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January 1996, Vol 53, No. 1 >
Article | January 1996

Anterior Paralimbic Mediation of Procaine-Induced Emotional and Psychosensory Experiences

Terence A. Ketter, MD; Paul J. Andreason, MD; Mark S. George, MD; Chulhee Lee, PhD; Debra S. Gill, MA; Priti I. Parekh; Mark W. Willis, MEng; Peter Herscovitch, MD; Robert M. Post, MD
Arch Gen Psychiatry. 1996;53(1):59-69. doi:10.1001/archpsyc.1996.01830010061009
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Background:  Procaine activates limbic structures in animals. In humans, acute intravenous administration of procaine yields emotional and psychosensory experiences and temporal lobe fast activity. We studied procaine's acute effects on cerebral blood flow (CBF) in relationship to clinical responses.

Methods:  Cerebral blood flow was assessed by positron emission tomography with oxygen-15—labeled water in 32 healthy volunteers. Data were analyzed with statistical parametric mapping and magnetic resonance imaging—directed regions of interest.

Results:  Procaine increased global CBF and, to a greater extent, anterior paralimbic CBF. Subjects with intense procaine-induced fear compared with those with euphoria had greater increases in left amygdalar CBF. Absolute and normalized left amygdalar CBF changes tended to correlate positively with fear and negatively with euphoria intensity. Procaine-induced visual hallucinations appeared associated with greater global and occipital CBF increases. Absolute occipital CBF increases appeared to correlate positively with visual hallucination intensity.

