Catatonia Top Down Modulation

This new orientation, of which Jellife spoke, and of which hehimself was a notable exemplar, did not involve merely combin-ing neurological and psychiatric knowledge, but conjoiningthem, seeing them as inseparable, seeing how psychiatric phe-nomena might emerge from the physiological, or how, con-versely, they might be transformed into it.

(O. Sacks 1989, p. 157)

Comparison between Parkinsons disease and catatonia re-veals distinction between two kinds of modulation, verticaland horizontal. Vertical modulation concerns cortical-sub-cortical relations and apparently allows for bidirectionalmodulation. This is reflected in the possibility of both top-down and bottom-up modulation and the appearance ofmotor symptoms in Parkinsons disease as well as catatonia.Horizontal modulation concerns cortical-cortical relationsand apparently allows only for unidirectional modulation.This is reflected in one-way connections from prefrontal tomotor cortex and the absence of major affective and be-havioural symptoms in Parkinsons disease. It is concludedthat comparison between Parkinsons disease and catatoniamay reveal the nature of modulation of cortico-cortical andcortico-subcortical relations in further detail.

1. IntroductionDifferential diagnosis in neuropsychiatry is often rather dif-ficult since similar symptoms may be related to different

diseases, being either neurologic or psychiatric. For exam-ple, the symptom of akinesia can be caused either byParkinsons disease (PD), classified as a neurological dis-ease, or by catatonia, usually classified as a psychiatric dis-ease. Moreover, the same symptom, that is, akinesia may beaccompanied by different psychological alterations: eitherdepression, as in PD, or uncontrollable anxieties, as in cata-tonia. Consequently, consideration of both symptomaticorigin and complexity makes classification of diseases as ei-ther neurologic or psychiatric rather difficult. This is re-flected in a so-called conflict of paradigms pointing outthe inability to draw a clear dividing line between neuro-logic and psychiatric disturbances (Rogers 1985).

If symptoms of different origin, either psychiatric or neu-

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2002 Cambridge University Press 0140-525X/02 $12.50 555

What catatonia can tell us abouttop-down modulation:A neuropsychiatric hypothesis

Georg NorthoffLaboratory for Magnetic Brain Stimulation, Department of Neurology, BethIsrael Deaconess Medical Center, Harvard Medical School, Boston, MA [email protected]

Abstract: Differential diagnosis of motor symptoms, for example, akinesia, may be difficult in clinical neuropsychiatry. Symptoms maybe either of neurologic origin, for example, Parkinsons disease, or of psychiatric origin, for example, catatonia, leading to a so-calledconflict of paradigms. Despite their different origins, symptoms may appear more or less clinically similar. Possibility of dissociationbetween origin and clinical appearance may reflect functional brain organisation in general, and cortical-cortical/subcortical relations inparticular. It is therefore hypothesized that similarities and differences between Parkinsons disease and catatonia may be accounted forby distinct kinds of modulation between cortico-cortical and cortico-subcortical relations. Catatonia can be characterized by concurrentmotor, emotional, and behavioural symptoms. The different symptoms may be accounted for by dysfunction in orbitofrontal-prefrontal/parietal cortical connectivity reflecting horizontal modulation of cortico-cortical relation. Furthermore, alteration in top-down mod-ulation reflecting vertical modulation of caudate and other basal ganglia by GABA-ergic mediated orbitofrontal cortical deficits mayaccount for motor symptoms in catatonia. Parkinsons disease, in contrast, can be characterized by predominant motor symptoms. Mo-tor symptoms may be accounted for by altered bottom-up modulation between dopaminergic mediated deficits in striatum and pre-motor/motor cortex. Clinical similarities between Parkinsons disease and catatonia with respect to akinesia may be related with in-volvement of the basal ganglia in both disorders. Clinical differences with respect to emotional and behavioural symptoms may be relatedwith involvement of different cortical areas, that is, orbitofrontal/parietal and premotor/motor cortex implying distinct kinds of modu-lation vertical and horizontal modulation, respectively.

Keywords: Bottom-up modulation; catatonia; horizontal modulation; Parkinsons disease; top-down modulation; vertical modulation

Georg Northoff, Visiting Associate Professor of theDepartment of Neurology at Harvard University inBoston/USA, is the author of numerous publicationsabout the psychopathology and pathophysiology of cata-tonia. Since catatonia can be characterized by severeemotional disturbances he focused most recently onfunctional imaging of the neural correlates of emotions.In addition, he investigates the neurophilosophical im-plications of both catatonia and emotions having pub-lished several books and articles in the field of neuro-philosophy.

rologic, show similar clinical appearance, one may assumesimilar or at least overlapping pathophysiological substratesreflecting functional brain organisation in general. Func-tional relation between prefrontal/frontal cortex and basalganglia may account for similarity between PD and catato-nia with respect to motor symptoms. Relation between pre-frontal/frontal cortex and basal ganglia can be character-ized by various functional circuits (see Mastermann &Cummings 1997 for a nice overview) allowing for bidrec-tional modulation with both top-down and bottom-upmodulation as forms of vertical modulation. In additionto the cortico-subcortical relation, one may consider thecortico-cortical relation as well reflecting horizontal mod-ulation, which may be rather unidirectional (see below).

Comparison between pathophysiological mechanismsunderlying PD and those subserving catatonia may revealthe nature of these distinct kinds of modulation of cortico-cortical/subcortical relation in further detail. The followinghypothesis are postulated: (1) apparent clinical similarityand underlying pathophysiological differences in motorsymptoms between PD and catatonia; (2) differences inpsychiatric (affective and behavioural) symptoms betweenPD and catatonia; (3) double dissociation between cata-tonia and PD with respect to underlying pathophysiologicalmechanisms accounting for clinical differences; (4) oppo-site kinds of vertical modulation between prefrontal/frontal cortex and basal ganglia in PD and catatonia (bot-tom-up and top-down modulation) accounting for subtledifferences in motor symptoms; (5) presence/absence of al-terations in cortico-cortical relation reflecting horizontalmodulation in catatonia and PD respectively, accountingfor major differences in emotional-behavioural symptoms.

First, we describe similarities and differences in clinicalsymptoms and therapy between PD and catatonia. This isfollowed by illustration of neuropsychological and patho-physiological findings. Third, we develop pathophysiologi-cal hypotheses for the different kinds of symptoms observedin PD and catatonia. On the basis of these pathophysiolog-ical hypotheses, a distinction between horizontal and ver-tical modulation of cortico-cortical/subcortical relationswith respect to directionality is suggested.

2. Catatonia as a psychomotor syndrome:Comparison with Parkinsonism as motorsyndrome

2.1. Motor symptomsCatatonia is a rather rare (incidence: 2%8% of all acuteadmissions) psychomotor syndrome. As such it can be as-sociated with psychiatric disturbances such as schizophre-nia (one subtype is denoted as catatonic schizophrenia) andmanic-depressive illness, as well as with various neurologi-cal and medical diseases (Gelenberg 1976; Northoff 1997a;Taylor 1990). Some authors (see Northoff 1997a, for anoverview) consider periodic catatonia as an idiopathic dis-ease showing psychomotor characteristics of catatonic syn-drome while not being associated with any other kind of dis-ease. Parkinsonism is a motor syndrome which can beeither of idiopathic, that is, primary, or of symptomatic, thatis, secondary, nature. In the first case one speaks of Parkin-sons disease (PD), which may be considered as a nosologi-cal analogue of periodic catatonia, whereas in the secondcase one generally speaks of Parkinsonism which, similar to

catatonia, may be associated with various neurological andmedical diseases.

The most characteristic feature of catatonia is postur-ing, where patients show a specific, uncomfortable, and of-ten bizarre position of parts of their body against gravity,with complete akinesia in which they remain for hours,days, and weeks (and in earlier times even for years; see Fig.1). If that position is taken actively and internally by the pa-tient himself, one speaks of posturing; if such a positioncan be induced passively and externally by the examiner,one speaks of catalepsy. Posturing can occur in limbs(classic posturing), head (psychic pillow), and eyes(staring).

We saw one patient who postured every morning duringshaving. He started to shave himself and then remained,with the razor in his hand and a lifted arm, for hours in thatposition until his wife came in and depositioned him (seeNorthoff 1997a for detailed description). Another exampleis a woman who, every morning when opening her wardrobe,remained in a position with a lifted arm keeping the door ofthe wardrobe open in her hand. Both patients were admit-ted into the clinic where they neither spoke nor moved atall. On admission, it was possible to position their limbsin the most bizarre and uncomfortable positions againstgravity without any resistance by the patients themselves.Once the examiner positioned the limbs into one particularposition, they remained in that position without showingeven the slightest change.

The cases demonstrated in Figure 1 are typical examplesof posturing and catalepsy where patients are well able toinitiate and execute movements but seem to be unable toreturn to the initial or resting position in order to start a newmovement. Similar to PD, catatonic patients do show aki-nesia, but, unlike Parkinsonian patients, only in associationwith posturing and catalepsy. Furthermore, in contrast toPD, catatonic akinesia is not necessarily accompanied bymuscular hypertonus, that is, rigidity, since patients mayalso show muscular normo- or hypotonus (Northoff 1997a).Even if catatonic patients show muscular hypertonus, it isnot the kind of rigidity cogwheel rigidity that is typicalof PD. Instead, they show a rather smooth type of rigiditywhich is called flexibilitas cerea (Northoff 1997a). In ad-dition to hypokinetic features, catatonic patients may showintermittent and fluctuating hyperkinesias like stereotyp-

Northoff: What catatonia can tell us about top-down modulation: A neuropsychiatric hypothesis

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Figure 1. Active posturing in a group of catatonic patients (fromKraepelin 1927).

ies, dyskinesias, and tics which, unlike in PD, are indepen-dent of medication.

