Epilepsy and brain function: common ideas of Hughlings-Jackson and Wilder Penfield

From studies of epilepsy, Hughlings-Jackson proposed a model of brain function including levels of consciousness, a hierarchy of nervous centers, and a sensory-motor relationship. Hughlings-Jackson's ideas influenced Wilder Penfield, a pioneer of electrical stimulation for mapping of the human cerebral cortex. From his work with electrocortical stimulation in patients with epilepsy, Penfield observed what he referred to as a "record of the stream of consciousness," similar to Hughlings-Jackson's "subject consciousness." Penfield expanded upon Hughlings-Jackson's work and suggested that although higher and lower centers explained reflex movements, another separate unaccounted for force controlled voluntary movements. These two functional units he termed the "computer (or automatic sensory-motor mechanism)" and the "mind's mechanism (or highest brain mechanism)." The ideas of John Hughlings-Jackson and Wilder Penfield represent a continuum of thought about the relationship of epilepsy and brain function and continue to be relevant to our current understanding of memory function and the mind-brain relationship.     

Ferrier and the study of auditory cortex

David Ferrier was a British physician who studied the localization of function in the cerebral hemispheres during the latter half of the 19th century. Using stimulation and ablation techniques, Ferrier demonstrated that auditory cortex was located in the superior temporal gyrus of the monkey and that ablation of auditory cortex resulted in deafness. Although he was substantially correct, Ferrier's location of auditory cortex was not accepted by his contemporaries, and his observations of cortical deafness were, until recently, discounted by modern researchers. Just why his findings were rejected is of interest to the study of cortical function.     

The Goltz-Ferrier debates and the triumph of cerebral localizationalist theory

OBJECTIVE: To analyze the significance of the Goltz-Ferrier debates held at the International Medical Congress of 1881 for the development of ideas on cerebral localization. BACKGROUND: Cerebral localization was the subject of vigorous debate throughout the 19th century. At the Congress of 1881, David Ferrier, a leading proponent of cerebral localization, and Friedrich Leopold Goltz, an equally prominent anti-localizationist, had the opportunity to present their experimental research before 3,000 of the world's leading medical figures. METHODS: The authors reviewed and translated the presentations by Goltz and Ferrier at the Congress and supporting publications in contemporary medical journals. RESULTS: In his presentation to the Physiology Section, Goltz criticized localizationists for their widely divergent conclusions about the exact anatomic sites of cortical centers and for their failure to adequately explain functional restitution after cortical ablations. He noted that localizationist theories could, like an apple, "look very tempting and still have a worm inside." He described his own studies on massive decerebrations in dogs and noted that despite complete destruction of the cortices of both hemispheres these animals failed to exhibit motor weakness or deficits in primary sensation. Ferrier noted that Goltz's results were irreconcilable with his own experiments in monkeys, in which circumscribed lesions produced clear and reproducible functional deficits. Both investigators exhibited animals with cortical ablations. Ferrier's presentation of a hemiplegic monkey prompted Charcot's famous utterance, "C'est un malade!" ["It's a patient!"]. A distinguished committee examined the brains of the animals, and confirmed that Ferrier had indeed succeeded in producing a circumscribed lesion in the frontoparietal cortex, whereas the cortical ablations in Goltz's dogs were much less widespread than anticipated. CONCLUSIONS: Ferrier's dramatic demonstration of the effects produced by localized lesions in macaques triumphed over Goltz's unitary view of brain function, providing a major impetus for the subsequent successful development of neurologic surgery.     

Magnetoencephalographic spike sources associated with auditory auras in paediatric localisation-related epilepsy

Objective

To characterise magnetoencephalographic spike sources in paediatric patients with auditory auras and recurrent localisation‐related epilepsy.

