Computational neuroscience

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https://en.wikipedia.org/wiki/Computational_neuroscience

Computational neuroscience (also known as theoretical neuroscience or mathematical neuroscience) is a branch of neuroscience which employs mathematical models, computer simulations, theoretical analysis and abstractions of the brain to understand the principles that govern the development, structure, physiology and cognitive abilities of the nervous system.

Computational neuroscience employs computational simulations to validate and solve mathematical models, and so can be seen as a sub-field of theoretical neuroscience; however, the two fields are often synonymous. The term mathematical neuroscience is also used sometimes, to stress the quantitative nature of the field.

Computational neuroscience focuses on the description of biologically plausible neurons (and neural systems) and their physiology and dynamics, and it is therefore not directly concerned with biologically unrealistic models used in connectionism, control theory, cybernetics, quantitative psychology, machine learning, artificial neural networks, artificial intelligence and computational learning theory; although mutual inspiration exists and sometimes there is no strict limit between fields, with model abstraction in computational neuroscience depending on research scope and the granularity at which biological entities are analyzed.

Models in theoretical neuroscience are aimed at capturing the essential features of the biological system at multiple spatial-temporal scales, from membrane currents, and chemical coupling via network oscillations, columnar and topographic architecture, nuclei, all the way up to psychological faculties like memory, learning and behavior. These computational models frame hypotheses that can be directly tested by biological or psychological experiments.

History

The term 'computational neuroscience' was introduced by Eric L. Schwartz, who organized a conference, held in 1985 in Carmel, California, at the request of the Systems Development Foundation to provide a summary of the current status of a field which until that point was referred to by a variety of names, such as neural modeling, brain theory and neural networks. The proceedings of this definitional meeting were published in 1990 as the book Computational Neuroscience. The first of the annual open international meetings focused on Computational Neuroscience was organized by James M. Bower and John Miller in San Francisco, California in 1989. The first graduate educational program in computational neuroscience was organized as the Computational and Neural Systems Ph.D. program at the California Institute of Technology in 1985.

The early historical roots of the field can be traced to the work of people including Louis Lapicque, Hodgkin & Huxley, Hubel and Wiesel, and David Marr. Lapicque introduced the integrate and fire model of the neuron in a seminal article published in 1907, a model still popular for artificial neural networks studies because of its simplicity (see a recent review).

About 40 years later, Hodgkin and Huxley developed the voltage clamp and created the first biophysical model of the action potential. Hubel and Wiesel discovered that neurons in the primary visual cortex, the first cortical area to process information coming from the retina, have oriented receptive fields and are organized in columns. David Marr's work focused on the interactions between neurons, suggesting computational approaches to the study of how functional groups of neurons within the hippocampus and neocortex interact, store, process, and transmit information. Computational modeling of biophysically realistic neurons and dendrites began with the work of Wilfrid Rall, with the first multicompartmental model using cable theory.

Major topics

Research in computational neuroscience can be roughly categorized into several lines of inquiry. Most computational neuroscientists collaborate closely with experimentalists in analyzing novel data and synthesizing new models of biological phenomena.

Single-neuron modeling

Main article: Biological neuron models

Even a single neuron has complex biophysical characteristics and can perform computations (e.g.). Hodgkin and Huxley's original model only employed two voltage-sensitive currents (Voltage sensitive ion channels are glycoprotein molecules which extend through the lipid bilayer, allowing ions to traverse under certain conditions through the axolemma), the fast-acting sodium and the inward-rectifying potassium. Though successful in predicting the timing and qualitative features of the action potential, it nevertheless failed to predict a number of important features such as adaptation and shunting. Scientists now believe that there are a wide variety of voltage-sensitive currents, and the implications of the differing dynamics, modulations, and sensitivity of these currents is an important topic of computational neuroscience.

The computational functions of complex dendrites are also under intense investigation. There is a large body of literature regarding how different currents interact with geometric properties of neurons.

Some models are also tracking biochemical pathways at very small scales such as dendritic spines or synaptic clefts.

There are many software packages, such as GENESIS and NEURON, that allow rapid and systematic in silico modeling of realistic neurons. Blue Brain, a project founded by Henry Markram from the École Polytechnique Fédérale de Lausanne, aims to construct a biophysically detailed simulation of a cortical column on the Blue Gene supercomputer.

Modeling the richness of biophysical properties on the single-neuron scale can supply mechanisms that serve as the building blocks for network dynamics. However, detailed neuron descriptions are computationally expensive and this computing cost can limit the pursuit of realistic network investigations, where many neurons need to be simulated. As a result, researchers that study large neural circuits typically represent each neuron and synapse with an artificially simple model, ignoring much of the biological detail. Hence there is a drive to produce simplified neuron models that can retain significant biological fidelity at a low computational overhead. Algorithms have been developed to produce faithful, faster running, simplified surrogate neuron models from computationally expensive, detailed neuron models.

Modeling Neuron-glia interactions

Glial cells participate significantly to the regulation of neuronal activity at a cellular but also at a network level. Modeling this interaction allows to clarify the potassium cycle, so important for maintaining homeostatis and to prevent epileptic seizures. Modeling reveals the role of glial protrusions that can penetrate in some cases the synaptic cleft to interfere with the synpatic transmission and thus control synaptic communication.

Development, axonal patterning, and guidance

Computational neuroscience aims to address a wide array of questions. How do axons and dendrites form during development? How do axons know where to target and how to reach these targets? How do neurons migrate to the proper position in the central and peripheral systems? How do synapses form? We know from molecular biology that distinct parts of the nervous system release distinct chemical cues, from growth factors to hormones that modulate and influence the growth and development of functional connections between neurons.

Theoretical investigations into the formation and patterning of synaptic connection and morphology are still nascent. One hypothesis that has recently garnered some attention is the minimal wiring hypothesis, which postulates that the formation of axons and dendrites effectively minimizes resource allocation while maintaining maximal information storage.

Sensory processing

Early models on sensory processing understood within a theoretical framework are credited to Horace Barlow. Somewhat similar to the minimal wiring hypothesis described in the preceding section, Barlow understood the processing of the early sensory systems to be a form of efficient coding, where the neurons encoded information which minimized the number of spikes. Experimental and computational work have since supported this hypothesis in one form or another. For the example of visual processing, efficient coding is manifested in the forms of efficient spatial coding, color coding, temporal/motion coding, stereo coding, and combinations of them.

Further along the visual pathway, even the efficiently coded visual information is too much for the capacity of the information bottleneck, the visual attentional bottleneck. A subsequent theory, V1 Saliency Hypothesis (V1SH), has been developed on exogenous attentional selection of a fraction of visual input for further processing, guided by a bottom-up saliency map in the primary visual cortex.