Catatonic patients are well able to plan, initiate, andexecute movements which could be demonstrated in ballexperiments. We performed systematic ball experiments in32 catatonic patients in an acute akinetic state before theyreceived any medication (i.e., lorazepam; see Northoff et al.1995a). To our surprise almost all patients, despite showingconcurrent akinesia and posturing, were able to play ball ei-ther with the hands or with the legs. Patients were able tocatch and throw the ball, doing slightly better during exter-nal initiation (i.e., catching) than during internal initiation(i.e., throwing). Most patients, however, remained in a finalposture keeping the ball in a position against gravity, ap-parently unable to change posture and terminate the re-spective movement. Subjectively, catatonic patients experi-enced these ball experiments as funny and relaxing and astaking off my inner tension although they were not awareof their inability to terminate movements, therefore pos-turing (Northoff et al. 1995a; 1998). Furthermore, in con-trast to PD, posturing in catatonic patients cannot be re-versed by external sensory stimulation, as for example,drawing a line in front of their feet. Accordingly, catatonicpatients did not experience any starting problems or deficitsin internal initiation.

In summary, catatonia and PD can be characterized bothby clinical similarities, as reflected in akinesia and rigiditiy,and differences, as reflected in posturing/initiation andcogwheel rigidity/flexibilitas cerea, with respect to motorsymptoms.

2.2. Behavioural and affective symptomsIn addition to motor symptoms, catatonia can be charac-terized by concurrent behavioural and affective anomalies.Behavioural anomalies include mutism (patients do notspeak, as was the case in both patients described above),stupor (no reaction to the environment), automatic obedi-ence (patients do everything that they are asked to do), neg-ativism (patients always do the opposite of what they areasked), echolalia/praxia (patients repeat sentences or ac-tions given by other persons several times or even end-lessly), perseverative-compulsive behavior (uncontrollablerepetitive behavioural patterns), and mitmachen/mitgehen(patients always follow other persons and do the same asthey do). In contrast to catatonia, such behavioural anom-alies cannot be observed in PD, which is characterized pre-dominantly by motor symptoms.

Affective alterations in catatonia include strong anxietiesor euphoria/happiness, staring, grimacing, and inadequateemotional reactions. Catatonic patients may show compul-sive emotions (involuntary and uncontrollable repetitiveemotional reactions), emotional lability (labile and unstableemotional reactions), aggression (often accompanied by ex-treme emotional states such as anxiety or rage), excitement(extreme hyperactivity with extreme and uncontrollableemotional reactions), affective latence (taking a long timeto show emotional reactions), ambivalence (simultaneouspresence of conflicting emotions), and flat affect (de-creased and/or passive emotional reactivity). Such symp-toms are not present in PD. Patients with PD can, rather,be characterized by depression, where they neither show anuncontrollable intensity of emotions nor a comparable va-riety of emotional reactivity like that of catatonic patients.

In summary, catatonia can be characterized by strong af-fective and bizarre behavioural anomalies, which do not oc-cur in PD.

2.3. TherapyTherapeutically, 60%80% of all acute catatonic patientsreact to lorazepam, a GABA-A receptor potentiator, eitheralmost immediately within the first 510 minutes, or within24 hours (Bush et al. 1996a; Northoff et al. 1995b; Rose-bush et al. 1990), whereas chronic catatonic patients showno improvements on lorazepam (Ungvari et al. 1999). If lo-razepam does not work, some catatonic patients show grad-ual and delayed improvements (within 2 to 4 days) on theNMDA-antagonist amantadine (Northoff et al. 1997;1999c) and/or on electroconvulsive treatment (ECT) (Finket al. 1993; Petrides et al. 1997).

Dopaminergic substances like L-Dopa and D1/2 recep-tor agonists are therapeutically effective in PD. Unlike incatatonia, lorazepam and other benzodiazepines remaintherapeutically ineffective in PD. Similar to catatonia, theNMDA-antagonist amantadine is therapeutically effectivein PD as well (Merello et al. 1999). In addition to pharma-cotherapy, surgical therapies with implantation of eitherelectrodes or fetal tissue in specific structures of the basalganglia (putamen, caudate, subthalamic nuclei, internalpallidum) may be applied especially in drug-resistant pa-tients with PD.

In summary, treatment in catatonia and PD can be char-acterized by differences (GABA-ergic agents versus dopa-minergic agents) and similarities (NMDA-antagonists).

2.4. Subjective experienceIn order to further reveal the nature of psychological alter-ations and their relation to motor symptoms, we investi-gated subjective experience in catatonic patients with a self-questionnaire. Due to mutism and akinesia in almost allpatients with hypokinetic catatonia, such an investigationremains possible only retrospectively. Catatonic patientswere compared with akinetic Parkinsonian patients andnoncatatonic depressive and schizophrenic patients (seeNorthoff et al. 1998, for details).

Parkinsonian patients suffered severely from akinesia;for example, one felt locked into my body, anotherwanted to move but was unable to do so. A catatonic pa-tient, in contrast, did not realize any alterations in mymovements and said that they [the movements] werecompletely normal. When asked why they positioned theirlimbs in a particular posture, catatonic patients either an-swered There was nothing abnormal with my move-ments, or couldnt say anything. The patient posturing dur-ing shaving said, My movements were completely normaland I could shave in the normal way. No patient said thathe subjectively suffered from any changes in his move-ments. Moreover, no catatonic patient reported any feelingof pain or tiredness even if he postured and remained in thesame position for hours (n 5 5), days (n 5 10) or weeks (n5 5). Instead of changes in their movements, many cata-tonic patients reported extremely intense emotions, whichthey experienced as uncontrollable and overwhelming.Patients felt totally blocked by these emotions whichoverwhelmed them and led to a blockade of [theirselves]. The dominating emotion was anxiety (due to para-


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noid delusions, acoustic hallucinations, depressive mood, ortraumatic experiences). For example, the patient posturingduring shaving as described above, said that I couldnt con-trol my emotions anymore, they were overflooding me sothat I had the feeling that I was just anxiety. Nevertheless,some patients reported positive emotions like euphoria although, similar to anxiety, they were unable to control thisanymore. One patient, for example, became catatonic everytime she fell in love (5 times in total), reporting the follow-ing: I am so happy when I fall in love, this feeling reallyoverwhelms me so that I cant control it anymore. Everytime I fall in love, I am admitted to clinic. I dont under-stand this.

Catatonic patients did not subjectively experience anysensation of effort during posturing. Although they kepttheir limbs or head in a position against gravity, where everynormal person and patient with PD would feel a sensationof tiredness or pain, catatonic patients do not experienceany tiredness, pain, or a sensation of effort during pos-turing. For example, catatonic patients lying in bed maykeep their head up for hours or even days (i.e., a so-calledpsychic pillow) without getting tired and/or reporting anyfeeling of tiredness. When inquiring after these patientswith such a psychic pillow, they usually answer, My headwas in a completely normal position, I wasnt tired at all;they seem to, instead, experience a sense of weightless-ness.

No catatonic patient was able to give an account of theposition in which he kept his limbs, thus remaining unawareof posturing. It seems as if they have no access to any kindof subjective experience of the actual spatial position dur-ing posturing the objective position and the corre-sponding subjective experience of the spatial positionseem to be decoupled from each other. Unfortunately,there are no data available whether post-acute patients rec-ognize the posturing characterizing their acute state as theirown. Such data could provide information about the exactnature of the deficit in awareness. If they could recognizethe posturing as their own, they would show only an alter-ation in motor awareness but not in self-awareness. How-ever, if they were unable to do so, there would have to be ageneral deficit in self-awareness. Since, however, catatonicpatients are well able to recognize themselves in a post-acute state, one may rather hypothesize a deficit in motorawareness only.

Furthermore, catatonic patients are not aware of theconsequences of their movements (Snowdon et al. 1998):The patient posturing during shaving claimed that he fin-ished shaving every morning completely without any timedelay so that he wasnt aware of the consequences of pos-turing. Finally, catatonic patients do not show any objec-tive or any kind of subjective sensory abnormality, so alter-ations in subjective experience cannot be accounted for bysensory dysfunction.

Almost all catatonic patients reporting strong, intense,and uncontrollable emotions responded well to lorazepam,whereas patients without such emotional experiences didnot respond well to lorazepam (Northoff et al. 1998). Non-responders to lorazepam for example, the patient de-scribed above as posturing in front of her wardrobe hadexperiences such as a blockade of my will with contradic-tory and ambivalent thoughts about my dresses since Icouldnt decide myself. For several days this patient stoodin front of her wardrobe remaining in the same quite un-

comfortable position with raised arms and standing tip-toe.She wasnt aware of any alterations in her movements,denying any feeling of tiredness during that position (Iwasnt tired at all). All catatonic patients experienced theiradmission on a psychiatric ward as terrible (I thought it wasthe hell) and/or could not understand it (I was so happy,there was no reason for admission at this time.) Moreover,they remembered very well the physician and other personswho treated them on admission. Consequently, catatonicpatients seem to show neither deficits in memory (except inworking memory; see below), nor deficits in general aware-ness.

