In an important and timely book, Anneli Jefferson outlines a view according to which a given mental disorder is a brain disorder if it is a (harmful) mental dysfunction realised by a brain dysfunction. Prima facie, Jefferson’s book is a study in the metaphysics of dysfunction: how does mental dysfunction relate to brain dysfunction, and what does this imply for the status of mental disorders and brain disorders? In what follows, I shall argue that Jefferson’s contribution (...) to this debate is better understood as a conceptual explication of how psychiatrists, some philosophers, scientists and clinicians in the field (broadly construed) think of the label ‘brain disorder’. I infer this on the basis that Jefferson’s thesis would not follow from any serious, well-worked out theory of proper function. Despite initial appearances, Jefferson’s book about brain dysfunction is not about function at all. (shrink)

Despite many authors in psychiatry endorsing a naturalist view of the mind, many still consider that mental dysfunctions cannot be reduced to brain dysfunctions. This paper investigates the main reasons for this view. Some arguments rely on the analogy that the mind is like software while the brain is like hardware. The analogy suggests that just as software can malfunction independently of hardware malfunctions, similarly the mind can malfunction independently of any brain malfunction. This view has been (...) critically examined in recent literature. However, other less discussed reasons suggest that mental dysfunctions cannot be reduced to brain dysfunctions because mental dysfunctions are appropri- ately ascribed at the level of intentional mental states, while brain dysfunctions are solely related to abnormalities in anatomy and physiological processes. This paper questions why such a view would be upheld. The discussion is framed within the interface problem in the philosophy of cognitive science, which concerns the relationship between personal and subpersonal levels of explanation. The paper examines the view that an autonomist perspective on the personal/ subpersonal distinction could justify the separation of mental dysfunctions, described in intentional terms, from brain dysfunctions, described in anatomical or physiological terms. Ultimately, the paper argues that the autonomist view cannot be upheld in psychiatry and, consequently, does not provide a principled justification for rejecting the reduction of mental dysfunctions to brain dysfunctions. (shrink)

In her book “Are Mental Disorders Brain Disorders?” (2022), Anneli Jefferson proposes that brain processes that always realize mental dysfunctions are brain dysfunctions. This paper explores possible interpretations of two underdeveloped aspects of this thesis. First, it argues that “realization” should be interpreted as partial rather than full realization. Second, it argues that the “always” should only quantify over biologically normal situations. Taken together, these changes can account for the fact that some psychological dysfunctions are partially realized (...) by functional mechanisms, for the existence of psychological dysfunctions due to mismatches rather than brain dysfunctions, and for the fact that brain dysfunctions do not cease to be brain dysfunctions just because they can be compensated. (shrink)

Grafts of embryonic neural tissue into the brains of adult patients are currently being used to treat Parkinson's disease and are under serious consideration as therapy for a variety of other degenerative and traumatic disorders. This target article evaluates the use of transplants to promote recovery from brain injury and highlights the kinds of questions and problems that must be addressed before this form of therapy is routinely applied. It has been argued that neural transplantation can promote functional recovery (...) through the replacement of damaged nerve cells, the reestablishment of specific nerve pathways lost as a result of injury, the release of specific neurotransmitters, or the production of factors that promote neuronal growth. The latter two mechanisms, which need not rely on anatomical connections to the host brain, are open to examination for nonsurgical, less intrusive therapeutic use. Certain subjective judgments used to select patients who will receive grafts and in assessment of the outcome of graft therapy make it difficult to evaluate the procedure. In addition, little long-term assessment of transplant efficacy and effect has been done in nonhuman primates. Carefully controlled human studies, with multiple testing paradigms, are also needed to establish the efficacy of transplant therapy. (shrink)

