chance to explore this process. Rhythm is an aspect of music that can be presented in various modalities. We designed an fMRI (...) experiment in which professional pianists and non-musicians discriminated between two sequences of rhythms presented auditorily or visually. Behavioral results showed that musicians performed in both visual and auditory rhythmic tasks better than non-musicians. We found no significant between-group differences in fMRI activations within the auditory cortex. However, we observed that musicians had increased activation in the right Inferior Parietal Lobe when compared to non-musicians. We conclude that the musicians’ superior visual rhythm discrimination is not related to cross-modal recruitment of the auditory cortex; instead, it could be related to activation in higher-level, multimodal areas in the cortex. (shrink)

Recent studies suggest that lucid dreaming might be associated with increased brain activity over frontal regions during rapid eye movement sleep. By applying transcranial direct current stimulation , we aimed to manipulate the activation of the dorsolateral prefrontal cortex during REM sleep to increase dream lucidity. Nineteen participants spent three consecutive nights in a sleep laboratory. On the second and third nights they randomly received either 1 mA tDCS for 10 min or sham stimulation during each REM period starting (...) with the second one. According to the participants’ self-ratings, tDCS over the DLPFC during REM sleep increased lucidity in dreams. The effects, however, were not strong and found only in frequent lucid dreamers. While this indicates some preliminary support for the involvement of the DLPFC in lucid dreaming, further research, controlling for indirect effects of stimulation and including other brain regions, is needed. (shrink)

In this critical, feminist account of the management of intersex conditions under 2006's controversial “Disorders of Sex Development” (DSD) treatment model, I argue that like the “Optimal Gender of Rearing” (OGR) treatment model it replaced, DSD aims at securing a cisgendered future for the intersex patient, referring to a normalized trajectory of development across the lifespan in which multiple sexed, gendered, and sexual characteristics remain in “coherent” alignment. I argue this by critically analyzing two ways that intersex management has changed (...) between OGR and DSD: 1) regarding sex‐assignment recommendations for three patient populations and, 2) with the prenatal treatment of pregnant individuals at risk of conceiving a fetus with congenital adrenal hyperplasia with the steroid hormone dexamethasone. I conclude that like OGR before it, DSD also unjustifiably presumes that typical genitalia are necessary for cisgendered development. However, unlike OGR, it appeals to the empirically inadequate, theoretically suspect, and biologically determinist model of gender development known as brain‐organization theory. Given this, I conclude that the treatment of intersex people under DSD continues to be driven by problematically heterosexist and transphobic assumptions regarding the value and normalcy of cisgendered life, while practically and discursively constituting it as such. (shrink)

The parahippocampal cortex and hippocampus are brain structures known to be involved in memory. However, the unique contribution of the parahippocampal cortex remains unclear. The current study investigates memory for object identity and memory of the configuration of objects in patients with small thermo-coagulation lesions to the hippocampus or the parahippocampal cortex. Results showed that in contrast to control participants and patients with damage to the hippocampus leaving the parahippocampal cortex intact, patients with lesions that included (...) the right parahippocampal cortex (RPH) were severely impaired on a task that required learning the spatial configuration of objects on a computer screen; these patients, however, were not impaired at learning the identity of objects. Conversely, we found that patients with lesions to the right hippocampus (RH) or left hippocampus (LH), sparing the parahippocampal cortex, performed just as well as the control participants. Furthermore, they were not impaired on the object identity task. In the functional Magnetic Resonance Imaging (fMRI) experiment, healthy young adults performed the same tasks. Consistent with the findings of the lesion study, the fMRI results showed significant activity in the RPH in the memory for the spatial configuration condition, but not memory for object identity. Furthermore, the pattern of fMRI activity measured in the baseline control conditions decreased specifically in the parahippocampal cortex as a result of the experimental task, providing evidence for task specific repetition suppression. In summary, while our previous studies demonstrated that the hippocampus is critical to the construction of a cognitive map, both the lesion and fMRI studies have shown an involvement of the RPH for learning spatial configurations of objects but not object identity, and that this takes place independent of the hippocampus. (shrink)

IntroductionPrevious transcranial magnetic stimulation studies have revealed that the activity of the primary motor cortex ipsilateral to an active hand plays an important role in motor control. The aim of this study was to investigate whether the ipsi-M1 excitability would be influenced by goal-directed movement and laterality during unilateral finger movements.MethodTen healthy right-handed subjects performed four finger tapping tasks with the index finger: simple tapping task, Real-word task, Pseudoword task, and Visually guided tapping task. In the Tap task, the (...) subject performed self-paced simple tapping on a touch screen. In the real-word task, the subject tapped letters displayed on the screen one by one to create a Real-word. Because the action had a specific purpose, this task was considered to be goal-directed as compared to the Tap task. In the Pseudoword task, the subject tapped the letters to create a pseudoword in the same manner as in the Real-word task; however, the word was less meaningful. In the VT task, the subject was required to touch a series of illuminated buttons. This task was considered to be less goal-directed than the Pseudoword task. The tasks were performed with the right and left hand, and a rest condition was added as control. Single- and paired-pulse TMS were applied to the ipsi-M1 to measure corticospinal excitability and short- and long-interval intracortical inhibition in the resting first dorsal interosseous muscle.ResultsWe found the smaller SICI in the ipsi-M1 during the VT task compared with the resting condition. Further, both SICI and LICI were smaller in the right than in the left M1, regardless of the task conditions.DiscussionWe found that SICI in the ipsi-M1 is smaller during visual illumination-guided finger movement than during the resting condition. Our finding provides basic data for designing a rehabilitation program that modulates the M1 ipsilateral to the moving limb, for example, for post-stroke patients with severe hemiparesis. (shrink)

The Fist-Edge-Palm task, a manual hand task, has been used to detect frontal dysfunctions in clinical situations: its performance failures are observed in various prefrontal cortex -related disorders, including schizophrenia. However, previous imaging studies reported that the performance of the FEP task activated motor-related areas, but not the PFC. Here, we aimed to investigate the relationships between the performance of the FEP task and PFC functions. Hemodynamic activity in the PFC, including the dorsolateral PFC and frontal pole, was recorded. (...) Healthy young subjects performed the FEP task as well as a palm tapping task three times. The subjects also completed a Wisconsin Card Sorting Test and Schizotypal Personality Scale questionnaire. We found that hemodynamic activity in the PFC increased in the first trial of the FEP task but decreased considerably in the second and third trials compared to the PT task. The number of performance errors in the FEP task also decreased in the second and third trials. Error reduction in the FEP task between the first and second trials was negatively correlated with schizotypal trait and the number of perseveration errors in the WCST. Furthermore, changes in the PFC hemodynamic activity between the first and second trials were positively correlated with error reduction in the FEP task between the first and second trials, and negatively correlated with the number of perseveration errors in the WCST. These results suggest that learning in the FEP task requires PFC activation, which is negatively associated with perseveration errors in the WCST. The results further suggest that the FEP task, in conjunction with near-infrared spectroscopy, may be useful as a diagnostic method for various disorders with PFC dysfunction. (shrink)