Functional disconnection

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

Functional disconnection is the disintegrated function in the brain in the absence of anatomical damage, in distinction to physical disconnection of the cerebral hemispheres by surgical resection, trauma or lesion. Applications have included alexia without agraphia dyslexia, persistent vegetative state and minimally conscious state as well as autistic spectrum disorders. Functional disconnection itself is not a medically recognized condition. It is a theoretical concept used to facilitate research into the causes and symptoms within recognized conditions. 

History

In 1977, Witleson reported that developmental dyslexia may be associated with (i) bi-hemisphere representation of spatial functions, in contrast to the unitary right hemisphere control of these functions observed in normal individuals. The bilateral neural involvement in spatial processing may interfere with the left hemisphere's processing of its own specialized functions and result in deficient linguistic, sequential cognitive processing and in overuse of the spatial, holistic cognitive mode, reflecting a functional disconnection syndrome in these individuals confirmed by Leisman in the 1980s and in the 2000s.

The concept of functional disconnection developed further with Stachowiak and Poeck in 1976. who reported on a case in 1976 of a 67-yr-old male with hemianopia resulting from a cerebrovascular accident resulting in pure alexia and a color naming deficit that he suggested was due to a functional disconnection mechanism. He noted that the underlying disconnection mechanism is improved by the facilitating effect of unblocking methods (in the tactile, somesthetic, auditory, and visual systems), so that pathways other than the one impaired by the brain lesion are used.

In 1998, Fritson presented a mechanistic account of how dysfunctional integration among neuronal systems arises, based on the central role played by synaptic plasticity in shaping the connections. He hypothesized that the pathophysiology of schizophrenia is expressed at the level of modulation of associative changes in synaptic efficacy; specifically the modulation of plasticity in those brain systems responsible for emotional learning and emotional memory in the postnatal period. This modulation is mediated by ascending neurotransmitter systems that: (i) have been implicated in schizophrenia; and (ii) are known to be involved in consolidating synaptic connections during learning. The pathophysiology results in a disruption of the reinforcement of adaptive behavior consistent with the disintegrative aspects of the disorder. Kim and colleagues in 2003 further described the disconnection hypothesis in schizophrenia as the result of a prefrontal-parietal lobe functional disconnection, particularly prefrontal dissociation and abnormal prefrontal-parietal interaction during working memory processing.

The concept of functional disconnection developed still further when it was applied to the understanding of the nature of autistic spectrum disorder. Geschwind and Levitt in 2007 suggested a model of the symptoms of autism in which higher-order association areas of the brain (that normally connect to the frontal lobe) are partially disconnected during development, thereby explaining the heterogeneity of autism etiology. The autism group at Cambridge University provided evidence that the functional connectivity of medial temporal lobe structures specifically is abnormal in people with Asperger’s syndrome, at least during fearful face processing. Melillo and Leisman have similarly concluded that a functional disconnection syndrome is a basis for explaining the symptoms of autistic spectrum disorder.

Disconnection syndrome

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

Diffusion tensor imaging of the brain showing the right and left arcuate fasciculus (Raf & Laf), the right and left superior longitudinal fasciculus (Rslf & Lslf), and tapetum of corpus callosum (Ta).

Disconnection syndrome is a general term for a collection of neurological symptoms caused – via lesions to associational or commissural nerve fibres – by damage to the white matter axons of communication pathways in the cerebrum (not to be confused with the cerebellum), independent of any lesions to the cortex. The behavioral effects of such disconnections are relatively predictable in adults. Disconnection syndromes usually reflect circumstances where regions A and B still have their functional specializations except in domains that depend on the interconnections between the two regions.

Callosal syndrome, or split-brain, is an example of a disconnection syndrome from damage to the corpus callosum between the two hemispheres of the brain. Disconnection syndrome can also lead to aphasia, left-sided apraxia, and tactile aphasia, among other symptoms. Other types of disconnection syndrome include conduction aphasia (lesion of the association tract connecting Broca’s area and Wernicke’s), agnosia, apraxia, pure alexia, etc.

Anatomy of cerebral connections

Theodore Meynert, a neuroanatomist of the late 1800s, developed a detailed anatomy of white matter pathways. He classified the white matter fibers that connect the neocortex into three important categories – projection fibers, commissural fibers and association fibers. Projection fibers are the ascending and descending pathways to and from the neocortex. Commissural fibers are responsible for connecting the two hemispheres while the association fibers connect cortical regions within a hemisphere. These fibers make up the interhemispheric connections in the cortex.

Callosal disconnection syndrome is characterized by left ideomotor apraxia and left-hand agraphia and/or tactile anomia, and is relatively rare.

