PERSPECTIVES

Coalescence of Psychiatry, Neurology, and Neuropsychology: From Theory to Practice

Miles G. Cunningham, MD, PhD, Martin Goldstein, MD, David Katz, PhD, Sarah Quimby ONeil, MD, Anthony Joseph, MD, and Bruce Price, MD

In a climate of renewed interest in the synergy between neurology and psychiatry, practitioners are increasingly recognizing the importance of exchange and collaboration between these two disciplines. However, there are few working models of interdisciplinary teams that freely share expertise in real time, while providing clinical and academic training to future physicians who specialize in the central nervous system. Over the past 11 years, the McLean Hospital Neuropsychiatry and Behavioral Neurology service has provided proof-of-principle for such collaboration, demonstrating that a team comprising psychiatrists, neurologists, and neuropsychologists can function effectively as a unit while maintaining the autonomy of these three disciplines and also synthesizing their combined knowledge. In addition to delivering enhanced patient care and promoting medical research, this clinical service has provided enriched cross-specialty training for fellows, residents, and medical students. The practical functioning of the team is described, and case vignettes are presented to illustrate the teams collaborative synergism in practice. (HARV REV PSYCHIATRY 2006;14:127140.) Keywords: collaboration, cross-training, multidisciplinary, neurology, neuropsychiatry, psychiatry

From the Departments of Psychiatry (Drs. Cunningham, Quimby ONeil, and Joseph) and Neurology (Dr. Price), Harvard Medical School; McLean Hospital, Belmont, MA (Drs. Cunningham, Quimby ONeil, Joseph, and Price); Department of Neurology, Mount Sinai School of Medicine (Dr. Goldstein); Department of Psychology, University of British Columbia, Vancouver (Dr. Katz); Department of Neurology, Massachusetts General Hospital, Boston, MA (Dr. Price). Supported, in part, by the Sidney R. Baer Foundation. Original manuscript received 4 September 2005, accepted for publication subject to revision 25 October 2005; revised manuscript received 6 January 2006. Correspondence: Miles G. Cunningham, MD, PhD, MRC 333, McLean Hospital, 115 Mill St., Belmont, MA 02478. Email: mcunningham@mclean.harvard.edu
c 2006 President and Fellows of Harvard College

RENEWED INTEREST, REDISCOVERY

One hundred ninety years ago, Benjamin Rush, considered the father of American psychiatry, in a letter to John Adams, wrote: The [diseases of the mind] have hitherto been enveloped in mystery . . . I have endeavored to bring them down to the level of all other diseases of the human body, and to show that the mind and body are moved by the same causes and subject to the same laws.1 Modern neurologists- and psychiatrists-in-training interested in behavioral neurology and neuropsychiatry have seen themselves as venturing onto new ground, on the cutting edge, and yet as being in the minority of mainstream neurologic and psychiatric training. In fact, however, their conceptualization of mind, brain, and behavior was shared by the forefathers of neurology and psychiatry, including Freud, Kraepelin, Charcot, Alzheimer, Breuer, and many others.2 Sigmund Freud, the founder of psychoanalysis, was trained as a neurologist. Alois Alzheimer, best known for describing the dementing neurologic disorder subsequently named after him, was a psychiatrist. A

DOI: 10.1080/10673220600748536

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century ago, however, while some recognized that mind and brain were inseparable, most diseases of the brain could not be visualized, measured, or readily treated. Now, advances in neuroscience have illuminated anatomical, cellular, and molecular substrates of mental illness. Once again, we recognize that the mind and brain are inseparable. The pathophysiologic bases of many mental illnesses are beginning to be empirically identied,38 and many can be characterized microscopically.911 Moreover, mechanisms of recovery with pharmacologic and psychotherapeutic treatment are being dened.1214 As reviewed by Price, Coyle, and Adams,15 as well as by Martin,16 historically there was much less conceptual and practical separation between neurology and psychiatry. Practitioners were trained in both; they were neuropsychiatrists committed to the study of the biologic substrates of psychiatric disease. Ironically, by the middle of the twentieth century, the penetrance of psychoanalysisthe brainchild of one of the most prominent neuropsychiatrists, Sigmund Freudresulted in his followers virtually abandoning efforts to explain cognition and behavior in biological terms. A rift developed between neurology and some elements of psychological psychiatry, separated by a false void. That void, in fact, was an artifact of inadequate scientic sophistication and consequent missing knowledge, and it was maintained and perhaps widened by frank resistance to neural models of behavior.17 While neurology essentially detached itself from mental phenomena, psychiatry progressively adopted psychological conceptualization and methodology. In the midst of the divide, writing in Brain in 1946, A. S. Paterson observed:18 Freud, faced with the barrenness of contemporary neurology and physiology in accounting for mans emotional and instinctive behaviour, canalized and developed the popular explanation of behaviour in terms of vital principles . . . [T]he psychogenic theory was elaborated in isolation from other considerations, and unfortunately became, in the eyes of some of its adherents, entirely self-sufcient . . . [T]here has been . . . a tendency for [neurology and psychiatry] to pursue separate paths, to be not a little suspicious of each other and to maintain in isolation their own traditional concepts . . . In the face of the ckleness of emotional reactions and personality traits compared with the relative uniformity and consistency of the perceptual process, it is small wonder that the clinical neurologist has devoted little time to the study of the former . . . The psychiatrist, on the other hand, has made some sense of the problems presented by human behaviour in the emotional sphere.

