I much appreciate the honour of being invited to deliver the first Manson lecture, which, its founder has laid down, is to be devoted to the consideration of some subject of common interest to philosophy and medicine. I cannot think of anything which better fulfils that condition than the neurological approach to the problem of perception. The neurologist holds the bridge between body and mind. Every day he meets with examples of disordered perception and he learns from observing the effects (...) of lesions produced by disease, or by the physiologist's experiments, something of how the neural basis of perception is organized. It is possible to study perception as though this was largely irrelevant. How far that view is right will be for you to judge when I have finished. (shrink)

A hypothesis on the physiological conditions of consciousness is presented. It is assumed that the occurrence of states of consciousness causally depends on the formation of complex representational structures. Cortical neural networks that exhibit a high representational activity develop higher-order, self-referential representations as a result of self-organizing processes. The occurrence of such states is identical with the appearance of states of consciousness. The underlying physiological processes can be identified. It is assumed that neural assemblies instantiate mental representations; hence consciousness depends (...) on the rate at which large active assemblies are generated. The formation of assemblies involves the activation of the N-methyl-D-aspartate receptor channel complex which controls different forms of synaptic plasticity including rapid changes of the connection strengths. The various causes of unconsciousness (e.g., anaesthetics or brain stem lesions) have a common denominator: they directly or indirectly inhibit the formation of assemblies. (shrink)

The goal of this article is to review some aspects of brain anatomy and neurophysiology that are important for consciousness, and which hopefully may be of benefit to philosophers investigating the conscious mind. Taking as an initial point of reference the distinction between “the hard problem” and “the weak problems” of consciousness, we shall concentrate on questions pertaining to the second of these. A putative “consciousness system” in the brain will be presented, paying special attention to diffuse projection (...) systems. The “center of gravity” will be brain connectivity, since consciousness must, critically, be dependent on coherent activity and timing. “Detectors” of synchronicity and coincidence, like NMDA receptors, also necessarily play a role here. To be conscious, we do not need an entire brain. While even large hemispherectomies need not unequivocally affect consciousness, far smaller brain-stem lesions may be devastating in this regard. Even so, the recent discovery by Matthew F. Glasser et al. of 180 separate areas in the human brain cortex is intriguing from a teleological perspective, as it is quite unthinkable that any of them could be “redundant. (shrink)

We present evidence disputing the hypothesis that memories are processed or consolidated in REM sleep. A review of REM deprivation (REMD) studies in animals shows these reports to be about equally divided in showing that REMD does, or does not, disrupt learning/memory. The studies supporting a relationship between REM sleep and memory have been strongly criticized for the confounding effects of very stressful REM deprivation techniques. The three major classes of antidepressant drugs, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), and (...) selective serotonin reuptake inhibitors (SSRIs), profoundly suppress REM sleep. The MAOIs virtually abolish REM sleep, and the TCAs and SSRIs have been shown to produce immediate (40–85%) and sustained (30–50%) reductions in REM sleep. Despite marked suppression of REM sleep, these classes of antidepressants on the whole do not disrupt learning/memory. There have been a few reports of patients who have survived bilateral lesions of the pons with few lingering complications. Although these lesions essentially abolished REM sleep, the patients reportedly led normal lives. Recent functional imaging studies in humans have revealed patterns of brain activity in REM sleep that are consistent with dream processes but not with memory consolidation. We propose that the primary function of REM sleep is to provide periodic endogenous stimulation to the brain which serves to maintain requisite levels of central nervous system (CNS) activity throughout sleep. REM is the mechanism used by the brain to promote recovery from sleep. We believe that the cumulative evidence indicates that REM sleep serves no role in the processing or consolidation of memory. Key Words: antidepressant drugs; brain stem lesions; dreams; functional imaging; memory consolidation; REM deprivation; REM sleep; theta rhythm. (shrink)

