Content uploaded by Albert M Galaburda
Author content
All content in this area was uploaded by Albert M Galaburda
Content may be subject to copyright.
The Return of Phineas Gage: Clues About the Brain from the Skull of a Famous Patient
Abstract
When the landmark patient Phineas Gage died in 1861, no autopsy was performed, but his skull was later recovered. The brain
lesion that caused the profound personality changes for which his case became famous has been presumed to have involved the
left frontal region, but questions have been raised about the involvement of other regions and about the exact placement of
the lesion within the vast frontal territory. Measurements from Gage's skull and modern neuroimaging techniques were used
to reconstitute the accident and determine the probable location of the lesion. The damage involved both left and right prefrontal
cortices in a pattern that, as confirmed by Gage's modern counterparts, causes a defect in rational decision making and the
processing of emotion.
... That man being Phineas Gage, who inadvertently ushered in the modern era of neuroscience by allowing doctors to observe the changes of a brain-damaged man who, surprisingly, lived. (Damasio et al., 1994) In the early part of the 20 th century, case studies of a single patient with interesting syndromes were one of the few ways medical science, especially neuroscience, was explored. (Shallice, 1979) The problem with case reports of noteworthy individuals is that the ^indings of a single case cannot be extrapolated to a larger group of people -they have low external validity. ...
Case studies allow for in-depth, data-rich explorations of a single participant in their real-life settings. The value of the case study was once well recognised in health and medical research but was supplanted by research higher in the hierarchy of best evidence. However, case studies are still written, so what is a case study, why would one go to the effort of writing one, and what is worth reporting? This paper aims to provide insights into why anyone would still write a case study, what they are useful for, and what makes a good case study.
... Phineas Gage's personality change after his misadventure in the 1840's when an iron rod plunged through his forebrain brought attention to this region of the brain in decision making, executive functions and emotions (Damasio et al., 1994). Since then, much progress has been made discovering functional correlates of that region, its projections into the brain, and reciprocal effects of substance use (Frankin TR et al., 2002, Volkow et al., 1996. ...
Neurons project long axons that contact other distant neurons. Projections can be mapped by hijacking endogenous membrane trafficking machinery by introducing tracers. To witness functional connections in living animals, we developed a tracer detectible by magnetic resonance imaging (MRI), Mn(II). Mn(II) relies on kinesin-1 and amyloid-precursor protein to travel out axons. Within 24h, projection fields of cortical neurons can be mapped brain-wide with this technology. MnCl2 was stereotactically injected either into anterior cingulate area (ACA) or into infralimbic/prelimbic (IL/PL) of medial forebrain (n=10-12). Projections were imaged, first by manganese-enhanced MRI (MEMRI) live, and then after fixation by microscopy. MR images were collected at 100um isotropic resolution (~5 neurons) in 3D at four time points: before and at successive time points after injections. Images were preprocessed by masking non-brain tissue, followed by intensity scaling and spatial alignment. Actual injection locations, measured from post-injection MR images, were found to be 0.06, 0.49 and 0.84mm apart between cohorts, in R-L, A-P, and D-V directions respectively. Mn(II) enhancements arrived in hindbrains by 24h in both cohorts, while co-injected rhodamine dextran was not detectible beyond immediate subcortical projections. Data-driven unbiased voxel-wise statistical maps after ACA injections revealed significant progression of Mn(II) distally into deeper brain regions: globus pallidus, dorsal striatum, amygdala, hypothalamus, substantia nigra, dorsal raphe and locus coeruleus. Accumulation was quantified as a fraction of total volume of each segment containing significantly enhanced voxels (fractional accumulation volumes), and results visualized in column graphs. Unpaired t-tests between groups of brain-wide voxel-wise intensity profiling by either region of interest (ROI) measurements or statistical parametric mapping highlighted distinct differences in distal accumulation between injection sites, with ACA projecting to periaqueductal gray and IL/PL to basolateral amygdala (p<0.001 FDR). Mn(II) distal accumulations differed dramatically between injection groups in subdomains of the hypothalamus, with ACA targeting dorsal medial, periventricular region and mammillary body nuclei, while IL/PL went to anterior hypothalamic areas and lateral hypothalamic nuclei. Given that these hypothalamic subsegments communicate activity in the central nervous system to the body, these observations describing distinct forebrain projection fields will undoubtedly lead to newer insights in mind-body relationships.