Methods

Six patients (four boys and two girls (ages 7–14 years) were retrospectively studied. All patients had auditory auras as part of their initial seizure manifestation, including four patients who underwent previous brain surgery. Scalp video electroencephalography and magnetoencephalography (MEG) were carried out in six patients, intraoperative electrocorticography in three patients and extraoperative intracranial video electroencephalography in one patient. MEG auditory‐evoked fields (AEFs) were studied in four patients.

Results

Three patients had elementary auditory auras, one had complex auditory aura and two had both complex and elementary auras. All six patients had clustered MEG spike sources with coexisting scattered spike sources. MEG clusters were localised in the superior temporal gyrus with surrounding scatters in four patients (two left and two right); two patients had scattered spikes in the superior temporal gyrus in addition to clustered MEG spike sources in the left inferior and middle frontal gyri or parieto‐occipital region. AEFs were located within an MEG cluster in one patient and within 3 cm of a cluster in two patients. Surgical resection, including the regions of MEG clusters, was carried out in four patients. Three of four patients who had previous surgeries were seizure free at 2 years after excision of the MEG cluster region.

Conclusions

MEG spike sources clustered in the superior temporal gyrus in six patients with auditory auras. These spike sources were in close proximity or seemed to engulf the magnetic AEF. Areas with MEG spike sources contained the residual or recurrent epileptogenic zone after incomplete cortical excision for lesional epilepsy.Auditory auras are considered to be reliable indicators of temporal‐lobe seizure onset.^1,2,3,4 Epileptic auditory phenomena include elementary and complex auras. Elementary auditory auras are simple sounds, such as buzzing or ringing, provoked either by direct cortical stimulation of the medial part of Heschl''s gyrus or by spontaneously elicited epileptic discharges involving the primary auditory cortex.^3,5 Complex auditory auras can be hallucinations or illusions of sounds. The auditory hallucinations consist of elaborate phenomena of music or voices, whereas the illusions consist of modifications of intensity, tonality or resonance of surrounding voices. Unlike elementary auditory auras, which have a focal origin on the auditory cortex, complex auditory hallucinations and illusions tend to be elicited from more widespread areas involving the planum temporale or the lateral part of the superior temporal gyrus.^3,5Magnetoencephalography (MEG) localises the sources of intraneuronal electric currents that contribute to extracranial magnetic fields. MEG analysis uses an equivalent current dipole (ECD) model overlaid on to magnetic resonance images to localise sources of interictal epileptiform discharges. This technique can provide unique information about epileptogenic zones as reflected by interictal epileptiform discharges in patients with neocortical localisation‐related epilepsy secondary to lesions.^6,7 As magnetic fields are comparatively unaffected by the different electrical conductivities of the brain, cerebrospinal fluid, skull and skin, MEG can non‐invasively and accurately localise the residual epileptic spike sources in patients with recurrent seizures, even in the presence of skull defects after brain surgery.^8,9In a previous article,¹⁰ we reported on the significance of ear plugging as a behavioural manifestation of auditory auras in three patients. We now report on the localising value of MEG spike sources in six patients with localisation‐related epilepsy and auditory auras as the initial manifestations of their seizures. To our knowledge, this is the first report of MEG spike sources associated with auditory auras in paediatric patients with epilepsy.     

The contribution of Hughlings Jackson to an understanding of dissociation

The author provides a preliminary framework for a systematic and dynamic understanding of dissociation through a consideration of the theories of Hughlings Jackson. Jackson's ideas are briefly reviewed. He saw the proper scientific investigation of mental illness as an experimental investigation of mind. Accordingly, his argument begins with this fundamental concept. His views of the brain-mind relationship and of mind, or self, resemble modern conceptions. He viewed the self as double and focused on those disruptions of the self system which he called the "dreamy state." This state involves an "uncoupling" of normal consciousness, resulting in the loss of the most recently developed forms of memory and of the stream of consciousness. Dissociation is seen here as analogous to the dreamy state. Jacksonian theory predicts the main features of dissociation, i.e., constriction of consciousness, a particular form of amnesia, disaggregation of perceptual phenomena, depersonalization, derealization, and hallucinosis. It leads to the view that dissociation can be seen, in essence, as an uncoupling of consciousness.     