In summary, subjective experience differs between cata-tonic and Parkinsonian patients with respect to motorsymptoms (motor anosognosia vs. motor awareness) andpsychological state (anxiety vs. depressive reaction).

3. Neuropsychological and pathophysiologicalfindings in catatonia and Parkinsons

Presentation of findings in this section focuses predomi-nantly on comparison between catatonia and PD with re-spect to distinct kinds of modulation. Therefore the wholevariety of differential and subtle pathophysiological alter-ations obtained especially in PD cannot be considered inthe present context. Furthermore, it should be mentionedthat systematic pathophysiological investigations with mod-ern techniques are rather rare in catatonia, which is a cer-tain focus within my own studies.

3.1. Neuropsychological findingsWe pointed out that the ability to registrate the spatial po-sition of movements, as required for termination of move-ments (see above), involves spatial abilities as potentiallyrelated to the right posterior parietal cortical function. Wetherefore investigated post-acute akinetic catatonic pa-tients with neuropsychological tests for measurement ofspatial abilities (Northoff et al. 1999a). Among other mea-sures, we applied the visual-object-space and perceptiontest (VOSP), a test specifically designed for measurementof spatial abilities related to right parietal cortical function.(See Table 1.)

Catatonic patients showed significantly lower perfor-mance in VOSP compared to psychiatric and healthy con-trols (Northoff et al. 1999a). No significant differences be-tween catatonic and noncatatonic psychiatric patients wereobtained in any other visuo-spatial test unrelated to rightparietal cortical function, or in any other neuropsycholog-ical measure such as general intelligence, attention, and ex-ecutive functions. Furthermore, catatonic patients showedsignificant correlations between right parietal cortical vi-suo-spatial abilities (as measured with VOSP) and atten-tional abilities (as measured with d2 and CWI), which werepresent neither in psychiatric controls nor in healthy sub-jects (Northoff et al. 1999a). In addition, motor symptomsin catatonia correlated significantly with both visuo-spatialabilities and attentional function. Catatonia may be char-acterized by relatively intact psychological functions con-cerning attention, executive functions, general intelli-gence, and non-right parietal visuo-spatial abilities. Incontrast, visuo-spatial abilities specifically related to rightparietal cortex may be altered in catatonic patients, distin-



guishing them from noncatatonic psychiatric controls. Also,catatonic patients show severe deficits in a gambling test(unpublished observations) requiring emotionally guideddecisions and intact orbitofrontal cortical function (Bech-ara et al. 1997).

In contrast, patients with PD show severe neuropsycho-logical deficits in executive functions (Wisconsin Card Sort-ing test, verbal fluency, etc.). These include, among others,abilities of categorization, shifting, sequencing, and so on,as subserved by dorsolateral prefrontal cortical function. Incontrast to catatonia, PD can be characterized neither bydeficits in visuo-spatial attention as specifically related toright parietal cortical function, nor by alterations in thegambling test specifically designed for orbitofrontal corti-cal function.

In summary, catatonia can be characterized by specificdeficits in visuo-spatial abilities, related to right parietalcortical function, and by emotionally guided intuitive deci-sions, related to orbitofrontal cortical function. PD, in con-trast, can be characterized by specific alterations in execu-tive functions predominantly related to lateral prefrontalcortical function.

3.2. Postmortem findingsEarly postmortem studies in the preneuroleptic time re-vealed discrete but not substantial alterations in basal gan-glia (caudate, N. accumbens, pallidum) and thalamus (seeBogerts et al. 1985 and Northoff 1997a, for an overview).Because these early investigations yielded rather inconsis-tent results, they were not pursued. Most studies were per-formed on brains of patients who were never exposed toneuroleptics, implying that these alterations in basal gangliacannot be related to neuroleptic (antipsychotic) medica-tion. Nevertheless, findings should be considered rathercautiously since the methods and techniques available at

that time may have produced artifacts themselves. Fur-thermore, these findings were obtained in patients withcatatonic schizophrenia. Therefore, it remains unclearwhether these alterations are specifically related to eithercatatonia itself or the underlying disease of schizophrenia.Neuropathologic investigations of catatonic syndrome ingeneral, rather than of catatonic schizophrenia in particu-lar, are currently not available.

In contrast to catatonia, substantial alterations in post-mortem investigation can be obtained in PD. PD can becharacterized by degeneration of dopaminergic cells in sub-stantia nigra pars compacta, leading consecutively to de-generation in striatum (especially putamen and caudate). Inmany cases of Parkinsonism, vascular or other kinds of al-terations may be observed in striatum.

In summary, valid postmortem results in catatonia arecurrently not available since those obtained showing dis-crete alterations in basal ganglia relied on insufficientmethods. In contrast, PD can be characterized by major de-generation of dopaminergic cells in substantia nigra and itspathways to striatum.

3.3. Animal modelsDeJong and Baruk (1930) performed various experimentswith the D2-receptor antagonist bulbocapnine. Accordingto DeJong and Baruk, bulbocapnine induced catatonia inanimals with a neocortex (mice, rats, cats), whereas in an-imals without a neocortex, catatonic symptoms could notbe induced. Lower (12 mg) doses of bulbocapnine leadto catalepsy, whereas higher doses (45 mg) induced im-pulsive and convulsive reactions. As demonstrated byLoizzo et al. (1971), amantadine as an NMDA-antagonistled to reversal of bulbocapnine-induced catatonia; how-ever, relying on my own experiments (unpublished obser-vations), bulbocapnine-induced catatonia rather resem-



Table 1. Comparison between catatonia and Parkinsons disease

Catatonia Parkinsons

Neuropsychology Visuospatial attention Executive functionsOn-line monitoringEmotionally-guided decisions

Postmortem Caudate, N. accumbens, Pallidum, Substantia nigra, Putamen, CaudateThalamus

Animal models Bulbocapnine, Stress, GABA 6-OHDH, MPTPStructural imaging Prefrontal and parietal cortex Basal gangliaFunctional imaging Right prefronto-parietal CBF SMA/MC

Right OFC Lateral prefrontal cortexPrefrontal connectivity Fronto-striatal connectivity

Electrophysiology Late and postural RP Early RPRP modulation by Lorazepam RP modulation by dopamine

Neurochemistry GABA-A receptors D-2 receptors in striatumNMDA receptors NMDA receptors5 HT1a/2a 5 HT2a

Abbreviations:RP 5 Readiness PotentialSMA 5 Supplementary motor areaOFC 5 Orbitofrontal cortexMC 5 Motor Cortex

bled haloperidol-induced catalepsy. Furthermore, it couldnot be determined by lorazepam, as is the case in humancatatonia (see above). Bulbocapnine exerts an inhibitoryeffect on dopamine synthesis (Shin et al. 1998). Conse-quently, it remains unclear whether DeJong and Baruk re-ally describe catatonia, or, rather, a kind of catalepsy anal-ogous to neuroleptic-induced catalepsy.

Stille and Sayers (1975) induced a catatonia-like reactionin animals using strong sensory stimuli (electric footshock).They postulated an excitement of the ascending arousal sys-tem, that is, formatio reticularis with overexcitation of thestriatal system via thalamic nuclei. Injection of the GABA-A antagonist bicucullin into dopaminergic cells of the ven-tral tegmental area (VTA) induced a catatonia-like picturein cats with increased arousal, withdrawal, anxiety, staring,and catalepsy (Stevens 1974). Furthermore, injection ofmorphine may lead to a so-called morphine-induced cata-tonia (Northoff 1997a). Despite the existence of these var-ious models, none of them has really been established as ananimal model of human catatonia.

Freezing as an isolated phenomenon independent fromcatatonia has been studied in animals and humans. Lesionsin amygdala and/or in the periaqueductal gray may inducefreezing in animals whether these results can be extrapo-lated to humans remains unclear (Fendt & Fansolow 1999).

Animal models of PD focus on specific lesion of nigro-striatal dopaminergic cells and pathways as provided by 6-OHDH in rats and MPTP in nonhuman primates.

In summary, no animal model of human catatonia has yet been established. The ones available focus either onGABA-ergic- or morphine-induced lesions. In contrast, an-imal models of PD focus on lesions of nigrostriataldopamine by either 6-OHDH or MPTP.

3.4. Structural imagingA computerized tomographic (Head CT) investigation of37 patients with catatonic schizophrenia showed a diffuseand significant enlargement in most cortical areas (seeNorthoff et al. 1999d). Alterations in temporal cortical ar-eas were present in all three subtypes of schizophrenia,whereas catatonic schizophrenia could be specifically char-acterized by prefrontal and parietal enlargement. More-over, prefrontal and parietal enlargement correlated signif-icantly with illness duration in catatonic schizophrenia.

Other authors (Joseph et al. 1985; Wilcox 1991) observeda cerebellar atrophy in catatonic patients, which was inves-tigated neither systematically nor quantitatively. To myknowledge, no study specifically investigating catatonicsyndrome (and not only catatonic schizophrenia as a sub-type) has been published so far.

In summary, findings in structural imaging in catatoniasuggest cortical involvement predominantly in prefrontaland parietal cortex, whereas in PD subcortical structures,that is, the basal ganglia are altered.

