THERAPEUTIC AND RESEARCH IMPLICATIONS

Jeremy D. Schmahmann, M.D.

Department of Neurology, Massachusetts General Hospital and Harvard Medical School,
Boston, Massachusetts 02114

I. Introduction
II. Therapeutic Implications
A. The Need to Know
B. Rehabilitation Efforts
C. Potential Future Therapeutic Modalities
III. Research Implications
IV. Conclusions
References

Investigations into the relationship between the cerebellum and nonmotor

processing have produced a substantial body of evidence which seems to
require a revision of accepted notions about the functional role of the
cerebellum. This chapter presents a perspective on the contemporary and
possible future therapeutic and research implications of these findings.
These include the need for patients and their families to know of the
behavioral consequences of cerebellar disease processes; potential ap-
proaches for improvement through rehabilitation therapies; and future
treatment strategies, such as electrical stimulation of the cerebellum and
psychosurgical approaches applied to the cerebellum. In addition, some
areas of basic science investigation that could prove informative in under-
standing this relationship are addressed. It will be important to obtain a
more complete characterization of the anatomy, physiology, and func-
tional topography of the cerebellum in humans and in animal models, and
a greater understanding of the clinical consequences of cerebellar lesions.

I. Introduction

The realization that the role of the cerebellum in nervous system func-
tion is not limited to the coordination of voluntary movement has ushered
in an exciting new area of cognitive neuroscience investigation. There are
presently more questions than answers, but there is now a clearer notion
of where future research efforts may reasonably be directed. There is also

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638 JEREMY D. SCHMAHMANN

some hint of the clinical significance of the findings to date and of the
potential for therapeutic intervention. This chapter presents a view of
therapeutic and research implications derived from our current state of
knowledge in this field.

II. Therapeutic Implications

A THE NEED TO KNow

Dual clinical imperatives motivate the clinician in the management of

neurologically impaired individuals. The central directive is to provide
care in all cases, and cure when possible. A second consideration of great
importance to patients and their families is the need to know the diagnosis,
understand the disease process, and participate actively in their own medical
treatment. This facilitates a physician-patient partnership that is an essen-
tial ingredient in both acute and long-term management. The knowledge
that seemingly bizarre behavior, inappropriate social interactions, disinhib-
ited personality style, and limited intellectual flexibility and abilities may
be explained by the cerebellar insult itself (Bracke-Tolkrnitt et al., 1989;
Wallesch and Horn, 1990; Pollack, 1995; see chapter byJ. D. Schmahmann
andJ. C. Sherman), can provide the patient and family with an explanation
and understanding that was previously unavailable. It is too early to be
definitive in presenting this association, but there is sufficient evidence to
inform patients and families of the discussion of the probable role of the
cerebellum in the modulation of behavior. This is also valuable in providing
reassurance regarding the reversibility of the syndrome following acute
lesions (Botez-Marquard et al., 1994; see chapter byJ. D. Schmahmann and
J. C. Sherman) although the full extent and time course of the cognitive
recovery have yet to be adequately studied.
We do not yet understand the range of manifestations and rate of
progression of the cognitive and emotional disturbances that may accom-
pany degenerative cerebellar disease. Early indicators show that there is
an intellectual and emotional decline with time (Grafman et al., 1992;
Appollonio et al., 1993; Kish et al., 1994; Botez-Marquard and Botez, 1995;
see chapter by J. D. Schmahmann and J. C. Sherman) but the clinical
relevance and impact on occupational performance and personal life situa-
tions are essentially unknown. It will be important to establish these facts
in order to share them with patients and their families.
 THERAPEUTIC AND RESEARCH IMPLICATIONS 639