The goal of this article is to review some aspects of brain anatomy and neurophysiology that are important for consciousness, and which hopefully may be of benefit to philosophers investigating the conscious mind. Taking as an initial point of reference the distinction between “the hard problem” and “the weak problems” of consciousness, we shall concentrate on questions pertaining to the second of these. A putative “consciousness system” in the brain will be presented, paying special attention to diffuse projection (...) systems. The “center of gravity” will be brain connectivity, since consciousness must, critically, be dependent on coherent activity and timing. “Detectors” of synchronicity and coincidence, like NMDA receptors, also necessarily play a role here. To be conscious, we do not need an entire brain. While even large hemispherectomies need not unequivocally affect consciousness, far smaller brain-stem lesions may be devastating in this regard. Even so, the recent discovery by Matthew F. Glasser et al. of 180 separate areas in the human brain cortex is intriguing from a teleological perspective, as it is quite unthinkable that any of them could be “redundant. (shrink)

The paradigmatic assumption that REM sleep is the physiological equivalent of dreaming is in need of fundamental revision. A mounting body of evidence suggests that dreaming and REM sleep are dissociable states, and that dreaming is controlled by forebrain mechanisms. Recent neuropsychological, radiological, and pharmacological findings suggest that the cholinergic brain stem mechanisms that control the REM state can only generate the psychological phenomena of dreaming through the mediation of a second, probably dopaminergic, forebrain mechanism. The latter mechanism (...) (and thus dreaming itself) can also be activated by a variety of nonREM triggers. Dreaming can be manipulated by dopamine agonists and antagonists with no concomitant change in REM frequency, duration, and density. Dreaming can also be induced by focal forebrain stimulation and by complex partial (forebrain) seizures during nonREM sleep, when the involvement of brainstem REM mechanisms is precluded. Likewise, dreaming is obliterated by focal lesions along a specific (probably dopaminergic) forebrain pathway, and these lesions do not have any appreciable effects on REM frequency, duration, and density. These findings suggest that the forebrain mechanism in question is the final common path to dreaming and that the brainstem oscillator that controls the REM state is just one of the many arousal triggers that can activate this forebrain mechanism. The “REM-on” mechanism (like its various NREM equivalents) therefore stands outside the dream process itself, which is mediated by an independent, forebrain “dream-on” mechanism. Key Words: acetylcholine; brainstem; dopamine; dreaming; forebrain; NREM; REM; sleep. (shrink)

Background: There is limited research on brain lesions in children with cerebral visual impairment of heterogeneous etiologies and according to associated subtyping and vision dysfunctions. This study was part of a larger project establishing data-driven subtypes of childhood CVI according to visual dysfunctions. Currently there is no consensus in relation to assessment, diagnosis and classification of CVI and more information about brain lesions may be of potential diagnostic value.Aim: This study aimed to investigate overall patterns of (...) brain lesions and associations with level of visual dysfunction and to compare the patterns between the classification subgroups in children with CVI.Methods: School-aged children with CVI received ophthalmological and neuro-psychological/developmental assessments to establish CVI-related subtyping. Other pediatric information was collected from medical records. MRI scans were coded according to a semi-quantitative template including brain regions and summed for total scores. Non-parametric analyses were conducted.Results: 28 children had clinical brain MRI scans available [44% of total sample, Group A n = 16, Group B n = 12]. Total brain scores ranged between 0 and 18 and were widespread across regions. 71 per cent had post-geniculate visual pathway damage. The median total brain and hemisphere scores of Group B were higher than subgroup A but differences did not reach statistical significance. No statistically significant associations were found between brain scores and vision variables.Conclusion: This study found a spread of lesions across all regions on the brain scans in children with congenital CVI. The majority had damage in the postgeniculate visual pathways and visual cortex region suggesting this is an area of interest and potentially informative for diagnosis. However the subtyping classification did not show differences in number or region of lesions though the trend was higher toward Group B. This study confirms the complex diffuse and variable nature of brain lesions in children with congenital CVI, many of whom have other neurological impairments. (shrink)

