Human cerebral organoids (HCOs) are three-dimensional in vitro cell cultures that mimic the developmental process and organization of the developing human brain. In just a few years this technique has produced brain models that are already being used to study diseases of the nervous system and to test treatments and drugs. Currently, HCOs consist of tens of millions of cells and have a size of a few millimeters. The greatest limitation to further development is due to their lack of (...) vascularization. However, recent research has shown that human cerebral organoids can manifest the same electrical activity and connections between brain neurons and EEG patterns as those recorded in preterm babies. All this suggests that, in the future, HCOs may manifest an ability to experience basic sensations such as pain, therefore manifesting sentience, or even rudimentary forms of consciousness. This calls for consideration of whether cerebral organoids should be given a moral status and what limitations should be introduced to regulate research. In this article I focus particularly on the study of the emergence and mechanisms of human consciousness, i.e. one of the most complex scientific problems there are, by means of experiments on HCOs. This type of experiment raises relevant ethical issues and, as I will argue, should probably not be considered morally acceptable. (shrink)

Voluntary acts are preceded by electrophysiological (RPs). With spontaneous acts involving no preplanning, the main negative RP shift begins at about200 ms. Control experiments, in which a skin stimulus was timed (S), helped evaluate each subject's error in reporting the clock times for awareness of any perceived event.

Organoids are three-dimensional biological structures grown in vitro from different kinds of stem cells that self-organise mimicking real organs with organ-specific cell types. Recently, researchers have managed to produce human organoids which have structural and functional properties very similar to those of different organs, such as the retina, the intestines, the kidneys, the pancreas, the liver and the inner ear. Organoids are considered a great resource for biomedical research, as they allow for a detailed study of the development and pathologies (...) of human cells; they also make it possible to test new molecules on human tissue. Furthermore, organoids have helped research take a step forward in the field of personalised medicine and transplants. However, some ethical issues have arisen concerning the origin of the cells that are used to produce organoids and their properties. In particular, there are new, relevant and so-far overlooked ethical questions concerning cerebral organoids. Scientists have created so-called mini-brains as developed as a few-months-old fetus, albeit smaller and with many structural and functional differences. However, cerebral organoids exhibit neural connections and electrical activity, raising the question whether they are or will one day be somewhat sentient. In principle, this can be measured with some techniques that are already available, which are used for brain-injured non-communicating patients. If brain organoids were to show a glimpse of sensibility, an ethical discussion on their use in clinical research and practice would be necessary. (shrink)

Neurobiologist William Calvin explores the human brain, positing that the neurons in the brain operate in an accelerated version of biological evolution, evolving ideas through random variations and selections, and supports his hypothesis with numerous ca.

Patients with schizophrenia have a higher risk of cardiovascular diseases and higher mortality from them than does the general population; however, the underlying mechanism remains unclear. Impaired cerebral autoregulation is associated with cerebrovascular diseases and their mortality. Increased or decreased cerebral blood flow in different brain regions has been reported in patients with schizophrenia, which implies impaired cerebral autoregulation. This study investigated the cerebral autoregulation in 21 patients with schizophrenia and 23 age- and sex-matched healthy controls. (...) None of the participants had a history of cardiovascular diseases, hypertension, or diabetes. All participants underwent 10-min blood pressure and cerebral blood flow recording through finger plethysmography and Doppler ultrasonography, respectively. Cerebral autoregulation was assessed by analyzing two autoregulation indices: the mean blood pressure and cerebral blood flow correlation coefficient (Mx), and the phase shift between the waveforms of blood pressure and cerebral blood flow determined using transfer function analysis. Compared with the controls, the patients had a significantly higher Mx (0.257 vs. 0.399, p = 0.036) and lower phase shift (44.3° vs. 38.7° in the 0.07–0.20 Hz frequency band, p = 0.019), which indicated impaired maintenance of constant cerebral blood flow and a delayed cerebrovascular autoregulatory response. Impaired cerebral autoregulation may be caused by schizophrenia and may not be an artifact of coexisting medical conditions. The mechanism underlying impaired cerebral autoregulation in schizophrenia and its probable role in the development of cerebrovascular diseases require further investigation. (shrink)