Several million people are treated with neuroleptic medications in North America each year. A large percentage of these patients develop a chronic neurologic disorder-tardive dyskinesia-characterized by abnormal movements of the voluntary muscles. Most cases are permanent and there is no known treatment. Evidence has been accumulating that the neuroleptics also cause damage to the highest centers of the brain, producing chronic mental dysfunction, tardive dementia and tardive psychosis. These drug effects may be considered a mental equivalent of tardive dyskinesia. (...) Relevant data are derived from human autopsies, brain imaging , neurophysical tests, and clinical research. That the neuroleptics can damage higher brain centers is confirmed by their known neurotoxicity and neurophysiological impact, animal autopsies, and a comparison to diseases that mimic neuroleptic effects, such as Huntington's chorea and lethargic encephalitis. Patients and the public should be informed of the danger of both tardive dyskinesia and tardive dementia. The mental health professions should severely limit the use of neuroleptics and develop safer and better alternatives to these dangerous substances. (shrink)

I argue that despite the merits of Jefferson’s account of a brain disorder, which are many, the notion of function she deploys is unsuitable to the overall goals of that account. In particular, Jefferson accepts Cummins’ causal role theory of function and dysfunction. As the causal role view, in its standard elaborations, is wedded to human interests, goals, and values, it cannot serve as a value-neutral anchor for her hybrid “harm-dysfunction” account of disorder. I argue that the selected effects (...) theory, or some comparably value-neutral account, would serve her purposes better. (shrink)

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.

Adequate temporal abilities are required for most daily activities. Traumatic brain injury (TBI) patients often present with cognitive dysfunctions, but few studies have investigated temporal impairments associated with TBI. The aim of the present work is to review the existing literature on temporal abilities in TBI patients. Particular attention is given to the involvement of higher cognitive processes in temporal processing in order to determine if any temporal dysfunction observed in TBI patients is due to the disruption of an (...) internal clock or to the dysfunction of general cognitive processes. The results showed that temporal dysfunctions in TBI patients are related to the deficits in cognitive functions involved in temporal processing rather than to a specific impairment of the internal clock. In fact, temporal dysfunctions are observed when the length of temporal intervals exceeds the working memory span or when the temporal tasks require high cognitive functions to be performed. The consistent higher temporal variability observed in TBI patients is a sign of impaired frontally mediated cognitive functions involved in time perception. (shrink)

Anthropology of Consciousness, EarlyView.

ObjectiveThis study aimed to examine the effectiveness and safety of the Brain-computer interface in treatment of upper limb dysfunction after stroke.MethodsEnglish and Chinese electronic databases were searched up to July 2021. Randomized controlled trials were eligible. The methodological quality was assessed using Cochrane’s risk-of-bias tool. Meta-analysis was performed using RevMan 5.4.ResultsA total of 488 patients from 16 RCTs were included. The results showed that the meta-analysis of BCI-combined treatment on the improvement of the upper limb function showed statistical significance (...) [standardized mean difference : 0.53, 95% CI: 0.26–0.80, P < 0.05]; BCI treatment can improve the abilities of daily living of patients after stroke, and the analysis results are statistically significant ; and the BCI-combined therapy was not statistically significant for the analysis of the Modified Ashworth Scale.ConclusionThe meta-analysis indicates that the BCI therapy or BCI combined with other therapies such as conventional rehabilitation training and motor imagery training can improve upper limb dysfunction after stroke and enhance the quality of daily life. (shrink)

Scientists, philosophers, and even the lay public commonly accept that schizophrenia stems from a biological or internal ‘dysfunction.’ However, this assessment is typically accompanied neither by well-defined criteria for determining that something is dysfunctional nor empirical evidence that schizophrenia satisfies those criteria. In the following, a concept of biological function is developed and applied to a neurobiological model of schizophrenia. It concludes that current evidence does not warrant the claim that schizophrenia stems from a biological dysfunction, and, in fact, that (...) unusual neural structures associated with schizophrenia may have functional or adaptive significance. The fact that current evidence is ambivalent between these two possibilities (dysfunction versus adaptive function) implies that schizophrenia researchers should be much more cautious in using the ‘dysfunction’ label than they currently are. This has implications for both psychiatric treatment as well as public perception of mental disorders. (shrink)

This commentary examines the implications of the Depue & Collins model for the etiology and treatment of depression, specifically, whether it can account for findings concerning neurobiological, behavioral, and phenomenological facets of depression. Drawing upon the construct of self-regulation, I explore the fit of the model to current knowledge about depression, conceptualized as a dysfunction within a hypothetical brain/behavior system for maximizing positive outcomes.