In this paper, the problem of correct ascriptions of consciousness to patients in neurological intensive care medicine is explored as a special case of the general philosophical other minds problem. It is argued that although clinical ascriptions of consciousness and coma are mostly based on behavioral evidence, a behaviorist epistemology of other minds is not likely to succeed. To illustrate this, the so-called total locked-in syndrome, in which preserved consciousness is combined with a total loss of motor abilities due to (...) a lower ventral brain stem lesion, is presented as a touchstone for behaviorism. It is argued that this example of consciousness without behavioral expression does not disprove behaviorism specifically, but rather illustrates the need for a non-verificationist theory of other minds. It is further argued that a folk version of such a theory already underlies our factual ascriptions of consciousness in clinical contexts. Finally, a non-behaviorist theory of other minds for patients with total locked-in syndrome is outlined. (shrink)

With no statutory definition of death, the accepted medical definition relies on brain stem death criteria as a definitive measure of diagnosing death. However, the use of brain stem death criteria in this way is precarious and causes widespread confusion amongst both medical and lay communities. Through critical analysis, this paper considers the insufficiencies of brain stem death. It concludes that brain stem death cannot be successfully equated with either biological death or (...) the loss of integrated bodily function. The overemphasis of the brain-stem and its consequences leaves the criteria open to significant philosophical critique. Further, in some circumstances, the use of brain stem death criteria causes substantial emotional conflict for families and relatives. Accordingly, a more holistic and comprehensive definition of death is required. (shrink)

As philosophers of mind we seem to hold in common no very clear view about the relevance that work in psychology or the neurosciences may or may not have to our own favourite questions—even if we call the subject ‘philosophical psychology’. For example, in the literature we find articles on pain some of which do, some of which don't, rely more or less heavily on, for example, the work of Melzack and Wall; the puzzle cases used so extensively in discussions (...) of personal identity are drawn sometimes from the pleasant exercise of scientific fantasy, at times from surprising reports of scientific fact; and there are those who deny, as well as those who affirm, the importance of the discovery of rapid-eye-movement sleep to the philosophical treatment of dreaming. A general account of the relation between scientific, and philosophical, psychology is long overdue and of the first importance. Here I shall limit myself to just one area where the two seem to connect, discussing one type of neuropsychological research and its relevance to questions in the philosophy of mind and the philosophy of psychology. (shrink)

Adult stem cell populations must coordinate their own maintenance with the generation of differentiated cell types to sustain organ physiology, in a spatially controlled manner and over long periods. Quantitative analyses of clonal dynamics have revealed that, in epithelia, homeostasis is achieved at the population rather than at the single stem cell level, suggesting that feedback mechanisms coordinate stem cell maintenance and progeny generation. In the central nervous system, however, little is known of the possible community processes (...) underlying neural stem cell maintenance. Recent work, in part based on intravital imaging made possible in the adult zebrafish, conclusively highlights that homeostasis in neural stem cell pools may rely on population asymmetry and long‐term spatiotemporal coordination of neural stem cell states and fates. These results suggest that neural stem cell assemblies in the vertebrate brain behave as self‐organized systems, such that the stem cells themselves generate their own intrinsic niche. (shrink)

Falls are a leading cause of serious injury and restricted participation among persons with stroke (PwS). Reactive balance control is essential for fall prevention, however, only a few studies have explored the effects of lesion characteristics (location and extent) on balance control in PwS. We aimed to assess the impact of lesion characteristics on reactive and anticipatory balance capacity, gait, and hemiparetic lower limb function, in PwS. Forty-six subacute PwS were exposed to forward, backward, right and left unannounced horizontal surface (...) translations in 6 increasing intensities, while standing. Fall threshold (i.e., perturbation intensity that results in a fall into the harness system) was measured. In addition, the Berg Balance Scale (BBS), 6 Minute Walk Test (6MWT) and Lower Extremity Fugl-Meyer (LEFM) were measured. Lesion effects were analyzed separately for left- and right-hemisphere damaged (LHD, RHD) patients, using voxel-based lesion-symptom mapping (VLSM). Our results show that voxel clusters where damage exerted a significant impact on balance, gait and lower-limb function were found in the corticospinal tract, in its passage in the corona radiata and in the posterior limb of the internal capsule. Additional significant impact was found to lesions affecting the putamen and the external capsule. Balance, gait, and hemiparetic lower limb function showed much overlap of the corresponding ‘significant’ voxel clusters. Test scores of RHD and LHD patients were affected largely by damage to homologous regions, with the LHD group showing a wider distribution of ‘significant’ voxels. The study corroborates and extends previous findings by demonstrating that balance control, gait, and lower limb function are all affected mainly by damage to essentially the same brain structures, namely - the corticospinal tract and adjacent structures in the capsular-putaminal region. (shrink)

