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)

For more than two thousand years, almost all doctors in the West used bloodletting to treat a great variety of diseases and conditions. In an attempt to find out why they acted thus, Dr Brain has translated the three works on bloodletting by the second-century physician Galen, which provide by far the most comprehensive account of the practice in antiquity. This is the first published version of these works in a modern language. After a brief summary of Galen's (...) medical system, the author goes on to consider the origins of Galen's ideas and methods, with particular reference to the Hippocratic writings, and the question why Galen, in common with most of the ancient physicians, believed in the efficacy of the comedy. The effects of bloodletting are considered in terms of modem physiology and medicine, and the possibility is explored that it may indeed have been beneficial in the conditions prevailing in Galen's time. (shrink)

This article critically interrogates contemporary forms of addiction medicine that are portrayed by policy-makers as providing a ‘rational’ or politically neutral approach to dealing with drug use and related social problems. In particular, it examines the historical origins of the biological facts that are today understood to provide a foundation for contemporary understandings of addiction as a ‘disease of the brain’. Drawing upon classic and contemporary work on ‘styles of thought’, it documents how, in the period between the mid-1960s (...) and the mid-1970s, such facts emerged in relation to new neurobiological styles of explaining and managing social problems associated with drug abuse, and an alliance between a relatively marginal group of researchers and American policy-makers who were launching the ‘War on Drugs’. Beyond illustrating the political and material conditions necessary for the rise of addiction neuroscience, the article highlights the productivity of neurobiological thought styles, by focusing on the new biological objects, treatments and hopes that have emerged within the field of addiction studies over the last several decades. (shrink)

Major Depressive Disorder (MDD) is a serious condition with a large disease burden. It is often claimed that MDD is a “brain disease.” What would it mean for MDD to be a brain disease? I argue that the best interpretation of this claim is as offering a substantive empirical hypothesis about the causes of the syndrome of depression. This syndrome-causal conception of disease, combined with the idea that MDD is a disease of the brain, commits the (...) class='Hi'>brain disease conception of MDD to the claim that brain dysfunction causes the symptoms of MDD. I argue that this consequence of the brain disease conception of MDD is false. It incorrectly rules out genuine instances of content-sensitive causation between adverse conditions in the world and the characteristic symptoms of MDD. Empirical evidence shows that the major causes of depression are genuinely psychological causes of the symptoms of MDD. This rules out, in many cases, the “brute” causation required by the brain disease conception. The existence of cases of MDD with non-brute causes supports the reinstatement of the old nosological distinction between endogenous and exogenous depression. (shrink)

The author comments on the article “The neurobiology of addition: Implications for voluntary control of behavior,‘ by S. E. Hyman. The author agrees with Hyman that debate persists whether addiction is a brain disease or a moral condition. The author suggests that even if we understand the neurobiology of addiction, it will make sense to seek accountability from the addict and to modify his behavior. He also suggests that no facts about neurobiology will change these moral requirements. Accession Number: (...) 24077917; Authors: Cochrane, Thomas I. 1; Email Address: [email protected]; Affiliations: 1: Harvard Medical School; Subject: EDITORIALS; Subject: ADDICTIONS; Subject: NEUROBIOLOGY; Subject: BEHAVIOR; Subject: HYMAN, S. E.; Number of Pages: 2p. (shrink)

The claim that addiction is a brain disease is almost universally accepted among scientists who work on addiction. The claim’s attraction rests on two grounds: the fact that addiction seems to be characterized by dysfunction in specific neural pathways and the fact that the claim seems to the compassionate response to people who are suffering. I argue that neural dysfunction is not sufficient for disease: something is a brain disease only when neural dysfunction is sufficient for impairment. I (...) claim that the neural dysfunction that is characteristic of addiction is not sufficient for impairment, because people who suffer from that dysfunction are impaired, sufficiently to count as diseased, only given certain features of their context. Hence addiction is not a brain disease (though it is often a disease, and it may always involve brain dysfunction). I argue that accepting that addiction is not a brain disease does not entail a moralizing attitude toward people who suffer as a result of addiction; if anything, it allows for a more compassionate, and more effective, response to addiction. (shrink)