B. REHABILITATION EFFORTS

Cognitive rehabilitation has been helpful in patients who have suffered

closed head injury (Levin, 1992) and in those with aphasia (Wertz et al.,
1981; Pring, 1986). It is conceivable that patients with a behavioral syndrome
from cerebellar lesions may also benefit from such approaches, but one
first has to recognize that this syndrome exists before being able to treat it.
The awareness of a cerebellar role in sensory (Gao et al., 1996), auto-
nomic (Martner, 1975; see chapter by D. E. Haines et at.) , emotional (Coo-
per et al., 1978; Heath et al., 1979; see chapter by]. D. Schmahmann and
]. C. Sherman), and intellectual processing (Bracke-Tolkmitt et al., 1989;
Grafman et al., 1992; Appollonia et al., 1993; see chapters by T. Botez-
Marquard and M. I. Botez and by J. D. Schmahmann and]. C. Sherman)
may facilitate new approaches to the neurologically disabled patient that
capitalize on cerebrocerebellar communication. Could physical/occupa-
tional/cognitive/vestibular therapy approaches exploit the cerebellar com-
ponent of the cerebrocerebellar circuit to help compensate for functions
lost by cerebral hemispheric damage? That is, could vestibular physical
therapy (Shephard et al., 1993) improve dexterity in a partially paralyzed
extremity, e.g., by promoting cross-modal integration within cerebellum,
and thus benefiting the motor system? Could enhanced sensory stimulation
(posterior column or muscle spindle input) promote recovery from motor
incapacity by cerebellar as well as by cerebral mechanisms? These may be
fanciful notions, but the potential for utilizing compensatory mechanisms
across different modalities is at least an interesting possibility, derived in
large part from the evolving understanding of the convergence within the
cerebellum of afferents from multiple domains of neurologic function
and the tightly linked, highly organized, cerebro-cerebellar interactions
(Hampson et al., 1952; Henneman et al., 1952; Sasaki et al., 1975; Brodal,
1978, 1979; Haines and Dietrichs, 1984; Glickstein et al., 1985; Schmah-
mann, 1991, 1996; Leiner et al., 1993; Middleton and Strick, 1994; see
chapter by J. D. Schmahmann and D. N. Pandya).

C. POTENTIAL FUTURE THERAPEUTIC MODALITIES

1. Cerebellar Stimulation
The improvement in mood and aggression induced in some patients
by cerebellar cortical stimulation (Cooper et al., 1978) was believed to be
related to cerebellar connections with the limbic and autonomic systems
(Snider and Maiti, 1975; Martner, 1975). The techniques and results of
640 JEREMY D, SCHMAHMANN

cerebellar cortical stimulation were not always consistent, possibly reflecting

the fact that placement of the stimulating electrodes generally did not
respect established anatomic boundaries or the topographic (zonal) pattern
of cerebellar cortical afferent and efferent systems (Haines, 1981). Further-
more, the pathophysiology of the improvement, the extent and duration
of the clinical recovery, and the nature of the side effects or complications
were also not tully established.
Fastigial nucleus (FN) stimulation has been pursued experimentally in
the study of vasomotor influences of the cerebellum (Doba and Reis, 1972;
Martner, 1975; McKee et al., 1976; Chida et al., 1986; see chapter by D. J.
Reis and E. V. Golanov), and recent findings indicating a neuroprotective
effect of FN stimulation in the setting of cerebrovascular ischemia are
intriguing (Reis et al., 1991; see chapter by D.]. Reis and E. V. Golanov).
Stroke is a major cause of morbidity and mortality, and efforts to prevent
or limit neuronal injury and death from ischemic infarction are receiving
intense scrutiny. Could there be a role for some modified and clinically
applicable version of FN stimulation in this patient population? Are there
lessons to be learned about mechanisms of neuronal protect.ion from these
studies that could be more broadly applied to the protection of ischemic
neural tissue without having to resort to the use of a brain stimulator?
There is a contemporary precedent for the therapeutic use of electrical
stimulation ofthe nervous system. The transcutaneous electrical nerve stimu-
lator (TENS), based on the gate theory of Melzack and Wall (1965), has sub-
stantially helped some individuals with intractable pain syndromes (Katz et
al., 1989); and electroconvulsive therapy is still valuable in the treatment of
catatonia and profound depression not responsive to medication (Green-
blau, 1977; Frankel, 1984; Casey, 1994). As we learn more about the dynamic
interactions between the cerebellum and other neural systems that subserve
cognition, emotion, and autonomic function, there appears to be sufficient
reason, based on both early and contemporary work in this field, to warrant
a scientific reevaluation of the indications and techniques of therapeutic cer-
ebellar stimulation and of more sophisticated future adaptations thereof.