Postsurgical outcome in patients with auditory auras and drug-resistant epilepsy

PurposeWe assessed whether patients with auditory auras have similar outcomes after epilepsy surgery as patients without auditory auras, and hypothesized that patients with non-dominant hemisphere foci might fare better after temporal lobe surgery than patients with dominant resections.MethodsIn this retrospective study, outcome after temporal resection was assessed for patients with drug-resistant epilepsy. Preoperative demographic data, clinical data, and surgical outcome were prospectively registered in a database from 1986 through 2016. Seizure outcome was classified as either seizure-free or relapsed.ResultsData were available in 1186 patients. Forty five patients (3.8%) reported auditory auras; 42 patients (93%) had temporal lobe epilepsy (TLE), and three patients (7%) had extratemporal epilepsy. Since most patients with auditory auras had TLE and in order to have comparable groups, we selected 41 patients with auditory auras and compared them with patients without auditory auras who had temporal lobe resections (767 patients). There were no significant demographic or clinical differences between TLE patients with auditory auras and those without. Patients who had auditory auras were more likely to relapse after temporal lobe surgery than those without (p = 0.03). Among patients who had auditory auras and temporal lobe surgery, side of surgery was not related to postoperative outcome (p = 0.3).ConclusionAuditory auras are rare among patients with drug-resistant TLE. The presence of an auditory aura in a patient with drug-resistant TLE carries a worse prognosis for a postoperative seizure free outcome and this is not related to the side of surgery.     

The idiosyncratic aspects of the epilepsy of Fyodor Dostoevsky

The goal of this article is to review the idiosyncratic aspects of the epilepsy of Fyodor Dostoevsky, one of the greatest writers of all time. The onset of his seizures is controversial, with some evidence pointing to his childhood and other reports that would place the onset in his teens or his twenties. His life in prison in Siberia and then in the Russian army is reviewed. His lifestyle included many factors that exacerbated his epilepsy, especially stress and sleep deprivation. His compulsion for gambling played an important role in producing great stress in his life, as he tried to reverse his poverty in the casinos. The most idiosyncratic aspect of his epilepsy was his so-called ecstatic aura. The etiology of his seizures was probably inherited as revealed by the seizures of his father and the status epilepticus and death of his young son. This great writer died from lung hemorrhages in 1891. Discussed in this review is that he did not likely have an aura of ecstasy; only a few such possible cases can be found in the world literature. For those few cases, evidence from electrical self-stimulation studies in animals and humans, investigating "pleasure centers," can be found to involve the limbic system, especially the septal nucleus. Data from the human amygdala provide evidence why almost all auras are, in fact, unpleasant and not pleasant. A review of recent data on the risks to offspring of epileptic fathers confirms that the etiology of Dostoevsky's epilepsy was probably inherited and that he probably had an idiopathic generalized epilepsy with minor involvement of the temporal lobe. A relationship is seen between his severe obsession with gambling and his epilepsy. Finally, Fyodor Dostoevsky is an excellent example of the "temporal lobe personality."     