Free will has been the object of debate in the context of addiction given that addiction could compromise an individual’s ability to choose freely between alternative courses of action. Proponents of the brain-disease model of addiction have argued that a neuroscience perspective on addiction reduces the attribution of free will because it relocates the cause of the disorder to the brain rather than to the person, thereby diminishing the blame attributed to the person with an addiction. Others have (...) worried that such displacement of free will attribution would make the person with a drug addiction less responsible. Using the paradigmatic literature on the seductive allure of neuroscience explanations, we tested whether neuroscience information diminishes attributions of free will in the context of addiction and whether respondent characteristics influence these attributions and modulate the effect of neuroscience information. We performed a large-scale, web-based experiment with 2,378 German participants to explore how attributions of free will in the context of addiction to either alcohol or cocaine are affected by: (1) a text with a neurobiological explanation of addiction, (2) a neuroimage showing effects of addiction on the brain, and (3) a combination of a text and a neuroimage, in comparison to a control group that received no information. Belief in free will was measured using the FAD-Plus scale and was, subsequent to factor analysis, separated into two factors: responsibility and volition. The investigated respondent characteristics included gender, age, education, self-reported knowledge of neuroscience, substance-use disorder (SUD), and having a friend with SUD. We found that attributions of volition (in the cocaine-subsample) were reduced in the text and neuroimage-treatment compared to the control group. However, respondent characteristics such as education and self-reported knowledge of neuroscience were associated with lower attributions of responsibility for both substances, and education was associated with lower attribution of volition for the alcohol sub-sample. Interaction analyses showed that knowledge of neuroscience was found to generally decrease attribution of responsibility. Further research on attribution of free will should consider the effects of context and respondent characteristics, which appeared surprisingly larger than those induced by experimental treatments. (shrink)

This article uses Marc Lewis’ work as a springboard to discuss the socio-political context of the brain disease model of addiction. The claim that promotion of the BDMA is the only way the general public can be persuaded to withhold blame and punishment from addicts is critically examined. After a discussion of public understandings of the disease concept of addiction, it is pointed out that it is possible to develop a scientific account of addiction which is neither a disease (...) nor a moral model but which the public could understand. Evidence is reviewed to suggest that public acceptance of the disease concept is largely lip-service and that the claim the BDMA removes stigma among the public and professionals is unsupported by evidence. Further, there is good evidence that biogenetic explanations of mental/behavioural disorders in general have been counterproductive in the attempt to ally stigma. A model of addiction as a disorder of choice may attract special problems in public-facing communications and risks being misunderstood. However, ways of presenting this model to the public are suggested that may avoid such risks. Lastly, the claim that the BDMA is the only way of ensuring access to treatment and of maintaining research funding for addiction is disputed and a way in which these benefits can be retained under a disorder-of-choice model proposed. The article concludes by enthusiastically endorsing Lewis’ call for a third stage in the governing image of addiction. (shrink)

Where does normal brain or psychological function end, and pathology begin? The line can be hard to discern, making disease sometimes a tricky word. In addiction, normal ‘wanting’ processes become distorted and excessive, according to the incentive-sensitization theory. Excessive ‘wanting’ results from drug-induced neural sensitization changes in underlying brain mesolimbic systems of incentive. ‘Brain disease’ was never used by the theory, but neural sensitization changes are arguably extreme enough and problematic enough to be called pathological. This implies (...) that ‘brain disease’ can be a legitimate description of addiction, though caveats are needed to acknowledge roles for choice and active agency by the addict. Finally, arguments over ‘brain disease’ should be put behind us. Our real challenge is to understand addiction and devise better ways to help. Arguments over descriptive words only distract from that challenge. (shrink)

Addiction is increasingly described as a “chronic and relapsing brain disease”. The potential impact of the brain disease model on the treatment of addiction or addicted individuals’ treatment behaviour remains uncertain. We conducted a qualitative study to examine: (i) the extent to which leading Australian addiction neuroscientists and clinicians accept the brain disease view of addiction; and (ii) their views on the likely impacts of this view on addicted individuals’ beliefs and behaviour. Thirty-one Australian addiction neuroscientists and (...) clinicians (10 females and 21 males; 16 with clinical experience and 15 with no clinical experience) took part in 1 h semi-structured interviews. Most addiction neuroscientists and clinicians did not uncritically support the use of brain disease model of addiction. Most were cautious about the potential for adverse impacts on individuals’ recovery and motivation to enter treatment. While some recognised the possibility that the brain disease model of addiction may provide a rationale for addicted persons to seek treatment and motivate behaviour change, Australian addiction neuroscientist and clinicians do not assume that messages about “diseased brains” will always lead to increased treatment-seeking and reduced drug use. Research is needed on how neuroscience research could be used in ways that optimise positive outcomes for addicted persons. (shrink)

. The brain evolved not to think but to act, and ideology is an act of social affiliation which can be compared to kin affiliation, both satisfyingly emotional and expressing a perception about the nature of the real world central to the nature of being human. Males may affiliate to macrosocial ideologies more enthusiastically than females because of their relative lack of certainty of kin relationships. Exogamy was the necessary solution to kin‐related strife in prehistory. Perhaps what the world (...) needs is not only a moral equivalent to war but an ideological equivalent to exogamy to resolve social differences on a much larger scale. (shrink)