2. Cerebellar P~yc/!Osurgery
Psychosurgery has reemerged as a valid and effective treatment of se-
lected diseases. In vogue in the first half of this century as prefrontal
leukotomy for schizophrenia (Landis, 1949), this modality lost favor until
recent advances in neuroscience facilitated its careful and judicious use.
Knowledge of the functional neuroanatomy of obsessive compulsive disor-
der (Breiter et al., 1996; Jenike et al., 1996) has led to the successful use
of therapeutic cingulotomy in those severely afflicted individuals who do
not respond to medications (Spangler et al., 1996). Additionally, stereotactic
 THERAPEUTIC AND RESEARCH IMPLICATIONS 641

pallidotomy guided by magnetic resonance imaging and performed with

the assistance of physiologic recording has proven to be successful for
the treatment of disabling tremor and bradykinesia in Parkinson's disease
(Laitinen, 1995; Baron et al., 1996). Furthermore, temporal lobectomy,
which when first introduced resulted in the amnesia typified by patient
H.M. (Scoville and Milner, 1957; Milner et al., 1968), is now routinely
employed in epilepsy units utilizing contemporary diagnostic techniques
(Fried, 1993; Spencer, 1996).
The amelioration of aggression in monkeys by vermis and archicerebel-
lar lesions but not by neocerebellar lesions was an extraordinary finding
(Peters and Monjan, 1971; Berman et al., 1974). Is there a relationship
between the vermis/archicerebellum/fastigial nucleus complex and emo-
tional dyscontrol? This is surely a difficult area of study because aggression
and violence are so interwoven with psychological, social, and biological
factors. Nevertheless, there appears to be sufficient scientific rationale at
least to address the question in the context of hypothesis-driven research
protocols, and these observations in nonhuman primate need to be re-
peated. It may also be reasonable to open the debate regarding the use
of cerebellar psychosurgery for the management of unremitting affective
disorders, including emotional dyscontrol, in humans.

3. Cerebellar Transplantation
The study of transplanted cerebellar tissue has been ongoing for some
years (Sotelo and Alvarado-Mallart, 1987), and recent findings suggest some
hope for anatomic and functional success with this approach (Triarhou et
al., 1996). As the understanding of the neural circuitry of the cerebrocerebe-
llar system evolves, and the appreciation of the scope of cerebellar function
becomes evident, the transplantation of cerebellar tissue in neurodegenera-
tive disorders may find a role in clinical practice for its potential motor
as well as its nonmotor consequences. Furthermore, as neuroprotective
treatment options (Schultz et al., 1996), and eventually gene therapy (Ha-
hania et al., 1995), become available for cerebellar neurodegenerative disor-
ders, it is quite likely that the cognitive and affective improvements resulting
from these interventions will need to be monitored as closely as the course
of the cerebellar motor phenomena.

III. Research Implications

It is apparent that a number of issues related to therapeutic intervention

discussed earlier require thorough clinical and basic science investigation.
642 JE.REMY D. SCHMAHMANN

In addition, there are many intriguing questions in each discipline of the

neurosciences that have yet to be explored in understanding the relation-
ship between the cerebellum and higher order function.
Considerable strides have been made in understanding the complexities
of cerebrocerebellar organization in the nonhuman primate (Allen and
Tsukuhara, 1974; Brodal, 1979; Voogd and Bigare, 1980; Haines et al., 1982;
Glickstein et al., 1985; Dore et al., 1990; Schmahmann, 1994, see chapters
by F. A. Middleton and P. L. Strick, by]. D. Schmahmann and D. N. Pandya,
by D. E. Haines et al., and by]. D. Schmahmann). More detailed knowledge
of cerebellar interactions with the neuraxis will be gained by further studies
of the projections from pons to the cerebellum, the cerebellar cortical to
nuclear projection, and the cerebellar nuclear projection to thalamus.
There is currently only limited information available, for example, regard-
ing the anatomic relationship between discrete architectonic regions of
the cerebral hemispheres (Pandya and Yeterian, 1985) and individual cere-
bellar lobules, folia, and nuclei (Schmahmann et al., 1996).
In order to establish the functional relevance of the various anatomic
nodes within the distributed cerebrocerebellar circuitry, experimental in-
vestigations using physiologic recordings and behavioral studies need to be
undertaken. Current technical achievements permit multiple simultaneous
electrode recordings in different neural structures of awake behaving ani-
mals (e.g., Gardiner and Kitai, 1992). Cerebellar neuronal discharges have
been extensively studied in relation to motor activity (e.g., van Kan et al.,
1993). It would be of great interest to determine whether stimuli that
challenge attention, motivation, learning, visual-spatial analysis, working
memory, and other higher order functions also result in activation of the
cerebrocerehcllar circuitry and, if so, in what temporal sequence. Further-
more, measures of cognitive function in the nonhuman primate (Mountcas-
tle et al., 1975; Mishkin, 1982; Petrides 1987; Desimone and Ungerleider,
1989) could be employed in lesion studies of the cerebellum or its connec-
tions in order to perform lesion-behavior correlation analyses.
Studies of large groups of patients with discrete and well-characterized
cerebellar pathology (such as stroke) will be essential in further exploring
lesion-deficit correlations in humans. More searching tasks derived from
experimental psychology will be valuable in the study of the mechanisms
that subserve the cerebellar influence upon non motor function. This ap-
proach will be important in patients as well as in normal volunteers undergo-
ing functional neuroimaging. What is the functional topographic map of
the human cerebellum? Is there regional specialization in the cerebellum
as predicted from studies to date (Schmahmann, 1996), and how focused
are the variuus higher order functional properties within each folium or
lobule? Do motor and sensory cerebellar areas (primary, secondary, and
 THERAPEUTIC AND RESEARCH IMPLICATIONS 643