Conclusions:  Procaine increased anterior paralimbic CBF, and different clinical responses appeared to be associated with different patterns of CBF changes.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Papez JW.  A proposed mechanism of emotion . Arch Neurol Psychiatry . 1937;;38:725-743.
2 +
Post RM.  Does limbic system dysfunction play a role in affective illness?  In: Doane BK, Livingston KE, eds. The Limbic System: Functional Organization and Clinical Disorders . New York, NY: Raven Press; 1986;:229-249.
3 +
Stevens JR.  Interictal clinical manifestations of complex partial seizures and their treatment . Adv Neurol . 1975;;2:85-112.
4 +
Amaral DG, Price JL, Pitkanen A, Carmichael ST.  Anatomical organization of the primate amygdaloid complex . In: Aggleton JP, ed. The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction . New York, NY: Wiley-Liss Inc; 1992;:1-66.
5 +
Post RM, Uhde TW. Joffe RT, Bierer L.  Psychiatric manifestations and implications of seizure disorders . In: Extein I, Gold MS, eds. Medical Mimics of Psychiatric Disorders . Washington, DC: American Psychiatric Press; 1986;:33-91.
6 +
Gloor P, Olivier A, Quesney LF, Andermann F, Horowitz S.  The role of the limbic system in experiential phenomena of temporal lobe epilepsy . Ann Neurol . 1982;;12:129-144.
7 +
Halgren E, Walter RD, Cherlow DG, Crandall PH.  Mental phenomena evoked by electrical stimulation of the human hippocampal formation and amygdala . Brain . 1978;;101:83-117.
8 +
Racine R, Livingston K, Joaquin A.  Effects of procaine hydrochloride, diazepam, and diphenylhydantoin on seizure development in cortical and subcortical structures in rats . Electroencephalogr Clin Neurophysiol . 1975;;38:355-365.
9 +
Post RM, Kennedy C, Shinohara M, Squillace K, Miyaoka M, Suda S, Ingvar DH, Sokoloff L.  Metabolic and behavioral consequences of lidocaine-kindled seizures . Brain Res . 1984;;324:295-303.
10 +
Wagman IH, De Jong RH, Prince DA.  Effects of lidocaine on the central nervous system . Anesthesiology . 1967;;28:155-172.
11 +
Munson ES, Gutnick MJ, Wagman IH.  Local anesthetic drug-induced seizures in rhesus monkeys . Anesth Analg . 1970;;49:986-997.
12 +
Kellner CH, Post RM, Putnam F, Cowdry R, Gardner D, Kling MA, Minichiello MD, Trettau JR, Coppola R.  Intravenous procaine as a probe of limbic system activity in psychiatric patients and normal controls . Biol Psychiatry . 1987;;22:1107-1126.
13 +
Endicott J, Spitzer RL.  A diagnostic interview: the Schedule for Affective Disorders and Schizophrenia . Arch Gen Psychiatry . 1978;;35:837-844.
14 +
Koeppe RA, Holden JE, lp WR.  Performance comparison of parameter estimation techniques for the quantitation of local cerebral blood flow by dynamic positron computed tomography . J Cereb Blood Flow Metab . 1985;;5:224-234.
15 +
Friston KJ, Frith CD, Liddle PF, Frackowiak RS.  Comparing functional (PET) images: the assessment of significant change . J Cereb Blood Flow Metab . 1991;;11:690-699.
16 +
Woods RP, Cherry SR, Mazziotta JC.  Rapid automated algorithm for aligning and reslicing PET images . J Comput Assist Tomogr . 1992;;16:620-633.
17 +
Friston KJ, Passingham RE, Nutt JG, Heather JD, Sawle GV, Frackowiak RS.  Localisation in PET images: direct fitting of the intercommissural (AC-PC) line . J Cereb Blood Flow Metab . 1989;;9:690-695.
18 +
Talairach J, Tournoux P; Rayport M, trans. Co-Planar Stereotactic Atlas of the Human Brain . New York, NY: Thieme Medical Publishers Inc; 1988;.
19 +
Friston KJ, Frith CD, Liddle PF, Dolan RJ, Lammertsma AA, Frackowiak RS.  The relationship between global and local changes in PET scans . J Cereb Blood Flow Metab . 1990;;10:458-466.
20 +
American Psychiatric Association, Committee on Nomenclature and Statistics. Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition . Washington, DC: American Psychiatric Association; 1987;.
21 +
Gaykema RP, Gaal G, Traber J, Hersh LB, Luiten PG.  The basal forebrain cholinergic system: efferent and afferent connectivity and long-term effects of lesions . Acta Psychiatr Scand Suppl . 1991;;366:14-26.
22 +
Nieuwenhuys R.  Survey of chemically defined cell groups and pathways: acetylcholine . In: Nieuwenhuys R, ed. Chemoarchitecture of the Brain . New York, NY: Springer-Verlag; 1985;:7-11.
23 +
Mesulam MM.  Structure and function of cholinergic pathways in the cerebral cortex, limbic system, basal ganglia and thalamus of the human brain . In: Bloom FE, Kupfer DJ, eds. Psychopharmacology: The Fourth Generation of Progress . New York, NY: Raven Press; 1995;:135-146.
24 +
Mesulam MM.  Neural substrates of behavior: the effects of brain lesions upon mental state . In: Nicholi AM, ed. The New Harvard Guide to Psychiatry . Cambridge, Mass: Harvard University Press; 1988;:91-128.
25 +
Van Hoesen GW, Morecraft RJ, Vogt BA.  Connections of the monkey cingulate cortex . In: Vogt BA, Gabriel M, eds. Neurobiology of Cingulate Cortex and Limbic Thalamus: A Comprehensive Handbook . Boston, Mass: Birkhauser; 1993;:249-284.
26 +
Vogt BA.  Structural organization of cingulate cortex: areas, neurons, and somatodendritic transmitter receptors . In: Vogt BA, Gabriel M, eds. Neurobiology of Cingulate Cortex and Limbic Thalamus: A Comprehensive Handbook . Boston, Mass: Birkhauser; 1993;:19-70.
27 +
Vogt BA, Finch DM, Olson CR.  Functional heterogeneity in cingulate cortex: the anterior executive and posterior evaluative regions . Cereb Cortex . 1992;;2:435-443.
28 +
Elliot HW, Quilici GC, Elison C.  Central effects of local anesthetics . Fed Proc . 1960;;19:274.
29 +
Babb TL, Perryman KM, Lieb JP, Finch DM, Crandall PH.  Procaine-induced seizures in epileptic monkeys with bilateral hippocampal foci . Electroencephalogr Clin Neurophysiol . 1979;;47:725-737.
30 +
Adamec RE, Stark-Adamec C, Saint-Hilaire JM, Livingston KE.  Basic science and clinical aspects of procaine HCI as a limbic system excitant . Prog Neuropsychopharmacol Biol Psychiatry . 1985;;9:109-119.
31 +
Adamec RE, Stark-Adamec C.  The effects of procaine HCI on population cellular and evoked response activity within the limbic system of the cat: evidence for differential excitatory action of procaine in a variety of limbic circuits . Prog Neuropsychopharmacol Biol Psychiatry . 1987;;11:345-364.
32 +
Tanaka K, Yamasaki M.  Blocking of cortical inhibitory synapses by intravenous lidocaine . Nature . 1966;;209:207-208.
33 +
Scott DB.  Toxic effects of local anaesthetic agents on the central nervous system . Br J Anaesth . 1986;;58:732-735.
34 +
De Jong RH.  Central nervous system effects . In: de Jong RH, ed. Local Anesthetics . St Louis, Mo: Mosby-Year Book Inc; 1994;:264-303.
35 +
Silberman EK, Post RM, Nurnberger J, Theodore W, Boulenger JP.  Transient sensory, cognitive and affective phenomena in affective illness: a comparison with complex partial epilepsy . Br J Psychiatry . 1985;;146:81-89.
36 +
Rauch SL, Savage CR, Alpert NM, Miguel E, Baer L, Breiter HC, Fischman AJ, Manzo PA, Moretti C, Jenike MA.  A positron emission tomographic study of simple phobic symptom provocation . Arch Gen Psychiatry . 1995;;52:20-28.
37 +
Thomas SR, Lewis ME, Iversen SD.  Correlation of [3H]diazepam binding density with anxiolytic locus in the amygdaloid complex of the rat . Brain Res . 1985;;342:85-90.
38 +
Sanders SK, Shekhar A.  Anxiolytic effects of chlordiazepoxide blocked by injection of GABA-A and benzodiazepine receptor antagonists in the region of the anterior basolateral amygdala of rats . Biol Psychiatry . 1995;;37:473-476.
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