Deep Brain Stimulation is currently being investigated as an experimental treatment for patients suffering from treatment-refractory AN, with an increasing number of case reports and small-scale trials published. Although still at an exploratory and experimental stage, initial results have been promising. Despite the risks associated with an invasive neurosurgical procedure and the long-term implantation of a foreign body, DBS has a number of advantageous features for patients with SE-AN. Stimulation can be fine-tuned to the specific needs of the particular (...) patient, is relatively reversible, and the technique also allows for the crucial issue of investigating and comparing the effects of different neural targets. However, at a time when DBS is emerging as a promising investigational treatment modality for AN, lesioning procedures in psychiatry are having a renaissance. Of concern it has been argued that the two kinds of interventions should instead be understood as rivaling, yet “mutually enriching paradigms” despite the fact that lesioning the brain is irreversible and there is no evidence base for an effective target in AN. We argue that lesioning procedures in AN are unethical at this stage of knowledge and seriously problematic for this patient group, for whom self-control is particularly central to wellbeing. They pose a greater risk of major harms that cannot justify ethical equipoise, despite the apparent superiority in reduced short term surgical harms and lower cost. (shrink)

BackgroundFrontal brain dysfunction is a major challenge in neurorehabilitation. Neurofeedback (NF), as an EEG-based brain training method, is currently applied in a wide spectrum of mental health conditions, including traumatic brain injury.ObjectiveThis study aimed to explore the capacity of Infra-Low Frequency Neurofeedback (ILF-NF) to promote the recovery of brain function in patients with frontal brain injury.Materials and methodsTwenty patients hospitalized at a neurorehabilitation clinic in Switzerland with recently acquired, frontal and optionally other brain (...) class='Hi'>lesions were randomized to either receive NF or sham-NF. Cognitive improvement was assessed using the Frontal Assessment Battery (FAB) and the Test of Attentional Performance (TAP) tasks regarding intrinsic alertness, phasic alertness and impulse control.ResultsWith respect to cognitive improvements, there was no significant difference between the two groups after 20 sessions of either NF or sham-NF. However, in a subgroup of patients with predominantly frontal brain lesions, the improvements measured by the FAB and intrinsic alertness were significantly higher in the NF-group.ConclusionThis is the first double-blind controlled study using NF in recovery from brain injury, and thus also the first such study of ILF NF. Although the result of the subgroup has limited significance because of the small number of participants, it accentuates the trend seen in the whole group regarding the FAB and intrinsic alertness (p = 0.068, p = 0.079, respectively). We therefore conclude that NF could be a promising candidate promoting the recoveryfrom frontal brain lesions. Further studies with larger numbers of patients and less lesion heterogeneity are needed to verify the usefulness of NF in the neurorehabilitation of patients with frontal brain injury (NCT02957695 ClinicalTrials.gov). (shrink)

According to higher-order theories of consciousness, a mental state is conscious only when represented by another mental state. Higher-order theories must predict there to be some brain areas (or networks of areas) such that, because they produce (the right kind of) higher-order states, the disabling of them brings about deficits in consciousness. It is commonly thought that the prefrontal cortex produces these kinds of higher-order states. In this paper, I first argue that this is likely correct, meaning that, if (...) some higher-order theory is true, prefrontal lesions should produce dramatic deficits in visual consciousness. I then survey prefrontal lesion data, looking for evidence of such deficits. I argue that no such deficits are to be found, and that this presents a compelling case against higher-order theories. (shrink)

