The maturation of epilepsy surgery as a viable treatment option for medically refractory epilepsy began at roughly the same time at three major epilepsy centers: The University of Illinois, the University of London, and the Montreal Neurological Institute (MNI)/McGill University. At all three locations, there was close collaboration among the neurosurgeon, neurologist (or electrophysiologist), and neuropsychologist. Although the MNI's contributions to the development of contemporary neuropsychology are well known, in part reflecting the continuity of their program, all three epilepsy surgery programs made important discoveries informing the neuropsychology of epilepsy.
University of London/Guy's Maudsley Hospital
The University of London is probably the least well-known program outside of epilepsy surgery circles and was directed by the neurosurgeon Murray Falconer. Falconer developed en bloc
resections of the temporal lobe the facilitated pathological studies and identified hippocampal pathology as being critical for clinical outcome (Meador, Loring, & Flaningin, 1989
). Victor Meyer and Aubrey Yates were the psychology members of that program.
Meyer and Yates reported greater surgical effects for paired-associated learning compared with other psychological measures including a New Word Learning and Retention Test or 24 h retention (Meyer & Yates, 1955
). This early report indicates the sensitivity of paired-associated learning to hippocampal dysfunction and anticipated contemporary theories of hippocampal function as a critical structure involved in “binding” associations (Fig. ).
Fig. 5. First reported effects illustrating sensitivity of hard-word paired-associate learning to dominant hemisphere resection. Although there is a mild post-operative decline seen in the easy-word pairs following dominant hemisphere resection, the decline in (more ...)
Important observations by this group still reflect much of what we currently anticipate with neuropsychologist assessment. “Contrary to expectations, the group with operation on the nondominant temporal lobe failed to lower scores on nonverbal tests.” In addition, “the operation on the dominant side results in a severe deficit of auditory learning.” Important findings were also made about the distinction between linguistic capacity and verbal memory. “Despite the considerable amount of recovery from the manifest dysphasic disturbances a year after the operation, the auditory-verbal-learning impairment persists.” Unlike the MNI discussed below, there were no special precautions employed at the time of surgery such as functional stimulation mapping that were used explicitly to decrease the likelihood of post-operative language morbidity.
Montreal Neurological Institute/McGill University
The contributions of the MNI to neuropsychology and epilepsy surgery evaluation are unparalleled among epilepsy centers, with the MNI responsible for developing many techniques and approaches that continue to be widely employed. The interest in developing a multidisciplinary approach in order to better understand the effects of epilepsy and epilepsy surgery was primarily driven by their surgeon, Wilder Penfield (Penfield & Jasper, 1954
), and this multidisciplinary approach to epilepsy patient evaluation and management remains perhaps his longest enduring legacy. The Montreal Neurological Institute of McGill University, co-founded by Penfield with William V. Cone (who introduced twist-drill techniques for biopsy and ventriculoperitoneal shunting techniques), opened in 1934 after a generous grant by the Rockefeller Foundation (Preul, Stratford, Bertrand, & Feindel, 1993
The origins of many of Penfield's approaches to epilepsy surgery can be traced to the influences of Otfrid Foerster at the Brain Research Institute in Breslau, Germany (now Wroclaw, Poland; Piotrowska & Winkler, 2007
). Many World War I veterans returned home with post-traumatic epilepsy, and Foerster developed cortical stimulation techniques in awake patients to reproduce their aura and provide maximal resection of scarred cortex without involving eloquent cortex (Flanigin, King, & Gallagher, 1985
; Sarikcioglu, 2007
). Penfield spent 6 months with Foerster in 1928 learning techniques of cortical mapping and epilepsy surgery (Sarikcioglu, 2007
), and together with Foerster's published surgery outcomes of these patients only 2 years later (Foerster & Penfield, 1930
). Other prominent figures in the neurology/neurosurgery who studied with Foerster include Percival Bailey and Paul Bucy.
The development of the epilepsy program at the MNI could not have occurred without the many contributions of the neurophysiologist Herbert Jasper. Before arriving at the MNI in 1938, Jasper had developed the EEG laboratory and Brown University and had published a paper in Science
describing how visual stimulation would decrease the alpha rhythm, and the frequency of the alpha waves were constant over repeated evaluations, and how EEG frequency was a low as 2–3 Hz in two patients with brain injury (Feindel, 1999
). “It may well be that the electroencephalograms of the sort described in this note may prove significant in psychology and clinical neurology. It is even possible that this technique may provide information in regard to brain action which will be comparable in significance to the information in regard to heart function which is provided by the electrocardiograph” (Jasper & Carmichael, 1935
). After Penfield had toured Jasper's laboratory after giving a seminar at Brown University, Penfield commented that Jasper had told him that he could “localize of the focus of an epileptic seizure by the disturbance of brain rhythms outside the skull. I doubted but hoped it might be true” (Penfield & Jasper, 1972
). Jasper then obtained EEGs on two of Penfield's patients, and based on Jasper's localization, both patients went to surgery where Penfield confirmed Jasper's seizure focus localization (Feindel, 1999
Although the contributions of Brenda Milner are well known to clinical neuropsychologists, the systematic use of psychology at the MNI began years earlier. Penfield's desire for psychological input is reflected by his hire of Molly Harrower, who established what is likely the first clinical psychology service at a major hospital. Recruiting psychology into a medical environment was a novel approach at that time and began “a totally new chapter of the kinds of things [that can be done] with a rapport with medicine.” “I was really coping with really being the only woman in the hospital, the only woman fellow, the only woman on staff and the only psychologist” (http://www.uflib.ufl.edu/ufdc/?b=UF00006059&v=00001
). Harrower was at Montreal from 1938–1942.