Despite recent increasing support for the brain disease model of alcohol and drug addiction, the extent to which the model may clinically impact addiction treatment and client behaviour remains unclear. This qualitative study explored the views of community-based clinicians in Australia and examined: whether Australian community-based clinicians support the BDM of addiction; their attitudes on the impact the model may have on clinical treatment; and their views on how framing addiction as a brain disease may impact addicted clients’ (...) behaviour. Six Australian community-based clinicians participated in semi-structured in-depth interviews that were analysed using thematic analysis. Whilst the BDM was not fully supported by this purposive sample of Australian community-based clinicians, there was acceptance that addiction neuroscience formed a key part of a wider addiction framework. Participants believed the BDM ignored key social, psychological and environmental factors important for successful treatment. The BDM was seen as potentially irrelevant for certain client types, however the model was believed to integrate with particular therapies. Participants believed that for clients viewing their addiction in terms of a brain disease, there were potential positive and negative impacts on client behaviour. Implications for addiction treatment practice and public health policy are discussed. (shrink)

A modest opposition to the brain disease concept of addiction has been mounting for at least the last decade. Despite the good intentions behind the brain disease rhetoric – to secure more biomedical funding for addiction, to combat “stigma,” and to soften criminal approaches – the very concept of addiction as a brain disease is deeply conceptually confused. We question whether Lewis goes far enough in his challenge, robust as it is, of the brain disease concept. (...) For one thing, the notion that addiction is a disease is challenging to refute or confirm because the disease concept itself is poorly defined in medical and psychological nosology. More important, quibbling over what kind of disease addiction is unlikely to be productive. The rational response to adjudicating whether addiction is a brain disease is not to engage in potentially fruitless debates over the question of disease classification but rather to view addiction as an enormously complex set of behaviors that operate on several dimensions, ranging from molecular function and structure and brain physiology to psychology, the psychosocial environment, and social and cultural relations. (shrink)

People struggling with addiction are neither powerless over their addiction, nor are they fully in control. Lewis vigorously objects to the brain disease model of addiction, because it makes people lose belief in their self-efficacy, and hence hinders their recovery. Although he acknowledges that there is a compulsive state in addiction, he objects to the claim that this compulsion is carved in stone. Lewis argues that the BDMA underestimates the agency of addicted people, and hence hinder their recovery. Lewis’s (...) work offers us a very much to be welcomed neurobiology of recovery. It offers addicted people a hopeful and respectful narrative for their recovery that treats them as agents rather than as damaged brains. However, I argue that overestimating people’s agency can also result in people losing belief in their self-efficacy. Lewis’s strong focus on the agency of addicted people might not match their experiences of struggle, hence reinforcing their feelings of guilt when they fail to control their use. I propose to replace the notion of addiction as a disease with a notion of a disease-like stage in addiction. I call this stage the duress stage in addiction, in which the addictive behaviour is largely impervious to the agent’s values and to available techniques of self-control. However, the agent can overcome this stage by developing new techniques of self-control, by building on their self-concept and belief in self-efficacy, by changing their environments and habits, and by engaging in projects that are meaningful to the agent. (shrink)

The lack of specificity in neuroimaging studies of neurological and psychiatric diseases suggests that these different diseases have more in common than is generally considered. Potentially, features that are secondary effects of different pathological processes may share common neurobiological underpinnings. Intriguingly, many of these mechanisms are also observed in studies of normal (i.e., non‐pathological) brain ageing. Different brain diseases may be causing premature or accelerated ageing to the brain, an idea that is supported by (...) a line of “brain ageing” research that combines neuroimaging data with machine learning analysis. In reviewing this field, I conclude that such observations could have important implications, suggesting that we should shift experimental paradigm: away from characterizing the average case‐control brain differences resulting from a disease toward methods that place individuals in their age‐appropriate context. This will also lead naturally to clinical applications, whereby neuroimaging can contribute to a personalized‐medicine approach to improve brain health. (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)