Recent developments in 3D cultures exploiting the self‐organization ability of pluripotent stem cells have enabled the generation of powerful in vitro systems termed brain organoids. These 3D tissues recapitulate many aspects of human brain development and disorders occurring in vivo. When combined with improved differentiation methods, these in vitro systems allow the generation of more complex “assembloids,” which are able to reveal cell diversities, microcircuits, and cell–cell interactions within their 3D organization. Here, the ways in which human (...) brain organoids have contributed to demystifying the complexities of brain development and modeling of developmental disorders is reviewed and discussed. Furthermore, challenging questions that are yet to be addressed by emerging brain organoid research are discussed. (shrink)

Stem cells isolated from adult mammalian tissues may provide new approaches for the autologous treatment of disease and tissue repair. Although the potential of adult stem cells has received much attention, it has also recently been brought into question. This article reviews the recent work describing the ability of non‐hematopoietic stem cells derived from adult bone marrow to form neural derivatives and their potential for brain repair. Earlier transplantation experiments imply that grafted adult stem cells (...) can differentiate into neural derivatives. Recent reports suggest, however, that such findings may be misleading and grafted cells acquiring different identities may merely be explained by their fusion with host cells and not the result of radical changes to their program of cellular differentiation. Nonetheless, in vitro studies have shown that neural development by bone‐marrow‐derived stem cells also appears possible. Understanding the molecular mechanisms that specify the neural lineage will lead to the development of tools for the targeted production of neural cell types in vitro that may ultimately provide a source of material to treat specific neurological deficits. BioEssays 24:708–713, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

This paper discusses the evidence for the role of CREB in neural stem/progenitor cell (NSPC) function and oncogenesis and how these functions may be important for the development and growth of brain tumours. The cyclic‐AMP response element binding (CREB) protein has many roles in neurons, ranging from neuronal survival to higher order brain functions such as memory and drug addiction behaviours. Recent studies have revealed that CREB also has a role in NSPC survival, differentiation and proliferation. Recent (...) work has shown that over‐expression of CREB in transgenic animals can impart oncogenic properties on cells in various tissues and that aberrant CREB expression is associated with tumours in patients. It is the central position of CREB, downstream of key developmental and growth signalling pathways, which give CREB the ability to influence a spectrum of cell activities, such as cell survival, growth and differentiation in both normal and cancer cells. (shrink)

The impact of stroke on motor functioning is analyzed at different levels. ‘Impairment’ denotes the loss of basic characteristics of voluntary movement. ‘Activity limitation’ denotes the loss of normal capacity for independent execution of daily activities. Recovery from impairment is accomplished by ‘restitution’ and recovery from activity limitation is accomplished by the combined effect of ‘restitution’ and ‘compensation.’ We aimed to unravel the long-term effects of variation in lesion topography on motor impairment of the hemiparetic lower limb (HLL), and gait (...) capacity as a measure of related activity limitation. Gait was assessed by the 3 m walk test (3MWT) in 67 first-event chronic stroke patients, at their homes. Enduring impairment of the HLL was assessed by the Fugl–Meyer Lower Extremity (FMA-LE) test. The impact of variation in lesion topography on HLL impairment and on walking was analyzed separately for left and right hemispheric damage (LHD, RHD) by voxel-based lesion-symptom mapping (VLSM). In the LHD group, HLL impairment tended to be affected by damage to the posterior limb of the internal capsule (PLIC). Walking capacity tended to be affected by a larger array of structures: PLIC and corona radiata, external capsule and caudate nucleus. In the RHD group, both HLL impairment and walking capacity were sensitive to damage in a much larger number of brain voxels. HLL impairment was affected by damage to the corona radiata, superior longitudinal fasciculus and insula. Walking was affected by damage to the same areas, plus the internal and external capsules, putamen, thalamus and parts of the perisylvian cortex. In both groups, voxel clusters have been found where damage affected FMA-LE and also 3MWT, along with voxels where damage affected only one of the measures (mainly 3MWT). In stroke, enduring ‘activity limitation’ is affected by damage to a much larger array of brain structures and voxels within specific structures, compared to enduring ‘impairment.’ Differences between the effects of left and right hemisphere damage are likely to reflect variation in motor-network organization and post-stroke re-organization related to hemispheric dominance. Further studies with larger sample size are required for the validation of these results. (shrink)