Does a diagnosis of brain dysfunction matter for ascriptions of moral responsibility? This chapter argues that, while knowledge of brain pathology can inform judgments of moral responsibility, its evidential value is currently limited for a number of practical and theoretical reasons. These include the problem of establishing causation from correlational data, drawing inferences about individuals from group data, and the reliance of the interpretation of brain findings on well-established psychological findings. Brain disorders sometimes matter for moral (...) responsibility, however, because they change an individual’s moral psychology in a way that is beyond their control. While control over psychological changes is not an excusing factor, brain disorders can mitigate moral responsibility because they confront individuals with new psychological deficits or urges for which their previous moral education and existing external and internal moral resources have not prepared them. (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 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)

Inherited disorders of ion‐channels are associated with paroxysmal dysfunction of excitable tissues and manifest as diseases of the brain, heart and skeletal muscle. These so‐called channelopathies have now been described for most of the major categories of voltage‐dependent ion‐channels including those selectively permeable to sodium. Sodium channelopathies affecting the heart and brain are reviewed in this essay. They show striking differences and similarities including, for example, their responsiveness to changes in body temperature and sleep state. They represent a (...) paradigm for efforts to trace disturbed behaviour of physiological systems back to its molecular origins and understanding their molecular basis may provide clues to important health issues such as cardiac side effects of drugs and response to medication used to treat epilepsy. BioEssays 25:981–993, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Metabolic dysfunction is a ubiquitous underlying feature of many neurological conditions including acute traumatic brain injuries and chronic neurodegenerative conditions. A central problem in neurological patients, in particular those with traumatic brain injuries, is an impairment in the utilization of glucose, which is the predominant metabolic substrate in a normally functioning brain. In such patients, alternative substrates including ketone bodies and lactate become important metabolic candidates for maintaining brain function. While the potential neuroprotective benefits of ketosis (...) have been recognized for up to almost a century, the majority of work has focused on the use of ketogenic diets to induce such a state, which is inappropriate in cases of acute disease due to the prolonged periods of time (i.e., weeks to months) required for the effects of a ketogenic diet to be seen. The following review seeks to explore the neuroprotective effects of exogenous ketone and lactate preparations, which have more recently become commercially available and are able to induce a deep ketogenic response in a fraction of the time. The rapid response of exogenous preparations makes their use as a therapeutic adjunct more feasible from a clinical perspective in both acute and chronic neurological conditions. Potentially, their ability to globally moderate long-term, occult brain dysfunction may also be relevant in reducing lifetime risks of certain neurodegenerative conditions. In particular, this review explores the association between traumatic brain injury and contusion-related dementia, assessing metabolic parallels and highlighting the potential role of exogenous ketone and lactate therapies. (shrink)

Emotion is normally regulated in the human brain by a complex circuit consisting of the orbital frontal cortex, amygdala, anterior cingulate cortex, and several other interconnected regions. There are both genetic and environmental contributions to the structure and function of this circuitry. We posit that impulsive aggression and violence arise as a consequence of faulty emotion regulation. Indeed, the prefrontal cortex receives a major serotonergic projection, which is dysfunctional in individuals who show impulsive violence. Individuals vulnerable to faulty regulation (...) of negative emotion are at risk for violence and aggression. Research on the neural circuitry of emotion regulation suggests new avenues of intervention for such at-risk populations. (shrink)