In his interesting commentary, Joshua Shepherd raises two points—one related to epistemology, the other to ethics—about our article on human cerebral organoids.1 2 From the epistemological standpoint, he calls into question the need for a theory of consciousness. A theory of consciousness, for him, is not necessary because of the lack of consensus about the very nature of consciousness. Shepherd suggests that ‘given widespread disagreement, applying a theory of consciousness may not be helpful when attempting to diagnose the presence (...) of consciousness in cerebral organoids’. In Shepherd’s view, it would be better to transfer ‘concepts already under development in work on the presence and structure of consciousness in difficult marginal cases involving traumatic brain injury’.2 We could not agree more on this last point; detecting a minimal capacity for consciousness in the brain of comatose patients is a very similar challenge to inferring the presence of consciousness in cerebral organoids. Every day, as a by-product of saving many lives, intensive care medicine artificially produces thousands of brains that may remain isolated, split or fragmented; in the worst case, cortical islands, or an archipelago of islands, may survive while being disconnected from the outside world. Can these islands host some form of consciousness? That is, does it feel like anything to be a large piece of human cortex? Addressing this difficult question requires the development of general, objective brain-based indices of consciousness that are independent of sensory processing, executive functions and motor outputs.3 Consider, for example, a patient showing reflexive spontaneous behaviour, no response to command and no ability to communicate. In her brain, afferent pathways are damaged, thereby impairing the recruitment of cortical areas in response to sensory stimulation; basal ganglia, as well as other frontal structures supporting executive functions, are impaired. However, resting metabolism and significant electroencephalography …. (shrink)

In "The Cerebral Code," he has solidly embedded his ideas in experimental neurophysiology and neuropharmacology, deriving from his decades in the laboratory.

Arithmetical cognition is the result of enculturation. On a personal level of analysis, enculturation is a process of structured cultural learning that leads to the acquisition of evolutionarily recent, socio-culturally shaped arithmetical practices. On a sub-personal level, enculturation is realized by learning driven plasticity and learning driven bodily adaptability, which leads to the emergence of new neural circuitry and bodily action patterns. While learning driven plasticity in the case of arithmetical practices is not consistent with modularist theories of mental architecture, (...) it can be enriched by the theory of neural reuse. According to neural reuse, cerebral regions are reused to contribute to multiple neural circuits in functionally constrained ways throughout ontogeny. By hypothesis, learning driven plasticity is complemented by learning driven bodily adaptability, which suggests that there is an interesting functional relationship between finger gnosis, finger counting, and arithmetical practices. The emerging perspective on enculturated arithmetical cognition will be complemented by considerations on associated developmental and acquired disorders, namely developmental dyscalculia and acquired acalculia. The upshot is that we need to take the cerebral, extra-cerebral bodily, and socio-cultural dimensions of enculturation into account in order to arrive at a better understanding of the phylogenetic and ontogenetic conditions of arithmetical cognition. (shrink)

A half century ago electronic fetal monitoring was rushed into clinical use with the promise that the secrets of fetal heart rate decelerations had been discovered and that the newly discovered knowledge would prevent cerebral palsy with just in time cesarean sections preventing babies from experiencing asphyxia, which was thought to be the primary cause of cerebral palsy. In the years since electronic fetal monitoring’s debut, it has been discovered that asphyxia is a rare cause of cerebral (...) palsy. At the same time electronic fetal monitoring use increased to 85% of all labors, the C-section rate increased to 33% without an attributable decrease in the rate of cerebral palsy. What went wrong with electronic fetal monitoring? The answer lies in a new analysis of the physiologic theories concerning fetal heart rate decelerations, demonstrating that the earlier electronic fetal monitoring theories were wrong. This revelation is only the latest evidence that electronic fetal monitoring use today... (shrink)

We have studied a number of long-term meditators in previous studies. The purpose of this study was to determine if there are differences in baseline brain function of experienced meditators compared to non-meditators. All subjects were recruited as part of an ongoing study of different meditation practices. We evaluated 12 advanced meditators and 14 non-meditators with cerebral blood flow SPECT imaging at rest. Images were analyzed with both region of interest and statistical parametric mapping. The CBF of long-term meditators (...) was significantly higher compared to non-meditators in the prefrontal cortex, parietal cortex, thalamus, putamen, caudate, and midbrain. There was also a significant difference in the thalamic laterality with long-term meditators having greater asymmetry. The observed changes associated with long-term meditation appear in structures that underlie the attention network and also those that relate to emotion and autonomic function. (shrink)