Current research in sensory processing is divided among a biophysical modelling of different subsystems and a more theoretical modelling of perception. Current models of perception have suggested that the brain performs some form of Bayesian inference and integration of different sensory information in generating our perception of the physical world.

Motor control

Many models of the way the brain controls movement have been developed. This includes models of processing in the brain such as the cerebellum's role for error correction, skill learning in motor cortex and the basal ganglia, or the control of the vestibulo ocular reflex. This also includes many normative models, such as those of the Bayesian or optimal control flavor which are built on the idea that the brain efficiently solves its problems.

Memory and synaptic plasticity

Main article: Synaptic plasticity

Earlier models of memory are primarily based on the postulates of Hebbian learning. Biologically relevant models such as Hopfield net have been developed to address the properties of associative (also known as "content-addressable") style of memory that occur in biological systems. These attempts are primarily focusing on the formation of medium- and long-term memory, localizing in the hippocampus. Models of working memory, relying on theories of network oscillations and persistent activity, have been built to capture some features of the prefrontal cortex in context-related memory. Additional models look at the close relationship between the basal ganglia and the prefrontal cortex and how that contributes to working memory.

One of the major problems in neurophysiological memory is how it is maintained and changed through multiple time scales. Unstable synapses are easy to train but also prone to stochastic disruption. Stable synapses forget less easily, but they are also harder to consolidate. One recent computational hypothesis involves cascades of plasticity that allow synapses to function at multiple time scales. Stereochemically detailed models of the acetylcholine receptor-based synapse with the Monte Carlo method, working at the time scale of microseconds, have been built. It is likely that computational tools will contribute greatly to our understanding of how synapses function and change in relation to external stimulus in the coming decades.

Behaviors of networks

Biological neurons are connected to each other in a complex, recurrent fashion. These connections are, unlike most artificial neural networks, sparse and usually specific. It is not known how information is transmitted through such sparsely connected networks, although specific areas of the brain, such as the visual cortex, are understood in some detail. It is also unknown what the computational functions of these specific connectivity patterns are, if any.

The interactions of neurons in a small network can be often reduced to simple models such as the Ising model. The statistical mechanics of such simple systems are well-characterized theoretically. Some recent evidence suggests that dynamics of arbitrary neuronal networks can be reduced to pairwise interactions. It is not known, however, whether such descriptive dynamics impart any important computational function. With the emergence of two-photon microscopy and calcium imaging, we now have powerful experimental methods with which to test the new theories regarding neuronal networks.

In some cases the complex interactions between inhibitory and excitatory neurons can be simplified using mean-field theory, which gives rise to the population model of neural networks. While many neurotheorists prefer such models with reduced complexity, others argue that uncovering structural-functional relations depends on including as much neuronal and network structure as possible. Models of this type are typically built in large simulation platforms like GENESIS or NEURON. There have been some attempts to provide unified methods that bridge and integrate these levels of complexity.

Visual attention, identification, and categorization

Visual attention can be described as a set of mechanisms that limit some processing to a subset of incoming stimuli. Attentional mechanisms shape what we see and what we can act upon. They allow for concurrent selection of some (preferably, relevant) information and inhibition of other information. In order to have a more concrete specification of the mechanism underlying visual attention and the binding of features, a number of computational models have been proposed aiming to explain psychophysical findings. In general, all models postulate the existence of a saliency or priority map for registering the potentially interesting areas of the retinal input, and a gating mechanism for reducing the amount of incoming visual information, so that the limited computational resources of the brain can handle it. An example theory that is being extensively tested behaviorally and physiologically is the V1 Saliency Hypothesis that a bottom-up saliency map is created in the primary visual cortex to guide attention exogenously. Computational neuroscience provides a mathematical framework for studying the mechanisms involved in brain function and allows complete simulation and prediction of neuropsychological syndromes.

Cognition, discrimination, and learning

Computational modeling of higher cognitive functions has only recently begun. Experimental data comes primarily from single-unit recording in primates. The frontal lobe and parietal lobe function as integrators of information from multiple sensory modalities. There are some tentative ideas regarding how simple mutually inhibitory functional circuits in these areas may carry out biologically relevant computation.

The brain seems to be able to discriminate and adapt particularly well in certain contexts. For instance, human beings seem to have an enormous capacity for memorizing and recognizing faces. One of the key goals of computational neuroscience is to dissect how biological systems carry out these complex computations efficiently and potentially replicate these processes in building intelligent machines.

The brain's large-scale organizational principles are illuminated by many fields, including biology, psychology, and clinical practice. Integrative neuroscience attempts to consolidate these observations through unified descriptive models and databases of behavioral measures and recordings. These are the bases for some quantitative modeling of large-scale brain activity.

The Computational Representational Understanding of Mind (CRUM) is another attempt at modeling human cognition through simulated processes like acquired rule-based systems in decision making and the manipulation of visual representations in decision making.

Consciousness

One of the ultimate goals of psychology/neuroscience is to be able to explain the everyday experience of conscious life. Francis Crick, Giulio Tononi and Christof Koch made some attempts to formulate consistent frameworks for future work in neural correlates of consciousness (NCC), though much of the work in this field remains speculative. Specifically, Crick cautioned the field of neuroscience to not approach topics that are traditionally left to philosophy and religion.

Computational clinical neuroscience

Computational clinical neuroscience is a field that brings together experts in neuroscience, neurology, psychiatry, decision sciences and computational modeling to quantitatively define and investigate problems in neurological and psychiatric diseases, and to train scientists and clinicians that wish to apply these models to diagnosis and treatment.

Predictive computational neuroscience

Predictive computational neuroscience is a recent field that combines signal processing, neuroscience, clinical data and machine learning to predict the brain during coma or anesthesia. For example, it is possible to anticipate deep brain states using the EEG signal. These states can be used to anticipate hypnotic concentration to administrate to the patient.

Computational Psychiatry

Computational psychiatry is a new emerging field that brings together experts in machine learning, neuroscience, neurology, psychiatry, psychology to provide an understanding of psychiatric disorders.

Technology

Neuromorphic computing

Main article: Neuromorphic engineering

A neuromorphic computer/chip is any device that uses physical artificial neurons (made from silicon) to do computations (See: neuromorphic computing, physical neural network). One of the advantages of using a physical model computer such as this is that it takes the computational load of the processor (in the sense that the structural and some of the functional elements don't have to be programmed since they are in hardware). In recent times, neuromorphic technology has been used to build supercomputers which are used in international neuroscience collaborations. Examples include the Human Brain Project SpiNNaker supercomputer and the BrainScaleS computer.