Penfield took special precautions due to his concerns about the effects of epilepsy surgery in the language dominant hemisphere (Sarikcioglu, 2007
). As early as 1939, Penfield performed stimulation language mapping to identify areas of “eloquent cortex” to help guide surgical resection (Almeida, Martinez, & Feindel, 2005
). In this case of a left ATL, surgery was performed using local anesthesia. The awake patient was encouraged to talk with Donald Hebb, “who drew him out on various subjects while the area of the scar was being removed.”
Hebb's contributions to our understanding of basic brain function (e.g., Hebbian circuits and cell assemblies) are well known and anticipated many contemporary concepts of neural nets. His work also included important clinical contributions to abnormal brain function, and in particular, his seminal work on the frontal lobes. Prior to the 1930s, the frontal lobes were considered the seat of all that is “noble and good” about humans. Hebb demonstrated that “frontal release” neurological signs (e.g., snout, glabellar), which at that time were considered pathognomonic of focal frontal lobe disease, did not result from large prefrontal lesions, but rather occurred due to the combination of frontal lesions with diffuse pressure effects associated with expanding mass lesions. This difference from the traditional clinical dogma resulted from the MNI's early detection of tumor and more rapid referral for cognitive evaluation compared with other centers. When reporting his early findings at the American Psychological Association, Hebb's results were met with skepticism by more senior psychologists: “I don't think I was regarded as a liar, just an incompetent” (Hebb, 1977
Hebb was also the first to describe increased Full-Scale IQ following frontal lobe resection. Although not widely known, one of the early patients in Hebb's series on frontal lobe lesions was Penfield's sister. In fact, it was Penfield's sister who was being described as having trouble organizing family meals when describing the real-world effects in goal-directed behavior change following frontal lobe resection.
Milner was a graduate student of Hebb, and he recommended to Penfield that she evaluate his surgical patients pre- and post-operatively. The interested reader should read Milner's “autobiography” for a more thorough presentation of her many contributions to neuropsychology (Milner, 1998). On the basis of her study of patient H.M. and other patents developing post-operative amnesia, Milner demonstrated the important dissociation between episodic and procedural memory, which greatly facilitated the fractionation of “memory” into multiple and largely independent neural systems.
Because of Penfield's pursuit to document cognitive change following elective brain surgery, there are multiple ramifications for neuropsychology that I refer to as “Penfield” effects. On the broadest level, epilepsy was the first clinical disease to include neuropsychology programmatically to initially better characterize and subsequently guide the surgical treatment of epilepsy. In this context, epilepsy surgery represents the first systematic application of which is currently referred to as “Health Outcomes Research.” “Seizure free” with marked neuropsychological decline was a bad surgical outcome and constituted a surgical failure.
More narrowly, developing neuropsychology as a technique to establish surgical candidacy validated neuropsychological testing as a valuable diagnostic service. Although other approaches to neuropsychological assessment such as the Halstead Reitan Neuropsychological Battery were being used at that time, the HRNB was primarily employed to establish the presence of “organic brain disease.” Establishing “organicity” was an important contribution of neuropsychology at that time since diagnostic tools available during that era, namely EEG and pneumoencephalography, were gross measures of brain abnormalities. Pneumoencephalography was introduced in 1919 by Walter Dandy (Dandy, 1919
); EEG was discovered a decade later in 1929 by Hans Berger (Berger, 1929
). The goals of neuropsychological testing at MNI, however, were explicitly to identify specific neuropsychological deficits reflecting the integrity of focal brain regions so that resective surgery could be performed without significant cognitive morbidity.
The other major contribution of the MNI is its emphasis on stimulation/language mapping, again reflecting careful appreciation of brain function, and attempts to minimize post-operative cognitive morbidity. MNI was unique in the early centers in this respect and reflected to collaborations of neuropsychology, neurology, and neurosurgery at very high levels (Fig. ).
Operating theatre at the Montreal Neurological Institute ca. 1958. Assisting Wilder Penfield with the procedure is Herber Jasper (monitoring EEG up upper left portion of picture) and Brenda Milner (back to camera and interacting with patient).