3.5. Functional imaging3.5.1. Regional cerebral blood flow. Investigation of re-gional cerebral blood flow (r-CBF) in single catatonic pa-tients showed the following findings: (1) right-left asym-metry in basal ganglia with hyperperfusion of the left sidein one patient (Luchins et al. 1989); (2) hypoperfusion inleft medial temporal structures in two patients (Ebert et al.

1992); (3) alteration in right parietal and caudal perfusionin one patient (Liddle 1994); (4) decreased perfusion inright parietal cortex in six patients with catatonic schizo-phrenia (Satoh et al. 1993); (5) decreased perfusion in pari-etal cortex with improvement after ECT in one patient(Galynker et al. 1997). A systematic investigation of r-CBFin SPECT in 10 post-acute catatonic patients showed de-creased perfusion in right posterior parietal and right infe-rior lateral prefrontal cortex compared to noncatatonic psy-chiatric and healthy controls (Northoff et al. 2000c).

Furthermore, abnormal correlation between right pari-etal cortical function and visual-spatial and attentionalabilities were obtained (Northoff et al. 2000c). In psychi-atric and healthy controls, VOSP correlated significantlywith right lower parietal and right lower lateral prefrontalcortical r-CBF and iomazenil binding (reflecting the func-tion of GABA-A receptors), whereas in catatonia none ofthese correlations were found (Northoff et al. 1999e;2000c). Decreased perfusion in right parietal cortex cor-related significantly with motor and affective symptoms.Catatonic motor symptoms correlated significantly withVOSP, right lower parietal r-CBF and iomazenil binding inright lower lateral prefrontal cortex (Northoff et al. 1999e;2000c).

PD can be characterized by deficits of r-CBF in SMA,motor cortex and caudate, whereas no major alterations inprefrontal and parietal cortex can be observed (see Jahan-shahi & Frith 1998).

In summary, investigation of regional cerebral blood flowshows deficits in right lower inferior prefrontal and rightparietal cortex in catatonia. PD, in contrast, may rather becharacterized by predominant r-CBF deficits in motor cor-tex, SMA, and basal ganglia.

3.5.2. Motor activation. Functional imaging performedduring motor activation (i.e., sequential finger opposition)showed reduced activation of the contralateral motor cor-tex (MC) in right hand performance. Ipsilateral activationwas similar for both patients and (medication-matched)controls (Northoff et al. 1999b). There were no differencesin activation of the supplementary motor area (SMA). Dur-ing left hand performance, right-handed patients showedmore activation in ipsilateral motor cortex than in con-tralateral MC. This must be considered as a reversal in lat-erality since usually the contralateral side shows four to fivetimes more activation than the ipsilateral side (Northoff etal. 1999b). It should be noted that these results were ob-tained in only two post-acute catatonic patients. However,assumption of basically intact cortical motor activation (in-dependent from laterality) is further supported by resultsfrom an fMRI/MEG study during emotional-motor stimu-lation in 10 catatonic patients (Northoff et al. 2001a). Cor-tical motor function showed no alteration in these investi-gations.

During motor activation, patients with PD show majordeficits predominantly in SMA, which receives most affer-ences from thalamic (motor) nuclei, and the basal ganglia,predominantly the striatum. Furthermore, decreased acti-vation can be observed also in MC though to a lesser degreethan SMA. This may be due to the fact that the MC doesnot receive as many afferences from thalamic (motor) nu-clei as SMA does. In contrast to catatonia, no alteration inlaterality during motor performance can be observed in PD(Jahanshahi & Frith 1998).



In summary, catatonia may be characterized by alter-ations in laterality in the motor cortex during motor perfor-mance, while activation in SMA seems to remain basicallyintact. PD, in contrast, shows major deficits in activation ofSMA and, to a lesser degree, in the motor cortex, the lattershowing no alterations in laterality.

3.5.3. Emotional-motor activation. Based on subjective ex-perience showing intense emotional-motor interactions, anactivation paradigm for affective-motor interaction was de-veloped. This paradigm was investigated in fMRI and MEG(magnetoencephalography) in catatonic patients compar-ing them with noncatatonic psychiatric and healthy controls(Northoff et al. 2001a). During negative emotional stimu-lation, catatonic patients showed a hyperactivation in or-bitofrontal cortex and a shift of main activation to anteriorcingulate and medial prefrontal cortex. Furthermore, cata-tonic patients showed abnormal orbitofrontal-premotor/motor connectivity (Northoff et al. 2001a). Behavioural andaffective catatonic symptoms correlated significantly withreduced orbitofrontal cortical activity, whereas motor symp-toms correlated with premotor/motor activity.

PD, in contrast, can be characterized by altered activa-tion in left dorsolateral prefrontal cortex and anterior cin-gulate during emotional stimulation, whereas orbitofrontalcortical function remained unaffected (see Mayberg et al.1999).

In summary, catatonia can be characterized by reducedright orbitofrontal cortical activation and abnormal orbito-frontal-premotor/motor connectivity during negative emo-tional stimulation. PD, in contrast, shows alterations only inleft dorsolateral prefrontal cortex and anterior cingulate,not in orbitofrontal cortex.

3.5.4. On-line monitoring. Posturing as an inability to ter-minate movements may be related with alterations in on-line monitoring. Since on-line monitoring must be consid-ered as an essential part of working memory (Leary et al.1999; Petrides 1995), we investigated a one-back/two-backtask in fMRI in catatonia (Leschinger et al. 2001). Catatonicpatients showed significantly decreased activation in rightlateral orbitofrontal, including ventrolateral prefrontal cor-tex (VLPFC), during the working memory task in fMRI(Leschinger et al. 2001). In contrast to orbitofrontal activ-ity, activation in right dorsolateral prefrontal cortex wasrather increased. Catatonic behavioural symptoms corre-lated significantly with activation in right lateral orbito-frontal cortex, whereas motor symptoms showed a signifi-cant relationship with right dorsolateral prefrontal activity.

Catatonic patients showed significantly worse behav-ioural performance in both one-back and two-back tasks,and their deficit seems not to be limited to active storage/retrieval. In the latter case one would have expected worseperformance in the two-back task only. Instead, catatoniamay rather be characterized by principal problems in on-line processing and monitoring, which accounts for badperformance in both one-back and two-back task.

Investigation of working memory in PD revealed alter-ation in lateral prefrontal cortex, especially in left dorso-lat-eral prefrontal cortex (DLPFC), whereas orbitofrontal cor-tical function, including the ventrolateral prefrontal cortex,remained intact (Jahanshahi & Frith 1998).

In summary, catatonia can be characterized by majordeficits in on-line monitoring and right lateral orbitofrontal,

that is, ventrolateral prefrontal cortical (VLPFC) function,whereas PD shows deficits in left dorso-lateral prefrontalcortical (DLPFC) function.

3.6. Electrophysiological findings3.6.1. Initiation in catatonia and Parkinsons disease.Generation of willed action can be characterized by Plan/Strategy, Initiation, and Execution, which are sup-posed to be reflected in movement-related cortical poten-tials (MRCP) (see Northoff et al. 2001b).

We investigated MRCPs during finger tapping in 10post-acute akinetic catatonic patients, 10 noncatatonic psy-chiatric controls (same underlying diagnosis, same medica-tion, same age and sex), and 20 healthy controls (Northoffet al. 2000a; Pfennig 2001; Pfennig et al. 2001). We foundno significant differences in amplitudes between catatonicand noncatatonic subjects in early MRCPs; that is, in earlyreadiness potential (early RP) reflecting Plan/Strategyand Initiation of movements in DLPFC and anteriorSMA. Amplitudes in late MRCPs, that is, in late readinesspotential (late RP) and movement potential (MP) reflectingExecution of movements in posterior SMA and motorcortex, revealed differences.

Patients with PD show reduction of amplitude in earlyand late MRCPs, which can be modulated by dopaminer-gic agents resulting in an increase of amplitude (Dick et al.1987; 1989; Jahanshahi et al. 1995; Jahanshahi & Frith1998).

In summary, catatonia can be characterized by intactearly and late readiness potentials, reflecting the apparentlypreserved ability of Plan/Strategy, Initiation, and Exe-cution of movements in these patients. In contrast, pa-tients with PD show severe deficits in Initiation and Ex-ecution as electrophysiologically reflected in alterations inearly and late readiness potentials.

3.6.2. Termination in healthy subjects. Phenomena likeposturing and catalepsy can be observed in patients withright parietal cortical lesions, although they do not showany deficits in Initiation and Execution (Fukutake etal. 1993; Saver et al. 1993). This suggests that visuo-spatialattention and right parietal cortical function may be nec-essary for on-line monitoring and consecutive terminationof movements. In a first step, we therefore investigatedtermination of movements in healthy subjects with elec-trophysiological measurements of movement-related cor-tical potentials (MRCP) (Northoff et al. 2001a; Pfennig2001).

We compared normal MRCP as obtained by finger tap-ping with MRCP for simple lifting. The finger had to bekept up without going back into the initial position (MRCP1) reflecting Plan/Strategy, Initiation, and Execu-tion of finger tapping with exclusion of Termination.Termination of movements was measured by lowering ofthe finger after some seconds of posturing (MRCP 2), re-flecting initiation of termination and execution of termi-nation (see below). MRCP 1 and 2 differed significantly invarious onsets and amplitudes from MRCP, so that neitherMRCP 1 nor MRCP 2 can be equated with MRCP for sim-ple finger tapping. In addition, we obtained significant dif-ferences between MRCP 1 and MRCP 2, the latter show-ing significantly lower amplitudes in early parietal MRCPs,earlier onset of movement potential and more posterior



parietal localization of underlying dipoles, than the former(Northoff et al. 2001b; Pfennig et al. 2001).