Early intervention in psychosis

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Early_intervention_in_psychosis 

 

Further information: Pediatric schizophrenia

Early intervention in psychosis is a clinical approach to those experiencing symptoms of psychosis for the first time. It forms part of a new prevention paradigm for psychiatry and is leading to reform of mental health services, especially in the United Kingdom and Australia.

This approach centers on the early detection and treatment of early symptoms of psychosis during the formative years of the psychotic condition. The first three to five years are believed by some to be a critical period. The aim is to reduce the usual delays to treatment for those in their first episode of psychosis. The provision of optimal treatments in these early years is thought to prevent relapses and reduce the long-term impact of the condition. It is considered a secondary prevention strategy.

The duration of untreated psychosis (DUP) has been shown as an indicator of prognosis, with a longer DUP associated with more long-term disability.

Components of the model

There are a number of functional components of the early psychosis model, and they can be structured as different sub-teams within early psychosis services. The emerging pattern of sub-teams are currently:

Early psychosis treatment teams

Multidisciplinary clinical teams providing an intensive case management approach for the first three to five years. The approach is similar to assertive community treatment, but with an increased focus on the engagement and treatment of this previously untreated population and the provision of evidence based, optimal interventions for clients in their first episode of psychosis. For example, the use of low-dose antipsychotic medication is promoted ("start low, go slow"), with a need for monitoring of side effects and an intensive and deliberate period of psycho-education for patients and families that are new to the mental health system. In addition, research showed that family intervention for psychosis (FIp) reduced relapse rates, hospitalization duration, and psychotic symptoms along with increasing functionality in first-episode psychosis (FEP) up to 24 months. Interventions to prevent a further episodes of psychosis (a "relapse") and strategies that encourage a return to normal vocation and social activity are a priority. There is a concept of phase specific treatment for acute, early recovery and late recovery periods in the first episode of psychosis.

Early detection function

Interventions aimed at avoiding late detection and engagement of those in the course of their psychotic conditions. Key tasks include being aware of early signs of psychosis and improving pathways into treatment. Teams provide information and education to the general public and assist GPs with recognition and response to those with suspected signs, for example: EPPIC's Youth Access Team (YAT) (Melbourne); OPUS (Denmark); TIPS (Norway); REDIRECT (Birmingham); LEO CAT (London) "; STEP's Population Health approach to early detection.

The development and implementation of quantitative tools for early detection of at-risk individuals is an active research area. This includes development of risk calculators and methods for large-scale population screening.

Prodrome clinics

Prodrome or at risk mental state clinics are specialist services for those with subclinical symptoms of psychosis or other indicators of risk of transition to psychosis. The Pace Clinic in Melbourne, Australia, is considered one of the origins of this strategy, but a number of other services and research centers have since developed. These services are able to reliably identify those at high risk of developing psychosis and are beginning to publish encouraging outcomes from randomised controlled trials that reduce the chances of becoming psychotic, including evidence that psychological therapy and high doses of fish oil have a role in the prevention of psychosis. However, a meta-analysis of five trials found that while these interventions reduced risk of psychosis after 1 year (11% conversion to psychosis in intervention groups compared to 32% in control groups), these gains were not maintained over 2–3 years of follow-up. These findings indicate that interventions delay psychosis, but do not reduce the long-term risk. There has also been debate about the ethics of using antipsychotic medication to reduce the risk of developing psychosis, because of the potential harms involved with these medications.

In 2015, the European Psychiatric Association issued guidance recommending the use of the Cognitive Disturbances scale (COGDIS), a subscale of the basic symptoms scale, to assess psychosis risk; a meta-analysis conducted for the guidance found that while rates of conversion to psychosis were similar to those who meet Ultra High Risk (UHR) criteria up to 2 years after assessment, they were significantly higher after 2 years for those patients who met the COGDIS criteria. The COGDIS criteria measure subjective symptoms, and include such symptoms as thought interference, where irrelevant and emotionally unimportant thought contents interfere with the main line of thinking; thought block, where the current train of thought halts; thought pressure, where thoughts unrelated to a common topic appear uncontrollably; referential ideation that is immediately corrected; and other characteristic disturbances of attention and the use or understanding of language.

History

Early intervention in psychosis is a preventive approach for psychosis that has evolved as contemporary recovery views of psychosis and schizophrenia have gained acceptance. It subscribes to a "post Kraepelin" concept of schizophrenia, challenging the assumptions originally promoted by Emil Kraepelin in the 19th century, that schizophrenia ("dementia praecox") was a condition with a progressing and deteriorating course. The work of Post, whose kindling model, together with Fava and Kellner, who first adapted staging models to mental health, provided an intellectual foundation. Psychosis is now formulated within a diathesis–stress model, allowing a more hopeful view of prognosis, and expects full recovery for those with early emerging psychotic symptoms. It is more aligned with psychosis as continuum (such as with the concept of schizotypy) with multiple contributing factors, rather than schizophrenia as simply a neurobiological disease.

Within this changing view of psychosis and schizophrenia, the model has developed from a divergence of several different ideas, and from a number of sites, beginning with the closure of psychiatric institutions signaling a move toward community based care. In 1986, the Northwick Park study discovered an association between delays to treatment and disability, questioning the service provision for those with their first episode of schizophrenia. In the 1990s, evidence began to emerge that cognitive behavioural therapy was an effective treatment for delusions and hallucinations. The next step came with the development of the EPPIC early detection service in Melbourne, Australia in 1996 and the prodrome clinic led by Alison Yung. This service was an inspiration to other services, such as the West Midlands IRIS group, including the carer charity Rethink Mental Illness; the TIPS early detection randomised control trial in Norway; and the Danish OPUS trial. In 2001, the United Kingdom Department of Health called the development of early psychosis teams "a priority". The International Early Psychosis Association, founded in 1998, issued an international consensus declaration together with the World Health Organization in 2004. Clinical practice guidelines have been written by consensus.

Clinical outcome evidence

A number of studies have been carried out to see whether the early psychosis approach reduces the severity of symptoms, improves relapse rates, and decreases the use of inpatient care, in comparison to standard care. Advocates of early intervention for psychosis have been accused of selectively citing findings that support the benefits of early intervention, but ignoring findings that do not. It has been argued that the scientific reporting of evidence on early intervention in psychosis is characterized by a high prevalence of ‘spin’ and ‘bias’. An analysis of the summaries of articles found that 75% implied positive results, whereas examination of the findings with primary measures from these studies found that only 13% were positive. A prospective two-year follow-up of 114 patients hospitalized for a first episode psychotic illness reported 75% recovery, while 41% returned to baseline functioning, and nearly half experienced new episodes.