perhaps others) overlap or interdigitate with cognitive, affective, and auto-

nomic areas or are they separate and distinct from each other? What are
the mechanisms of cognitive recovery following acute cerebellar lesions?
Are there compensatory cerebellar mechanisms, or is recovery dependent
on cerebrocerebellar interactions as is the case in the sensory-motor realm
(Growdon et al., 1967; Mackel, 1987)?
Acceptance of the notion that the cerebellum was important only in
motor control precluded the consideration of its role in diseases with
principally behavioral manifestations. This essentially excluded all of psychi-
atry. It is now apparent that the pathology of early infantile autism includes
consistently abnormal morphological features in the cerebellum (Bauman
and Kemper, 1985; Courchesne et al., 1988); schizophrenia has been associ-
ated with cerebellar vermis abnormalities (Heath et al., 1979; Weinberger
et al., 1980); and mood and emotional dyscontrol are improved by cerebellar
cortical stimulation (Cooper et al., 1978). In addition, sham rage and preda-
tory attack can be induced by stimulation of the fastigial nucleus in cats
(Zanchetti and Zoccolini, 1954; Reis et al., 1973), and aggression was amelio-
rated in monkeys by destructive lesions of the vermis and flocculonodular
lobes (Peters and Monjan, 1971; Berman et al., 1978). The possibility of a
cerebellar role in psychiatric disease having been more frankly stated, it
may now be reasonable to use the available anatomic and functional neuroi-
maging techniques, as well as morphologic and immunohistochemical
pathologic study, to challenge old assumptions and provide new insights
into these psychiatric diseases. In this vein, it has been shown that methyl-
phenidate, the drug of choice in the treatment of attention deficit hyperac-
tivity disorder (ADHD) , significantly increases brain metabolism, most con-
sistently in the cerebellum, as well as in frontal and temporal lobes (Volkow
et al., 1997). Children with ADHD demonstrate impairments of attention,
as well as of memory and learning (Barkleyet al., 1992), and the possibility
of a cerebellar role in the manifestations or pathogenesis of this condition
is intriguing.

IV. Conclusions

There are a multitude of avenues to investigate in the evolving understand-

ing of the cerebellum and its role in the normally functioning nervous
system. The rapidly increasing sophistication of contemporary investigative
tools and concepts has facilitated the exploration of old ideas and novel
discoveries concerning the cerebellum. The study of the relationship be-
644 JEREMY D. SCHMAHMANN

tween the cerebellum and cognition opens a new and exciting chapter in
contemporary cognitive neuroscience.

Acknowledgment

The author is RTateful to Drs. Margaret L. Bauman, AaronJ. Berman, and Duane E. Haines
for their helpful comments regarding this manuscript.

References

Allen, G. 1., and Tsukuhara, N. (1974). Cercbrocerebcllar communication systems, Physiol.