EGO STRENGTH
The mind/brain dichotomy that ensued was not just intellectually debated, but passionately defended, by each elds respective practitioners. Those traditionally trained in neurology and psychiatry, as tends to happen to those being inducted into any specialized discipline, seemed to embrace explicit and implicit teachings as if those teachings were a part of their identity. Joseph Martin, a neurologist and neuroscientist by training and dean of the Faculty of Medicine at Harvard Medical School, remarked:16 To take full advantage of the enormous opportunities for elucidating the causes of neuropsychiatric disorders and seeking effective treatments for them, bold, revolutionary planning and experimentation will be required. Progress will also depend on overcoming social and psychological obstacles, including ingrained, dualistic concepts of brain and mind, rigid educational traditions, and protective instincts with regard to professional turf. It seems we have now come full circle in conceptualizing the mind/brain paradigm. With techniques such as immunohistochemistry, in situ hybridization, microdialysis, DNA microarray analysis, and progressively more sophisticated structural and functional imaging techniques, we are armed with powerful tools to investigate previously subtle cellular and molecular pathoetiology of diseases of the mind. But are psychiatrists prepared to acknowledge the neurology of psychiatry? Are neurologists prepared to acknowledge the psychiatry of neurology? More importantly, are the respective physicians prepared to collaborate to provide appropriate care for the (frequent) patient manifesting both psychiatric and neurologic symptoms?

THE NEUROSCIENCE OF PSYCHIATRY: INEVITABLE BIOLOGY

Mental illness has been conceptualized as organic if genetic, biochemical, cellular, histologic, or gross structural changes can be identied, and functional if such changes cannot be appreciated; that is, when the function of a cognitive, emotional, or perceptual process is disordered without a clear biologic cause. As psychiatric disease becomes increasingly understood in a biologic context, the terms organic and functionalwhile still in use to describe symptoms and syndromesare beginning to lose their signicance. We are approaching the point of being able to measure differences between the psychiatrically disordered and the normal brain. For example, schizophrenia and bipolar disease are associated with decreases in inhibitory interneurons in

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specic brain regions.9,11,19 While imaging studies remain inconclusive, single photon emission computerized tomography analysis has shown that patients with intractable unipolar depression have decreased blood ow in the caudate, cingulate gyrus, and the frontal and anterior temporal cortices.20 Moreover, positron emission tomography (PET) studies have demonstrated reduced 5-HT1A binding potential in limbic and neocortical regions of depressed patients.21 PET has shown activation of subcortical nuclei, limbic and paralimbic structures, and regions of auditory cortex during auditory hallucinations in schizophrenics.22 In fact, there is now also evidence for neurophysiologic correlations for personality or characterologic disorders. Volumetric structural MRI studies of patients with borderline personality disorder have found a tendency toward reduced hippocampal and amygdala volumes.23 And a functional MRI study has demonstrated in these patients increased activation of the amygdala and select prefrontal cortex regions compared to normal control subjects when presented with visual stimuli having emotional valence.24 Furthermore, violent offenders have been shown to have hypoperfusion of the head of the caudate nuclei and hippocampi.25 A debate that has paralleled the dichotomy of neurology and psychiatry is that of nature versus nurture. This conceptual framework has lost its signicance, as they are inextricably bound. It can be argued that nature is nurture and that nurture is natureas illustrated by a series of studies demonstrating proliferation of granule neurons within the dentate gyrus of mice exposed to an enriched environment.26,27 This environment provided animals more diversity in their living space, interaction with other animals, opportunity for increased physical activity, and exposure to colorful, complex objects. In more anthropomorphic terms, the animals were provided with new perceptions, new experiences, and new perspectives. The capacity of experience, learning, and cognitive processing to alter brain anatomy, physiology, and function was demonstrated in a landmark study by Baxter and colleagues.12 Patients diagnosed with obsessive-compulsive disorder were treated with either cognitive-behavioral therapy (CBT) or pharmacotherapy. The responders in each group demonstrated attenuation of glucose metabolic rate within the right caudate nucleus as measured by PET. These ndings are consistent with conceptualization of psychotherapy as a biological intervention, whereby gene expression and neural connectivity are altered through the therapeutic process,17 be it psychoanalysis, insight-guided therapy, CBT, or other approaches. In an editorial for the rst volume of Molecular Psychiatry, Joseph Coyle (professor of psychiatry and neuroscience at Harvard Medical School) commented,28 Genes, especially as they affect brain function, are not expressed in a vacuum but rather in the rich personal context of individual experience. And genomics promises a new con-

trol over the complex simultaneous equation of Nature and Nurture that shapes brain and behavior. As the substrates of mental illness continue to be actively explored and discovered, our understanding of the biology of mind is rapidly progressing. Consequently, this new knowledge will fundamentally alter how we conceptualize mental illness, practice medicine, and train future practitioners.

THE PSYCHIATRY OF NEUROLOGY: INEVITABLE BEHAVIOR

The unfortunate and arbitrary divide between the disciplines of neurology and psychiatry can be further illustrated by ndings of a study by Koponen and colleagues,29 who evaluated the occurrence of psychiatric disorders in patients with traumatic brain injury. Criteria for evaluation were that trauma was of sufcient severity to have caused neurologic symptoms lasting at least one week and also, at a minimum, loss of consciousness for at least one minute, posttraumatic amnesia for at least 30 minutes, or neuroradiological ndings suggesting traumatic brain injury. Over a 30-year observation period, approximately 50% of patients developed symptomatology consistent with an Axis I disorder, and 25% developed symptomatology consistent with a personality disorder. Another recent report30 highlighted the cognitive, personality, and mood disorders seen in patients with degenerative cerebellar syndromes and Huntingtons disease. Over 75% in both patient populations manifested psychiatric symptoms, in contrast to a much lower rate in a group of comparison subjects who were not neurologically impaired. These and numerous other studies3133 demonstrate that reducing complex brain disorders into simplistic categories and restricting pathophysiologic characterization to a single discipline is no longer tenable. Many patients with neurologic disease suffer from serious mood, cognitive, or behavioral changes that may be pathophysiologically related to the same disease process causing their neurologic manifestations; yet, because of articial clinical demarcations, these patients may remain underdiagnosed and undertreated. Grounded in the principles, language, and scientic rigor of anatomy, physiology, and pathology that characterize the terminology and constructs of modern medicine, neurology has commanded full membership in the family of medical specialties. In contrast, since psychiatry has not been amenable to traditional medical-scientic methodology and has adopted, instead, unconventional approaches to its unique array of diseases, it has not enjoyed the positive regard that such membership normally bestows. In point of fact, in the not-so-distant past, many teachers of psychiatry discouraged new thinking and devalued scientic inquiry.17 The result has been what may be perceived as an inadequacy