A systematic review investigated the effects of early intervention for psychosis:

Specialized team compared to standard care for psychosis

Summary
There is emerging, but as yet inconclusive evidence, to suggest that people in the prodrome of psychosis can be helped by some interventions. There is some support for specialized early intervention services, but further trials would be desirable, and there is a question of whether gains are maintained. There is some support for phase-specific treatment focused on employment and family therapy, but again, this needs replicating with larger and longer trials.

Outcome Findings in words Findings in numbers Quality of evidence

Evidence on cost

Studies have been published claiming that early psychosis services cost less than standard services, largely through reduced in-patient costs, and also save other costs to society. However, the claimed savings have been disputed. A 2012 systematic review of the evidence concluded that: "The published literature does not support the contention that early intervention for psychosis reduces costs or achieves cost-effectiveness".

Reform of mental health services

United Kingdom

The United Kingdom has made significant service reform with their adoption of early psychosis teams following the first service in Birmingham set up by Professor Max Birchwood in 1994 and used as a blueprint for national roll-out, with early psychosis now considered as an integral part of comprehensive community mental health services. The Mental Health Policy Implementation Guide outlines service specifications and forms the basis of a newly developed fidelity tool. There is a requirement for services to reduce the duration of untreated psychosis, as this has been shown to be associated with better long-term outcomes. The implementation guideline recommends:

• 14 to 35 year age entry criteria
• First three years of psychotic illness
• Aim to reduce the duration of untreated psychosis to less than 3 months
• Maximum caseload ratio of 1 care coordinator to 10–15 clients
• For every 250,000 (depending on population characteristics), one team
  • Total caseload 120 to 150
  • 1.5 doctors per team
  • Other specialist staff to provide specific evidence based interventions

Australia and New Zealand

In Australia the EPPIC initiative provides early intervention services. In the Australian government's 2011 budget, $222.4 million was provided to fund 12 new EPPIC centres in collaboration with the states and territories. However, there have been criticisms of the evidence base for this expansion and of the claimed cost savings.

On August 19, 2011, Patrick McGorry, South Australian Social Inclusion Commissioner David Cappo AO and Frank Quinlan, CEO of the Mental Health Council of Australia, addressed a meeting of the Council of Australian Governments (COAG), chaired by Prime Minister Julia Gillard, on the future direction of mental health policy and the need for priority funding for early intervention. The invitation, an initiative of South Australian Premier Mike Rann, followed the release of Cappo's "Stepping Up" report, supported by the Rann Government, which recommended a major overhaul of mental health in South Australia, including stepped levels of care and early intervention.

New Zealand has operated significant early psychosis teams for more than 20 years, following the inclusion of early psychosis in a mental health policy document in 1997. There is a national early psychosis professional group, New Zealand Early Intervention for Psychosis Society (NZEIPS), organising a biannual training event, advocating for evidenced based service reform and supporting production of local resources.

Scandinavia

Early psychosis programmes have continued to develop from the original TIPS services in Norway and the OPUS randomised trial in Denmark.

North America

Canada has extensive coverage across most provinces, including established clinical services and comprehensive academic research in British Columbia (Vancouver), Alberta (EPT in Calgary), Quebec (PEPP-Montreal), and Ontario (PEPP, FEPP).

In the United States, the Early Assessment Support Alliance (EASA) is implementing early psychosis intervention throughout the state of Oregon.

In the United States, the implementation of coordinated specialty care (CSC), as a recovery-oriented treatment program for people with first episode psychosis (FEP), has become a US health policy priority. CSC promotes shared decision making and uses a team of specialists who work with the client to create a personal treatment plan. The specialists offer psychotherapy, medication management geared to individuals with FEP, family education and support, case management, and work or education support, depending on the individual's needs and preferences. The client and the team work together to make treatment decisions, involving family members as much as possible. The goal is to link the individual with a CSC team as soon as possible after psychotic symptoms begin because a longer period of unchecked and untreated illness might be associated with poorer outcomes.

Asia

The first meeting of the Asian Network of Early Psychosis (ANEP) was held in 2004. There are now established services in Singapore, Hong Kong and South Korea

Alien hand syndrome

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Alien_hand_syndrome

Alien hand syndrome
Other names	AHS; alien limb syndrome; ALS; Dr. Strangelove syndrome
Specialty	Psychiatry, Neurology

Alien hand syndrome (AHS) or Dr. Strangelove syndrome is a category of conditions in which a person experiences their limbs acting seemingly on their own, without conscious control over the actions. There are a variety of clinical conditions that fall under this category, which most commonly affects the left hand. There are many similar terms for the various forms of the condition, but they are often used inappropriately. The affected person may sometimes reach for objects and manipulate them without wanting to do so, even to the point of having to use the controllable hand to restrain the alien hand. Under normal circumstances however, given that intent and action can be assumed to be deeply mutually entangled, the occurrence of alien hand syndrome can be usefully conceptualized as a phenomenon reflecting a functional "disentanglement" between thought and action.

Alien hand syndrome is best documented in cases where a person has had the two hemispheres of their brain surgically separated, a procedure sometimes used to relieve the symptoms of extreme cases of epilepsy and epileptic psychosis, e.g., temporal lobe epilepsy. It also occurs in some cases after brain surgery, stroke, infection, tumor, aneurysm, migraine and specific degenerative brain conditions such as Alzheimer's disease, corticobasal degeneration and Creutzfeldt–Jakob disease. Other areas of the brain that are associated with alien hand syndrome are the frontal, occipital, and parietal lobes. Signs and symptoms.

"Alien behavior" can be distinguished from reflexive behavior in that the former is flexibly purposive while the latter is obligatory. Sometimes the affected person will not be aware of what the alien hand is doing until it is brought to his or her attention, or until the hand does something that draws their attention to its behavior. There is a clear distinction between the behaviors of the two hands in which the affected hand is viewed as "wayward" and sometimes "disobedient" and generally out of the realm of their own voluntary control, while the unaffected hand is under normal volitional control. At times, particularly in patients who have sustained damage to the corpus callosum that connects the two cerebral hemispheres (see also split-brain), the hands appear to be acting in opposition to each other.

A related syndrome described by the French neurologist François Lhermitte involves the release through disinhibition of a tendency to compulsively utilize objects that present themselves in the surrounding environment around the patient. The behavior of the patient is, in a sense, obligatorily linked to the "affordances" (using terminology introduced by the American ecological psychologist, James J. Gibson) presented by objects that are located within the immediate peri-personal environment.