Objectives: Neuroplastic changes that drive recovery of shoulder/elbow function after stroke have been poorly understood. The purpose of this study was to determine the relationship between neuroplastic brain changes related to shoulder/elbow movement control in response to treatment and recovery of arm motor function in chronic stroke survivors.Methods: Twenty-three chronic stroke survivors were treated with 12 weeks of arm rehabilitation. Outcome measures included functional Magnetic Resonance Imaging (fMRI) for the shoulder/elbow components of reach and a skilled motor function test (...) (Arm Motor Abilities Test, AMAT), collected before and after treatment.Results: We observed two patterns of neuroplastic changes that were associated with gains in motor function: decreased or increased task-related brain activation. Those with significantly better motor function at baseline exhibited a decrease in brain activation in response to treatment, evident in the ipsilesional primary motor and contralesional supplementary motor regions; in contrast, those with greater baseline motor impairment, exhibited increased brain activation in response to treatment. There was a linear relationship between greater functional gain (AMAT) and increased activation in bilateral primary motor, contralesional primary and secondary sensory regions, and contralesional lateral premotor area, after adjusting for baseline AMAT, age, and time since stroke.Conclusions: Recovery of functional reach involves recruitment of several contralesional and bilateral primary motor regions. In response to intensive therapy, the direction of functional brain change (i.e., increase or decrease in task-related brain recruitment) for shoulder/elbow reach components depends on baseline level of motor function and may represent either different phases of recovery or different patterns of neuroplasticity that drive functional recovery. (shrink)

The way in which we characterize the structural and functional differences between psychopath and normal brains – either as biological disorders or as mere biological differences – can influence our judgments about psychopaths’ responsibility for criminal misconduct. However, Marga Reimer (Neuroethics 1(2):14, 2008) points out that whether our characterization of these differences should be allowed to affect our judgments in this manner “is a difficult and important question that really needs to be addressed before policies regarding responsibility... can be implemented (...) with any confidence”. This paper is an attempt to address Reimer’s difficult and important question; I argue that irrespective of which of these two characterizations is chosen, our judgments about psychopaths’ responsibility should not be affected, because responsibility hinges not on whether a particular difference is (referred to as) a disorder or not, but on how that difference affects the mental capacities required for moral agency. (shrink)

Awareness of deficits in patients with neurological disorders may be described as a theoretical unitary phenomenon, which has been analysed reaching interesting results in the last decades. Awareness of deficits manifests itself in a continuum ranging from full awareness to total absence. In line with a neurocognitive approach, a reduction in self-awareness could be explained considering executive dysfunction associated with prefrontal cortex anatomo-functional changes. Our mini-review will focus on reduced self-awareness in neurological disorders, such as Alzheimer’s disease, behavioural Frontotemporal Dementia (...) and Acquired Brain Injuries. Results achieved thanks to an explanatory investigative approach combined with a theoretical reference model will be presented. Data suggest the key role of executive functions in supporting adequate self-awareness towards patients’ cognitive-behavioural profile and instrumental activity autonomy. The Cognitive Awareness Model seems to be one of the best theoretical model to better approach this phenomenon. (shrink)

The question of whether mental disorders are disorders of the brain has led to a long- running and controversial dispute within psychiatry, psychology and philosophy of mind and psychology. While recent work in neuroscience frequently tries to identify underlying brain dysfunction in mental disorders, detractors argue that labelling mental disorders as brain disorders is reductive and can result in harmful social effects. This book brings a much- needed philosophical perspective to bear on this important question.

A mechanism-based approach was developed focusing on the psychodynamic, psychological and neuronal mechanisms in healthy and depressed persons. In this integrative concept of depression, the self is a core dimension in depression. It is attributed to negative emotions (e.g., failure, guilt). The increased inward focus in depression is connected with a decreased environmental focus. The development of neuropsychodynamic hypotheses of the altered self-reference is based on the investigation of the emotional-cognitive interaction in depressed patients. It may be hypothesized that the (...) increased negative self-attributions—as typical characteristics of an increased self-focus in depression—may result from altered neuronal activity in subcortical-cortical midline structures in the brain, especially from hyperactivity in the cortical-subcortical midline regions and hypoactivity in the lateral regions. The increased resting state activity in depression is especially associated with an increased resting state activity in the default mode network (DMN) and a dysbalance between DMN and executive network (EN) activity. Possible therapeutic consequences of the neuropsychodynamic approach to depression involve the necessary emotional attunement in psychotherapy of depressed patients and the adequate timing of therapeutic interventions. The hypotheses which have been developed in the context of the neuropsychodynamic model of depression may be used for more specific psychotherapeutic interventions, aiming at specific mechanisms of compensation and defence, which are related to the increased resting state activity and the disturbed resting state-stimulus-interaction. (shrink)