Hemispheric disconnection

Many studies have shown that disconnection syndromes such as aphasia, agnosia, apraxia, pure alexia and many others are not caused by direct damage to functional neocortical regions. They can also be present on only one side of the body which is why these are categorized as hemispheric disconnections. The cause for hemispheric disconnection is if the interhemispheric fibers, as mentioned earlier, are cut or reduced.

An example is commissural disconnect in adults which usually results from surgical intervention, tumor, or interruption of the blood supply to the corpus callosum or the immediately adjacent structures. Callosal disconnection syndrome is characterized by left ideomotor apraxia and left-hand agraphia and/or tactile anomia, and is relatively rare.

Other examples include commissurotomy, the surgical cutting of cerebral commissures to treat epilepsy and callosal agenesis which is when individuals are born without a corpus callosum. Those with callosal agenesis can still perform interhemispheric comparisons of visual and tactile information but with deficits in processing complex information when performing the respective tasks.

Sensorimotor disconnection

Hemispheric disconnection has impacted behaviors relating to the sensory and motor systems. The different systems affected are listed below:

• Olfaction – The olfactory system is not crossed across hemispheres like the other senses, which means that left input goes to the left hemisphere and right input goes to the right hemisphere. Fibers in the anterior commissure control the olfactory regions in each hemisphere. A patient who lacks an anterior commissure cannot name odors entering the right nostril or use the right hand to pick up the object corresponding to the odor because the left hemisphere, responsible for language and controlling the right hand, is disconnected from the sensory information.
• Vision – Information from one visual field travels to the contralateral hemisphere. Therefore, with a commissurotomy patient, visual information presented in the left visual field travelling to the right hemisphere would be disconnected from verbal output since the left hemisphere is responsible for speech.
• Somatosensory – If the two hemispheres are disconnected, the somatosensory functions of the left and right parts of the body become independent. For example, when something is placed on the left hand of a blindfolded patient with the two hemispheres disconnected, the left hand can pick the correct object within a set of objects but the right hand cannot.
• Audition – Though most of the input from one ear would go through the same ear, the opposite ear also receives some input. Therefore, the disconnection effects seems to be reduced in audition compared to the other systems. However, studies have shown that when the hemispheres are disconnected, the individual does not hear anything from the left and only hears from the right.
• Movement – Apraxia and agraphia may occur where responding to any verbal instructions by movement or writing in the left hand is inhibited because the left hand cannot receive these instructions from the right hemisphere,

History

The concept of disconnection syndrome emerged in the late nineteenth century when scientists became aware that certain neurological disorders result from communication problems among brain areas. In 1874, Carl Wernicke introduced this concept in his dissertation when he suggested that conduction aphasia could result from the disconnection of the sensory speech zone from the motor speech area by a single lesion in the left hemisphere to the arcuate fasciculus. As the father of the disconnection theory, Wernicke believed that instead of being localized in specific regions of the brain, higher functions resulted from associative connections between the motor and sensory memory areas.

Lissauer, a pupil of Wernicke, described a case of visual agnosia as a disconnection between the visual and language areas.

Dejerine in 1892 described specific symptoms resulting from a lesion to the corpus callosum that caused alexia without agraphia. The patient had a lesion in the left occipital lobe, blocking sight in the right visual field (hemianopia), and in the splenium of the corpus callosum. Dejerine interpreted this case as a disconnection of the speech area in the left hemisphere from the right visual cortex.

In 1965, Norman Geschwind, an American neurologist, wrote ‘Disconnexion syndromes in animals and man’ where he described a disconnectionist framework that revolutionized neurosciences and clinical neurology. Studies of the monkey brain led to his theory that disconnection syndromes were higher function deficits. Building on Wernicke and previously mentioned psychologists’ idea that disconnection syndromes involved white matter lesion to association tracts connecting two regions of the brain, Geschwind was more detailed in explaining some disconnection syndromes as lesions of the association cortex itself, specifically in the parietal lobe. He described the callosal syndrome, an example of a disconnection syndrome, which is a lesion in the corpus callosum that leads to tactile anomia in just the patient’s left hand.

Though Geschwind made significant advances in describing disconnection syndromes, he was not completely accurate. He didn’t think the association cortex had any specialized role of its own besides acting as a relay station between the primary sensory and motor areas. However, in the 1960s and 1970s, Mesulam and Damasio incorporated specific functional roles for the association cortex. With Mesulam and Damasio’s contributions, Geschwind’s model has evolved over the past 50 years to include connections between brain regions as well as specializations of association cortices.

More recently, neurologists have been using imaging techniques such as diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) to visualize association pathways in the human brain to advance the future of this disconnection theme.