Rev. 54, 9.~7-1008.
Appollonio, l. M., Grahnan,J., Schwartz, V., Massaquoi, S., and Hallett, M. (1993). Memory
in patients with cerebellar degeneration. Neurology 43, 15::\6-1544.
Barkley, R. A., Crodzinsky, G., and Du Paul, G. J. (1992). Frontal lube functions in attention
deficit disorder with and without hyperactivity: A review and research report. J. Almunn.
Child Psychol. 20, 163-188.
Baron, M. S., Vitek, J. L., Bakay, R. A., Green, .l- Kaneoke, Y, Hashimoto, T., Turner, R. S.,
Woodard,]. 1.., Cole, S. A., McDunald, W. M., and Del.ong, M. R. (l!IY6). Treatment of
advanced Parkinson's disease by posterior Gpi pallidotomy: l-year results of a pilot study.
Ann. Neurol. 40, 355-366.
Bauman, M., and Kemper, T. L. (1985). Histoanatornic observations of the brain in early
infantile autism. Nl!Urology 35, 8fi6-874.
Berman, A. j., Berman, D., and Prescott,]. W. (1974). The effects of cerebellar lesions on
emotional behavior in the rhesus monkey. In "The Cerebellum, Epilepsy and Behavior"
(I. S. Cooper, M. Riklan, and R. S. Snider, eds.), pp. 277-284, Plenum Press, New York.
Botcz-Marquard, T., and Botez, M. 1. (1!l!J5). Reaction time and intelligence in patients with
olivoponrocerebellar atrophy. Nr.uropsychiat. Neurop.<ychol. Behau. Neural. 8, 168-175.
Botez-Marquard, T., Leveille ]., and Botez, M. 1. (1994). Neuropsychological functioning in
unilateral cerebellar damage. Cnn. J. Neural. Sci. 21, 353-357.
Bracke-Tolkmitt, R., Linden, A., Canavan, A. G. M., Rockstroh, B., Scholz, E., Wessel, K.,
and Diener, H.-C. (1989). The cerebellum contributes to mental skills. &11l1.1I. Neurosa.
103, 442-446.
Breuer, H. C., Rauch, S. L., Kwong, K. K., Baker, j. R., Weiskotr, R. M., Kennedy, D. N.,
Kendrick, A. D., Davis, T. 1.., Jiang, A., Cohen, M. S., Stern, C. E., Belliveau, J. W., Baer,
1.." O'Sullivan, R. L., Savage, C. R., and Rosen, B. R. (1996). Functional magnetic resonance
imaging of symptom provocation in obsessive-compulsive disorder. Arch. Cen. Psychiat.
53, 595-606.
Brodal, P. (1978). The corticopontine projection in the rhesus monkey: Origin and principles
of organization. Brain 101, 251-283.
Brodal, P. (1979). The pontocerebellar projection in the rhesus monkey: An experimental
study with retrograde axonal transport ofhorseradish peroxidase. Neuroscienre 4, 193-208.
Casey, D. A. (1994). Depression in the elderly. South. Med. .f. 87, 559-563.
 THERAPEUTIC AND RESEARCH IMPLICATIONS 645