Based on recent insight into the thalamocortical system and its role in perception and conscious experience, a unified pathophysiological framework for hallucinations in neurological and psychiatric conditions is proposed, which integrates previously unrelated neurobiological and psychological findings. Gamma-frequency rhythms of discharge activity from thalamic and cortical neurons are facilitated by cholinergic arousal and resonate in networks of thalamocortical circuits, thereby transiently forming assemblies of coherent gamma oscillations under constraints of afferent sensory input and prefrontal attentional mechanisms. If perception is based (...) on synchronisation of intrinsic gamma activity in the thalamocortical system, then sensory input to specific thalamic nuclei may merely play a constraining role. Hallucinations can be regarded as underconstrained perceptions that arise when the impact of sensory input on activation of thalamocortical circuits and synchronisation of thalamocortical gamma activity is reduced. In conditions that are accompanied by hallucinations, factors such as cortical hyperexcitability, cortical attentional mechanisms, hyperarousal, increased noise in specific thalamic nuclei, and random sensory input to specific thalamic nuclei may, to a varying degree, contribute to underconstrained activation of thalamocortical circuits. The reticular thalamic nucleus plays an important role in suppressing random activity of relay cells in specific thalamic nuclei, and its dysfunction may be implicated in the biological vulnerability to hallucinations in schizophrenia. Combined with general activation during cholinergic arousal, this leads to excessive disinhibition in specific thalamic nuclei, which may allow cortical attentional mechanisms to recruit thalamic relay cells into resonant assemblies of gamma oscillations, regardless of their actual sensory input, thereby producing an underconstrained perceptual experience. Key Words: Charles Bonnet syndrome; gamma oscillations; hallucinations; late paraphrenia; Lewy body dementia; perception; schizophrenia; thalamocortical system. (shrink)

In this introduction we set out some salient themes that will help structure understanding of a complex set of intersecting issues discussed in this special issue on the work of Marc Lewis: conceptual foundations of the disease model, tolerating the disease model given socio-political environments, and A third wave: refining conceptualization of addiction in the light of Lewis’s model.

Applying Behrendt & Young's (B&Y's) model of thalamocortical synchrony to complex visual hallucinations in neurodegenerative disorders, such as dementia with Lewy bodies and progressive supranuclear palsy, leads us to propose that the primary pathology may be cortical rather than thalamic. Additionally, the extinction of active hallucinations by eye closure challenges their conception of the role of reduced sensory input.

I review the brain disease model of addiction promoted by medical, scientific, and clinical authorities in the US and elsewhere. I then show that the disease model is flawed because brain changes in addiction are similar to those generally observed when recurrent, highly motivated goal seeking results in the development of deep habits, Pavlovian learning, and prefrontal disengagement. This analysis relies on concepts of self-organization, neuroplasticity, personality development, and delay discounting. It also highlights neural and behavioral parallels between (...) substance addictions, behavioral addictions, normative compulsive behaviors, and falling in love. I note that the short duration of addictive rewards leads to negative emotions that accelerate the learning cycle, but cortical reconfiguration in recovery should also inform our understanding of addiction. I end by showing that the ethos of the disease model makes it difficult to reconcile with a developmental-learning orientation. (shrink)

Parkinson´s disease (PD) is a neurodegenerative disorder characterized by motor symptoms following dopaminergic depletion in the substantia nigra. Besides motor impairments however, several non-motor detriments can have the potential to considerably impact subjectively perceived quality of life in patients. Particularly emotion recognition of facial expressions has been shown to be affected in PD, and especially the perception of negative emotions like fear, anger or disgust is impaired. While emotion processing generally refers to automatic implicit as well as conscious explicit processing, (...) the focus of most previous studies in PD was on explicit recognition of emotions only, while largely ignoring implicit processing deficits. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is widely accepted as therapeutic measure in the treatment of PD and has been shown to advantageously influence motor problems. Among various concomitant non-motor effects of STN-DBS, modulation of facial emotion recognition under subthalamic stimulation has been investigated in previous studies with rather heterogeneous results. While there seems to be consensus regarding the processing of disgust which significantly deteriorates under STN stimulation, findings concerning emotions like fear or happiness report heterogeneous data and seem to depend on various experimental settings and measurements. In the present review, we summarized previous investigations focusing on STN-DBS influence on recognition of facial emotional expressions in patients suffering from PD. In a first step, we provide a synopsis of disturbances and problems in facial emotion processing observed in patients with PD. Secondly, we present findings of STN-DBS influence on facial emotion recognition and especially highlight different impacts of stimulation on implicit and explicit emotional processing. (shrink)

In the future, policies surrounding end-of-life decisions will be faced with the question of whether competent people in a completely locked-in state should be enabled to make end-of-life decisions via brain-computer interfaces (BCI). This article raises ethical issues with acting through BCIs in the context of these decisions, specifically self-administration requirements within assisted suicide policies. We argue that enabling patients to end their life even once they have entered completely locked-in state might, paradoxically, prolong and uphold their quality of (...) life. (shrink)