... Por outro lado, mesmo em situações altamente recompensadoras, a dopamina não é o único determinante do comportamento, mas o córtex pré-frontal também tem circuitos que atuam na tomada de decisão. Em especial, a região orbitofrontal (OFC) participa na codificação da recompensa e interfere com a tomada de decisão, atuando de forma inibitória (Fuster, 2017) e promovendo importante controle de impulsos (Damasio, Grabowski, Frank, Galaburda, & Damasio, 1994). Uma atuação fundamental nesse processo é garantir a escolha da melhor recompensa. ...
A despeito da educação formal existir há milênios e a psicologia contribuir com a compreensão da aprendizagem há mais de cem anos, técnicas eficazes de aprendizagem continuam ausentes do repertório de estratégias dos estudantes. Este trabalho teórico foca em insights da neurociência para a aprendizagem de estudantes e examina a efetividade das estratégias de estudo comumente empregadas. Um achado fundamental é que as memórias tendem ao esquecimento a menos que as emoções sejam engajadas no momento da aquisição da informação ou que ocorra uma repetição explícita do processo de aprendizagem. Além disso, prestar atenção integral ao conteúdo desejado é fundamental para otimizar a formação de traços de memória efetivos. Dessa forma, não é surpreendente que técnicas com baixa relevância para os mecanismos de atenção ou com interação limitada com as informações – como grifar textos, fazer uma leitura simples, usar palavras-chave ou imagens mentais e até mesmo fazer resumos – tenham eficácia baixa. Por outro lado, envolver-se em exercícios de resolução de problemas e estabelecer uma rotina de estudos que distribui e promove acessos espaçados à informação, engaja aspectos fundamentais dos circuitos de atenção e facilita a formação de traços de memória robustos, o que maximiza a probabilidade de aprendizagem efetiva. Por fim, direções para pesquisas futuras são apresentadas, além de uma estratégia menos conhecida, mas com potencial para promover repetição e raciocínio crítico sobre os conteúdos, a aprendizagem por meio do ensino, incluindo o método de aprendizagem Feynman.
... were assessed with the methods available at the time, and in some circumstances, the brain (Dronkers et al., 2007;Signoret et al., 1984), skull (Damasio et al., 1994;Ratiu et al., 2004;Van Horn et al., 2012), or digital data (Annese et al., 2014;Augustinack et al., 2014;Corkin et al., 1997) were preserved. With the emergence of novel methods, neuroscience's famous cases are regularly re-evaluated ((Dronkers et al., 2007;Signoret et al., 1984;Thiebaut de Schotten et al., 2015)), most recently using diffusion-weighted tractography to visualise the networks damaged by each lesion (Thiebaut de Schotten et al., 2015). ...
The brain is the most magnificent structure, and we are only at the cusp of unravelling some of its complexity. Neuroanatomy is the best tool for mapping the brain’s structural complexity. As such, neuroanatomy is not just an academic exercise; it serves our fundamental understanding of the neurobiology of cognition and improves clinical practice. A deepened anatomical understanding has advanced our conceptual grasp of the evolution of the brain, interindividual variability of cognition in health and disease, and the conceptual shift toward the emergence of cognition. For the past 20 years, diffusion imaging tractography has dramatically facilitated these advances by enabling the study of the delicate networks that orchestrate brain processes (for review, see (Thiebaut de Schotten and Forkel, 2022).