For hundreds of years, death had been defined by cardiopulmonary criteria. When heart and respiratory functions were permanently absent, doctors declared their patients dead. Three developments in intensive care medicine called into question these widely-accepted criteria, however: the advent of positive pressure ventilation and the promotion of cardiopulmonary resuscitation, both in the early 1950s, and the first successful heart transplantation in 1967. What had previously been diagnosed as the permanent absence of vital functions, suddenly became reversible. Not only could doctors (...) replace a defective heart with a functioning transplant; patients could also be kept oxygenated in the total absence of spontaneous respiratory function. The traditional boundaries between life and death became blurred. Patients for whom there was not the remotest possibility of regaining consciousness following massive brain damage continued to consume valuable medical resources. Moreover, their organs could not be procured for transplantation. Were those patients still alive or could the ventilators be switched off? A criterion suited to indicate a patient’s death despite the provision of external life support was needed. In 1968 an ad hoc committee of the Harvard Medical School published the first comprehensive definition of what would soon become the new clinical standard: brain death. The brain bears a special relation to other organs; it directs bodily functions without carrying them out. When the brain is destroyed, it was argued, this control mechanism is irreversibly dysfunctional, so that the organism becomes unable to maintain its vital functions, loses its somatic unity and, consequently, ceases to exist. This neurological criterion has been controversial ever since its introduction. Whether brain death is indeed death is what I shall be investigating in this thesis. I will be asking three main questions: What are we? Is brain death the death of an organism? Is brain death the death of a psychological being? The question of personal identity and the question of the appropriate definition of death are intimately related. Only when we have determined what kind of entity we essentially are can we specify what conditions must apply for this entity to persist or to cease to exist. I shall argue that we are essentially psychological beings, which entails that our death is distinct from the death of our organisms. Hence, we need two different criteria – one for the death of each entity. I shall try to establish whether brainstem death and whole-brain death correspond to the irreversible cessation of organismic functioning. I will then determine by which criterion the death of a psychological being can be diagnosed. (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)

Owen, Freyenhagen, and Martin present a novel discussion of the meaning of decision-making capacity. They frame their discussion in the context of deficits in executive function after traumatic brain injury, but their observations and suggestions for expansion of how DMC is appropriately assessed have potential implications for people with other disorders that can potentially affect executive functioning, including those with certain forms of neurodegenerative conditions and some of those with serious mental illnesses such as schizophrenia or bipolar disorder....

The Journal of Mind and Behavior, Winter 2003, Volume 24, Number 1, Pages 91–118, ISSN 0271–0137 This paper focuses on a logical systems flow-down of a set of consciousness requirements, which together with biological quantification of human brain anatomy sets limits on the neurological network in the cerebrum in order to produce the mind. It employs data to validate inferences, or when data do not exist, proposes methods for acquiring valid evidence. Many of these systems requirements will be imposed (...) after some fundamental assumptions are made. These assumptions are not new to theories on consciousness. However, their application as fundamentals may actually represent a new approach. Concurrent with these fundamentals, explicit periods of awareness while conscious are employed. Justification for their use is found in a theoretical process described as cerebral fusion. Additionally, storage of memory elements is postulated within local glia sites, proximal to synaptic nodes, and conductive transport through the astrocytes responsible for recall of data. The model permits variations in neural–glial interface physics and allows forecasts of mind/brain dysfunctions to be inferred. One key result from the model is hypothesized and expanded upon, and may have impact in certain types of dementia, such as Alzheimer’s disease. (shrink)