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in psychiatric training and patient care. The consequences for neurology are equally unfortunate. That is, while neurology attempts to diagnose and treat disorders in a context that is scientically grounded, dysfunction of the mind often complicates the presentation of neurologic disease with the ambiguity and subjectivity of emotional discord. Some neurologists choose not to attend to a patients affective and behavioral components, perhaps seeing these symptoms as irrelevant to the biology and successful treatment of the disease. However, clinical manifestations that are dening elements of certain disordersand that are thus often essential to their diagnosiscan span the neurologic-psychiatric disease spectrum. Examples include auras and other affective, thought, and perceptual phenomena associated with complex partial seizure disorders; hallucinations seen early in the course of Lewy body disease; and prodromal depression seen with Alzheimers and Parkinsons disease. Table 1 lists examples of psychiatric conditions associated with neurologic diseases.

COALESCENCE IN THEORY
Thought leaders in neurology, psychiatry, and neuroscience have encouraged a rapprochement of disciplines and have called for a revision in medical education that crosses traditional boundaries.1517,36 Kandel17 has outlined an intellectual framework designed to align, within modern biology, the current psychiatric thinking and the training of future practitioners within modern biology. This framework is based on three principles: (1) the functions of mind reect functions of brain, (2) genes and their products underlie neural connectivity patterns and their function, including mental illness, and (3) experience, behavior, and other variables that affect learning alter gene expression, neural connectivity, and, in turn, perception, affect, and behavioral patterns. Leon Eisenberg, professor of psychiatry (emeritus) at Harvard Medical School, has asked: Is it time to integrate neurology and psychiatry?37 He proposes that residency programs be restructured, incorporating training within

TABLE 1. Psychiatric Conditions and Associated Neurologic Diseases Psychiatric condition

Depression

Associated neurologic diseases

Stroke, Parkinsons disease, Huntingtons disease, epilepsy, traumatic brain injury, multiple sclerosis, Alzheimers disease, HIV, vascular dementia Stroke, Parkinsons disease, Huntingtons disease, Fahrs disease, traumatic brain injury, multiple sclerosis, epilepsy, frontotemporal dementias, syphilitic encephalitis Stroke, epilepsy, Parkinsons disease, migraine, multiple sclerosis, encephalitis, posttraumatic/concussive syndromes Seizure disorders, pseudobulbar palsy, Angelmans syndrome Epilepsy (esp. TLE), degenerative and vascular dementias, Huntingtons disease, posttraumatic encephalopathy, Creutzfeldt-Jakob disease, multiple sclerosis, B12 deciency, temporal lobe tumors/strokes, mental retardation Migraine, TLE, narcolepsy, neurodegenerative diseases, Lewy body disease, drug intoxication or withdrawal, Tay-Sachs disease TLE, stroke, tumor Picks disease, Huntingtons disease, Alzeheimers disease, Tourettes syndrome, Sydenhams chorea, progressive supranuclear palsy, CO poisoning, Mn toxicity TLE, migraine, postconcussive states, encephalitis, toxic-metabolic disorders Basal ganglia disorders, vascular dementia, Huntingtons disease, Alzheimers disease, TLE, B12 deciency

Relevant neuroanatomy
Usually left hemisphere lesions: frontal and temporal lobes, basal ganglia Usually right hemisphere lesions: orbitofrontal cortex, caudate nuclei, thalamus, basotemporal area Limbic lesions, esp. right-sided

Mania/hypomania

Anxiety

Mood lability Delusions

Lesions of orbitofrontal cortex, basal ganglia dysfunction Limbic system dysfunction (esp. subcortical structures), temporal lobe dysfunction

Visual hallucinations/ illusions Auditory hallucinations OCD/repetitive behavior Dissociative disorders Personality change

Lesions of eyes, optic nerves, geniculo-calcarine projections, occipital or temporal cortex Auditory association cortex, paralimbic cortex, hippocampus, striatum, thalamus Frontotemporal lobe degeneration, lesions of caudate, globus pallidus Temporal and parietal lobe dysfunction, notably the angular gyrus Lesions of medial frontal, orbitofrontal, and temporal lobes

Source: Adapted from Cummings and Trimble (1995)34 and Price (1999).35 TLE, temporal lobe epilepsy.

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each specialty that will help build sophistication in the other. He also proposes that medical students be exposed early to a consolidation, or coalescence, of brain medicine and science through a combined neuroscience/neurology/psychiatry track. Jack Gorman, editor of CNS Spectrums and president and psychiatrist in chief at McLean Hospital, also intrepidly champions collaboration among psychiatry, neurology, and neuropsychology.3840 George Murray, emeritus director of the consultative-liaison psychiatry service at Massachusetts General Hospitalusing seizure disorders to emphasize his pointobserves that if you know temporal lobe epilepsy, you know how contemporary psychiatry should be [approached].41 Murray argues, too, that psychiatrists should become more knowledgeable in neuroanatomy and imaging techniques since neuroimaging is becoming an important diagnostic tool in psychiatric diseaseyet most psychiatrists, including trainees, are not trained in the interpretation of brain images. Similarly, Donald Schomer, professor of neurology at Harvard Medical School, argues that there should be more psychiatry for neurologists in the formative years of training.41 Despite these and other experts opinions, the American Board of Psychiatry and Neurology has only recently recognized even the most minimal need for psychiatry rotations within neurology residency programs, and, in parallel, the board has progressively reduced medicine-rotation requirements for psychiatry residencies. Interestingly, despite the persisting wall between the two disciplines, on Part IB of the boards written examinations, approximately 30% of questions pertain to the other discipline, while many of the remaining 100 questions overlap the two disciplines. Even so, as a specialty, psychiatry stands alone in not requiring the study of the functional anatomy and physiology of the organ from which its diseases arise. While leaders in neurology and in psychiatry have openly expressed their support for a rapprochement, there are few clinical models for effectively converting theory into practice. Even within larger teaching hospitals, doctors-intraining rarely have the opportunity to simultaneously address patients neurologic and psychiatric signs and symptoms under the supervision of experts in the respective disciplines. Likewise, practitioners in these elds rarely have a forum available in which to share their experiences and knowledge, thereby enriching their own clinical judgment. However, with forward-thinking leadership, continued progress in medical neuroscience, the progressive effacement of the boundaries between disciplines, and increasing demands by students for a more integrated curriculum, there will surely come a time when collaborative programs and teams are more practical. They could also become more cost-effective through potentially greater efciencies in diagnostic assessment, treatment formulation, and plan implementation.