Purpose: Clinical society faces tremendous difficulties while treating people with mental illnesses, and the best possible care can only be provided by using an integrative approach to assessment and therapy. Particularly, the field of "psychosurgery," or the neurosurgical management of mental diseases, has piqued interest as a possible means of changing behavior and awareness throughout human history. In cases of severe refractory mental disease, psychological surgery - including "deep brain stimulation" and "stereotactic ablation" - is a key therapy option. Recent developments in neuroimaging, as well as psychosurgery, have increased the focus on these therapy techniques. In this paper, the benefits and drawbacks associated with psychological surgery will be thoroughly examined. Objective: The main objective of the paper is to aid individuals in understanding the basics of psychosurgery and its applications. Additionally, it focuses on how to remove the stigma associated with psychosurgery by providing reliable scientific data. Basic information and an overview were supplied thoroughly and simply to fulfill the aforementioned claim. In order to address the "psychosurgery versus psychopharmacology" debate, this paper focuses on analyzing information from many sources and outlining the core principles of each of these treatment modalities. Design/Methodology/Approach: Psychological surgery, which includes "deep brain stimulation as well as "stereotactic ablation," is a crucial treatment strategy in situations of severe refractory mental illness. The fact that several large studies have shown a median rate of response of approximately fifty percent highlights the importance of choosing and selecting participants beforehand. This concept has received attention as a result of recent developments in neurological imaging. Markers of reaction in scientific journals on neuroimaging in psychological operations have also been carefully investigated in order to evaluate the current state of knowledge for imaging prior to surgery. Scientific information was acquired for this research from a variety of trustworthy and legitimate sources. Information has also been extracted from a variety of journal papers. Findings/Result: Even today, managing patients with mental diseases can be challenging, especially when it is felt that they lack the capacity to make intelligent decisions. Due to all of these factors, the practice of psycho-surgery should adopt an integrated method for assessment and therapy. The way psychological therapies are provided in the future will undoubtedly be impacted by concurrent breakthroughs in the fields of behavioral neuroscience, brain imaging, psychological medications, and neurosurgical procedures. According to studies, ablative neurosurgery and “deep brain stimulation” are successful experimental therapies for people with chronic, acute, and “treatment-resistant obsessive-compulsive disorder”, “major depressive disorder”, and “Tourette syndrome”. The careful identification of competent applicants has been guided by suggested criteria. After presenting the details and the expected outcome of the procedure, it is imperative to obtain the person's consent. Originality and Value: In order for readers from all academic disciplines to understand the basic concepts behind psychosurgery and how it can be used to treat a variety of psychological issues, all of the clinical material has been extracted from reliable, scientific publications and organized effectively in this paper without the use of many medical expressions. The scientific complexity of any theoretical or clinical information was avoided, and the material was organized so as to preserve consistency and systematization. Paper Type: Clinical/Healthcare management
The brain is a dynamic system, demonstrating measurable changes as the result of influences from the environment, learning and reinforcement, aging and development, as well as injury and disease. Relationships between brain structure, brain function, and behavior play important roles in neurocriminology. Brain tissue may also be surgically removed to intervene in pathophysiological processes such as epilepsy. A number of different technologies make it possible to evaluate physical properties of the brain and nervous system without interfering with their function. Among the oldest methods of creating images of the brain, computerized tomography utilizes x-rays, taken at a number of angles and reconstructed by computers into navigable images. A number of brain imaging studies have been directed at cognitive traits and abnormalities that accompany criminal behaviour. Understanding the role of genetics in promoting antisocial behavior requires an understanding of physiology and cognition.
In the past decades, a growing interest of neuroscience on moral judgment and decision-making has shed new light on the neurobiological correlates of human morality. It is now understood that moral cognition relies on a complex integration of cognitive and affective information processes that implicate a widely distributed brain network. Moral cognition relies on the coordination of several domain-general processes, subserved by domain-general neural networks, rather than a specific moral cognition system subserved by a specific neural network. In this chapter, we will first briefly review what is currently known about the "moral brain," i.e., the network of brain regions consistently implicated in studies of moral cognition, which include decision-making, affective processing, mentalizing, and perspective-taking processing regions. We will then review the evidence of the impairments found in this network in individuals with psychopathy, a condition whose characteristics indicate profound disturbances in appropriate moral processing. We will present data from neuroimaging studies with forensic/clinical, general population, as well as child and adolescent samples, which seem to converge to support the notion that the moral dysfunction observed in individuals with psychopathy may stem from a disruption of affective components of moral processing rather than from an inability to compute moral judgments per se.
A traumatic brain injury (TBI) is a significant factor in injury-related deaths in the United States and may lead to complex psychological disorders. Auto-cannibalism as a sequela of a TBI has yet to be reported in the literature. The current literature regarding such behavior is often associated with psychosis, intellectual disability, or substance use. A 35-year-old male had a past medical history significant for a TBI a decade ago. He was transferred to the emergency department due to a self-inflicted wound. The patient had been scratching his arms and legs for the last few months and displayed an intense new pattern of self-destructive behavior in the past week. He went through surgical wound debridement and psychiatric evaluation before he was discharged home. This case depicts the importance of regular, long-term psychiatric, and neurological follow-up for patients sustaining TBIs, regardless of whether or not they were previously deemed stable. A greater understanding of many factors leading to self-destructive behavior following TBIs is needed to improve patient outcomes.