The aim of this study was to explore the relationship between the protein S100B level, cognitive dysfunction, and Glasgow Outcome Scale (GOS) in moderate traumatic brain injury patients. Thirty patients suffering from head injuries undergoing neurosurgery in Dr. Hasan Sadikin General Hospital Bandung, Indonesia, and who were considered eligible based on the inclusion and exclusion criteria participated in this double-blind experimental Randomized Controlled Trial (RCT). The treatment groups (COX-2) were assigned as COX2-I, COX2II, and COX3-IV, six patients in each (...) group. The treatment group was given another dose of sCOX-2 inhibitor 12 hours, 12 and 24 hours after the first dose, and 12, 24 and 36 hours after pre-induction sCOP-2 inhibitor was administered. The GOS score was obtained during the before the surgery and 1 month, 1.5 months, and 2 months postoperative days. The MMSE was performed preoperatively and then on the first to seventh day after the surgery. The results showed that there was a significant decrease in the protein level in all treatment groups including the control group, where the resulting p-value was less than 0.05. Moreover, the treatment group showed a faster time in reaching GOS 5 or be discharged from the hospital compared to the control. In conclusion, it has been demonstrated that the provision of 3 or 4 times of the sCox-2 inhibitor leads to the achievement of a score of 5, while the recovery of the cognitive dysfunction into the normal level is obtained when the SCox2 inhibitor is given 4 times. (shrink)

The possible dysfunction of [gamma] aminobutyric acid (GABA) and opioid inhibitory mechanisms following central and peripheral nervous system injury is an important and potentially useful finding. However, effective clinical application must take into account the specific characteristics of the models used in the studies and the relationship of these models to specific clinical conditions. [dickenson; wiesenfeld-hallin et al.].

Background: It has been reported that type 2 diabetes is associated with olfactory identification impairments and cognitive decline. However, the relationship between OI impairments and cognitive decline is largely unknown in T2DM patients.Methods: Sixty-eight T2DM patients and 68 healthy controls underwent 3D-T1 MRI scans, olfactory and cognitive assessments. The cortical thickness of olfaction-related brain regions, olfactory and cognitive scores were compared between groups. Correlation analyses were carried out among cognition, olfaction, and cortical thickness of olfaction-related brain regions.Results: First, (...) the cognitive and olfactory test scores of T2DM patients were lower than healthy subjects. Second, higher olfactory scores were associated with increased cortical thickness in the left parahippocampal gyrus and bilateral insula in T2DM. Third, higher olfactory scores were associated with higher cognitive performance in T2DM. Fourth, some cognitive performances were related to cortical thickness in the left parahippocampal gyrus and left insula in T2DM.Conclusion: These findings indicated that olfactory dysfunction may be useful for future applications that attempt to predict cognitive decline or develop tailored therapies in T2DM patients. (shrink)

A substantial portion of the human genome has been found to consist of simple sequence repeats, including microsatellites and minisatellites. Microsatellites, tandem repeats of 1–6 nucleotides, form the template for dynamic mutations, which involve heritable changes in the lengths of repeat sequences. In recent years, a large number of human disorders have been found to be caused by dynamic mutations, the most common of which are trinucleotide repeat expansion diseases. Dynamic mutations are common to numerous nervous system disorders, including Huntington's (...) disease, various spinocerebellar ataxias, fragile X syndrome, fragile X tremor/ataxia syndrome, Friedreich ataxia and other neurodegenerative disorders. The involvement of dynamic mutations in brain disorders will be reviewed, with a focus on the large group caused by CAG/glutamine repeat expansions. We will also outline a proposed role of tandem repeat polymorphisms (TRPs), with unique ‘digital’ genetic distributions, in modulating brain development and normal function, so as to generate additional mutational diversity upon which natural selection may act. BioEssays 29:525–535, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The cognitive and behavioral functions of the frontal lobes have been of great interest to neuroscientists, neurologists, psychologists and psychiatrists. Recent technical advances have made it possible to trace their neuroanatomical connections more precisely and to conduct evoked potential and neuroimaging studies in patients. This book presents a broad and authoritative synthesis of research progress in this field. It encompasses neuroanatomical studies; experiments involving temporal organization and working memory tasks in non-human primates; clinical studies of patients following frontal lobe excisions (...) for intractable epilepsy; metabolic imaging in schizophrenia and affective disorder; neurobehavioral studies of patients with dementia, frontal lobe tumors, and head injuries; magnetic resonance imaging methods for studying human frontal lobe anatomy; theoretical approaches to describing frontal lobe functions; and rehabilitation of patients with frontal lobe damage including their core problem of diminished awareness. Written by a distinguished group of neuroscientists, psychologists and clinicians, Frontal Lobe Function and Dysfunction provides the best current source of information on this region of the brain and its role in cognition, behavior and clinical disorders. (shrink)