Chida, K., ladecola, c., Underwood, M. D., and Reis, D.]. (1986). A novel vasodepressor
response elicited from the rat cerebellar fastigial nucleus: The fastigial depressor response.
Brain /Us. 370, 378-382.
Cooper, I. S., Riklan, M., Amin, I., and Cullinan, T. (1978). A long term follow-up study of
cerebellar stimulation f01" the control of epilepsy. In "Cerebellar Stimulation in Man"
(I. S. Cooper, ed.), pp. 19-38, Raven Press, New York.
Courchesne, E., Yeung-Courchesne, R., Press, G. A., Hesselink,]. R., and Jernigan, T. L.
(1988). Hypoplasia of cerebellar vermallobules VI and VII in autism. N. Engl. I Med.
318, 1349-1354. Elsevier, New York.
Desimone, R., and Ungerleider, L. G. (1989). Neural mechanisms of visual processing in
monkeys. In "Handbook of Neuropsychology" (F. Boller and]. Grafman eds.), Vol. 2,
pp. 267-299. Elsevier, New York.
Doba, N., and Reis, D.]. (1972). Changes in regional blood flow and cardiodynamics evoked
by electrical stimulation of the fastigial nucleus in the cat and their similarity to orthostatic
reflexes. I Physiol. (Lond.) 227,729-747.
Dore, L.,Jacobson, C. D., and Hawkes, R. (1990). Organization and postnatal development
of Zebrin II antigenic cornpartmentation in the cerebellar vermis of the grey opossum,
Monodelphis domestica. j. Compo Neurol. 291, 431-449.
Frankel, F. H. (1984). The use of electroconvulsive therapy in suicidal patients. Am. I Psychother.
38, 384-391.
Fried, I. (1993). Anatomic temporal lobe resections for temporal lobe epilepsy. Neurosurg.
cu« N. Am. 4, 233-242.
Gao,].-H., Parsons, L. M., Bower,]. M., Xiong,]., u.j., Brannon, S., and Fox, P. T. (1996).
Cerebellar dentate-nucleus activated by sensory and perceptual discrimination, imagined
hand movement, and mental rotation of objects. Science 272, 545-547.
Gardiner, T. W., and Kitai, S. T. (1992). Single-unit activity in the globus pallidus and neostria-
tum of the rat during performance of a trained head movement. Exp. Brain Res. 88,
517-530.
Glickstein, M., May,]. G., and Mercier, B. E. (1985). Corticopontine projection in the macaque:
The distribution of labelled cortical cells after large injections of horseradish peroxidase
in the pontine nuclei. I Camp. Neural: 235, 343-359.
Grafman.j., Litvan, L, Massaquoi, S., Stewart, M., Sirigu, A., and Hallett, M. (1992). Cognitive
planning deficit in patients with cerebellar atrophy. Neurology 42,1493-1496.
Greenblatt, M. (1977). Efficacy of ECT in affective and schizophrenic illness. Am. I Psychiat.
134, 1001-1005.
Growdon,]. H., Chambers, W. W., and Liu, C. N. (1967). An experimental study of cerebellar
dyskinesia in the rhesus monkey. Brain 90, 603-632.
Hahania, E. G., Kavanagh, ]., Hortobagyi, G., Giles, R. E., Champlin, R., and Deisseroth,
A. B. (1995). Recent advances in the application of gene therapy to human disease. Am.
I Med. 99, 537-552.
Haines, D. E. (1981). Zones in the cerebellar cortex: Their organization and potential relevance
to cerebellar stimulation. .f. Neurosurg. 55, 254-264.
Haines, D. E., and Dietrichs, E. (1984). An HRP studyofhypothalamo-cerebellar and cerebello-
hypothalamic connections in squirrel monkey (Saimiri sciureus). I Camp. Neurol. 229,
559-575.
Haines, D. E., Patrick, G. W., and Satrulee, P. (1982). Organization of cerebellar corticonuclear
fiber systems. In "The Cerebellum: New Vistas" (5. L. Palay, and V. Chan-Palay eds.),
pp. 320-371. Springer-Verlag, Berlin.
Hampson,]. L., Harrison, C. R. and Woolsey, C. N. (1952). Cerebro-cerebellar projections
and somatotopic localization of motor function in the cerebellum. Res. Publ. Assn. Nero.
Ment. Dis. 30, 299-316.
646 JEREMY D. SCHMAHMANN