BackgroundPublic health guidelines have recommended that elective medical procedures, including deep brain stimulation surgery for Parkinson’s disease, should not be scheduled during the coronavirus pandemic to prevent further virus spread and overload on health care systems. However, delaying DBS surgery for PD may not be in the best interest of individual patients and is not called for in regions where virus spread is under control and inpatient facilities are not overloaded.MethodsWe administered a newly developed phone questionnaire to 20 consecutive (...) patients with PD who received DBS surgery in Ruijin Hospital in Shanghai during the COVID-19 pandemic. The questionnaire was designed to gather the patients’ experiences and perceptions on the impact of COVID-19 on their everyday activities and access to medical care.ResultsMost of the patients felt confident about the preventive measures taken by the government and hospitals, and they have changed their daily living activities accordingly. Moreover, a large majority of patients felt confident obtaining access to regular and COVID-19-related health care services if needed. Routine clinical referral, sense of security in the hospital during the outbreak, and poor control of PD symptoms were the three main reasons given by patients for seeking DBS surgery during the COVID-19 pandemic.ConclusionThe COVID-19 pandemic has considerably impacted medical care and patients’ lives but elective procedures, such as DBS surgery for PD, do not need to be rescheduled when the health care system is not overloaded and adequate public health regulations are in place. (shrink)

Cognitive symptoms after COVID-19 have been increasingly recognized several months after the acute infection and have been designated as “brain fog.” We report a patient with cognitive symptoms that started immediately after COVID-19, in which cerebrospinal fluid biomarkers were highly suggestive of Alzheimer’s disease. Our case highlights the need to examine patients with cognitive symptoms following COVID-19 comprehensively. A detailed assessment combining clinical, cognitive, and biomarker studies may help disentangle the underlying mechanisms associated with cognitive dysfunction in each case. (...) The investigation of neurodegenerative processes in an early stage, especially in older patients, is probably warranted. (shrink)

Introduction As deep brain stimulation (DBS) has shifted to being used earlier during Parkinson’s disease (PD), data is lacking regarding patient specific attitudes, preferences, and factors which may influence the timing of and decision to proceed with DBS in the United States. This study aims to identify and compare attitudes and preferences regarding the earlier use of DBS in Parkinson’s patients who have and have not undergone DBS. Methods We developed an online survey concerning attitudes about DBS and its (...) timing in PD. The survey was distributed nationally in the United States via the Michael J. Fox Foundation Trial Finder, the American Parkinson Disease Association flyers, and as a link on the Parkinson Alliance website. Differences in responses between PD DBS and non-DBS patients were assessed. Results A total of 445 patients with PD met eligibility criteria for the survey of which 160 self-identified as having undergone DBS. Fifty-five percent (n = 124) of non-DBS patients believed that DBS for PD should only be considered after all medication options have been tried. Patients favoring early DBS had fewer concerns regarding the surgery than those favoring later DBS. Conclusion Our findings highlight a variety of important considerations and concerns patients have regarding DBS and its timing. These viewpoints are important aspects of shared decision-making, as they help to identify patients’ preferences, values, and goals, which should enable providers to better navigate, with their patients, the decision path for therapeutic options to consider. (shrink)

ObjectiveTo explore alterations in white matter network topology in de novo Parkinson's disease patients with rapid eye movement sleep behavior disorder.Materials and MethodsThis study included 171 de novo PD patients and 73 healthy controls recruited from the Parkinson's Progression Markers Initiative database. The patients were divided into two groups, PD with probable RBD and PD without probable RBD, according to the RBD screening questionnaire. Individual structural network of brain was constructed based on deterministic fiber tracking and analyses were performed (...) using graph theory. Differences in global and nodal topological properties were analyzed among the three groups. After that, post hoc analyses were performed to explore further differences. Finally, correlations between significant different properties and RBDSQ scores were analyzed in PD-pRBD group.ResultsAll three groups presented small-world organization. PD-pRBD patients exhibited diminished global efficiency and increased shortest path length compared with PD-npRBD patients and HCs. In nodal property analyses, compared with HCs, the brain regions of the PD-pRBD group with changed nodal efficiency were widely distributed mainly in neocortical and paralimbic regions. While compared with PD-npRBD group, only increased Ne in right insula, left middle frontal gyrus, and decreased Ne in left temporal pole were discovered. In addition, significant correlations between Ne in related brain regions and RDBSQ scores were detected in PD-pRBD patients.ConclusionsPD-pRBD patients showed disrupted topological organization of white matter in the whole brain. The altered Ne of right insula, left temporal pole and left middle frontal gyrus may play a key role in the pathogenesis of PD-RBD. (shrink)