Objetivo. Verificar si el procesamiento semántico de estímulos visuales complejos, como la repetición, la identidad, el orden y la doble incongruencia, es recursivo o computable. Sujetos y métodos. Veintisiete universitarios respondieron a un paradigma adaptado N400 con cinco condiciones, cada una con 80 tareas, mientras se registraba su actividad cerebral con un gorro de 64 electrodos. Resultados. Dos ventanas temporales de 400 a 550 ms y de 550 a 800 ms se analizaron mediante un contraste ANOVA del factor condición (...) por regiones de interés. Además, se calculó la solución inversa de las ventanas mediante tomografía electromagnética de baja resolución para identificar las fuentes corticales subyacentes a los potenciales eléctricos. Se corroboran diferencias significativas (p< 0, 05) en los potenciales N400 y P600 en áreas frontales y centroparietales asociadas a los operadores lógicos estudiados. Conclusión. Se confirma que el procesamiento cerebral de imágenes complejas (congruentes/incongruentes) es modulado por la repetición, la identidad y el orden, pero no por la negación. Por consiguiente, se puede decir que el procesamiento semántico de imágenes complejas es semicomputable. (shrink)

The article “Consciousness in a Bioreactor? Science and Ethics of Potentially Conscious Human Cerebral Organoids” (Zillo and Lavazza 2023) presents a thoughtful discussion on the potential ethical...

To begin with -- Genealogy of the cerebral subject -- Disciplines of the neuro -- Cerebralizing distress -- Brains on screen and paper -- Up for grabs.

In the late 19th century, physiologists such as David Ferrier, Eduard Hitzig, and Hermann Munk argued that cerebral brain functions are localized in discrete structures. By the early 20th century, this became the dominant position. However, another prominent physiologist, Friedrich Goltz, rejected theories of cerebral localization and argued against these physiologists until his death in 1902. I argue in this paper that previous historical accounts have failed to comprehend why Goltz rejected cerebral localization. I show that Goltz (...) adhered to a falsificationist methodology, and I reconstruct how he designed his experiments and weighted different kinds of evidence. I then draw on the exploratory experimentation literature from recent philosophy of science to trace one root of the debate to differences in how the German localizers designed their experiments and reasoned about evidence. While Goltz designed his experiments to test hypotheses about the functions of predetermined cerebral structures, the localizers explored new functions and structures in the process of constructing new theories. I argue that the localizers relied on untested background conjectures to justify their inferences about functional organization. These background conjectures collapsed a distinction between phenomena they produced direct evidence for (localized symptoms) and what they reached conclusions about (localized functions). (shrink)

The risk of creating cerebral organoids/assembloids conscious enough to suffer is a recurrent concern in organoid research ethics. On one hand, we should, apparently, avoid discovering how to distinguish between organoids that it would be permissible (non-conscious) and impermissible (conscious) to use in research, since if successful we would create organoids that suffer. On the other, if we do not, the risk persists that research might inadvertently continue to cause organoids to suffer. Moreover, since modeling some brain disorders may (...) require inducing stress in organoids, it is unclear how to eliminate the risk, if we want to develop effective therapies. We are committed to harm avoidance but hamstrung by a presumption that we should avoid research that might tell us clearly when suffering occurs. How can we negotiate this challenge and maximize the therapeutic benefits of cerebral organoid research? The author interrogates the challenge, suggesting a tentative way forward. (shrink)

James’s positivism is different from Comte’s, Clifford’s, and the logical positivists’. Notably, itpresupposes a difference between natural–scientific inquiries and the metaphysical inquiry he callsradical empiricism. Equally importantly, the positivism of James’s great book, The Principles ofPsychology, studies the cerebral conditions of the will. This cerebralism is necessary background forunderstanding James’s voluntarism, the will–to–believe doctrine that came later. James’s positivismgoes hand–in–hand with his value pluralism; they are responsible for different domains of inquiry,natural-scientific and ethical, respectively. It is a mistake to (...) impose a “master moral syllogism” ontothe former, implying that all facts are constituted by the will as guided by a utilitarian moral principle.Cerebral shaping of the will occurs not only through the “front door” of experience, especially in theformation of habit, but also through the “back stairs” of mutation and natural selection, which createsbrains suited to different pursuits. The brain is no tabula rasa. (shrink)