This condition is known as utilization behavior. It is most often associated with extensive bilateral frontal lobe damage and might actually be thought of as "bilateral" alien hand syndrome in which the patient is compulsively directed by external environmental contingencies (such as the presence of a hairbrush on the table in front of them elicits the act of brushing the hair) and has no capacity to "hold back" and inhibit pre-potent motor programs that are obligatorily linked to the presence of specific external objects in the peri-personal space of the patient. When the frontal lobe damage is bilateral and generally more extensive, the patient completely loses the ability to act in a self-directed manner and becomes totally dependent upon the surrounding environmental indicators to guide their behavior in a general social context, a condition referred to as "environmental dependency syndrome".

In order to deal with the alien hand, some patients engage in personification of the affected hand. Usually these names are negative in nature, from mild such as "cheeky" to malicious "monster from the moon". For example, Rachelle Doody and Jankovic described a patient who named her alien hand "baby Joseph". When the hand engaged in playful, troublesome activities such as pinching her nipples (akin to biting while nursing), she would experience amusement and would instruct baby Joseph to "stop being naughty". Furthermore, Bogen suggested that certain personality characteristics, such as a flamboyant personality, contribute to frequent personification of the affected hand.

Neuroimaging and pathological research shows that the frontal lobe (in the frontal variant) and corpus callosum (in the callosal variant) are the most common anatomical lesions responsible for the alien hand syndrome. These areas are closely linked in terms of motor planning and its final pathways.

The callosal variant includes advanced willed motor acts by the non-dominant hand, where patients frequently exhibit "intermanual conflict" in which one hand acts at cross-purposes with the other "good hand". For example, one patient was observed putting a cigarette into her mouth with her intact, "controlled" hand (her right, dominant hand), following which her left hand rose, grasped the cigarette, pulled it out of her mouth, and toss it away before it could be lit by the right hand. The patient then surmised that "I guess 'he' doesn't want me to smoke that cigarette." Another patient was observed to be buttoning up her blouse with her controlled dominant hand while the alien non-dominant hand, at the same time, was unbuttoning her blouse. The frontal variant most often affects the dominant hand, but can affect either hand depending on the lateralization of the damage to medial frontal cortex, and includes grasp reflex, impulsive groping toward objects or/and tonic grasping (in other words, difficulty in releasing grip).

In most cases, classic alien-hand signs derive from damage to the medial frontal cortex, accompanying damage to the corpus callosum. In these patients, the main cause of damage is unilateral or bilateral infarction of cortex in the territory supplied by the anterior cerebral artery or associated arteries. Oxygenated blood is supplied by the anterior cerebral artery to most medial portions of the frontal lobes and to the anterior two-thirds of the corpus callosum, and infarction may consequently result in damage to multiple adjacent locations in the brain in the supplied territory. As the medial frontal lobe damage is often linked to lesions of the corpus callosum, frontal variant cases may also present with callosal form signs. Cases of damage restricted to the callosum however, tend not to show frontal alien-hand signs.

Cause

The common emerging factor in alien hand syndrome is that the primary motor cortex controlling hand movement is isolated from premotor cortex influences but remains generally intact in its ability to execute movements of the hand.

A 2009 fMRI study looking at the temporal sequence of activation of components of a cortical network associated with voluntary movement in normal individuals demonstrated "an anterior-to-posterior temporal gradient of activity from supplemental motor area through premotor and motor cortices to the posterior parietal cortex". Therefore, with normal voluntary movement, the emergent sense of agency appears to be associated with an orderly sequence of activation that develops initially in the anteromedial frontal cortex in the vicinity of the supplementary motor complex on the medial surface of the frontal aspect of the hemisphere (including the supplementary motor area) prior to activation of the primary motor cortex in the pre-central gyrus on the lateral aspect of the hemisphere, when the hand movement is being generated. Activation of the primary motor cortex, presumed to be directly involved in the execution of the action via projections into the corticospinal component of the pyramidal tracts, is then followed by activation of the posterior parietal cortex, possibly related to the receipt of recurrent or re-afferent somatosensory feedback generated from the periphery by the movement which would normally interact with the efference copy transmitted from primary motor cortex to permit the movement to be recognized as self-generated rather than imposed by an external force. That is, the efference copy allows the recurrent afferent somatosensory flow from the periphery associated with the self-generated movement to be recognized as re-afference as distinct from ex-afference. Failure of this mechanism may lead to a failure to distinguish between self-generated and externally generated movement of the limb. This anomalous situation in which re-afference from a self-generated movement is mistakenly registered as ex-afference due to a failure to generate and successfully transmit an efference copy to sensory cortex, could readily lead to the interpretation that what is in actuality a self-generated movement has been produced by an external force as a result of the failure to develop a sense of agency in association with emergence of the self-generated movement (see below for a more detailed discussion).

A 2007 fMRI study examining the difference in functional brain activation patterns associated with alien as compared to non-alien "volitional" movement in a patient with alien hand syndrome found that alien movement involved anomalous isolated activation of the primary motor cortex in the damaged hemisphere contralateral to the alien hand, while non-alien movement involved the normal process of activation described in the preceding paragraph in which primary motor cortex in the intact hemisphere activates in concert with frontal premotor cortex and posterior parietal cortex presumably involved in a normal cortical network generating premotor influences on the primary motor cortex along with immediate post-motor re-afferent activation of the posterior parietal cortex.

Combining these two fMRI studies, one could hypothesize that the alien behavior that is unaccompanied by a sense of agency emerges due to autonomous activity in the primary motor cortex acting independently of premotor cortex pre-activating influences that would normally be associated with the emergence of a sense of agency linked to the execution of the action.

As noted above, these ideas can also be linked to the concept of efference copy and re-afference, where efference copy is a signal postulated to be directed from premotor cortex (activated normally in the process associated with emergence of an internally generated movement) over to somatosensory cortex of the parietal region, in advance of the arrival of the "re-afferent" input generated from the moving limb, that is, the afferent return from the moving limb associated with the self-generated movement produced. It is generally thought that a movement is recognized as internally generated when the efference copy signal effectively "cancels out" the re-afference. The afferent return from the limb is effectively correlated with the efference copy signal so that the re-afference can be recognized as such and distinguished from "ex-afference", which would be afferent return from the limb produced by an externally imposed force. When the efference copy is no longer normally generated, then the afferent return from the limb associated with the self-generated movement is mis-perceived as externally produced "ex-afference" since it is no longer correlated with or canceled out by the efference copy. As a result, the development of the sense that a movement is not internally generated even though it actually is (i.e. the failure of the sense of agency to emerge in conjunction with the movement), could indicate a failure of the generation of the efference copy signal associated with the normal premotor process through which the movement is prepared for execution.