Todd, Faraday, and the electrical basis of epilepsy

PURPOSE: To consider the origins of our understanding of the electrical basis of epilepsy in the light of the Lumleian lectures to the Royal College of Physicians in London for 1849, "On the pathology and treatment of convulsive diseases," by Robert Bentley Todd (1809-1860). METHODS: I have reviewed Todd's neglected Lumleian lectures and his observations and concepts of the electrical basis of epilepsy in relation to the influence of Michael Faraday (1791-1867), his contemporary in London, and in relation to later nineteenth century writings on the subject by Jackson, Ferrier, and Hitzig, all of whom overlooked Todd's lectures. RESULTS: Todd was a clinical scientist as well as Professor of Physiology and Morbid Anatomy, with a special interest in the nervous system, at King's College, where he came into contact with Michael Faraday, the greatest electrical scientist of all time, at the nearby Royal Institution. On the basis of his own clinical and experimental studies and his cutting-edge knowledge of neuroanatomy, neurophysiology, neuropathology, and electrical science, Todd brilliantly developed his concepts of the electrical basis of brain activity and of epilepsy in particular. With his microscope, he perceived each nerve vesicle and its related fibres (neurone in later terminology) as distinct entities for the generation of nervous polarity (force) and its transmission in the white nerve fibres throughout the nervous system by unknown molecular mechanisms. In epilepsy, an increase in electrical tension, especially in the grey matter of the hemispheres, led to periodic, sudden explosive discharges, based on Faraday's concept of disruptive discharges. CONCLUSIONS: Todd was the United Kingdom's first outstanding neurologist and neuroscientist before these disciplines existed. Influenced by Faraday, he proposed and confirmed the electrical basis of nervous discharges in epilepsy more than 20 years ahead of Jackson, Ferrier, and Hitzig, who did not refer to his priority, although Ferrier also worked at King's College, and Jackson also gave his own famous Lumleian lectures on the same subject in 1890. Todd deserves the credit for laying the foundations of our modern understanding of epilepsy.     

Magnetic resonance imaging abnormalities in familial temporal lobe epilepsy with auditory auras

BACKGROUND: Two forms of familial temporal lobe epilepsy (FTLE) have been described: mesial FTLE and FTLE with auditory auras. The gene responsible for mesial FTLE has not been mapped yet, whereas mutations in the LGI1 (leucine-rich, glioma-inactivated 1) gene, localized on chromosome 10q, have been found in FTLE with auditory auras. OBJECTIVE: To describe magnetic resonance imaging (MRI) findings in patients with FTLE with auditory auras. DESIGN AND METHODS: We performed detailed clinical and molecular studies as well as MRI evaluation (including volumetry) in all available individuals from one family, segregating FTLE from auditory auras. RESULTS: We evaluated 18 of 23 possibly affected individuals, and 13 patients reported auditory auras. In one patient, auditory auras were associated with déjà vu; in one patient, with ictal aphasia; and in 2 patients, with visual misperception. Most patients were not taking medication at the time, although all of them reported sporadic auras. Two-point lod scores were positive for 7 genotyped markers on chromosome 10q, and a Zmax of 6.35 was achieved with marker D10S185 at a recombination fraction of 0.0. Nucleotide sequence analysis of the LGI1 gene showed a point mutation, VIIIS7(-2)A-G, in all affected individuals. Magnetic resonance imaging was performed in 22 individuals (7 asymptomatic, 4 of them carriers of the affected haplotype on chromosome 10q and the VIIIS7[-2]A-G mutation). Lateral temporal lobe malformations were identified by visual analysis in 10 individuals, 2 of them with global enlargement demonstrated by volumetry. Mildly reduced hippocampi were observed in 4 individuals. CONCLUSIONS: In this family with FTLE with auditory auras, we found developmental abnormalities in the lateral cortex of the temporal lobes in 53% of the affected individuals. In contrast with mesial FTLE, none of the affected individuals had MRI evidence of hippocampal sclerosis.     

Auditory aura in frontal opercular epilepsy: sounds from afar

Auditory auras are typically considered to localize to the temporal neocortex. Herein, we present two cases of frontal operculum/perisylvian epilepsy with auditory auras. Following a non‐invasive evaluation, including ictal SPECT and magnetoencephalography, implicating the frontal operculum, these cases were evaluated with invasive monitoring, using stereoelectroencephalography and subdural (plus depth) electrodes, respectively. Spontaneous and electrically‐induced seizures showed an ictal onset involving the frontal operculum in both cases. A typical auditory aura was triggered by stimulation of the frontal operculum in one. Resection of the frontal operculum and subjacent insula rendered one case seizure‐ (and aura‐) free. From a hodological (network) perspective, we discuss these findings with consideration of the perisylvian and insular network(s) interconnecting the frontal and temporal lobes, and revisit the non‐invasive data, specifically that of ictal SPECT.     