James’s positivism is different from Comte’s, Clifford’s, and the logical positivists’. Notably, it presupposes a difference between natural–scientific inquiries and the metaphysical inquiry he calls radical empiricism. Equally importantly, the positivism of James’s great book, The Principles of Psychology, studies the cerebral conditions of the will. This cerebralism is necessary background for understanding James’s voluntarism, the will–to–believe doctrine that came later. James’s positivism goes hand–in–hand with his value pluralism; they are responsible for different domains of inquiry, natural-scientific and ethical, (...) respectively. It is a mistake to impose a “master moral syllogism” onto the former, implying that all facts are constituted by the will as guided by a utilitarian moral principle. Cerebral shaping of the will occurs not only through the “front door” of experience, especially in the formation of habit, but also through the “back stairs” of mutation and natural selection, which creates brains suited to different pursuits. The brain is no tabula rasa. (shrink)

The claim of consistent hemispheric specialisations across classes of chordates is undermined by the absence of population-based directional asymmetry of paw/hand use in rodents and primates. No homologue of the cerebral torque from right frontal to left occipital has been established in a nonhuman species. The null hypothesis that the torque is the sapiens-specific neural basis of language has not been disproved.

Functional imaging techniques, such as positron emission tomography and functional magnetic resonance imaging, present a unique opportunity to examine, in humans, the cerebral representation of space in vivo. Space is ubiquitous and not a unitary phenomenon, and the brain uses visual, vestibular and proprioceptive inputs to produce multiple representations of space subserving spatial cognition, ranging from gaze control to remembering multiple complex large-scale environments. Functional imaging studies have shown the importance of the parietal cortex in perceptual, motor, attention and (...) working memory aspects of body-centred human spatial cognition. Functional imaging has also revealed pathways in humans homologous to those found in monkeys for the separate processing of spatial location and object identity. There are further suggestions of similar differentiation in working memory. The importance of the medial temporal region in the recall of spatial location has been confirmed also and novel virtual reality paradigms are now providing insights into the cerebral representation of spatially-extended large-scale environments. We still have much to learn about the cerebral representation of space in the human brain and functional brain imaging, in concert with patient studies and animal models, will allow us to continue investigating. (shrink)

K L Kahlbaum published in 1874 the first recorded description of catatonia. Akinetic catatonia is now defined as a neuropsychiatric syndrome principally characterised by akinesia, mutism, stupor, and catalepsy. 1 Even if some advances have been made in the recognition of catatonia, in particular by the development of different rating scales, 1 the pathophysiology of this syndrome is not clearly established. A right handed 14 year old girl presented with akinetic catatonia during an episode of depression in the context of (...) a bipolar type I disorder. Her catatonic status was characterised by akinesia with brief episodic spontaneous stereotyped movements, mutism, no spontaneous oral intake, catalepsy, waxy flexibility, and stupor with brief occasional eye contacts. This corresponded to a total score of 19 on the Northoff Catatonia Scale.1 Electroencephalogram performed one day after onset of symptoms showed diffuse theta activity with sporadic diffuse delta activity. Cerebral magnetic resonance imaging was normal. Brain positron emission tomographies (PET) were obtained on a CTI-Siemens HR+ tomograph. A first PET (PET1) using (18F(- fluorodeoxyglucose (FDG) was performed on day 2 in a drug free state. Thereafter, intramuscular injection of 2 mg of lorazepam induced rapid clinical remission of the akinetic phase. Oral lorazepam was then given (3.75 mg/day) during five days. On day 8, a second PET with FDG was performed while the patient was treated by olanzapine (15 mg/day) and presented hyperactivity, logorrhoea, and disinhibition characterised by uncontrolled social interactions and physical contacts. Neuropsychological testing performed some days after remission revealed no apraxia or language disturbances but dysfunction of executive tasks manifested in the revised Wisconsin card sorting, the Tower of London, Stroop, and Trailmaking tests. Voxel based analyses comparing patient’s cerebral glucose metabolism with that of 29 right handed healthy controls (16 women and 13 men, mean age 32) were performed using Statistical Parametric Mapping (SPM99) (Wellcome Department of Cognitive Neurology, London, UK).. (shrink)

Facial fat grafting techniques often offer impressive surgical results. However, fatal complications, such as irreversible cerebral ischemia, blindness, and hemiplegia are associated with them. We have presented a case report of a patient who presented with a massive cerebral infarction, a serious complication of facial autologous fat injection. The patient was a 28-year-old female who experienced motor dysfunction of the left extremities, which was accompanied with loss of consciousness immediately following fat grafting for facial augmentation. Imaging studies suggested (...) that the patient had a large cerebral infarction on the right frontal, temporal, and parietal lobes due to complete occlusion of her right external carotid artery. Emergency decompressive craniectomy was completed in addition to multiple follow-up medical treatments. The patient recovered after 4 months with reduced motor function in her left upper extremity. This report further summarizes published cases of massive cerebral ischemia after facial injection of autologous fat, as well as lists high-risk facial areas and critical warnings. (shrink)