Lorazepam as a GABA-A potentiator had a differentialinfluence on early and late components of MRCPs duringInitiation and Termination. During Initiation, loraze-pam led to a delay in onsets of late MRCPs in frontal elec-trodes (MRCP 1), whereas during Termination (MRCP2), early onsets in parietal electrodes were delayed. Theseresults were further supported by dipole source analysis.MRCP 1 reflecting Plan/Strategy, Initiation, and Ex-ecution showed dipole sources in anterior/posterior SMAand motor cortex. In contrast, MRCP 2 reflecting Termi-nation was characterized by initial location of the early di-pole in right posterior parietal cortex, later shifting to pos-terior SMA and motor cortex (Pfennig et al. 2001).

The following conclusions with respect to Terminationof movements can be drawn. First, some kind of initiationmust be involved, because otherwise there would havebeen no readiness potential we call this the initiation oftermination. Second, the initiation for execution (i.e.,MRCP 1) and the initiation for termination (i.e., MRCP2) can apparently be distinguished from each other, sinceotherwise there would have been no differences in ampli-tudes between MRCP 1 and MRCP 2 in early MRCPs.Third, MRCPs during Termination could be characterizedby right posterior parietal localization. In order to avoid ter-minological confusion, we reserve the term Initiation forthe Initiation of Execution, whereas the initiation of Ter-mination will be subsumed under the term Termination.Fourth, Execution and Termination involve differentmovements (lifting and lowering), which is reflected in dis-tinct movement potentials in MRCP 1 and MRCP 2. Fifth,the Termination of movements seems to be particularlyrelated with right parietal cortical function and GABA-ergic neurotransmission. Otherwise, there would have beenno differences between MRCP 1 and MRCP 2 in parietalcortical dipole source location and reactivity to lorazepam.

In summary, Termination of movements may be char-acterized by two distinct aspects, initiation and execution.These may be subserved by involvement of right parietalcortical function and GABA-ergic neurotransmission. Neu-ropsychologically, on-line monitoring of the spatial positionof the ongoing movement, as related to right parietal corti-cal function, may be considered as crucial for Termina-tion, distinguishing it from Plan/Strategy, Initiation,and Execution.

3.6.3. Termination in catatonia. Kinematic measurementsduring Initiation and Termination of finger tapping re-vealed that catatonic patients needed significantly longerfor Termination than psychiatric and healthy controls. Incontrast, no deficits were observed in Initiation (Pfennig2001; Pfennig et al. 2001). These results contrast with thosein patients with PD who needed significantly longer timeduration for Initiation, but not for Termination.

Catatonic patients showed no abnormalities in MRCPsof Initiation, that is, lifting (MRCP 1). Instead, theyshowed significantly delayed onsets in early MRCPs in cen-tral and parietal electrodes during Termination, that is,lowering (MRCP 2), compared to psychiatric and healthycontrols (Pfennig et al. 2001). The fact that the early onsetwas altered only in MRCP 2 but not in MRCP 1, indicatesa delay specifically in initiation of termination, while Ini-tiation itself seems to remain principally intact. This is fur-

ther supported by results from dipole source analysis show-ing decreased source strength in right posterior parietalcortex in catatonic patients, while sources in SMA showedno abnormalities. In addition, catatonic motor and behav-ioural symptoms correlated significantly with delayed earlyonset in MRCP 2 in parietal electrodes.

In summary, posturing in catatonia may be characterizedby a specific deficit in Termination of movements whilePlan/Strategy, Initiation, and Execution seem to re-main basically intact. Such an assumption is supported byobservation of alterations in temporal duration, onset ofearly MRCPs, right parietal cortical localization andGABA-ergic reactivity in MRCPs specifically related toTermination of movements.

3.7. Neurochemical findings3.7.1. GABA. Recent interest in neurochemical alterationsin catatonia has focused on GABA-A receptors. The GABA-A receptor potentiator lorazepam is therapeutically effec-tive in 6080% of all acute catatonic patients (Bush et al.1996a; Northoff et al. 1995b; Rosebush et al. 1990). Onestudy investigated iomazenil-binding, reflecting number,and function of GABA-A receptors in 10 catatonic pa-tients in single photon emission computerized tomography(SPECT) and compared them with 10 noncatatonic psy-chiatric controls and 20 healthy controls (Northoff et al.1999e). Catatonic patients showed significantly lowerGABA-A receptor binding and altered right-left relations inleft sensorimotor cortex. In addition, catatonic patientscould be characterized by lower GABA-A binding in rightlateral orbitofrontal and right posterior parietal cortex, cor-relating significantly with motor and affective (but not withbehavioural) catatonic symptoms.

Furthermore, emotional-motor stimulation in fMRI/MEG (see above) was performed after neurochemical stim-ulation with lorazepam (see Northoff et al. 2001d; Richteret al. 2001). After lorazepam, healthy subjects activationshifted from orbitofrontal cortex to medial prefrontal cor-tex, resembling the pattern of activity from catatonic pa-tients before lorazepam. Catatonic patients, in contrast,showed a reversal in activation/deactivation pattern afterlorazepam: Activation in medial prefrontal cortex was re-placed by deactivation, and deactivation in lateral pre-frontal cortex was transformed into activation. It was con-cluded that prefrontal cortical activation/deactivationpattern during negative emotional processing may be mod-ulated by GABA-A receptors.

In addition to fMRI and MEG, kinematic measurementsand movement-related cortical potentials were investigatedin catatonic patients before and after lorazepam (Northoffet al. 2000a; Pfennig et al. 2001). After injection of theGABA-A potentiator lorazepam, time duration for Termi-nation reversed between groups and was now significantlyshorter in catatonic patients than in psychiatric and healthycontrols. In contrast, no influence of lorazepam was ob-served on temporal duration of Initiation in either group.After lorazepam, the early onset in parietal electrodes inMRCP 2 was reversed between groups, being now signifi-cantly earlier in catatonics than in psychiatric and healthycontrols. Lorazepam thus normalized that is, shortened delayed early onsets in MRCPs during Termination incatatonia. In contrast, it delayed early onsets in both psy-chiatric and healthy controls. In contrast to MRCP 2, lo-



razepam had no abnormal influence on MRCP 1 in cata-tonic patients (Pfennig et al. 2001). Moreover, it should benoted that, psychologically, lorazepam induced a paradox-ical reaction in all catatonic patients. Instead of reactingwith sedation, as was the case in psychiatric and healthycontrols, they became rather agitated.

In contrast to catatonia, GABA-ergic transmission in or-bitofrontal and prefrontal cortex, does not seem to revealany abnormalities in PD, whereas there are subcorticalGABA-ergic alterations in basal ganglia.

In summary, catatonia can be characterized by major al-terations and abnormal reactivity of GABA-A receptors inright orbitofrontal, motor cortex, and right parietal cortex.In PD, in contrast, no such orbitofrontal cortical GABA-ergic abnormalities can be observed.

3.7.2. Dopamine. In early studies, Gjessing (1974) foundincreased dopaminergic (homovanillic acid and vanillicacid) and adrenergic/noradrenergic (norepinephrine, meta-nephrine, and epinephrine) metabolites in the urine of patients with periodic catatonia. In addition, he obtainedcorrelations between vegetative alterations and these metab-olites. He suggested a close relationship between catatoniaand alterations in posterior hypothalamic nuclei. Recent in-vestigations of the dopamine metabolite homovanillic acidin the plasma of 32 acute catatonic patients showed in-creased levels in the acute catatonic state (Northoff et al.1996), particularly in those responding well to lorazepam(Northoff et al. 1995b). Accordingly, the dopamine agonistapomorphine exerted no therapeutic effect at all in acutecatatonic patients (Starkstein et al. 1996). Instead, one wouldexpect therapeutic efficacy of dopamine-antagonists likeneuroleptics. However, neuroleptics such as haloperidol mayrather induce a catatonia, that is, so-called neuroleptic-induced catatonia (Fricchione et al. 2000). Involvement ofthe striatal dopaminergic system, especially of D-2 recep-tors in catatonia, therefore remains controversial. No sys-tematic studies investigating D2 receptors in catatonia havebeen reported so far.

In contrast to catatonia, dopamine is the major transmit-ter affected in PD. Several studies showed decreased stri-atal D2-receptor binding in patients with PD.

In summary, exact involvement of the dopaminergic sys-tem in catatonia remains unclear. In contrast, PD can becharacterized by reduction of striatal D-2 receptors.

3.7.3. Glutamate. The glutamatergic system, in particularthe NMDA-receptors, may be involved in catatonia as well. Some catatonic patients being nonresponsive to lo-razepam have been treated successfully with the NMDA-antagonist amantadine. Therapeutic recovery occurredrather gradually and delayed (Northoff et al. 1997; 1999c).Such gradual and delayed improvement suggests thatNMDA-receptors may be involved only secondarily in cata-tonia, whereas GABA-A receptors seem to be primarily altered. Such an assumption remains rather speculative,since neither the NMDA-receptors nor their interactionswith GABA-A receptors have been investigated in cata-tonia.