The model presented here for a collaborative initiative between psychiatry and neurology is drawn from the ongoing program at McLean Hospital. Another potential model, not discussed in this article, is the one used by the Geriatric Treatment Center of the Colorado Mental Health Institute at Pueblo, which treats patients with psychiatric disorders, behavioral syndromes that result from neurologic disease, or a combination thereof.42 These changes within neurology and psychiatry should also be seen within a larger perspective as representing the ongoing evolution of medical education. In 1910, the Flexner Report43 concluded that for medical education to ourish from one generation to the next, it [has] . . . to recongure itself in response to changing scientic, social, and economic circumstances. Almost 100 years later, medicine continues to react to these ever changing forces to ensure that a physicians education and training keep pace with an ever expanding base of medical knowledge, coupled with changes in venues and in the manner that care is provided to patients. For these reasons, Harvard Medical School and other institutions are in the midst of a major curriculum evaluation and reform, with a particular focus on the third and fourth years of medical school. Residency and fellowship training programs have been similarly affected, as alternative approaches to training are being explored.

COALESCENCE IN PRACTICE
Founded in 1811, McLean Hospital was the rst psychiatric hospital established in New England and the third in the United States. Considered the worlds birthplace of hospitalbased laboratory research in psychobiology,44 the hospitals neuroscience research program is larger than that of any other private psychiatric hospital in the United States and also of any other department or afliated institution of Harvard University. Moreover, with a current inpatient census of 170 beds, the hospitals psychiatric teaching facility is the largest at Harvard Medical School. And with its diversity in both patient population and psychiatric/neuropsychiatric diseases, the hospital offers an ideal setting for research and training. Reecting McLeans reputation as the setting for the beginnings of conjoint medicine,45 we constructed a multidisciplinary team whose members work together synergistically; the interchange of perspectives and knowledge makes each team member more effective. This approach generates a comprehensive, insightful formulation for patients with comorbid neurologic and psychiatric diseaseone that is superior to what either discipline would produce on its own. Neuropsychology, an integral component of the service, is itself a working model for the coalescence of neurologic and psychiatric principles. The eld evolved as an

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interdisciplinary approach synthesizing information from diverse, but interrelated, areasfunctional neuroanatomy, ethnology, cognitive psychology, and comparative neurophysiology, as well as clinical neurology and psychiatry. It provides expertise in performing standardized and normed tests that quantitatively measure cognitive domains (e.g., attention, language, memory, and visuospatial function), myriad executive functions (e.g., decision making, error monitoring, behavioral-motor control, socio-emotional regulation, working memory), and affective modulation of behavior (e.g., motivation, approach/withdrawal). Neuropsychologists also perform psychodiagnostic testing, a standardized mixture of qualitative and quantitative evaluations of thought content, affect, and personality. Remarkably, despite neuropsychologys broad relevance to both psychiatry and neurology, it has remained a relatively uneven presence across academic neurology and psychiatry departments. It has nonetheless experienced a signicant renaissance in connection with the emergence of new research methodologies such as functional neuroimaging; neuropsychologys indisputable utility has been catalyzing the elds transition from lesion-based traditions. Moreover, the increased recognition of both the profound cognitive consequences of primary psychiatric disorders (e.g., the working memory and language decits of schizophrenia that are neglected by the limited criteria sets of DSM-IV) and the profound affective consequences of primary neurologic disorders (such as those associated with stroke or epilepsy) positions neuropsychology as an important clinical and research discipline for contemporary psychiatry and neurology. Even with regard to non-CNS-related interventions (e.g., coronary artery bypass surgery), the attention now given to their cognitive and behavioral consequences is requiring sophisticated neuropsychological studies. The eld of neuropsychology thus continues to increase in importance, for it provides a bridge between psychiatry and neurology, promoting an interdisciplinary formulation of complex cases. McLean Hospitals Neuropsychiatry and Behavioral Neurology (NBN) consult service began in 1994 as an academic forum bringing together neurologists, psychiatrists, and neuropsychologists to formulate diagnoses and treatment plans for clinically challenging inpatients. The NBN service was inspired by a prior model, the Beth Israel Behavioral Neurology Program, as pioneered by Norman Geschwind, under whom the founder of the NBN service trained. Collaborations such as these serve many functions. They dismantle perceived barriers between the disciplines. They promote the free interchange of knowledge and techniques between the disciplines, through which all of the specialists gain new clinical insights and tools. This collaborative setting also provides for rich cross-training for medical students, residents, and fellows, and offers enhanced service to patients