The cortex of the anterior pole of the brain can be subdivided, histologically and physiologically, into three major parts. They have been most clearly identified and extensively investigated in the frontal lobe of the primate: (1) the primary motor cortex, a strip of agranular cortex rostral and adjacent to the central sulcus; (2) the premotor cortex, a conglomerate of cytoarchitectonically transitional areas, including the supplementary motor area (SMA); and (3) the prefrontal cortex, which constitutes the largest and most anterior of the three components and which, in the primate at least, has a prominent internal granular layer (IV) and for this reason is known as the granular frontal cortex. The three components can be well distinguished in the external convexity of the frontal lobe; in the cingulate and inferior (orbital) aspects of the lobe, the first two components are absent and the granular cytoarchitecture of the prefrontal cortex blends more or less gradually into that of limbic cortex behind it.
Neuropsychologists commonly use the Wisconsin Card Sorting Test as a test of the integrity of frontal lobe functions. However, an account of its range of validity and of the neuronal mechanisms involved is lacking. We analyze the test at 3 different levels. First, the different versions of the test are described, and the results obtained with normal subjects and brain-lesioned patients are reviewed. Second, a computational analysis is used to reveal what algorithms may pass the test, and to predict their respective performances. At this stage, 3 cognitive components are isolated that may critically contribute to performance: the ability to change the current rule when negative reward occurs, the capacity to memorize previously tested rules in order to avoid testing them twice, and the possibility of rejecting some rules a priori by reasoning. Third, a model neuronal network embodying these 3 components is described. The coding units are clusters of neurons organized in layers, or assemblies. A sensorimotor loop enables the network to sort the input cards according to several criteria (color, form, etc.). A higher-level assembly of rule-coding clusters codes for the currently tested rule, which shifts when negative reward is received. Internal testing of the possible rules, analogous to a reasoning process, also occurs, by means of an endogenous auto-evaluation loop. When lesioned, the model reproduces the behavior of frontal lobe patients. Plausible biological or molecular implementations are presented for several of its components.
: The concept of attention as central to human performance extends back to the start of experimental psychology, yet even a few years ago, it would not have been possible to outline in even a preliminary form a functional anatomy of the human attentional system. New developments in neuroscience have opened the study of higher cognition to physiological analysis, and have revealed a system of anatomical areas that appear to be basic to the selection of information for focal (conscious) processing. The importance of attention is its unique role in connecting the mental level of description of processes used in cognitive science with the anatomical level common in neuroscience. Sperry describes the central role that mental concepts play in understanding brain function. As is the case for sensory and motor systems of the brain, our knowledge of the anatomy of attention is incomplete. Nevertheless, we can now begin to identify some principles of organization that allow attention to function as a unified system for the control of mental processing. Although many of our points are still speculative and controversial, we believe they constitute a basis for more detailed studies of attention from a cognitive-neuroscience viewpoint. Perhaps even more important for furthering future studies, multiple methods of mental chronometry, brain lesions, electrophysiology, and several types of neuro-imaging have converged on common findings.
We describe a multistep technique for three-dimensional reconstruction and analysis of brain lesions in vivo, based on the manipulation of magnetic resonance raw data obtained with a special protocol. The technique permits the direct visual identification of neuroanatomical landmarks in each brain specimen and eliminates the need to rely on averaged templates of human brain sections, which can be a source of lesion localization error. The technique also allows for the bidirectional cross-reference between data points in two-dimensional slices and in volume reconstruction and for the projection of subcortical structures onto the three-dimensional cortical surface. The three-dimensional lesion mapping technique can be applied to research with the lesion method in both human and nonhuman primates, to the planning of neurosurgical lesion approach, and to the teaching of neuroanatomy.