In PD, a modulation of glutamatergic-mediated corti-co-striatal pathway by NMDA-antagonists has been sug-gested as a model for explanation of therapeutic efficacy ofamantadine/memantine (Merello et al. 1999). Alterna-tively, modulation of glutamatergic pathways within basal

ganglia themselves, that is, between subthalamic nuclei andinternal pallidum, has been discussed.

In summary, both catatonia and PD may be character-ized by glutamatergic abnormalities especially in NMDA-receptors. Amantadine as a NMDA antagonist is thera-peutically effective in both diseases and may modulateglutamatergic-mediated cortical and subcortical connec-tivity.

3.7.4. Serotonin. The serotonergic system has been as-sumed to be involved in catatonia. Atypical neurolepticsthat have serotonergic properties may induce catatonic fea-tures (Carroll 2000). Therefore, it has been hypothesizedthat catatonia may be characterized by a dysequilibrium inthe serotonergic system with up-regulated 5-HT1a recep-tors and down-regulated 5-HT2a receptors (Carroll 2000).However, no investigations of the serotonergic system incatatonia have yet been reported, so that this hypothesis re-mains speculative.

Similar to catatonia, the serotonergic system may be in-volved in PD, which may be related to dopaminergic ab-normalities.

In summary, the serotoninergic system seems to be in-volved in both catatonia and PD. This may reflect sec-ondary modulation by another primarily altered transmit-ter system, that is, GABA in catatonia and dopamine in PD.

4. Pathophysiological hypothesis

The present hypothesis focuses predominantly on similari-ties and differences between PD and catatonia with respectto distinct kinds of modulation. Similar to the presentationof data (see sect. 3), various subtle aspects of pathophysiol-ogy, especially in PD, will therefore not be discussed in de-tail. In addition, the present hypothesis primarily focuseson catatonic responders to lorazepam. This is important tomention, since responders and nonresponders may be char-acterized by distinct underlying pathophysiological mecha-nisms (Northoff et al. 1995b; 1998; Ungvari et al. 1999). In-stead of giving an overview of the pathophysiology in itsentirety, the focus will be on the distinct kinds of modula-tion.

4.1. Pathophysiology of motor symptoms4.1.1. Deficit in Execution of movements: Akinesia.Both catatonia and PD can be characterized by akinesiawhich may be related to functional alterations in the so-called direct motor loop. The motor loop includes con-nections from MC/SMA to putamen, from putamen to in-ternal pallidum, and from there via mediodorsal thalamicnuclei back to MC/SMA (Masterman & Cummings 1997).Decrease in striatal dopamine leads to down-regulation ofthe direct motor loop (exclusion of external pallidum) andconcurrent up-regulation of the indirect motor loop (in-clusion of external pallidum), resulting in a net effect of de-creased activity in premotor/motor cortex.

In contrast to PD, functional imaging studies during per-formance of movements yielded no alterations in SMA andMC in catatonia. However, effective connectivity rangingfrom orbitofrontal cortex to premotor/motor cortex was sig-nificantly reduced during emotional-motor stimulation incatatonic patients. Premotor/motor cortical function re-



mains apparentely intact during isolated motor stimulation,whereas it seems to become dysregulated during emotionalstimulation via cortico-cortical connectivity in orbito-frontal/prefrontal cortex. Consequently, the motor loopitself seems to remain intact in catatonia, whereas it is dys-regulated by orbitofrontal and prefrontal cortex via cor-tico-cortical, that is, horizontal modulation.

In summary, akinesia is closely related to down-regula-tion of the motor loop. This down-regulation may becaused either by dopamine and subcortical-cortical bot-tom-up modulation, as in PD, or by GABA and cortico-cortical, that is, horizontal modulation with consecutivetop-down modulation, as in catatonia.

4.1.2. Deficits in Initiation of movements: Starting prob-lems. Parkinsonian patients could be characterized by def-icits in initiation, which may be considered as one essentialcomponent of the willed action system.

Movements have to be planned and a strategy formed,to get an idea what kind of movement shall be performedwhich may be closely related to lateral orbitofrontal corti-cal function (Deecke 1996). This aspect is referred to as

the Plan/Strategy of movements, later in this article.There must be an idea of how to move, including a deci-sion to perform a movement, which can be initiated eitherinternally (i.e., voluntary) or externally (i.e., involuntary).Internally initiated movements can be considered as willedmovement/actions, which may be subserved by a so-calledwilled action system involving the dorsolateral prefrontalcortex (DLPFC), the anterior cingulate, the anterior sup-plementary motor area (SMA), and fronto-striatal circuits(Deecke 1996; Jahanshahi et al. 1995; Jahanshahi & Frith1998, pp. 494, 51799.). This aspect is referred to as Ini-tiation in the further course of the article. Once a move-ment is initiated, it can be executed which probably isclosely related to function of posterior SMA and the mo-tor cortex (Deecke 1996; Jahanshahi & Frith 1998); this isreferred to as Execution in the rest of this article. Theexecuted movement can be characterized by dynamic andkinematic properties. Dynamic properties refer to forceand velocity of the movements that may be encoded pri-marily in neurons of the motor cortex (Dettmers et al.1995). Fronto-mesial structures such as the SMA, as wellas the putamen and the ventrolateral thalamus, may be im-



Table 2. Pathophysiological correlates of symptoms in catatonia and Parkinsons disease

Catatonia Parkinsons

Motor symptoms Akinesia Cortico-cortical Subcortico-corticalGABA-ergic Dopaminergic

Starting problems Top-down-regulation of SMA/ Deficit in SMA/MC in relation toMC altered bottom-up modulation

Posturing Right orbitofrontalRight posterior parietal

Rigidity Top-down modulation of striatal Deficit in striatal D-2 receptorsD-2 receptors

Behavioural Motor anosognosia Network between ventrolateral,symptoms dorsolateral, and parietal cortex

Mutism and stupor Anterior cingulate and medial prefrontal cortex

Preservative- Concomitant dysfunction incompulsive behavior dorso- and ventrolateral

prefrontal cortexAffective Anxieties Medial orbitofrontal cortex

symptoms Unbalance between medial and lateralprefrontal cortical pathway

Inability to control Unfunctional relation between medialanxieties and lateral orbitofrontal cortex

Depression Anterior cingulateTherapeutic GABA GABA-ergic mediated neuronal

agents (lorazepam) inhibition in medial orbitofrontal cortex

Modualtion of functional andbehavioural inhibition

NMDA Down-regulation of Down-regulation of glutamatergic-glutamatergic-mediated mediated overexcitation in

(amantadine) overexcitation in prefrontal and subcortical pathwaysorbitofrontal-parietal pathways

dopamine Top-down modulation of striatal Compensation for striatal D-2D-2 receptors predisposing for receptor deficit withneuroleptic-induced catatonia normalization of bottom-up

modualtion

portant for coding of temporal properties, that is, the tim-ing of movements (Deecke 1996, Jahanshahi & Frith 1998,p. 493). Kinematic properties describe spatial characteris-tics of movements such as angles, and so on, which may beencoded by neurons in parietal cortex (areas 5, 39, 40)( Jeannerod 1997, pp. 5758, 7273; Kalaska 1996.). Fi-nally, the movement must be terminated, which is referredto as Termination, implying postural change with on-linemonitoring of the spatial position of the movement.

PD can be characterized by severe deficits in SMA,which, as part of the willed action system, is closely re-lated to the ability of Initiation. Parkinsonian patients doindeed show severe deficits in internal initiation, althoughthey are well able to execute them once they have overcometheir initiation problems. Consequently, PD may be char-acterized by disturbance in the willed action system withproblems in the voluntary generation of movements by it-self (Jahanshahi & Frith 1998).

In contrast to PD, catatonia cannot be characterized byprimary alterations in the willed action system, since bothInitiation and the function of SMA seem to remain moreor less intact in these patients. Therefore, voluntary gener-ation and initiation imply that the willed action systemitself remains basically intact. Instead, the willed actionsystem becomes dysregulated by cortico-cortical connec-tivity so that it only appears as if there is a deficit in Initi-ation in catatonia.

In summary, initiation as part of the willed action sys-tem is disturbed in PD, clinically accounting for startingproblems. Whereas, in catatonia, the intact functioningwilled action system becomes dysregulated by cortico-cortical modulation, resulting in motor similarity betweencatatonic and Parkinsonic patients.

4.1.3. Deficit in Termination of movements: Posturing.In order to terminate a movement, on-line monitoring ofthe spatial position of the respective movement is neces-sarily required. Neuropsychologically, such on-line moni-toring may be subserved by visuo-spatial attention, asclosely related to function of the right posterior parietal cor-tex.

The posterior parietal cortex has been shown to bespecifically involved in location and direction of the spatialposition of movements and limbs in relation to intraper-sonal space of the body (Anderson 1999; Colby & Duhamal1996; Roland et al. 1980.). On the basis of spatial attentionwith a redirection to extrapersonal or sensory space, move-ments will be selected in orientation on the respective spa-tial context. Providing the spatial frame of reference, theposterior inferior parietal cortex, as contrasted to the pos-terior superior parietal cortex, is specifically involved in ab-stract spatial processing and exploration (Karnath 1999). Assuch, the right posterior inferior parietal cortex may pro-vide the intrapersonal spatial frame of reference of thebody necessary for the conscious organization of move-ments thus making spatial codes available for prefrontalcortical representation (Vallar 1999, p. 45). In addition tospatial monitoring, the posterior inferior parietal cortexseems to be specifically involved in early initiation of move-ments (Castiello 1999; Desmurget et al. 1999; Driver &Mattingley 1998; Mattingley et al. 1998; Snyder et al. 1997),which, in the present context, may be interpreted as a spe-cific relationship between initiation of Termination andposterior inferior parietal cortical function. Consequently,

posterior inferior parietal cortical function may provide thelinkage between spatial registration as internal spatialmonitoring, and initiation of Termination as necessarilyrequired for postural change and consecutive execution ofTermination.