and their treatment teams through coordinated insights and recommendations for difcult clinical problems. The model we describe below has been adjusted and polished over a number of years. Throughout this period, however, our ongoing assumption has been that medical education, developments in neuroscience, and the delivery of high quality care to patients must continue to develop synergistically and in parallel. The structure of the McLean NBN consult service is based on a multitiered system of collegial interaction among attendings, fellows, residents, and medical students. Senior staff neurologists, psychiatrists, and neuropsychologists participate as clinician-mentors. A two-year fellowship in neuropsychology, funded by clinical income, was initiated in 1995. A privately funded one- or two-year fellowship in behavioral neurology and neuropsychiatry was started in 1999one of the rst fellowships of this kind available anywhere. Residents from psychiatry training programs within the Harvard Medical School system rotate through the NBN service for one or two months to satisfy their two-month neurology requirement as set by the Residency Review Committee for Psychiatry and Neurology. Neurology residents electively rotate for one-month intervals. Harvard medical students participate one day per week during their psychiatry rotation at McLean Hospital. Fellows, residents, and medical students are also encouraged to participate in clinical and basic science investigationespecially in connection with the ongoing research of the NBN services core team members. Moreover, during their NBN rotations, residents are asked to produce at least one case study suitable for publication in the NBN online periodical or in a peer-reviewed journal. We have also made these opportunities available to doctors-in-training visiting from other U.S. programs, as well as from abroad. The NBN consult service meets for two to three hours twice weekly to round on patients who are presented primarily by residents, but also by fellows and occasionally medical students. During each session, two to four patients are presented in detail, including: history; psychiatric evaluation; and mental status, physical, and neurologic examinations. Each patient then meets with the entire team, which enables the members to observe and interact with the patient and apply their expertise. This meeting also allows patients to express specic concerns regarding their psychiatric experiences and physical symptoms. For each patient, the team provides a focused neurologic exam that takes into account the results of all relevant diagnostic investigations (e.g., EEG, imaging studies, and other laboratory ndings). Many of these patients have also been given neuropsychological testing, which further promotes the teams comprehensive synthesis of the case. Diagnosis and treatment plans are then formulated and reported to the patients treatment team on the hospital ward. The text box lists conditions

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involving brain-cognition-behavior relationships for which NBN consults are frequently requested.
Conditions for Which the NBN Service Is Commonly Consulted Delirium/confusional states Neurodegenerative diseases First-break psychosis Atypical intractable psychiatric syndromes Traumatic brain injury Cerebrovascular disease/strokes Temporal lobe epilepsy/spells Abnormal laboratory studies (MRI, EEG, etc.) Movement disorders Chronic pain syndromes Viral, metabolic, toxic, hypoxic encephalopathies Somatoform disorders Developmental syndromes Multiple sclerosis Brain tumors

The multidisciplinary product of these evaluations allows relevant aspects of neurology, psychiatry, and psychology to be addressed in the same patient at the same time. Illustrative cases include the following:

Vignette 1
A 25-year-old right-handed man with a prior diagnosis of Aspergers syndrome, psychosis NOS, and seizure disorder was admitted to McLean Hospital for depression and psychotic symptoms. The patient began to decompensate upon the recent death of a loved one, to whom he was strongly attached emotionally. He became severely depressed with suicidal ideation and began experiencing auditory hallucinations. The NBN service was asked to assess for neurologic causes of his psychotic behaviors. The patient had a history of a developmental disorder and psychotic behavior diagnosed at age 6. At age 16 he was diagnosed with a seizure disorder (partial complex) after being admitted to the hospital for psychosis. A thorough history revealed that the patients psychotic symptoms appeared to correlate positively with seizure activity. His seizures had been well controlled with divalproex for a number of years. However, he continued to demonstrate at affect, slowed speech, and apparent thought-blocking, with long response latencies. Nine months prior to his current admission, divalproex was replaced with topiramate (since the patient remained seizure free and had gained a considerable amount of weight on divalproex). The psychiatric history of the patients family was remarkable for his mothers depression and his fathers history of psychotic episodes. His educational history was notable for receiving special education during high school but nevertheless graduating. Other than the aforementioned seizure disorder, his medical history was remarkable only for a benign heart murmur. He had no substance abuse history.

The patient presented to the team in an apparent altered state of consciousness. His verbal responses were delayed, appearing abulic, and he ritualistically stared into the distance, often with three to ten beats of eyelid utter, accompanied by covering of his eyes with his hands. His speech was hypophonic, slowed, and devoid of prosody. His stated mood was sad, confused, and scared, and his affect was severely blunted. He endorsed difculty sleeping, anhedonia, depleted energy, poor appetite, and difculty concentrating, and he reportedly was unable to carry out activities of daily living. His thought processing was tangential, and he responded to questions or followed simple instructions only after some latency. He endorsed auditory hallucinations of voices that said Dont do it, and reported bifrontal headaches concurrent with these hallucinations. He was unable to provide an interpretation for his auditory hallucinations. His insight was poor, stating the reason for his admission to be restlessness. Physical exam was notable for truncal obesity with decreased muscle mass in arms and legs bilaterally. A 2/6 systolic ejection murmur was corroborated. The elemental neurologic exam was normal except for bilateral slowness in rapid alternating movement with sluggish ne motor movement, and a slowed, unstable gate, with difculty in tandem walking. Laboratory values were all within normal limits. Medications (all by mouth) at the time of the consult were: topiramate, 75 mg daily; uoxetine, 20 mg daily; clonazepam, 1 mg twice daily; risperidone, 2 mg at bedtime; and benztropine, 1 mg twice daily. A routine sleep-wake EEG was read as normal. However, based on the patients hallucinations and thought disorder, appearance of possible stereotopies, and distant history of epileptiform activity coincident with psychotic symptoms, the NBN service ordered 48-hour EEG telemetry. An MRI with contrast was also obtained with thin slices through the hypothalamus and pituitary in order to rule out lesions that could be associated with Cushingoid signs and symptoms. The MRI and cortisol and magnesium levels were normal. During the two-day ambulatory EEG recording, there occurred approximately 700 automated interictal epileptiform detections, most of which showed either 1 to 3 second bursts of bifrontal 1315 Hz activity or right-greater-than-left independent or occasionally synchronous temporal sharp waves and spikes (Figure 1). No denite ictal patterns were detected. Since unequivocal seizure behavior was not witnessed, and telemetry EEG recordings did not detect denite ictal patterns, epileptiform activity as the antecedent cause for the patients psychotic states remained speculative. However, the patient had a number of risk factors for development of psychosis associated with epilepsy: early onset of a seizure disorder, a positive family history for psychosis, and borderline intellectual functioning.46 Based on psychiatric evaluation, neurologic observation, and a thorough