Creativity is commonly thought of as a positive advance for society that transcends the status quo knowledge. Humans display an inordinate capacity for it in a broad range of activities, with art being only one. Most work on creativity’s neural substrates measures general creativity, and that is done with laboratory tasks, whereas specific creativity in art is gleaned from acquired brain damage, largely in observing established visual artists, and some in visual de novo artists (became artists after the damage). (...) The verb “to create” has been erroneously equated with creativity; creativity, in the classic sense, does not appear to be enhanced following brain damage, regardless of etiology. The turning to communication through art in lieu of language deficits reflects a biological survival strategy. Creativity in art, and in other domains, is most likely dependent on intact and healthy knowledge and semantic conceptual systems, which are represented in several pathways in the cortex. It is adversely affected when these systems are dysfunctional, for congenital reasons (savant autism) or because of acquired brain damage (stroke, dementia, Parkinson’s), whereas inherent artistic talent and skill appear less affected. Clues to the neural substrates of general creativity and specific art creativity can be gleaned from considering that art is produced spontaneously mainly by humans, that there are unique neuroanatomical and neurofunctional organizations in the human brain, and that there are biological antecedents of innovation in animals. (shrink)

Specifying exact selection pressures for identifying adaptations is unnecessary. Novel behaviors are not spandrels since they can only develop because of prior functions. An adaptationist approach has a high prior probability, whereas spandrel hypotheses attempt to prove a negative. The concept of maladaptive spandrel is criticized. The utility of dysfunctional states for identification of adaptations gone wrong is emphasized.

In the target article, Sagvolden and collaborators propose that attentional-deficit/hyperactivity disorder (ADHD) is the result of a general behavioral deficit which is mainly caused by a hypofunctioning mesolimbic dopaminergic system. Although we partly agree with this view, we think that it tends to overlook the dysfunction of prefrontal and frontostriatal executive functions by considering them to be a consequence of alterations in reward and extinction mechanisms. Rather, we believe that ADHD is the result of an overall cognitive and behavioral condition, (...) associated to a generalized dopaminergic network dysfunction, and may not be easily attributable to a single basic behavioral function. (shrink)

N-methyl-d-aspartate receptor (NMDAR) dysfunction plays a crucial role in schizophrenia, leading to impairments in cognitive coordination. NMDAR agonists (e.g., glycine) ameliorate negative and cognitive symptoms, consistent with NMDAR models. However, not all types of cognitive coordination use NMDAR. Further, not all aspects of cognitive coordination are impaired in schizophrenia, suggesting the need for specificity in applying the cognitive coordination construct.

Measuring neuronal activity with electrophysiological methods may be useful in detecting neurological dysfunctions, such as mild traumatic brain injury (mTBI). This approach may be particularly valuable for rapid detection in at-risk populations including military service members and athletes. Electrophysiological methods, such as quantitative electroencephalography (qEEG) and recording event-related potentials (ERPs) may be promising; however, the field is nascent and significant controversy exists on the efficacy and accuracy of the approaches as diagnostic tools. For example, the specific measures derived from (...) an electroencephalogram (EEG) that are most suitable as markers of dysfunction have not been clearly established. A study was conducted to summarize and evaluate the statistical rigor of evidence on the overall utility of qEEG as an mTBI detection tool. The analysis evaluated qEEG measures/parameters that may be most suitable as fieldable diagnostic tools, identified other types of EEG measures and analysis methods of promise, recommended specific measures and analysis methods for further development as mTBI detection tools, identified research gaps in the field, and recommended future research and development thrust areas. The qEEG study group formed the following conclusions: 1. Individual qEEG measures provide limited diagnostic utility for mTBI. However, many measures can be important features of qEEG discriminant functions, which do show significant promise as mTBI detection tools. 2. ERPs offer utility in mTBI detection. In fact, evidence indicates that ERPs can identify abnormalities in cases where EEGs alone are nondisclosing. 3. The standard mathematical procedures used in the characterization of mTBI EEGs should be expanded to incorporate newer methods of analysis including nonlinear dynamical analysis, complexity measures, analysis of causal interactions, graph theory and information dynamics. 4. and 5. are too long to include here. (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)