Heath, R. G., Franklin, D. E., and Shraberg, D. (1979). Gross pathology of the cerebellum
in patients diagnosed and treated as functional psychiatric disorders. J Nero. Ment. Dis.
167, 585-5!l2.
Henneman, E., Cooke, P. M., and Snider, R. S. (1952). Cerebellar projections to the cerebral
cortex. Res. Publ. Asm. Neru. Menl. Dis. 30, 17-3:13 .
.lenike, M. A., Breiter, II. C., Baer, 1.., Kennedy, D. N., Savage, C. R., Olivares, M.J., O'Sullivan,
R. 1.., Shera, D. M., Rauch, S. 1.., Keuthen, N., Rosen, B. R., Caviness, V. S., and Filipek,
P. A. (1996). Cerebral structural abnormalities in obsessive-compulsive disorder: A quanti-
tative morphometric magnetic resonance imaging study. A,·ch. em. Psychiat. 53,625-032.
Katz, j., France, C., and Melzack, R. (1989). An association between phantom limb sensations
and stump skin conductance during transcutaneous electrical nerve stimulation (TENS)
applied to the contralateral leg: A case study. Pain 36, 367-377.
Kish, S. j., El-Awar, M., Stuss, D., Nobrega,.J., Currier, R., Aita, j. F., Schut, L., Zoghbi,
H. Y., and Freedman, M. (1!J!:l4). Neuropsychological test performance in patients with
dominantly inheriterl spinocerebellar ataxia: Relationship to ataxia severity. Neurology
44, 1738-1746.
Laitinen, 1.. V. (1995). Pallidotomy for Parkinson's disease. Neurosurg. Clin. N. Am. 6,105-112.
Landis, C. (1949). Psychology. In "Selective Partial Ablation of the Frontal Cortex" (F. A.
Mettler ed.), pp. 492-290. Paul B. Hoebcr, New York.
Leiner, H. C., Leiner, A. L., anrl Dow, R. S. (1993). Cognitive and language functions of the
human cerebellum. Trends NPlLTrJ.'(.;. 16, 444-454.
Levin, H. S. (1992). Head injury and its rehabilitation. Curro Opi7l. Neural. Neurosurg. 5, 673-676.
Mackel, R. (1987). The role of the monkey sensory cortex in the recovery from cerebellar
injury. lixp. Brain R.s. 66, 638-652.
McKee,j. C, Denn, M.j., and Stone, H. I.. (1976). Neurogenic cerebral vasodilatation from
electrical stimulation of the cerebellum in the monkey. StrokR 7. 17\1-186.
Melzack, R., and Wall, P. D. (1965). Pain mechanisms: A new theory. Science 150,971-979.
Marmer,.J. (1975). Cerebellar influences on autonomic mechanisms. Acta. Physiol. Scand.
(Su/1,1.) 425, 1-42.
Middleton, F. A., and Strick, P. I.. (1994). Anatomical evidence for cerebellar anrl basal ganglia
involvement in higher cognitive function. Saence 266, 458-451.
Milner, B., Corkin, S., and Teuber, H. 1. (1908). Further analysis of the hippocampal amnesic
syndrome: 14 years follow-up study of H.M. Neuropsycholo{?;ia 6, 21!l-234.
Mishkin, M. (\ !182). A memory system in the monkey. Trans. R Sor. l.ond. B 298, 85-95.
Mountcastle, V. B., Lynch,j. C., and Georgopuulos, A. (1975). Posterior parietal association
cortex of the monkey: Command functions fur operations within extrapersonal space.
j. Neurophysial. 38, 871-908.
Pandya, D. N., and Yeterian, E. H. (1985). Architecture and connections of cortical association
areas. In "Cerebral Cortex" (A. Peters and E. C.Jones, eds.), Vol, 4, pp. 3-61, Plenum
Press, New York.
Peters, M., and Monjan, A. A. (1971). Behavior after cerebellar lesions in cats and monkeys.
Ph.V.!iol. Behau. 6, 205-206.
Petrides, M. (1987). Conditional learning and the primate frontal cortex. In "The Frontal
Lobes Revisited" (E. Perecrnan, erl.), pp. 91-108, IRBN Press, New Yurko
Pollack, I. F. (1995). Mutism and pseudobulbar symptoms after resection of posterior fossa
tumors in children: Incidence and pathophysiology. NerLm"'urgery 37, 885-893.
Pring, T. R. (1986). Evaluating the effects of speech therapy for aphasics: Developing the
single case methodology. Br. j. Disord. Commun. 21, 103-115.
Reis, D.j., Doha, N., and Nathau, M. A. (1973). Predatory attack, grooming and consummatory
behaviors evoked by electrical stimulation of cat cerebellar nuclei. Some" 182,
845-847.
Sasaki, K., Oka, H., Matsuda, Y., Shimono, T., and Mizuno, N. (1975). Electrophysiological
 THERAPEUTIC AND RESEARCH IMPLICATIONS 647