Acquired damage to ventromedial frontal cortices produces abnormalities of decision-making that are especially marked in the realm of social conduct. The pathogenesis of this disorder remains unexplained. One possible mechanism posits that patients with lesions of ventromedial frontal cortices, while retaining the ability to recognize the entities and events that compose social situations, lose the ability to generate an appropriate array of response options to social stimuli, and to conceptualize the future consequences of choosing a particular option. To explore the validity of this mechanism, we tested a prototypical patient with bilateral ventromedial frontal injury and social conduct disorder, along with a group of matched controls, in a series of laboratory probes designed to examine the manipulation of response options and projected outcomes to social stimuli. The experimental subject (patient E.V.R.) exhibited normal or superior performance on tasks that measure the ability to (1) generate possible response options to social situations, (2) consider the future consequences of pursuing particular response options, (3) conceptualize effective measures to achieve given social objectives, (4) predict the likely outcome of a particular configuration of social stimuli, and (5) perform moral reasoning at an advanced developmental level. These findings suggest that: (1) the base of social knowledge that E.V.R. acquired during his normal development is still intact; and that (2) his capacity to access and process components of such knowledge is also intact, in the conditions specified in our experiment.
An investigation of the architectonic organization and intrinsic connections of the prefrontal cortex was conducted in rhesus monkeys. Cytoarchitectonic analysis indicates that in the prefrontal cortex there are two trends of gradual change in laminar characteristics that can be traced from limbic periallocortex towards isocortical areas. The stepwise change in laminar features is characterized by the emergence and gradual increase in the width of granular layer IV, by an increase in the size of pyramidal cells in layers III and V, and by a higher cell-packing density in the supragranular layers. Myeloarchitectonic analysis reveals that the limbic areas are poorly myelinated, adjacent areas have a diffuse myelin content confined to the deep layers, and in isocortices the myelinated fibers are distributed in organized horizontal bands (of Baillarger) and a vertical plexus. Using the above architectonic criteria, we observed that one of the architectonic trends takes a radial basoventral course from the periallocortex in the caudal orbitofrontal region to the adjacent proisocortex and then to area 13. The next stage of architectonic regions includes orbital areas 12, 11, and 14, which is followed by area 10, lateral area 12, and the rostral part of ventral area 46. The last group includes the caudal part of ventral area 46 and ventral area 8. The other trend takes a mediodorsal course from the periallocortex around the rostral portion of the corpus callosum to the adjacent proisocortical areas 24, 25, and 32 and then to the medially situated isocortical areas 9, 10, and 14. The next stage includes lateral areas 10 and 9 and the rostral part of dorsal area 46. The last group includes the caudal part of dorsal area 46 and dorsal area 8.
Phineas Gage was injured by his tamping iron nearly 140 years ago, and only one similar case has been reported since then. In this paper, the contemporary popular and medical responses to the news of Gage's accident are summarized. An attempt is made to evaluate the contribution of Harlow's treatment of Gage as well as the successive bearings which the case was thought to have on analyses of brain function, aphasia, and frontal lobe function.
Extant methods for anatomical localization within a physiological image are inadequate for precise regional correlations between anatomy and physiology. We have developed a method for determining the location of any region of interest within a positron emission tomographic (PET) image by transformation of the tomographic location coordinates into coordinates within a stereotactic atlas of the human brain. The specific anatomical assumptions of this approach were identified and validated within groups of normal subjects by means of measurements made from lateral skull radiographs and nuclear magnetic resonance proton images. A high degree of accuracy and reproducibility was demonstrated when this technique was applied to groups of normal subjects by determining the anatomical location of two physiologically defined PET areas: the cavernous sinus and visually responsive cortex. This method is simple to implement and highly objective. Generalization of the localization procedure for use with structural tomography is readily accomplished.
Seventy-nine patients with unilateral frontal- or temporal-lobe excisions and 18 normal control subjects were tested on four self-ordered tasks requiring the organization of a sequence of pointing responses. There were two verbal and two nonverbal tasks. Patients wih excisions from the left frontal lobe exhibited significant impairments on all four tasks, whilst patients with excisions from the right frontal lobe showed deficits only on the two nonverbal tasks. Patients with temporal-love lesions not extending posteriorly, on the medial side, beyond the pes of the hippocampus were unimpaired on all tasks, whereas those with more radical hippocampal excisions exhibited material-specific deficits that varied with the side of the lesion.