Male sexual arousal (SA) has been known as a multidimensional experience involving closely interrelated and coordinated neurobehavioral components that rely on widespread brain regions. Recent functional neuroimaging studies have shown relation between abnormal/altered dynamics in these circuits and male sexual dysfunction. However, alterations in the topological1 organization of structural brain networks in male sexual dysfunction are still unclear. Here, we used graph theory2 to investigate the topological properties of large-scale structural brain networks, which were constructed using inter-regional (...) correlations of cortical thickness between 78 cortical regions (subcortical regions were not included due to the used cortical surface model) in 40 patients with psychogenic erectile dysfunction (pED) and 39 normal controls. Compared with normal controls, pED patients exhibited a less optimal global topological organization with reduced global and increased local efficiencies. Our results suggest disrupted neural integration among distant brain regions in pED patients, consistent with previous reports of impaired white matter structure and abnormal functional integrity in pED. Additionally, disrupted global network topology in pED was observed to be primarily relevant to altered subnetwork and nodal properties within the networks mediating the cognitive, motivational and inhibitory processes of male SA, possibly indicating disrupted integration of these networks in the whole brain networks and might account for pED patients’ abnormal cognitive, motivational and inhibitory processes for male SA. In total, our findings provide evidence for disrupted integrity in large-scale brain networks underlying the neurobehavioral processes of male SA in pED and provide new insights into the understanding of the pathophysiological mechanisms of pED. (shrink)

BackgroundPrevious studies on voxel-based morphometry have found that there were gray matter alterations in patients with hepatic encephalopathy. However, the reported results were inconsistent and lack a quantitative review. Therefore, this study aims for a quantitative meta-analysis of VBM analysis on patients with HE.MethodsThe studies in our meta-analysis were collected from Pubmed, Web of Science, and Embase, which were published from January 1947 to October 2021. The seed-based d mapping method was applied to quantitatively estimate the regional gray matter abnormalities (...) in patients with HE. A meta-regression analysis was applied to evaluate the relationship between plasma ammonia and gray matter alteration.ResultsThere were nine studies, with sixteen datasets consisting of 333 participants with HE and 429 healthy controls. The pooled and subgroup meta-analyses showed an increase in gray matter volume in the bilateral thalamus and the calcarine fissure but a decrease in the GMV in the bilateral insula, the basal ganglia, the anterior cingulate gyrus, and the cerebellum. The meta-regression showed that plasma ammonia was positively associated with the GMV in the left thalamus but was negatively associated with the GMV in the cerebellum and the bilateral striatum.ConclusionGray matter volume in patients with HE largely varied and could be affected by plasma ammonia. The findings of this study could help us to better understand the pathophysiology of cognitive dysfunction in patients with HE. (shrink)

Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, (...) psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression. (shrink)

Sensory dysfunction has been shown to be a part of the pathophysiology of schizophrenia. Nowadays we have an objective, non-invasive tool with which to measure neural manifestations of sensory dysfunction. Defined as time-locked changes to external stimuli in the EEG, event-related potentials (ERPs) provide an objective index of information processing in the human brain. Importantly, ERPs may be analyzed through a variety of approaches such as conventional ERP analysis, analysis in the time-frequency domain, microstate segmentation and topographical analysis, as (...) well as source localisation analysis. Each of the methods gives distinct information; they also supplement each other. Here, an attempt is made to verify the validity of combining different approaches to study sensory dysfunction in neuropsychiatric disorders. For example, the data from a schizophrenic patient and an age- and sex-matched healthy subject generate a picture of the events which emerges after visual, proprioceptive and simultaneous presentation of stimuli in both modalities. This approach, though time-consuming, allows the visualisation of changes appearing in the malfunctioning brain as compared to the healthy brain. These methods could ultimately lead to a better establishment of one or more endophenotypes for the schizophrenic disorders. They might also serve as a way to track changes in response to various medications and therapies. (shrink)