Auditory auras in patients with postencephalitic epilepsy: case series

Many previously healthy patients who present with new seizures or status epilepticus appear to have encephalitis for which no specific pathogen is identified. A significant portion of these patients develop epilepsy. We describe five patients with adult-onset, medically intractable, postencephalitic epilepsy characterized by auditory auras ranging from unformed buzzing to structured language. Auras of any type were common among patients with postencephalitic epilepsy in our referral database: 62% experienced at least one type of aura. The proportion of postencephalitic patients with auditory auras (38%), which may reflect lateral temporal cortical pathology, was higher than that of other adult epilepsy populations. Although no pathogen was identified in four of the five cases, we suggest that the pathophysiology of viral encephalitides may share common targets in the temporal lobes, especially the superior temporal gyrus and surrounding areas, which may account for possibly increased occurrence of auditory auras in this population.     

癫痫患者先兆症状的临床定位意义

目的 探讨癫痫患者先兆症状的临床定位意义。方法 31例癫痫患者按照有无先兆分为有先兆组(n=19)和无先兆组（n=12）,采用独立样本t检验比较两组之间的发病年龄差异有无统计学意义。采用x2检验比较两组之间患者的头颅MRI的异常率及手术有效率差异有无统计学意义。结果 有先兆组的19例患者,分别为精神症状、自主神经症状、躯体感觉、视觉、听觉、头晕共6种先兆,术后先兆症状均消失,以上6种先兆可分别定位于颞叶、颞叶、对侧顶叶或颞叶、枕叶或颞叶、对侧颞叶、颞顶叶。两组间患者的首次发病年龄差异、头颅MRI的异常率差异均无统计学意义。有先兆组和无先兆组患者的手术有效率（分别为15/19和5/12）差异有统计学意义(x2=4.456,P=0.035)。结论 先兆具有一定的定位意义,可以协助判断致痫灶的起源部位,指导外科手术治疗。     

Pediatric extratemporal epilepsy presenting with a complex auditory aura.

INTRODUCTION: Ear plugging (placing fingers in or covering the ears) is a clinical seizure semiology that has been described as a response to an unformed, auditory hallucination localized to the superior temporal neocortex. The localizing value of ear plugging in more complex auditory hallucinations may have more involved circuitry. We report on one child, whose aura was a more complex auditory phenomenon, consisting of a door opening and closing, getting louder as the ictus persisted. METHODS: This child presented, at four years of age, with brief episodes of ear plugging followed by an acute emotional change that persisted until surgical resection of a left mesial frontal lesion at 11 years of age. Scalp video-EEG, magnetic resource imaging, magnetoencephalography, and invasive video-EEG monitoring were carried out. RESULTS: The scalp EEG changes always started after clinical onset. These were not localizing, and encompassed a wide field over the bi-frontal head regions, the left side predominant over the right. Intracranial video-EEG monitoring with subdural electrodes over both frontal and temporal regions localized the seizure-onset to the left mesial frontal lesion. The patient has remained seizure-free since the resection on June 28, 2006, approximately one and a half years ago. CONCLUSION: Ear plugging in response to simple auditory auras localize to the superior temporal gyrus. If the patient has more complex, formed auditory auras, not only may the secondary auditory areas in the temporal lobe be involved, but one has to entertain the possibility of ictal-onset from the frontal cortex.     

Age at onset of epilepsy and aura sensations: Understanding aura sensations from the developmental viewpoint

The temporal sequence of the age at onset of epilepsy in 274 patients with different aura sensations was examined. Cephalic sensation, elementary visual hallucination, anxiety aura, epigastric sensation, and feeling of derealization were associated with significantly earlier onset than déjà vécu, complex visual hallucination, thought disorder, ictal aphasia, complex auditory hallucination, experiential phenomena, and elementary auditory aura. Reassigning this sequence to the neocortical group and the limbic group separately, we confirmed the thesis of Taylor and Lochery that the onset of epilepsy is earlier in crude sensation than in elaborate sensation and found delay of the onset of epilepsy in auditory-related aura in comparison with visual aura.     