In catatonia, alterations in right parietal cortical functionwere found in neuropsychology and SPECT. Neuropsycho-logically, catatonic patients showed deficits in visuo-spatialabilities correlating with attentional function. SPECT re-sults revealed decreased r-CBF in right parietal cortex andabnormal correlations with visuo-spatial abilities. Involve-ment of right posterior parietal cortex in pathophysiology ofcatatonia is further supported by consideration of anatomo-functional parcellation in this region. Distinct areas repre-senting eye movements, arm movements, and head move-ments may be distinguished within posterior parietal cortex(Anderson 1999; Colby & Duhamel 1996). Such distinctrepresentational areas for eyes, head, and arm coincide withclinical observations that posturing in catatonia can occur ineyes, arms, and/or head. Posturing of eyes may be reflectedin staring, posturing of head is reflected in psychic pillow,and posturing of arm is the classical type of posturing (seeabove). All three kinds of posturing can occur simultane-ously, but they may also dissociate from each other, so that,for example, patients may show only the psychic pillowwithout staring and posturing of limbs. It is therefore pos-tulated that such a clinical dissociation between these threekinds of posturing may have its physiological origin inanatomo-functional parcellation in posterior parietal cortex.

It may be hypothesized that the deficit in right parietalvisuo-spatial attention in catatonic patients leads to an in-ability in initiation of Termination. The spatial position ofthe ongoing movement can no longer be registrated in anappropriate way, resulting in an impossibility to initiate theterminating movement. This may result in an inability ofexecution of Termination with a consecutive blockade inpostural change, which clinically is reflected in posturing.Assumption of relation between posturing and right pari-etal cortical dysfunction is supported by electrophysiologi-cal findings during termination (Pfennig 2001; Pfennig etal. 2001). Furthermore, patients with lesions in right pari-etal cortex show posturing as well (Fukutake et al. 1993;Saver et al. 1993).

Due to additional disturbances in orbitofrontal cortex,catatonia has to be distinguished from disorders related toisolated lesions in right parietal cortex as, for example, ne-glect showing the following differences: (1) patients withneglect do not show posturing; (2) unlike patients with ne-glect, catatonic patients neither deny the existence of limbsor parts of their body, nor overlook these body parts in re-lation to the environment, so that they do not strike withthese body parts against walls, doors, and so on; (3) patientswith neglect show attentional deficits, whereas in catatonicpatients no such deficits could be found; (4) patients withneglect do often show sensory deficits which cannot be ob-served in catatonia; (5) unlike patients with neglect, cata-tonic patients do not show a right-left pattern with respectto their symptoms, that is, posturing; (6) unlike patientswith neglect, catatonic patients do not suffer from alter-ations in peripersonal and extrapersonal space (as reflectedin successful ball experiments; Northoff et al. 1995),whereas they may be characterized by alterations in per-sonal space, being unable to locate the position of his/herown limbs in relation to the rest of the body. Since personal



and peri/extrapersonal space may be subserved by distinctneural networks (Galati et al. 1999), distinction betweenboth kinds of spaces may be not only phenomenologicallyrelevant but physiologically as well. Hence, catatonia can-not be compared with neglect as an attentional disorder, sothat posturing cannot be accounted for by disturbances inattention, which is further supported by neuropsychologi-cal findings showing no specific alterations in attentionalmeasures (see above).

Other disorders related to right posterior parietal corti-cal dysfunction must be distinguished from catatonia aswell. Patients with Balint Syndrome show symptoms like aninability to fixate objects and an optic ataxia, neither ofwhich can be observed in catatonia. Since Balint Syndromeand especially optic ataxia indicate involvement of rightposterior superior parietal cortex, differences betweencatatonia and Balint Syndrome do further underline theparticular importance of the right posterior inferior parietalcortex in catatonia.

In contrast to catatonia, Parkinsonian patients show nei-ther posturing nor alterations in right parietal cortex.

In summary, catatonia can be characterized by specificdeficits in initiation of termination, while PD showsdeficits in initiation of execution, implying functional dis-sociation between both diseases with respect to initiation ofmovements. Whereas the deficit in initiation of termina-tion seems to be related with dysfunction in right posteriorinferior parietal cortex, lack of initiation of executionseems to be accounted for by functional deficits in SMA.

4.1.4. Alteration in tonus of movements: Cogwheel rigid-ity and flexibilitas cerea. Parkinsonian patients could becharacterized by muscular hypertonus with a so-calledcogwheel rigidity which may be accounted for by a deficitin striatal D2-receptors and consecutive dyscoordination ofactivity in internal pallidum.

Catatonic patients may show muscular hypertonus butwithout cogwheel rigidity instead, they show a smoothkind of rigidity, a so-called flexibilitas cerea. Since there isno primary, that is, direct deficit of striatal D2-receptors incatatonia, dyscoordination of the internal pallidum may benot as strong as in PD, implying that there may be some kindof smooth muscular hypertonus without cogwheel rigidity.Assumption of discrete down-regulation of striatal D2-receptors may be supported by symptomatic overlap be-tween catatonia and neuroleptic malignant syndrome, pos-sibility of neuroleptic-induced catatonia, and central roleof striatum in animal models of catatonia (see Carroll 2000).

Origin of down-regulation in striatal D2-receptors incatatonia remains, however, unclear. Down-regulation ofstriatal D2-receptors may be related to cortical alterations:Orbitofrontal cortical alterations may lead to down-regula-tion in D2-receptors in caudate via top-down modulationwithin the orbitofrontal cortical loop (see Fig. 4 below).Or striatal D2-receptors may be top-down modulatedwithin the motor loop, which by itself may be dysregu-lated by cortico-cortical connectivity. However, due to lackof specific investigation of basal ganglia in catatonia, bothassumptions remain speculative.

In summary, rigidity may be related to alterations in in-ternal pallidum as induced by down-regulation of striatalD2-receptors. Abnormal modulation of D2-receptors maybe due to alterations in either subcortical-subcortical con-nectivity, as in PD, or abnormal cortico-cortical connectiv-

ity with consecutive horizontal modulation and concur-rent cortico-subcortical top-down modulation, as may bethe case in catatonia.

4.2. Pathophysiology of behavioral symptoms4.2.1. Deficit in on-line monitoring: Motor anosognosia.Subjective experience in catatonic patients could be char-acterized by unawareness of posturing and movement dis-turbances in general, whereas Parkinsonian patients werewell aware of their motor deficits. This raises the questionof difference between catatonic and Parkinsonian patientswith respect to internal monitoring of the movement. Itshould be noted that catatonic patients showed unaware-ness only with respect to their motor disturbances, sincethey were well aware or even hyperaware of emotional al-terations, which excludes the possibility of a deficit in gen-eral awareness.

Awareness of movements is closely related to the abilityof on-line monitoring as an internal monitoring, which byitself necessarily requires generation of an internal modelof the respective movement. According to Miall andWolpert (1996), distinct kinds of models can be distin-guished (see Fig. 2). There is a causal representation of themotor apparatus that can be described as a Forward dy-namic model. The model of the behavior and the environ-ment can be called Forward output model. Finally, anInverse model can be assumed where the causal flow ofthe motor system is inverted by representing the causalevents that produced the respective motor state (for moredetailed discussion, see Miall & Wolpert 1996).

In orientation on the model by Miall and Wolpert (1996),predicted and actual state are compared with eachother, necessarily presupposing the estimation of the actualspatial position. Both estimation of spatial position andcomparison between actual and predicted state seem to bedisturbed in catatonia, as indicated by quadrats with crossesleading consecutively to alterations in initiation and exe-cution of Termination, and finally resulting in postur-ing, which is the most bizarre symptom in catatonia. Parkin-sons disease, in contrast, may rather be characterized bydeficit in Initiation leading to difficulties in Executionwhereas, unlike in catatonia, estimation of spatial positionand comparison between actual and predicted spatial stateremain intact by themselves.

Note that there is double dissociation between catatoniaand Parkinsons disease with regard to feedforward and feed-back: Feedback is disturbed in catatonia and feedforwardseems to be preserved by itself, whereas in Parkinsons dis-ease, feedforward is disturbed with feedback remaining in-tact.

The internal monitoring of movements could itself beeither implicit or explicit. Following Jeannerod (1997),only certain aspects of movements are internally monitoredin an explicit mode of processing. Plan/Strategy and, tosome extent, Initiation are accessible to consciousnessand can be characterized by explicit internal monitoring.In contrast Execution by itself is not accessible to con-sciousness and can be related only with implicit internalmonitoring (Jeannerod 1997). Accordingly, Jeannerod dis-tinguishes between an implicit How system and an ex-plicit Who system of movements/action, the former beingresponsible for Execution, whereas the latter includesPlan/Strategy and Initiation.