Hemispherectomy

From Wikipedia, the free encyclopedia

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

Hemispherectomy is a surgery that is performed by a neurosurgeon where an unhealthy hemisphere of the brain is disconnected or removed. There are two types of hemispherectomy. Functional hemispherectomy refers to when the diseased brain is simply disconnected so that it can no longer send signals to the rest of the brain and body. Anatomical hemispherectomy refers to when not only is there disconnection, but also the diseased brain is physically removed from the skull. This surgery is mostly used as a treatment for medically intractable epilepsy, which is the term used when anti-seizure medications are unable to control seizures.

History

The first anatomical hemispherectomy was performed and described in 1928 by Walter Dandy. This was done as an attempt to treat glioma, a brain tumor. The first known anatomical hemispherectomy performed as a treatment for intractable epilepsy was in 1938 by Kenneth McKenzie, a Canadian neurosurgeon. Krynaw, a neurosurgeon from South Africa, was one of the first to perform and report a case series on hemispherectomies in 1950. He performed the surgery on pediatric patients with infantile hemiplegia, specifically as a treatment for their seizures and cognitive impairment. His hemispherectomy technique removed the damaged hemisphere except the thalamus and caudate structures. Krynaw reported good outcomes overall, although there was one post-operative death. Specifically, there was an overall theme of improvement in weakness, spasticity and cognition. Amazingly, ten out of the twelve patients had seizures prior to the operation and none of the patients had seizures afterwards. Other neurosurgeons began performing hemispherectomies as well, primarily for the treatment of seizures. For the most part, the surgeries would go well initially, but there was a general theme of subsequent deterioration and even death years after the surgery. As a result of the complication risk and the introduction of new anti-seizure medications, the popularity of the procedure began to decline in the 1950s. Oppenheimer and Griffith were one of the first to describe the potential complications, and they reported their findings in 1966, describing superficial hemosiderosis, granular ependymitis and obstructive hydrocephalus. They posited a theoretical solution to this problem, a surgery that is now known as a functional hemispherectomy. Rasmussen was one of the first neurosurgeons to develop and apply a functional hemispherectomy in practice. He initially made modifications to the original hemispherectomy by preserving the least epileptogenic quarter or third of the hemisphere, hoping this would ameliorate the known complications of the original anatomic hemispherectomy. Although this modification seemed to solve this issue, patients undergoing the modified hemispherectomy continued to have seizures, which was problematic. Therefore, he further modified his surgery to functionally sever residual portions of the frontal and parieto-occipital lobes. This surgery, the functional hemispherectomy, has been further modified over the years by several different neurosurgeons, and to this day there is not a consensus as to which exact technique should be used. Hemispherotomy refers to some of the more recently developed approaches to disconnect the epileptic hemisphere while minimizing brain removal and the risk for complications.

Nomenclature

There are two main types of hemispherectomy: Anatomical and Functional.

Anatomical hemispherectomy refers to the resection and removal of an entire hemisphere of the brain, which includes all four lobes, with or without the removal of basal ganglia and thalamus.

Functional hemispherectomy refers to surgeries that disable the function of one hemisphere, while maintaining its blood supply and without physically removing the entire hemisphere from the skull. Functional hemispherectomies are performed more frequently than anatomical hemispherectomies due to their lower complication rates. However, they do carry a risk of incomplete disconnection, which refers to when the surgeon inadvertently leaves remnants of fibers that continue to connect the hemisphere to the brain and body. These remaining fibers can be problematic, as they may lead to seizure recurrence.

Another term that falls under the hemispherectomy umbrella includes hemidecortication, which is the removal of the cortex from one half of the cerebrum, while attempting to preserve the ventricular system by maintaining the surrounding white matter. Hemidecortication was originally developed as a possible strategy to mitigate some of the complications seen with complete anatomical hemispherectomy.

The term hemispherotomy refers to a surgery that is akin to a functional hemispherectomy in that it functionally severs the damaged hemisphere from the other and leaves some of the severed hemisphere within the skull, but the difference is that it removes even less tissue from the skull. The term hemispherotomy is now used as an umbrella term to describe the group of modern techniques and procedures that predominate at most contemporary epilepsy centers.

There is no statistically significant difference in seizure-free rates between the four different types of surgeries:  Hemispherotomy, functional hemispherectomy, anatomical hemispherectomy and hemidecortication. The overall rate of seizure freedom is estimated to be 73.4%.  However, hemispherotomy procedures may be associated with a more favorable complication profile.

Candidates

The typical candidates for hemispherectomy are pediatric patients who have intractable epilepsy due to extensive cerebral unilateral hemispheric injuries. In addition, the seizures should ideally be emanating from that same hemisphere. In some situations, a hemispherectomy may still be performed if there are seizures from both hemispheres, as long as the majority come from one side. In order to assess the patient’s epilepsy completely, patients undergo extensive testing, including EEG and MRI. Most patients also undergo other studies including functional MRI (fMRI), positron emission tomography (PET) or magnetoencephalography (MEG).