Phineas Gage and the enigma of the prefrontal cortex

Perhaps the most famous brain injury in history was a penetrating wound suffered by a rail road worker named Phineas Gage on September 13, 1848. Twelve years after his injury, on the 21st of May, 1860 Phineas Gage died of an epileptic seizure. In 1868 Dr. Harlow gave an outline of Gage's case history and first disclosed his remarkable personality change. One might think this report would assure Gage a permanent place in the annals of neurology, but this was not the case. There was a good reason for this neglect: hardly anyone knew about Harlow's 1868 report. Dr. David Ferrier, an early proponent of the localisation of cerebral function, rescued Gage from obscurity and used the case as the highlight of his famous 1878 Goulstonian lectures. Gage had, through a tragic natural experiment, provided proof of what Ferrier's studies showed: the pre-frontal cortex was not a "non-functional" brain area. A rod going through the prefrontal cortex of Phineas Gage signalled the beginning of the quest to understand the enigmas of this fascinating region of the brain.     

Unpleasant auditory illusions and related avoidance behaviour in a child.

Auditory aura is a rare symptom in focal epilepsy. It has been described in autosomal dominant partial epilepsy with auditory features, but is, in general, poorly documented. We report on a 7-year-old, right-handed boy, who suffered seizures characterized by positive auditory illusions with verbal and gestural automatisms and noticeable attempts at covering his ears. Clinical evaluation and video-recording of the seizures, confirmed that most of the ictal behavior was deliberately directed at trying to prevent the unpleasant sensations reaching his ears. [Published with video sequences].     

The significance of ear plugging in localization-related epilepsy

PURPOSE: The localizing value of ear plugging in the treatment of auditory onset partial seizures, to our knowledge, has not been previously described. We propose that ear plugging is a clinical response to a sensory seizure manifested as an auditory hallucination and a tool for identifying the seizure focus in the auditory cortex on the superior temporal gyrus. METHODS: We report on three children who had prior epilepsy surgery for recurrent symptomatic localization-related epilepsy and who, subsequent to their surgery, displayed stereotyped unilateral or bilateral ear plugging at the onset of partial seizures. We studied scalp video electroencephalography (VEEG), magnetoencephalography (MEG), and magnetic resonance imaging (MRI) in all three. Additionally, we used electrocorticography (ECoG) in two patients, intracranial VEEG monitoring in one patient, and functional MRI language mapping in two patients. RESULTS: All three patients plugged their ears with their hands during auditory auras that localized to the superior temporal gyrus and were followed by partial seizures that spread to a wider field, as shown on scalp and intracranial VEEG. All three patients had MEG interictal discharges in the superior temporal gyrus. One patient who was nonverbal and unable to describe an auditory phenomenon plugged the ear contralateral to where temporal lobe-onset seizures and MEG interictal discharges occurred. CONCLUSIONS; Ear-plugging seizures indicate an auditory aura and may also lateralize seizure onset to the contralateral temporal lobe auditory cortex. Stereotyped behaviors accompanied by epileptic seizures in children who have poor communication skills are important in the seizure semiology of localization-related epilepsy.     

Focal visual status epilepticus

Epileptic visual auras are elementary to complex and sometimes occur as colourful visual phenomena located close to or within the central part of the contralateral hemi‐field. They typically last from seconds to a few minutes, which discriminates them from the usually longer‐lasting visual auras (5‐30 minutes) of patients suffering from migraine. We present an adult patient with occipital lobe epilepsy whose visual aura under epilepsy monitoring lasted for more than 30 minutes with almost no propagation, demonstrating a rare, but remarkable, sustained local epileptic network activity associated with resection of an occipital arterio‐venous malformation.