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FIGURE 1. Abnormal telemetry EEG tracing with bifrontal polyspike bursts and bitemporal sharp waves in this 25-year-old man with stereotypies and psychosis.

neuropsychiatric history, interictal psychosis remained a distinct possibility as a contributor to the patients presentation. The team recommended discontinuing topiramate and placing the patient on extended-release divalproex in order to minimize side effects (particularly weight gain) and eliminate the possibility of topiramate neurotoxitya recommendation that took into account that the patient had a history of successful control of seizures with the standard formulation of divalproex. The NBN team also recommended neuropsychological testing to better quantify cognitive strengths and weaknesses, and to better characterize psychiatric signs. Upon discharge ve days later, the patients psychotic symptoms had disappeared. The patient continued to exhibit peculiar mannerisms, including delayed verbal responses and occasional eyelid uttering, but with decreased frequency. The patient also remained somewhat anhedonic and melancholicwhich was likely associated with a superimposed grief reaction or a persisting mood disorder. This case illustrates the teams proactive approach resulting in the discovery of persisting abnormal EEG activity. Although these readings were considered epileptiform in nature, the patient did not meet criteria for a seizure disorder.

Had an ambulatory EEG not been ordered, epileptiform activity contributing to the patients psychiatric symptoms may not have been suspected in light of the patients routine EEG, which has been normal. The patient would likely have received only psychotropic medications targeting his psychiatric symptoms and would not have been administered the antiseizure agent, which quickly resulted in marked improvement. In addition, the team consolidated the patients history, psychiatric symptoms, and electroencephalographic ndings while incorporating psychopharmacological expertise into a formulation and treatment plan that provided etiologic insight and guidance to the patients treatment team.

Vignette 2
A 41-year-old single woman was admitted to McLean Hospital with new onset of auditory and visual hallucinations. The NBN service was asked to rule out a neurologic cause for her psychosis. After terminating a long-standing and volatile relationship, the patient found herself homeless and unemployed. As a result, her mood deteriorated, and she experienced suicidal ideation in addition to her auditory and visual hallucinations. Her auditory hallucinations included a threatening voice that was derogatory and commanding

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her to kill herself. Her visual hallucinations comprised shadows taking the form of animal or human gures; they were usually perceived in her peripheral vision (never within her central elds) and disappeared upon attempts to look directly at the shadows. The patient described occasional episodes of binge drinking but did not endorse other recreational drug use. She had experienced two events with potential for being complicated by traumatic brain injury: rst, in childhood, with loss of consciousness for an unknown period of time, and later, as a teenager, when involved in a motor vehicle accident, also losing consciousness for an indeterminate period. Neither event required hospitalization. On review of systems she noted intermittent left arm tingling and a recent episode of vertigo lasting several days before spontaneously resolving. In addition, she complained of intermittent difculty in walking and described her gate as feeling as though she were drunk. These episodes were not associated with alcohol or drug use. Her psychiatric history was remarkable for a standing diagnosis of depression with a signicant anxiety component. She had attempted suicide once by cutting both wrists transversely. Medical history was remarkable for lower extremity cellulitis, lower extremity venous-stasis dermatitis, and chronic neck and low back pain. Her family medical history was remarkable for

her father and one of her sisters with depression, another sister with an anxiety disorder, and her mother dying of a cerebral hemorrhage. Her medications at the time of the consult were: trazodone, 50 mg each morning and 300 mg at bedtime; clonazepam, 2 mg twice daily; uoxetine, 80 mg daily; penicillin for cellulitis; acetaminophen as needed for back pain; and rofecoxib as needed for joint pain. Thorough physical and neurologic exams were unrevealing. On mental status exam, she endorsed neurovegetative symptoms of depression, including suicidal ideation, and auditory hallucinations as described above. She displayed insight into her situation and understood that the voices were hallucinations. Her language, memory, and executive function were intact. Her comportment was contextually appropriate. With a compelling history and curious temporal variability of neurologic signs, our team requested an MRI of the brain (Figure 2). Axial T2 FLAIR MRI revealed multiple focal subcortical white matter hyperintensities. Although differential diagnosis for lesion etiology was broad (e.g., ischemia, metastatic disease), a demyelinating process (e.g., multiple sclerosis [MS]), was suggested by the overall clinical context, including the patients report of periods of vertigo, ataxia, and parasthesias. The patients depressive syndrome47 and her

FIGURE 2. Axial T2 FLAIR MRI demonstrating bihemispheric subcortical white matter hyperintensities (arrows).

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auditory hallucinations were also considered possible manifestations of early MS. The NBN team alerted the patients treatment team to this possibility and recommended a lumbar puncture to survey for abnormal cells, myelin basic protein, and oligoclonal bands. In the event that MS was diagnosed, administration of an interferon agent was suggested as a possible intervention for her cognitive and behavioral symptoms. In addition, the NBN service recommended repeating an MRI with contrast in one month to assess any progression of the patients lesions. The service also recommended an EEG to rule out seizure foci as a source of symptoms, and suggested reevaluation of the patients high dosages of uoxetine and trazodone as possible contributors to her symptoms (e.g., parasthesias, vertigo, anxiety symptoms), particularly since inhibition of CYP 2D6 by uoxetine interferes with the metabolism of the active metabolite of trazodone, mCPP, which could potentially result in untoward side effects. This patients psychiatric symptoms had overshadowed her neurologic signs for an unknown period of time. Even soft neurologic signs, however, are brought to the forefront by the NBN teams methodology, which in this case prompted studies that revealed pathology that may have played a signicant contributory role in the patients psychiatric symptoms. In the context of severe psychosocial stress and a depressive syndrome, the patients neurologic signs could easily have been overlooked or considered a form of somatization. But the NBN consult led to the discovery of anatomic ndings consistent with a highly morbid, yet treatable, neurologic disorder.