IntroductionThis study aimed to evaluate, in adults with mild cognitive impairment, the brain atrophy that may distinguish between three AT biomarker-based profiles, and to determine its clinical value.MethodsStructural MRI was employed to evaluate the volume and cortical thickness differences in MCI patients with different AT profiles, namely, A−T−−: normal AD biomarkers; A+T−−: AD pathologic change; and A+T++: prodromal AD. Sensitivity and specificity of these changes were also estimated.ResultsAn initial atrophy in medial temporal lobe areas was found in the A+T−− (...) and A+T++ groups, spreading toward the parietal and frontal regions in A+T++ patients. These structural changes allowed distinguishing AT profiles within the AD continuum; however, the profiles and their pattern of neurodegeneration were unsuccessful to determine the current clinical status.ConclusionsMRI is useful in the determination of the specific brain structural changes of AT profiles along the AD continuum, allowing differentiation between MCI adults with or without pathological AD biomarkers. (shrink)

La psychiatrie est souvent présentée comme la science sexiste par excellence, les experts du psychisme ayant non seulement nourri les discours sur l’infériorité du « sexe faible », mais aussi très concrètement contribué à l’exclusion des femmes en acceptant « d’hospitaliser » celles qui refusaient de se conformer aux désirs masculins. Sans pour autant mettre en cause ce constat du rôle détestable joué par les psychiatres dans la répression des femmes, cet article propose de voir cette histoire sous un autre (...) angle en réfléchissant aux répercussions de cette prise de position sexiste sur l’agencement du savoir médical et, inversement, sur celui des représentations des patientes. L’exemple britannique montre en effet que les théories sur l’infériorité mentale des femmes n’ont pas été partagées par l’ensemble du corps médical et ont, en outre, parfois été fortement combattues par les malades – poussant ainsi à nuancer l’image d’un « pouvoir psychiatrique » univoque et tout-puissant. En retraçant les débats qui ont entouré l’émergence de la thèse du « cerveau faible » dans la Grande-Bretagne du xixe siècle, il s’agit donc de jeter un autre regard sur la construction (et la déconstruction) des catégories du savoir psychiatrique et de comprendre comment les sujets de ce savoir – les patientes – ont pu, par « en bas », influencer leur évolution. (shrink)

BackgroundThe cognitive outcomes induced by subthalamic nucleus deep brain stimulation (STN-DBS) remain unclear, especially in PD patients with mild cognitive impairment (MCI). This study explored the cognitive effects of STN-DBS in PD patients with MCI.MethodsThis was a retrospective cohort study that included 126 PD patients who underwent STN-DBS; all patients completed cognitive and motor assessments before and at least 6 months after surgery. Cognitive changes were mainly evaluated by the Montreal cognitive assessment (MoCA) scale and the seven specific MoCA (...) domains, including visuospatial/executive function, naming, attention, language, abstract, delayed recall, and orientation. Motor improvement was evaluated by the UPDRS-III. Cognitive changes and motor improvements were compared between PD-MCI and normal cognitive (NC) patients. Logistic regression analyses were performed to explore predictors of post-operative cognitive change.ResultsAt the time of surgery, 61.90% of the included PD patients had MCI. Compared with the PD-MCI group, the PD-NC group had a significantly higher proportion of cases with post-operative cognitive decline during follow-up of up to 36 months (mean 17.34 ± 10.61 months), mainly including in global cognitive function, visuospatial/executive function and attention. Covariate-adjusted binary logistic regression analyses showed that pre-operative global cognitive status was an independent variable for post-operative cognitive decline. We also found that pre-operative cognitive specific function could predict its own decline after STN-DBS, except for the naming and orientation domains.ConclusionPD-MCI patients are at a lower risk of cognitive decline after STN-DBS compared with PD-NC patients. (shrink)

Background: Treating medication-refractory freezing of gait in Parkinson’s disease remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus deep brain stimulation. Pedunculopontine nucleus region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS.Methods: In this clinical trial, five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop stimulation. Additionally, (...) PPN DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when “on” PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate.Findings: The feasibility of this approach was demonstrated as we recruited five subjects with both “on” and “off” medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit.Interpretation: This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes. (shrink)

“Exercise starts and ends in the brain”: this was the title of a review article authored by Dr. Bengt Kayser back in 2003. In this piece of work, the author highlights that pioneer studies have primarily focused on the cardiorespiratory-muscle axis to set the human limits to whole-body exercise tolerance. In some circumstances, however, exercise cessation may not be solely attributable to these players: the central nervous system is thought to hold a relevant role as the ultimate site of (...) exercise termination. In fact, there has been a growing interest relative to the “brain” response to exercise in chronic cardiorespiratory diseases, and its potential implication in limiting the tolerance to physical exertion in patients. To reach these overarching goals, non-invasive techniques, such as near-infrared spectroscopy and transcranial magnetic stimulation, have been successfully applied to get insights into the underlying mechanisms of exercise limitation in clinical populations. This review provides an up-to-date outline of the rationale for the “brain” as the organ limiting the tolerance to physical exertion in patients with cardiorespiratory diseases. We first outline some key methodological aspects of neuromuscular function and cerebral hemodynamics assessment in response to different exercise paradigms. We then review the most prominent studies, which explored the influence of major cardiorespiratory diseases on these outcomes. After a balanced summary of existing evidence, we finalize by detailing the rationale for investigating the “brain” contribution to exercise limitation in hitherto unexplored cardiorespiratory diseases, an endeavor that might lead to innovative lines of applied physiological research. (shrink)