Since there is no disturbance of the sense of ownership of the limb in this situation, and there is no apparent physical explanation for how the owned limb could be moving in a purposive manner without an associated sense of agency, a cognitive dissonance is created which may be resolved through the assumption that the goal-directed limb movement is being directed by an "alien" unidentifiable external force with the capacity for directing goal-directed actions of one's own limb.

Disconnection

It is theorized that alien hand syndrome results when disconnection occurs between different parts of the brain that are engaged in different aspects of the control of bodily movement. As a result, different regions of the brain are able to command bodily movements, but cannot generate a conscious feeling of self-control over these movements. As a result, the sense of agency that is normally associated with voluntary movement is impaired or lost. There is a dissociation between the process associated with the actual execution of the physical movements of the limb and the process that produces an internal sense of voluntary control over the movements, with this latter process thus normally creating the internal conscious sensation that the movements are being internally initiated, controlled and produced by an active self.

Recent studies have examined the neural correlates of emergence of the sense of agency under normal circumstances. This appears to involve consistent congruence between what is being produced through efferent outflow to the musculature of the body, and what is being sensed as the presumed product in the periphery of this efferent command signal. In alien hand syndrome, the neural mechanisms involved in establishing that this congruence has occurred may be impaired. This may involve an abnormality in the brain mechanism that differentiates between "re-afference" (the return of kinesthetic sensation from the self-generated "active" limb movement) and "ex-afference" (kinesthetic sensation generated from an externally produced 'passive' limb movement in which an active self does not participate). This brain mechanism is proposed to involve the production of a parallel "efference copy" signal that is sent directly to the somatic sensory regions and is transformed into a "corollary discharge", an expected afferent signal from the periphery that would result from the performance driven by the issued efferent signal. The correlation of the corollary discharge signal with the actual afferent signal returned from the periphery can then be used to determine if, in fact, the intended action occurred as expected. When the sensed result of the action is congruent with the predicted result, then the action can be labelled as self-generated and associated with an emergent sense of agency.

If, however, the neural mechanisms involved in establishing this sensorimotor linkage associated with self-generated action are faulty, it would be expected that the sense of agency with action would not develop as discussed in the previous section.

Loss of inhibitions

One theory posed to explain these phenomena proposes that the brain has separable neural "premotor" or "agency" systems for managing the process of transforming intentions into overt action. An anteromedial frontal premotor system is engaged in the process of directing exploratory actions based on "internal" drive by releasing or reducing inhibitory control over such actions.

A 2011 paper reporting on neuronal unit recording in the medial frontal cortex in human subjects showed a clear pre-activation of neurons identified in this area up to several hundred milliseconds prior to the onset of an overt self-generated finger movement and the authors were able to develop a computational model whereby volition emerges once a change in internally generated firing rate of neuronal assemblies in this part of the brain crossed a threshold. Damage to this anteromedial premotor system produces disinhibition and release of such exploratory and object acquisition actions which then occur autonomously. A posterolateral temporo-parieto-occipital premotor system has a similar inhibitory control over actions that withdraw from environmental stimuli as well as the ability to excite actions that are contingent upon and driven by external stimulation, as distinct from internal drive. These two intrahemispheric systems, each of which activates an opposing cortical "tropism", interact through mutual inhibition that maintains a dynamic balance between approaching toward (in other words, with "intent-to-capture" in which contact with and grasping onto the attended object is sought) versus withdrawing from (that is, with "intent-to-escape" in which distancing from the attended object is sought) environmental stimuli in the behavior of the contralateral limbs. Together, these two intrahemispheric agency systems form an integrated trans-hemispheric agency system.

When the anteromedial frontal "escape" system is damaged, involuntary but purposive movements of an exploratory reach-and-grasp nature – what Denny-Brown referred to as a positive cortical tropism – are released in the contralateral limb. This is referred to as a positive cortical tropism because eliciting sensory stimuli, such as would result from tactile contact on the volar aspect of the fingers and palm of the hand, are linked to the activation of movement that increases or enhances the eliciting stimulation through a positive feedback connection (see discussion above in section entitled "Parietal and Occipital Lobes").

When the posterolateral parieto-occipital "approach" system is damaged, involuntary purposive movements of a release-and-retract nature, such as levitation and instinctive avoidance – what Denny-Brown referred to as a negative cortical tropism – are released in the contralateral limb. This is referred to as a negative cortical tropism because eliciting sensory stimuli, such as would result from tactile contact on the volar aspect of the fingers and palm of the hand, are linked to the activation of movement that reduces or eliminates the eliciting stimulation through a negative feedback connection (see discussion above in section entitled "Parietal and Occipital Lobes").

Each intrahemispheric agency system has the potential capability of acting autonomously in its control over the contralateral limb although unitary integrative control of the two hands is maintained through interhemispheric communication between these systems via the projections traversing the corpus callosum at the cortical level and other interhemispheric commissures linking the two hemispheres at the subcortical level.

Disconnection of hemispheres due to injury

One major difference between the two hemispheres is the direct connection between the agency system of the dominant hemisphere and the encoding system based primarily in the dominant hemisphere that links action to its production and through to its interpretation with language and language-encoded thought. The overarching unitary conscious agent that emerges in the intact brain is based primarily in the dominant hemisphere and is closely connected to the organization of language capacity. It is proposed that while relational action in the form of embodied inter-subjective behavior precedes linguistic capacity during infant development, a process ensues through the course of development through which linguistic constructs are linked to action elements in order to produce a language-based encoding of action-oriented knowledge.

When there is a major disconnection between the two hemispheres resulting from callosal injury, the language-linked dominant hemisphere agent which maintains its primary control over the dominant limb loses, to some degree, its direct and linked control over the separate "agent" based in the nondominant hemisphere, and the nondominant limb, which had been previously responsive and "obedient" to the dominant conscious agent. The possibility of purposeful action occurring outside of the realm of influence of the conscious dominant agent can occur and the basic assumption that both hands are controlled through and subject to the dominant agent is proven incorrect. The sense of agency that would normally arise from movement of the nondominant limb now no longer develops, or, at least, is no longer accessible to consciousness. A new explanatory narrative for understanding the situation in which the now inaccessible nondominant hemisphere based agent is capable of activating the nondominant limb is necessitated.

Under such circumstances, the two separated agents can control simultaneous actions in the two limbs that are directed at opposing purposes although the dominant hand remains linked to the dominant consciously accessible language-linked agent and is viewed as continuing to be under "conscious control" and obedient to conscious will and intent as accessible through thought, while the nondominant hand, directed by an essentially non-verbal agent whose intent can only be inferred by the dominant agent after the fact, is no longer "tied in" and subject to the dominant agent and is thus identified by the conscious language-based dominant agent as having a separate and inaccessible alien agency and associated existence. This theory would explain the emergence of alien behavior in the nondominant limb and intermanual conflict between the two limbs in the presence of damage to the corpus callosum.