BackgroundSonographic mesenteric pattern in celiac disease (CD) suggests a hyperdynamic circulation. Despite the well-known CD-related neurological involvement, no study has systematically explored the cerebral hemodynamics to transcranial Doppler sonography.Materials and methodsMontreal Cognitive Assessment (MoCA) and 17-item Hamilton Depression Rating Scale (HDRS) were assessed in 15 newly diagnosed subjects with CD and 15 age-, sex-, and education-matched healthy controls. Cerebral blood flow (CBF) velocities and indices of resistivity (RI) and pulsatility (PI) from the middle cerebral artery (MCA), bilaterally, (...) and the basilar artery (BA) were recorded. We also assessed cerebral vasomotor reactivity (CVR) through the breath-holding test (BHT).ResultsWorse scores of MoCA and HDRS were found in patients compared to controls. Although patients showed higher values of CBF velocity from MCA bilaterally compared to controls, both at rest and after BHT, no comparison reached a statistical significance, whereas after BHT both RI and PI from BA were significantly higher in patients. A significant negative correlation between both indices from BA and MoCA score were also noted.ConclusionThese treatment-naïve CD patients may show some subtle CVR changes in posterior circulation, thus possibly expanding the spectrum of pathomechanisms underlying neuroceliac disease and in particular gluten ataxia. Subclinical identification of cerebrovascular pathology in CD may help adequate prevention and early management of neurological involvement. (shrink)

The notion of cerebral death is examined in relation to those of cardiopulmonary and whole-brain death. It is argued that rather than being a new concept of death, it is merely a new criterion that leaves the old concept — death as loss of personhood — intact. The argument begins on a theoretical level with the distinction between criteria and concepts, places both into context with the notion of a conceptual framework in its relation to empirical reality, and then (...) particularizes the result to criteria for the determination of death. It is argued that the suggestion of the cerebral criterion is nothing more than an attempt to realign the concept of death with the empirical data with which it has come out of step due to new developments in the empirical field. The paper considers tutioristic objections to the criterion, and shows its compatibility with dualistic religio-metaphysical positions by considering an actual example. It also addresses briefly the ethical impact of the criterion on medical practice. (shrink)

Nielsen Busch and Mjaaland argue that controlled donation after circulatory death (DCD), and normothermic regional perfusion (NRP) do not violate the dead donor rule (DDR) (Nielsen Busch and Mjaala...

This article investigated the paradox between church response to apartheid and resulting action at the local level in the South African churches of European origin from the perspective of the Presbyterian Church of South(ern) Africa (PCSA). It indicated that this discrepancy arose between the reflections (cerebral faith) at the highest levels of church councils, which operated in an intermittent manner and at a distance, compared with the responses (praxis as faith in action) of local church members who lived at (...) the coalface of the struggle and sought to witness in a society dominated by racism, where the tension between faith and politics was most evident. The primary focus was on two inter-racial congregations, one of the PCSA, the other a united congregation in which the PCSA participated. This study used primary and secondary sources. The theoretical framework of the article was Thomas Groome’s approach of shared praxis.Contribution: This article contributed to the history of the apartheid era in ecclesiastical contexts. It demonstrated the anomalies that arose within different constituencies within churches of European origin by investigating the situation in one particular denomination. This was a discussion of the relationship of faith and politics in the private and public domains, which takes account of developments within a shared praxis approach. (shrink)

Using positron emission tomography (PET) and regional cerebral blood flow (rCBF) measurements, we investigated the cerebral correlates of consciousness in a sequence learning task through a novel application of the Process Dissociation Procedure, a behavioral paradigm that makes it possible to separately assess conscious and unconscious contributions to performance. Results show that the metabolic response in the anterior cingulate / mesial prefrontal cortex (ACC / MPFC) is exclusively and specifically correlated with the explicit component of performance during recollection (...) of a learned sequence. This suggests a significant role for the ACC / MPFC in the explicit processing of sequential material.  2003 Elsevier Science B.V. All rights reserved. (shrink)

We describe a possible link between coordinated lateralised group behaviour serving species survival in lower vertebrates and a striking lateralisation phenomenon found in human social behaviour: the universal preference for cradling a young infant on the left side. Our exploration offers a different perspective on the role of cerebral asymmetry for the survival of both the individual and the species.