Higher-order thought (HOT) theory says that a mental state is conscious when and only when represented by a conceptual, belief-like mental state. Plausibly, HOT theory predicts the impairment of HOT-producing brain areas to cause significant deficits in consciousness. This means that HOT theory can be refuted by identifying those brain areas that are candidates for producing HOTs, then showing that damage to these areas never produces the expected deficits of consciousness. Building this refutation is a work-in-progress, with several (...) key components of it already existing in the literature (e.g., Boly et al. in J Neurosci 37(40):9603–9613, 2017; Kozuch in Mind Lang, 37(5):790–813, 2022). This article pulls together and supplements these earlier components so as to provide a comprehensive lesion-based argument against HOT theory, one which offers extra data and arguments in support of it, and which also addresses common objections. (shrink)

Progress in the neurosciences is profoundly changing our conception of ourselves. Contrary to time-honored intuition, the mind turns out to be a complex of brain functions. And contrary to the wishful thinking of some philosophers, there is no stemming the revolutionary impact that brain research will have on our understanding of how the mind works. Brain-Wise is the sequel to Patricia Smith Churchland's Neurophilosophy, the book that launched a subfield. In a clear, conversational manner, this book examines (...) old questions about the nature of the mind within the new framework of the brain sciences. What, it asks, is the neurobiological basis of consciousness, the self, and free choice? How does the brain learn about the external world and about its own introspective world? What can neurophilosophy tell us about the basis and significance of religious and moral experiences? Drawing on results from research at the neuronal, neurochemical, system, and whole-brain levels, the book gives an up-to-date perspective on the state of neurophilosophy—what we know, what we do not know, and where things may go from here. (shrink)

Balancing self‐renewal and differentiation of stem cells is an important issue in stem cell and cancer biology. Recently, the Drosophila neuroblast (NB), neural stem cell has emerged as an excellent model for stem cell self‐renewal and tumorigenesis. It is of great interest to understand how defects in the asymmetric division of neural stem cells lead to tumor formation. Here, we review recent advances in asymmetric division and the self‐renewal control of Drosophila NBs. We summarize molecular (...) mechanisms of asymmetric cell division and discuss how the defects in asymmetric division lead to tumor formation. Gain‐of‐function or loss‐of‐function of various proteins in the asymmetric machinery can drive NB overgrowth and tumor formation. These proteins control either the asymmetric protein localization or mitotic spindle orientation of NBs. We also discuss other mechanisms of brain tumor suppression that are beyond the control of asymmetric division. (shrink)

For nearly two centuries, developmental biologists have known that body organs are derived from distinct germ layers. They have argued that adult stem cells formed in one of these, mesoderm for example, cannot give rise to cells that originate in another. We disagree. An exception to this “rule” has been described in crayfish recently. In this species, hemocytes appear to replenish neurogenic cells. This may happen in humans as well. In women who were given male bone marrow‐derived cells, Y (...) chromosome positive cheek cells and brain neurons were detected. While repopulation of these tissues by bone marrow derived cells may not occur normally, and while it does not appear to be terribly efficient, the phenomenon should be studied in more detail. Perhaps cells in the marrow could be used to regenerate tissues elsewhere. (shrink)

Are there persuasive approaches to embryonic stem cell (ESC) research that appeal, not just to those fellow-citizens in one’s own ideological camp, nor just to those undecided citizens in the middle, but to those citizens on the other side of the issue? I believe that there are such arguments and in this short paper I try to develop one of them. In particular, I argue that certain beliefs shared by some proponents and some opponents of ESC research—beliefs about the (...) personal identity and moral status of those who are victims of terrible brain diseases—are beliefs that should lead us to adopt a qualified endorsement of ESC research. (shrink)