The distinct anteromedial, frontal, and posterolateral temporo-parieto-occipital variants of the alien hand syndrome would be explained by selective injury to either the frontal or the posterior components of the agency systems within a particular hemisphere, with the relevant and specific form of alien behavior developing in the limb contralateral to the damaged hemisphere.

Diagnosis

Corpus callosum

Damage to the corpus callosum can give rise to "purposeful" actions in the person's non-dominant hand (an individual who is left-hemisphere-dominant will experience the left hand becoming alien, and the right hand will turn alien in the person with right-hemisphere dominance).

In "the callosal variant", the patient's hand counteracts voluntary actions performed by the other, "good" hand. Two phenomena that are often found in patients with callosal alien hand are agonistic dyspraxia and diagonistic dyspraxia.

Agonistic dyspraxia involves compulsive automatic execution of motor commands by one hand when the patient is asked to perform movements with the other hand. For example, when a patient with callosal damage was instructed to pull a chair forward, the affected hand would decisively and impulsively push the chair backwards. Agonistic dyspraxia can thus be viewed as an involuntary competitive interaction between the two hands directed toward completion of a desired act in which the affected hand competes with the unaffected hand to complete a purposive act originally intended to be performed by the unaffected hand.

Diagonistic dyspraxia, on the other hand, involves a conflict between the desired act in which the unaffected hand has been engaged and the interfering action of the affected hand which works to oppose the purpose of the desired act intended to be performed by the unaffected hand. For instance, when Akelaitis's patients underwent surgery to the corpus callosum to reduce epileptic seizures, one patient's left alien hand would frequently interfere with the right hand. For instance, while trying to turn over to the next page with the right hand, his left hand would try to close the book.

In another case of callosal alien hand, the patient did not have intermanual conflict between the hands but rather from a symptom characterized by involuntary mirror movements of the affected hand. When the patient was asked to perform movements with one hand, the other hand would involuntarily perform a mirror image movement which continued even when the involuntary movement was brought to the attention of the patient, and the patient was asked to restrain the mirrored movement. The patient had a ruptured aneurysm near the anterior cerebral artery, which resulted in the right hand being mirrored by the left hand. The patient described the left hand as frequently interfering and taking over anything the patient tried to do with the right hand. For instance, when trying to grasp a glass of water with the right hand with a right side approach, the left hand would involuntary reach out and grasp hold of the glass through a left side approach.

More recently, Geschwind et al. described the case of a woman with severe coronary heart disease.^[31] One week after undergoing coronary artery bypass grafting, she noticed that her left hand started to "live a life of its own". It would unbutton her gown, try to choke her while asleep and would automatically fight with the right hand to answer the phone. She had to physically restrain the affected hand with the right hand to prevent injury, a behavior which has been termed "self-restriction". The left hand also showed signs of severe ideomotor apraxia. It was able to mimic actions but only with the help of mirror movements executed by the right hand (enabling synkinesis). Using magnetic resonance imaging (MRI), Geschwind et al. found damage to the posterior half of the callosal body, sparing the anterior half and the splenium extending slightly into the white matter underlying the right cingulate cortex.

Park et al. also described two cases of infarction as the origin of alien hand symptoms. Both individuals had had infarction of the anterior cerebral artery (ACA). One individual, a 72-year-old male, had difficulty controlling his hands, as they often moved involuntarily, despite his trying to stabilize them. Furthermore, he often could not let go of objects after grasping them with his palms. The other individual, a 47-year-old female with an ACA in a different location of the artery, complained that her left hand would move on its own and she could not control its movements. Her left hand could also sense when her right hand was holding an object and would involuntarily, forcibly take the object out of her right hand.

Frontal lobe

Unilateral injury to the medial aspect of the brain's frontal lobe can trigger reaching, grasping and other purposeful movements in the contralateral hand. With anteromedial frontal lobe injuries, these movements are often exploratory reaching movements in which external objects are frequently grasped and utilized functionally, without the simultaneous perception on the part of the patient that they are "in control" of these movements. Once an object has been acquired and is maintained in the grasp of this "frontal variant" form of alien hand, the patient often has difficulty with voluntarily releasing the object from grasp and can sometimes be seen to be peeling the fingers of the hand back off the grasped object using the opposite controlled hand to enable the release of the grasped object (also referred to as tonic grasping or the "instinctive grasp reaction"). Some (for example, the neurologist Derek Denny-Brown) have referred to this behavior as "magnetic apraxia"

Goldberg and Bloom described a woman with a large cerebral infarction of the medial surface of the left frontal lobe in the territory of the left anterior cerebral artery which left her with the frontal variant of the alien hand involving the right hand. There were no signs of callosal disconnection nor was there evidence of any callosal damage. The patient displayed frequent grasp reflexes; her right hand would reach out and grab objects without releasing them. In regards to tonic grasping, the more the patient tried to let go of the object, the more the grip of the object tightened. With focused effort the patient was able to let go of the object, but if distracted, the behaviour would re-commence. The patient could also forcibly release the grasped object by peeling her fingers away from contact with the object using the intact left hand. Additionally, the hand would scratch at the patient's leg to the extent that an orthotic device was required to prevent injury. Another patient reported not only tonic grasping towards objects nearby, but the alien hand would take hold of the patient's penis and engage in public masturbation.

Parietal and occipital lobes

A distinct "posterior variant" form of alien hand syndrome is associated with damage to the posterolateral parietal lobe and/or occipital lobe of the brain. The movements in this situation tend to be more likely to withdraw the palmar surface of the hand away from sustained environmental contact rather than reaching out to grasp onto objects to produce palmar tactile stimulation, as is most often seen in the frontal form of the condition. In the frontal variant, tactile contact on the ventral surface of the palm and fingers facilitates finger flexion and grasp of the object through a positive feedback loop (i.e. the stimulus generates movement that reinforces, strengthens and sustains the triggering stimulation).

In contrast, in the posterior variant, tactile contact on the ventral surface of the palm and fingers is actively avoided through facilitation of extension of the fingers and withdrawal of the palm in a negative feedback loop (i.e. the stimulus, and even anticipation of stimulation of the palmar surface of the hand, generates movement of the palm and fingers that reduces and effectively counteracts and eliminates the triggering stimulation, or, in the case of anticipated palmar contact, decreases the likelihood of such contact). Alien movements in the posterior variant of the syndrome also tend to be less coordinated and show a coarse ataxic motion during active movement that is generally not observed in the frontal form of the condition. This is generally thought to be due to an optic form of ataxia since it is facilitated by the visual presence of an object with visual attention directed toward the object. The apparent instability could be due to an unstable interaction between the tactile avoidance tendency biasing toward withdrawal from the object, and the visually based acquisition bias tendency pushing toward an approach to the object.