Vignette 3
A 53-year-old woman with a diagnostic history of complex partial seizure disorder complicated by comorbid anxietyassociated, psychogenic seizures self-admitted to McLean Hospital with severe anxiety in the context of marital discord. She described worsening of her seizure disorder (now averaging three seizures a week) and reported that intense anxiety preceded each seizure. She explained that repeated intrusive thoughts about an imminent seizure attack resulted in an anxious state, which then seemed to culminate in an actual seizure. During these 5- to 15-minute events, she would experience tunnel and blurred vision, and she would place her hands to her head and often engage in loud nonverbal utterances. She would frequently nd herself in another area of her house after the event. Postictally, she described herself as being very lethargic. Her seizure disorder, which started when she was two years of age, had been well controlled by medication until puberty. Since her teens, however, these paroxysmal episodes have been more difcult to manage.

Eight years prior, the patient underwent an epilepsy presurgical evaluation (which included a neuropsychological evaluation and surface EEG monitoring), which conrmed complex partial seizures with secondary generalization. The neuropsychological evaluation at that time suggested compromise of the dominant hemisphere and frontotemporal lobe systems, perhaps consistent with a seizure disorder. The patient displayed impairment on tests involving aspects of attention, inhibition, psychomotor speed, and verbal and visual memory. It was suggested that episodic stress and anxiety increased the patients susceptibility to seizures. Prior to her evaluation by the NBN service, the patient had undergone CBT, which she reported was effective in controlling her anxiety. Coincidentally, her seizure disorder improved dramatically for about six months. However, due to a recent increase in life stressors, including severe marital difculties, she was unable to use her cognitive-behavioral techniques effectively, and she reported losing control of her seizure disorder. The patient reported no substance abuse history. Her family psychiatric history was noncontributory, and her family medical history was remarkable for epilepsy in several paternal family members. At the time of her NBN consult, a new neuropsychological evaluation revealed decits in cognitive function associated with the frontal region of the dominant hemisphere. These decits included inhibition of verbal responses and verbal uency, as well as secondary decits (e.g., verbal learning, memory) related to the mesial temporal region of the dominant hemisphere. It was evident from the specicity and lateralization of these ndings that some of her cognitive decits were consistent with an epileptiform disorder. Nevertheless, her high anxiety level, poor coping skills, and reported ability to control some of her seizures by applying cognitive-behavioral techniques were strongly suggestive of a complex emotional contributor to the manifestation of her seizures. The teams assessment was that, although there appeared to be a signicant psychological component, the patient likely suffered from a genuine complex partial seizure disorder that was refractory. The extent to which her seizures were emotionally driven nevertheless remained unclear. The NBN service recommended a comprehensive epilepsy workup, which led to a surgical evaluation, in which a deep electrode EEG study revealed bilateral foci in the temporal lobes. Instead of proceeding with a surgical treatment, however, we initiated a trial of vagal nerve stimulation (VNS, now also FDA approved for depression), which was found to reduce her seizure frequency by approximately 30%. Based on results from neuropsychological testing and psychiatric interview, CBT was resumed in order to help her control the anxious states that appeared to be associated with her seizures. Further, individual psychotherapy was begun in order to address her

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poor coping skills, anxiety, and stressful marital situation. This patient requested continued care by an NBN team member, and within four monthswith continued divalproex (1500 mg at bedtime) and VNSseizure frequency decreased to 12 events per week. In addition, her depression resolved, and signicant improvement in her anxiety was noted. When contemplating this patient, it becomes evident that the boundary between the patients psychogenic seizures (psychiatric/functional component) and her documented complex partial seizures (neurologic/organic component) is indistinct. Psychosocial stressors appear to have played a role in triggering both types of events, and both psychiatric (e.g., CBT) and neurologic (e.g., antiseizure medications and VNS) interventions were effective in reducing seizure episodes. Neuropsychological testing was helpful in mapping brain areas that were likely involved, as well as in providing insight as to the patients cognitive capability and type of therapy most suitable in the context of her specic neuropsychological impairment.

DISCUSSION
A continental drift has occurred between neurology and psychiatrytwo bodies of knowledge that, although having distinct virtues and resources, actually originated from the same land mass. Perhaps it was rst necessary to drift apart in order to develop a certain sophistication in each eld. For example, had psychological psychiatry not been explored, the effective modes of intervention still in use today might not have been formulated. But the costs polarization and indoctrinationwere signicant. Nevertheless, with the continuing maturation of neuroscience, it is clear that there is a neurology of psychiatry and also a psychiatry of neurologywith the consequence that the boundaries between these two disciplines are becoming more and more difcult to delineate. A proposed restructuring of neurology and psychiatry training would include both more formalized instruction in related foundation sciences and cross-training in behavioral and neurologic medicine.15 In many residency programs, cross-training is currently decient. Psychiatry training programs do not typically emphasize the importance of the many neurologic diseases that can manifest with psychiatric symptoms; few programs require their residents to become procient in conducting a thorough neurologic exam, reading neuroimaging studies, or interpreting EEGs; and the value of appropriate neuropsychological testing and its interpretation seems marginalized. Likewise, most neurology programs do not require prociency in diagnostic psychiatric evaluation, psychopharmacology, psychosocial considerations and intervention, and neuropsychological testing.