IntroductionDeep brain stimulation has become a standard treatment option for select patients with Parkinson’s disease. The selection process and surgical procedures employed have, to date, not been standardized.MethodsA comprehensive 58-question web-based survey was developed with a focus on DBS referral practices and peri-operative management. The survey was distributed to the Parkinson’s Foundation Centers of Excellence, members of the International Parkinson’s Disease and Movement Disorders Society, and the Parkinson Study Group between December 2015 and May 2016.ResultsThere were 207 individual respondents (...) drawn from 59 countries and 6 continents, of whom 64% received formal training in DBS. Thirteen percent of centers reported that DBS could proceed despite a confidence level of < 50% for PD diagnosis. A case-based approach to DBS candidacy was applied in 51.3% of centers without a cut-off for levodopa-responsiveness. Surprisingly, 33% of centers regularly used imaging for diagnostic confirmation of idiopathic PD. Thirty-one percent of centers reported that neuropsychological evaluation did not affect DBS target selection. Approximately half of the respondents reported determination of DBS candidacy based on a multidisciplinary committee evaluation and 1/3rd reported that a committee was used for target selection. Eight percent of respondents felt that psychosocial factors should not impact DBS candidacy nor site selection. Involvement of allied health professionals in the preoperative process was sparse. There was high variability in preoperative education about DBS outcome expectations. Approximately half of the respondents did not utilize a “default brain target,” though STN was used more commonly than GPi. Specific DBS procedure techniques applied, as well as follow-up timelines, were highly variable.ConclusionResults revealed high variability on the best approaches for DBS candidate selection, brain target selection, procedure type, and postoperative practices. Cognitive and mood assessments were underutilized. There was low reliance on multidisciplinary teams or psychosocial factors to impact the decision-making process. There were small but significant differences in practice across global regions, especially regarding multidisciplinary teams. The wide variability of responses across multiple facets of DBS care highlights the need for prospective studies to inform evidence-based guidelines. (shrink)

IntroductionParkinson’s disease patients have a significantly higher risk of developing dementia in later disease stages, leading to severe impairments in quality of life and self-functioning. Questions remain on how deep brain stimulation affects cognition, and whether we can individualize therapy and reduce the risk for adverse cognitive effects. Our aim in this systematic review is to assess the current knowledge in the field and determine if the findings could influence clinical practice.MethodsWe have conducted a systematic review according to PRISMA (...) guidelines through MEDLINE and Embase databases, with studies being selected for inclusion via a set inclusion and exclusion criteria.ResultsSixty-seven studies were included in this systematic review according to the selected criteria. This includes 6 meta-analyses, 18 randomized controlled trials, 17 controlled clinical trials, and 26 observational studies with no control arms. The total number of PD patients encompassed in the studies cited in this review is 3677, not including the meta-analyses.ConclusionCognitive function in PD patients can deteriorate, in most cases mildly, but still impactful to the quality of life. The strongest evidence is present for deterioration in verbal fluency, while inconclusive evidence is still present for executive function, memory, attention and processing speed. Global cognition does not appear to be significantly impacted by DBS, especially if cognitive screening is performed prior to the procedure, as lower baseline cognitive function is connected to poor outcomes. Further randomized controlled studies are required to increase the level of evidence, especially in the case of globus pallidus internus DBS, pedunculopontine nucleus DBS, and the ventral intermediate nucleus of thalamus DBS, and more long-term studies are required for all respective targets. (shrink)

This article compares health promotion attitudes towards prostate cancer and Alzheimer’s disease. Our aim is to demonstrate that these two apparently distinct conditions of the aging body – one affecting the male reproductive system, the other primarily the brain – are addressed in similar fashion in recent public health activities because of a growing emphasis on a ‘cardiovascular logic’. We suggest that this is a form of reductionism, and argue that it leaves us with a dangerous paradox: while re-transcending, (...) at least partially, the conceptual separation of body and brain, it clouds much-needed discussion and research, such as contingent issues of socio-economic and socio-cultural disease disparities. (shrink)