studies of the projections from the parietal association area to the cerebellar cortex. Exp.
Brain Res. 23, 91-102.
Schmahmann,]. D. (1991). An emerging concept: The cerebellar contribution to higher
function. Arch. Neural. 48, 1178-1187.
Schmahmann,]. D. (1994). The cerebellum in autism: Clinical and anatomic perspectives.
Tn "The Neurobiology of Autism" (M. 1. Bauman, and T. 1. Kemper, eds.), pp. 195-226,
Johns Hopkins University Press, Baltimore, MD.
Schmahmann,]. D. (1996). From movement to thought: Anatomic substrates of the cerebellar
contribution to cognitive processing. Hum. Brain Mapp. 4, 174-198.
Schmahmann,]. D., Doyon,]., Holmes, c., Makris, N., Petrides, M., Kennedy, D. N., and Evans,
A C. (1996). An MRI atlas of the human cerebellum in Talairach space. NeuraImage3, S122.
Schultz, ]. B., Matthews, R. T., Henshaw, D. R., and Beal, M. F. (1996). Neuroprotective
strategies for treatment of lesions produced by mitochondrial toxins: Implications for
neurodegenerative diseases. Neuroscience 71, 1043-1048.
Scoville, W. B., and Milner, B. (1957). Loss of recent memory after bilateral hippocampal
lesions. I Neural. Neurosurg. Psychiat. 20, 11-21.
Shephard, N. T., Telian, S. A, Smith-Wheelock, M., and Raj, A (1993). Vestibular and balance
rehabilitation therapy. Ann. Otol. Rhinol. Laryngol. 102, 198-205.
Snider, R. S., and Maiti, A (1976). Cerebellar contributions to the Papez circuit. I Neurosa.
Rl's. 2, 133-146.
Sotelo, C., and Alvarado-Mallart, R. M. (1987). Reconstruction of the defective cerebellar
circuitry in adult Purkinje cell degeneration mutant mice by Purkinje cell replacement
through transplantation of solid embryonic implants. Neuroscience 20, 1-22.
Spangler, W.]., Cosgrove, G. R., Ballantine, H. T.,Jr., Casem, E. H., Rauch, S. 1., Nierenberg,
A, and Price, B. H. (1996). Magnetic resonance image-guided stereotactic cingulotomy
for intractable psychiatric disease. Neurosurgery 38, 1071-1076.
Spencer, S. S. (1996). Long-term outcome after epilepsy surgery. Epilepsia 37, 807-813.
Triarhou, 1. C., Zhang, W., and Lee, W. H. (1996). Amelioration of the behavioral phenotype
in genetically ataxic mice through bilateral intracerebellar grafting offetal Purkinje cells.
Cell Transplant. 5, 269-277.
Van Kan, P. 1., Houk, ]. C., and Gibson, A. R (1993). Output organization of intermediate
cerebellum of the monkey. I Neurophysiol. 69, 57-73.
Volkow, N. D., Wang, G.:J., Fowler,J. S., Logan,]., Angrist, B., Hitzemann, R., Lieberman j.,
and Pappas, N. (1997). Effects of methylphenidate on regional brain glucose metabolism
in humans: Relationship to Dopamine D, receptors. Am. I Prychiat. 154, 50-55.
Voogd,]., and Bigare, F. (1980). Topographical distribution of olivary and corticonuclear
fibers in the cerebellum: A review. In "The Inferior Olivary Nucleus" (E. Courville, C.
de Montigny, and Y. Lamarre, eds.), pp. 207-234. Raven Press, New York.
Wallesch, C.-W., and Horn, A. (1990). Long-term effects of cerebellar pathology on cognitive
functions. Brain Cogn. 14,19-25.
Weinberger, D. R., Kleinman,]. E., Luchins, D.]., Bigelow, 1., and Wyatt, R. (1980). Cerebellar
pathology in schizophrenia: A controlled postmortem study. Am.I Psychiat. 137,359-361.
Welker, W. (1987). Spatial organization of somatosensory projections to granule cell cerebellar
cortex: Functional and connectional implications of fractured somatotopy (summary of
Wisconsin studies). In "New Concepts in Cerebellar Neurobiology" (]. S. King, ed.), pp.
239-280. Liss, New York.
Wertz, R T., Collins, M.]., Weiss, D., Kurtzke,]. F., Friden, T., Brookshire, R. H., Piercev ].,
Holzapple, P., Hubbard, D.]., Porch, B. E., West,]. A., Davis, 1., Matovich, v., Morley,
G. K., and Resurrection, E. (1981). Veterans Administration cooperative study on aphasia:
A comparison of individual and group treatment. I Speech Hear. Res. 24, 580-594.
Zancheui, A., and Zoccolini, A. (1954). Autonomic hypothalamic outbursts elicited by cerebel-
lar stimulation. .f Neurophysiol. 17, 475-483.