The construction of a subspecialty in Behavioral Neurology and Neuropsychiatrythrough the combined efforts of the American Neuropsychiatric Association and the Society for Behavioral and Cognitive Neurology, under the auspices of the United Council for Neurologic Subspecialtiesis a decisive step toward eliminating the shortcomings of training in the respective elds. Here, we do not propose that the elds of neurology and psychiatry merge, and we do not advocate that psychiatry should increasingly focus on biology to the exclusion of psychologically based techniques. Rather, we propose that a certain coalescence of disciplines is necessary in order to provide comprehensive care for the complex neuropsychiatric patient. Residents and medical students alike are becoming mindful of this unmet need and are increasingly expressing interest for more integrated training in neurology and psychiatry. In Table 2, we propose areas of extended training that could reasonably and appropriately complement the knowledge base of modern practitioners of medicine of the central nervous system. The proposed means of supplementing psychiatry and neurology training, while raising the bar of mastery for trainees in these disciplines, nevertheless remain realistic. Moreover, they align with both the core curriculum for fellowship training and the fund of knowledge required for board certication in Behavioral Neurology and Neuropsychiatry. We predict that neurologists and psychiatrists clinical repertoires will need to expand in response to, and parallel with, emerging neuroscience. For sufcient grasp of the relevant pathophysiology, psychiatrists will need to be trained in emerging principles of behavioral neuroanatomy underlying the affective- and thought-disorder phenomenology that they already study, and neurologists will need to be trained in the psychiatric phenomenology now recognized as attributable to normal and abnormal neuroanatomical function. Emerging neuroscience will, in effect, require cross-training such as that embodied in McLean Hospitals NBN service. In this article we have described a multidisciplinary team whose members, for more than a decade, have worked together to provide comprehensive evaluations of patients with comorbid neurologic and psychiatric disease. The clerkship that has spun out of the NBN service has implemented what has been described, in theory, by Eisenberg, Kandel, Martin, Price, and othersproof that an integrated clinical experience is both feasible and valuable. Such clerkships are essential in developing a framework for education designed to train practitioners comprehensively in neurology, psychiatry, and neuropsychology, while also recognizing the expertise and focus that each eld independently offers. We offer this model for further discussion and development, and with the hope that it will also help expedite similar attempts in other settings.

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TABLE 2. Proposed Areas of Extended Training for Modern CNS Physicians Psychiatry
Disorders Seizure disorders, e.g., TLE Neurodegenerative disorders, e.g., AD, FTLD, HD, LBD, PD Movement disorders Amyotrophic lateral sclerosis Multiple sclerosis Traumatic brain injury Headache Hydrocephalus Neoplastic disorders Cerebrovascular disorders Delirium and confusional states Toxic exposures CNS infections, e.g., HIV, neurosyphilis, Lyme, herpes, prion disease, viral encephalitides Cognitive disorders, e.g., aphasias, memory disorders EEG interpretation Psychodiagnostics Neurocognitive/mental status exam Functional neuroanatomy Neuropsychological testing Neurodevelopment Neurorehabilitation Cognitive neuroscience Neuroimaging (MRI, CT, PET/SPECT) Neurologic exam, including the fundoscopic exam

Neurology
Somatoform disorders Malingering and factitious disorders Formal thought disorders Mood disorders Anxiety disorders Impulse control disorders Attention-decit disorders Developmental disorders, e.g., PDD, autism, mental retardation, Aspergers syndrome Personality disorders Toxic exposures Addiction and substance abuse

Skills/fund of knowledge

Psychopharmacology Psychodiagnostics Neurocognitive/mental status exam Functional neuroanatomy Neuropsychological testing Neurodevelopment Neurorehabilitation Cognitive neuroscience Geriatric care Genetics/epidemiology of psychiatric diseases Electroconvulsive therapy

AD, Alzheimers disease; FTLD, frontotemporal lobar dementia; HD, Huntingtons disease; LBD, Lewy body disease; NVLD, nonverbal learning disorder, PD, Parkinsons disease; PDD, pervasive developmental disorder; TLE, temporal lobe epilepsy = partial complex seizures.

In addition to the aforementioned benets, we see the strengths of our model as including the purposeful slowing down of patient volume in favor of in-depth examinations of a more limited number of complex patients. (To compensate, other consultants will deal with simpler cases and, by design, maintain a rapid response time.) Our model emphasizes case-based teaching with an interdisciplinary team approach; the involvement of senior faculty who directly observe, and are accountable for, students and residents; and trainee exposure to the critical thinking, problem solving, and lifelong learning required for the effective practice of mind/brain medicine. The proposed model offers crosstraining in neurology, neuropsychology, and psychiatry for our residents, medical students, and fellows in Neuropsychiatry and Behavioral Neurology, as well as for established practitioners who are drawn to this model. The patients seen by the NBN team receive simultaneous evaluations across disciplines with real-time communication and formulations, as opposed to separate evaluations by individual specialists that may be separated temporally by days, weeks, or

months. This approach holds promise as being more costeffective and time-efcient since diagnosis and treatment can be improved and expedited. A case in point is presented in the rst vignette. Prior to his NBN consult, the patient underwent several months of evaluations by numerous specialists without a unied synthesis of his symptoms and diagnostic test results. By contrast, the NBN team consolidated existing data with current evaluations and diagnostic data into a working diagnosis and treatment plan within the time constraints of a single hospitalization (i.e., ve days). The limitations to our model are primarily scal. In the absence of proof that our integrated, multidisciplinary team approach ultimately increases efciency, this approach will be perceived as economically inefcient. Furthermore, there is little incentive for faculty to involve themselves in such labor-intensive teaching endeavors. We need to establish better mechanisms for supporting and rewarding senior clinical facultyincluding protected time, promotional merit, and nancial opportunities with equitable

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compensation. As we move forward, we should formulate an even clearer denition of our curriculum, with overarching goals that emphasize outcomes, cognitive rehabilitation, and neuropsychology. We realize, too, that this model may not be easily generalized. We offer it for its heuristic value and hope that it may be subject to further evaluation, revision, and innovation. We live in exciting times. We are gaining the ability to understand the biology of a memory, of a thought, of an emotion. This knowledge will surely improve our ability to treat profound and debilitating dysfunctions of the central nervous system. It could invigorate the exploration of mind,48 positioning psychotherapy as potentially one of the most elegant forms of noninvasive neurosurgery, through which neural circuits could be modied and reconstructed. Yet even as we face a future with its ever expanding arsenal of technology, we must also, as Dean Joseph Martin asks, proceed with humility.16 Indeed, the lack of humility, the seduction of arrogance, and deant ego defense have been our enemies, and stood in our way, for decades. By recognizing areas in need of improvement, by encouraging creative, open thinking, and by promoting innovative training and committed leadership, we will be further empowered in our ability to heal.
An earlier version of this manuscript was previously presented at the FebruaryMarch 2005 meeting of the American Neuropsychiatry Association in Bal Harbour, Florida.

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