Today, hemispherectomy is performed as a treatment for severe and intractable epilepsy, including for young children whose epilepsy has been found to be drug-resistant. The most common underlying etiologies include malformations of cortical development (MCD), perinatal stroke and Rasmussen’s encephalitis. MCD is an umbrella term for a wide variety of developmental brain anomalies, including hemimegalencephaly and cortical dysplasia. Other less common underlying etiologies include hemiconvulsion-hemiplegia epilepsy syndrome and Sturge-Weber syndrome.

Procedure

Patients often shave the area of the scalp that will be involved with the surgery. Patients undergo general anesthesia and are unconscious for the procedure. The surgical site is sterilized, after which the skin is incised. A substantial portion of the bone is removed, followed by incision of the dura, which is the outer covering of the brain. There are several blood vessels that have connections with both sides of the brain, and these are carefully identified and clipped in such a way that spares the healthy hemisphere. Ultimately, a bundle of fibers that connect both of the cerebral hemispheres, the corpus callosum, is removed which results in the functional separation of one hemisphere from the other. Portions of the cerebral lobes from the damaged side of the brain are removed, depending on the specific procedure being performed. The surgeon may leave some brain tissue, such as the thalamus or choroid plexus. After completing the resection, the surgical site is irrigated with saline, the brain covering called the dura is sutured back together, the bone that was removed is replaced and the skin is sutured. This surgery often takes four to five hours. Patients often spend a few nights in the hospital post-operatively, and they undergo physical and occupational therapy soon after the surgery.

Potential complications

The most common complication from surgery is hydrocephalus, a condition in which fluid accumulates within the brain, and this is often treated with a shunt to divert the fluid away. The rate of shunts following surgery ranges from 14–23%. Other complications include wound complications, epidural hemorrhages, subdural hemorrhages, intraparenchymal hemorrhages, intracranial abscesses, meningitis, ventriculitis and venous thrombosis. Additional epilepsy surgery following hemispherectomy is rare (4.5%),^[7] but may be recommended if there is a residual connection between the two hemispheres that is causing frequent seizures. Mortality rates are low and estimated to be <1% to 2.2%. Most patients do not experience changes in cognition, but some individuals may be at risk. A visual deficit called contralateral homonymous hemianopsia is expected to occur in most patients, where the entire visual field contralateral to the removed hemisphere is lost. There is a risk of motor deficits, and this is variable. Other possible complications include infection, aseptic meningitis, hearing loss, endocrine problems and transient neurologic deficits such as limb weakness.

Outcomes

Since seizures are the most common indication for hemispherectomy surgery, most research on hemispherectomy analyzes how the surgery affects seizures. Many patients undergoing surgery obtain good surgical outcomes, some obtaining complete seizure freedom (54–90%) and others having some degree of improvement in seizure burden. A recently developed scoring system has been proposed to help predict the probability of seizure freedom with more accuracy:  HOPS (Hemispherectomy Outcome Prediction Scale). Although it cannot definitively predict surgical outcome with exact precision, some physicians may use it as a guide. The scoring system takes certain variables into consideration including age at seizure onset, history of prior brain surgery, seizure semiology and imaging findings.

There is also data pertaining to how hemispherectomy affects the body in other ways. After surgery, the remaining cerebral hemisphere is often able to take over some cognitive, sensory and motor functions. The degree to which the remaining hemisphere takes on this additional workload often depends on several factors, including the underlying etiology, which hemisphere is removed and the age at which the surgery occurs.

In terms of postoperative motor function, some patients may have improvement or no change of their weaker extremity, and many can walk independently. Most patients postoperatively have minimal to no behavioral problems, satisfactory language skills, good reading capability, and only a minority of patients have a decline in IQ. Predictors of poor outcome may include seizure recurrence and structural abnormalities in the intact hemisphere.

Ultimately, risks and benefits should be weighed on an individual basis and discussed in detail with the neurosurgeon. Many patients have excellent outcomes, and the International League Against Epilepsy (ILAE) reports that “about one-fifth of hemispherectomy patients are gainfully employed and even fewer live independently.”

The Brain Recovery Project

The Brain Recovery Project is a non-profit corporation which funds new research and is based in the United States. This corporation hosts an annual two-day conference for patients who have had hemispherectomies and their families. There are several purposes to this reunion. The main goal is to educate patients and their families on the surgery and its necessary subsequent rehabilitation. It also serves as a way for patients and families to connect with one another, learn from specialists in the field and often offers research enrollment.