Recent studies have found abnormal levels of brain-derived neurotrophic factor in a variety of central nervous system diseases. This suggests that BDNF may be involved in the pathogenesis of these diseases. Moreover, regulating BDNF signaling may represent a potential treatment for such diseases. With reference to recent research papers in related fields, this article reviews the production and regulation of BDNF in CNS and the role of BDNF signaling disorders in these diseases. A brief introduction (...) of the clinical application status of BDNF is also provided. (shrink)

Patients with advanced Alzheimer's disease experience cognitive impairment and physical disabilities in daily life. Currently, there are no treatments available to slow down the course of the disease, and limited treatments exist only to treat symptoms. However, deep brain stimulation of the nucleus basalis of Meynert has been reported to improve cognitive function in individuals with AD. Here, we report the effects of NBM-DBS on cognitive function in a subject with severe AD. An 80-year-old male with severe AD underwent (...) surgery for bilateral NBM-DBS electrode placement. After 10 weeks of stimulation, Mini-Mental State Examination assessment improved from a score of 5 to 9 points, and assessment using the Alzheimer's Disease Assessment Scale–Cognitive Subscale showed a marked reduction in total score from 43 to 33 points, suggesting cognitive benefits from NBM-DBS. The patient's postoperative course was complicated by a subdural effusion that occurred several days after surgery, with complete recovery. Interestingly, the subject also displayed abnormal thermoregulation with stimulation initiation and stimulation parameter modifications. NBM-DBS may serve as a potential therapy for severe AD patients.Clinical Trial Registration: ChiCTR1900022324. (shrink)

In Patricia Churchland's 2006 essay on free will, she cites the case of a middle-aged man who, without any prior history of misbehavior, suddenly became obsessed with child pornography and started to molest his 8-year-old stepdaughter. He was subsequently discovered to have a brain tumor affecting the frontal lobes, and when it is successfully treated his aberrant behavior stopped.Thomas Szasz is famous for his denunciation of the concept of mental illness, and his critique is partly responsible for instigating an (...) enduring philosophical discourse about the nature of mental disorder. Szasz's key insight was the recognition that we find it important to distinguish between situations that are characterized by... (shrink)

Patients requiring deep brain stimulation due to intracerebral metallic foreign substances have not been reported elsewhere in the world. Additionally, the long-term effects of metallic foreign bodies on deep brain stimulation are unknown. A 79-year-old man with a 5-year history of Parkinson's disease reported that, 40 years ago, while playing with a pistol, a metallic bullet was accidentally discharged into the left brain through the edge of the left eye, causing no discomfort other than blurry vision in (...) the left eye. DBS was performed due to the short duration of efficacy for oral medication. Because the bullet was on the left subthalamic nucleus electrode trajectory and the patient's right limb was primarily stiff, the patient received globus pallidus interna -DBS implantation in the left hemisphere and STN-DBS implantation in the right hemisphere. During a 6-month postoperative follow-up, the patient's PD symptoms were effectively managed with no noticeable discomfort. (shrink)

BackgroundSubjective cognitive decline, non-amnestic mild cognitive impairment, and amnestic mild cognitive impairment are regarded to be at high risk of converting to Alzheimer’s disease. Amplitude of low-frequency fluctuations can reflect functional deterioration while diffusion tensor imaging is capable of detecting white matter integrity. Our study aimed to investigate the structural and functional alterations to further reveal convergence and divergence among SCD, naMCI, and aMCI and how these contribute to cognitive deterioration.MethodsWe analyzed ALFF under slow-4 and slow-5 bands and white matter (...) fiber integrity among normal controls, SCD, naMCI, and aMCI groups. Correlation analyses were further utilized among paired DTI alteration, ALFF deterioration, and cognitive decline.ResultsFor ALFF calculation, ascended ALFF values were detected in the lingual gyrus and superior frontal gyrus within SCD and naMCI patients, respectively. Descended ALFF values were presented mainly in the LING, SFG, middle frontal gyrus, and precuneus in aMCI patients compared to CN, SCD, and naMCI groups. For DTI analyses, white matter alterations were detected within the uncinate fasciculus in aMCI patients and within the superior longitudinal fasciculus in naMCI patients. SCD patients presented alterations in both fasciculi. Correlation analyses revealed that the majority of these structural and functional alterations were associated with complicated cognitive decline. Besides, UF alterations were correlated with ALFF deterioration in the SFG within aMCI patients.ConclusionsSCD shares structurally and functionally deteriorative characteristics with aMCI and naMCI, and tends to convert to either of them. Furthermore, abnormalities in white matter fibers may be the structural basis of abnormal brain activation in preclinical AD stages. Combined together, it suggests that structural and functional integration may characterize the preclinical AD progression. (shrink)