The alien limb in the posterior variant of the syndrome may be seen to "levitate" upward into the air withdrawing away from contact surfaces through the activation of anti-gravity musculature. Alien hand movement in the posterior variant may show a typical posture, sometimes referred to as a "parietal hand" or the "instinctive avoidance reaction" (a term introduced by neurologist Derek Denny-Brown as an inverse form of the "magnetic apraxia" seen in the frontal variant, as noted above), in which the digits move into a highly extended position with active extension of the interphalangeal joints of the digits and hyper-extension of the metacarpophalangeal joints, and the palmar surface of the hand is actively pulled back away from approaching objects or up and away from supporting surfaces. The "alien" movements, however, remain purposeful and goal-directed, a point which clearly differentiates these movements from other disorganized non-purposeful forms of involuntary limb movement (e.g. athetosis, chorea, or myoclonus).

Similarities between frontal and posterior variants

In both the frontal and the posterior variants of the alien hand syndrome, the patient's reactions to the limb's apparent capability to perform goal-directed actions independent of conscious volition is similar. In both of these variants of alien hand syndrome, the alien hand emerges in the hand contralateral to the damaged hemisphere.

Treatment

There is no cure for the alien hand syndrome. However, the symptoms can be reduced and managed to some degree by keeping the alien hand occupied and involved in a task, for example by giving it an object to hold in its grasp. Specific learned tasks can restore voluntary control of the hand to a significant degree. One patient with the "frontal" form of alien hand who would reach out to grasp onto different objects (e.g., door handles) as he was walking was given a cane to hold in the alien hand while walking, even though he really did not need a cane for its usual purpose. With the cane firmly in the grasp of the alien hand, it would generally not release the grasp and drop the cane in order to reach out to grasp onto a different object. Other techniques proven to be effective include; wedging the hand between the legs or slapping it; warm water application and visual or tactile contact. Additionally, Wu et al. found that an irritating alarm activated by biofeedback reduced the time the alien hand held an object.

In the presence of unilateral damage to a single cerebral hemisphere, there is generally a gradual reduction in the frequency of alien behaviors observed over time and a gradual restoration of voluntary control over the affected hand. Actually, when AHS originates from focal injury of acute onset, recovery usually occurs within a year. One theory is that neuroplasticity in the bihemispheric and subcortical brain systems involved in voluntary movement production can serve to re-establish the connection between the executive production process and the internal self-generation and registration process. Exactly how this may occur is not well understood, but a process of gradual recovery from alien hand syndrome when the damage is confined to a single cerebral hemisphere has been reported. In some instances, patients may resort to constraining the wayward, undesirable and sometimes embarrassing actions of the impaired hand by voluntarily grasping onto the forearm of the impaired hand using the intact hand. This observed behavior has been termed "self-restriction" or "self-grasping".

In another approach, the patient is trained to perform a specific task, such as moving the alien hand to contact a specific object or a highly salient environmental target, which is a movement that the patient can learn to generate voluntarily through focused training in order to effectively override the alien behavior. It is possible that some of this training produces a re-organization of premotor systems within the damaged hemisphere, or, alternatively, that ipsilateral control of the limb from the intact hemisphere may be expanded.

Another method involves simultaneously "muffling" the action of the alien hand and limiting the sensory feedback coming back to the hand from environmental contact by placing it in a restrictive "cloak" such as a specialized soft foam hand orthosis or, alternatively, an everyday oven mitt. Other patients have reported using an orthotic device to restrict perseverative grasping or restraining the alien hand by securing it to the bed pole. Of course, this can limit the degree to which the hand can participate in addressing functional goals for the patient and may be considered to be an unjustifiable restraint.

Theoretically, this approach could slow down the process through which voluntary control of the hand is restored if the neuroplasticity that underlies recovery involves the recurrent exercise of voluntary will to control the actions of the hand in a functional context and the associated experiential reinforcement through successful willful suppression of the alien behaviour.

History

The first known case described in the medical literature appeared in a detailed case report published in German in 1908 by the preeminent German neuro-psychiatrist, Kurt Goldstein. In this paper, Goldstein described a right-handed woman who had had a stroke affecting her left side from which she had partially recovered by the time she was seen. However, her left arm seemed as though it belonged to another person and performed actions that appeared to occur independent of her will.

The patient complained of a feeling of "strangeness" in relationship to the goal-directed movements of the left hand and insisted that "someone else" was moving the left hand, and that she was not moving it herself. When the left hand grasped an object, she could not voluntarily release it. The senses of touch and proprioception of the left side were impaired. The left hand would make spontaneous movements, such as wiping the face or rubbing the eyes, but these were relatively infrequent. With significant effort, she was able to move her left arm in response to spoken command, but conscious movements were slower or less precise than similar involuntary motions.

Goldstein developed a "doctrine of motor apraxia" in which he discussed the generation of voluntary action and proposed a brain structure for temporal and spatial cognition, will and other higher cognitive processes. Goldstein maintained that a structure conceptually organizing both the body and external space was necessary for object perception as well as for voluntary action on external objects.

In his classic papers reviewing the wide variety of disconnection syndromes associated with focal brain pathology, Norman Geschwind commented that Kurt Goldstein "was perhaps the first to stress the non-unity of the personality in patients with callosal section, and its possible psychiatric effects".

In popular culture

• In Stanley Kubrick's 1964 film Dr. Strangelove, the eponymous character, played by Peter Sellers, apparently has alien hand syndrome, as he can't stop himself from doing the Nazi salute. "Dr. Strangelove syndrome" was suggested as the official name for AHS. This was not approved, though it is sometimes used as an alternative name.
• In the 1999 movie Idle Hands the main character of the movie has his left hand possessed by the devil and cannot control it, though the title is a reference to "Idle hands are the Devil's playground," the fact that the hand literally has a mind of its own is highly similar.
• In the medical drama TV series House episode "Both Sides Now", a patient has alien hand syndrome.
• An episode of Dark Matters: Twisted But True – a documentary TV series on Discovery Science – described alien hand syndrome and traced its history. The 2017 Indian Tamil dark comedy film Peechankai is about a person with AHS.
• In Season 2 of the TV series Scream Queens, Dr. Brock Holt appears to have alien hand syndrome.