Figure 2. Forward model (in orientation on Miall and Wolpert 1996) of physiological motor control in catatonia and ParkinsonsdiseaseLegendh1 5 Disturbance in Parkinsons diseaseh3 5 Disturbance in catatonia* 5 Hypofunction in catatoniaThe figure shows the forward model as established by Miall and Wolpert (1996) supplemented by the distinct aspects of movementsPlan/Strategy, Initiation, Execution. In addition distinct processes involved in Termination of movements, feedback, estimatedspatial position, initiation and execution of Termination are included. In orientation on the model by Miall and Wolpert (1996) pre-dicted and actual state are compared with each other necessarily presupposing the estimation of the actual spatial position. Both es-timation of spatial position and comparison between actual and predicted state seem to be disturbed in catatonia as indicated by quadratswith crosses leading consecutively to alterations in initiation and execution of Termination finally resulting in posturing as the mostbizarre symptom in catatonia. Parkinsons disease in contrast may rather be characterized by deficit in Initiation leading to difficultiesin Execution whereas, unlike in catatonia, estimation of spatial position and comparison between actual and predicted spatial state re-main intact by themselves.Note that there is double dissociation bewteen catatonia and Parkinsons disease with regard to feedforward and feedback: Feedback isdisturbed in catatonia while feedforward seems to be preserved by itself whereas in Parkinsons disease feedforward is disturbed withfeedback remaining intact.

Empirically, such an assumption is further supported bya study from Grafton et al. (1995) investigating whetherpersons were conscious or unconscious of a particular or-der of sequences of movements they performed con-sciousness of the order of sequence necessarily presuppos-ing an explicit internal monitoring of Plan/Strategy.Subjects showing consciousness of the order of sequencecould be characterized by activation in right dorsolateralprefrontal cortex (Area 9), right posterior parietal cortex(Area 40), and right premotor cortex (Area 6), compared tothose subjects who were unconscious. Increasing demandof explicit internal monitoring, as induced by mirror ex-periments, led to activation in right lateral dorsolateral pre-frontal cortex (Area 9 and 46) and right posterior parietalcortex (Area 40) (Fink et al. 1999).

Following distinction between implicit and explicitinternal monitoring, an analogous hypothesis shall be de-veloped for Termination. Initiation of Termination andexecution of Termination can be distinguished from eachother, emphasizing the particular importance of internalspatial monitoring for initiation of Termination. Follow-ing phenomenological accounts of movements, one maywell be conscious about the spatial position from which oneinitiates the terminating movement initiation of Ter-mination may be characterized by explicit internal moni-toring. In contrast, execution of Termination may be as-sociated only with implicit internal monitoring. Hence,the spatial position from which the Termination is initi-ated may be accessible to consciousness, that is, explicit in-ternal monitoring, whereas execution of the terminatingmovement itself may rather remain unconscious, because itmay be characterized only by implicit internal monitor-ing.

Internal monitoring of the spatial position of move-ments may be regarded as a subset of on-line monitoring ingeneral and can be considered as an essential componentof working memory. On-line monitoring in general isclosely related to functional activity in ventrolateral anddorsolateral prefrontal cortex (i.e., VLPFC and DLPFC)(see Leary et al. 1999; Petrides 1995). Therefore, it may behypothesized that on-line monitoring of the spatial positionof their respective movements, may be subserved by aright-hemispheric network between VLPFC, DLPFC, andposterior parietal cortex (i.e., PPC). Consequently, func-tional connections between right posterior parietal, rightdorsolateral prefrontal, and right lateral orbitofrontal/ven-trolateral prefronal cortex may be of crucial importance forimplicit and explicit internal monitoring of the spatialposition of movements. As based on the above-mentionedstudies of motor awareness, the VLPFC seems to be relatedto implicit internal monitoring, whereas the DLPFC maybe involved in explicit internal monitoring.

The lateral orbitofrontal/ventrolateral prefrontal cortexshows similar cytoarchitectonic subdivisions as the poste-rior parietal cortex (Carmichael & Price 1994), and receivesreciprocal connections from both posterior parietal anddorsolateral prefrontal cortex that project to similar areas(Cavada & Goldman-Rakic 1989; Morecraft et al. 1992;1998; Selemon & Goldman-Rakic 1988). In accordancewith such reciprocal connectivity, co-activation of thesethree regions has been demonstrated in tasks requiring be-havioral flexibility and implicit and explicit spatial moni-toring (Athwal et al. 1999; Meyer-Lindenberg et al. 1999;Nobre et al. 1999; Quintana & Fuster 1999; Stephan et al.

1999). The orbitofrontal cortex may modulate activity indorsolateral and posterior parietal cortex, which has alreadybeen demonstrated in both animals (Quintana et al. 1989)and humans (Bchel et al. 1997; Drevets & Raichle 1998;Mayberg et al. 1999). Furthermore, the right orbitofrontalcortex shows a higher density of neurons and neuronal con-nections, which may account for predominance of righthemispheric activation (see below). Consequently, the righthemispheric neural network between posterior parietal,dorsolateral prefrontal, and lateral orbitofrontal/ventrolat-eral prefrontal cortex may be crucially involved in implicitand explicit internal monitoring of the spatial position ofmovements, resulting in updating of spatial location andrepresentation of movements (Colby 1999).

Catatonia can be characterized by major deficits in on-line monitoring and alterations in right ventro/dorsolateralprefrontal cortex (i.e., VLPFC, DLPFC) and right poste-rior parietal cortex (PPC) as has been demonstrated inSPECT and fMRI (see above). This right hemispheric net-work between VLPFC, DLPFC, and PPC may be alteredin catatonia, which may account for deficit in on-line mon-itoring of the spatial position of movements, consecutivelyleading to posturing. One may assume that both kinds ofon-line monitoring implicit and explicit internal mon-itoring may be deficient in catatonia: Catatonic patientsare neither able to terminate their movements requiringimplicit monitoring, nor are they aware of their motor dis-turbances requiring explicit internal monitoring, result-ing in concurrent posturing and motor anosognosia.

Furthermore, one may hypothesize that primary in-volvement of GABA-ergic transmission may be somehowrelated to motor anosognosia. Similar to catatonia patientswith movement, disturbances with primary alteration inGABA, such as Huntingtons chorea and Parkinsonian dys-kinesia, do show unawareness of their motor anomalies,that is, motor anosognosia (Snowdon et al. 1998). However,the exact relationship between GABA-ergic transmissionand motor anosognosia remains unclear.

In contrast to catatonia, Parkinsonian patients showdeficits neither in on-line monitoring in general, nor in im-plicit and explicit internal monitoring of movements inparticular. Physiologically, this may be reflected in the ab-sence of major deficits of function in VLPFC and GABA-ergic transmission, implying that these patients remain fullyaware of their motor disturbances.

In summary, catatonia can be characterized by ventrolat-eral prefrontal cortical dysfunction with consecutive def-icits in on-line monitoring in general. This deficit may leadto dysregulation of the right-hemispheric network betweenVLPFC, DLPFC, and PPC, resulting in lack of implicitand explicit internal monitoring of the spatial position ofmovements. Clinically, such a dysregulation is reflected inconcurrent occurrence of posturing and motor anosognosiain catatonic patients.

4.2.2. Deficit in verbal and nonverbal contact: Mutismand stupor. One of the most impressive clinical features incatatonic patients is mutism or even stupor, implying thatthere is no longer any kind of verbal contact (mutism) and/or nonverbal contact (stupor) with other persons neithermutism nor stupor occur in PD.

Catatonia could be characterized by alterations in medialand lateral orbitofrontal cortex during negative emotionalprocessing. These alterations shift the patterns of activity



towards anterior cingulate/medial prefrontal cortex and lat-eral prefrontal cortex, resulting in functional lack of balancebetween medial and lateral pathway in prefrontal cortex(see sect. 3).

The anterior cingulate (areas 24 and 32, according toBrodmann) shows anatomical, cytoarchitectonic, connec-tional, and functional subdivision into an affective (area24a), cognitive (area 24b), and motor (area 24c) part. Rela-tion between these three subdivisions may be characterizedby reciprocal suppression (Devinsky 1997): For example,strong emotional processing leads to activation in the af-fective part and concurrrent suppression of the cognitivepart, and vice versa (see Bush et al. 2000).

Because the patterns of activity shifted from orbito-frontal cortex to anterior cingulate/medial prefrontal cor-tex, there may be extremely strong and high activity in theaffective part (i.e., 24c) of the anterior cingulate. Via recip-rocal suppression, one may assume almost complete down-regulation of functional activity within the motor part of theanterior cingulate. Down-regulation of the motor part inthe anterior cingulate may account for mutism as an inabil-ity to speak (that is, making verbal contact with other per-sons). Such an assumption would be supported by observa-tion of mutism in patients with isolated lesions in theanterior cingulate. In addition, these patients can be char-acterized by a combination of akinesia and mutism aki-netic mutism, which, of course, is in full accordance withcatatonia. However, comparison between catatonia and aki-netic mutism should be restricted to concurrent occurrenceof akinesia and mutism. Unlike in catatonia, patients withakinetic mutism show neither hyperkinesias nor other be-havioral anomalies (like negativism, perseverative and com-pulsive behavior, etc.).

In addition to anterior cingulate alterations, catatonic pa-tients showed functional alterations in medial prefrontalcortex during negative emotional processing. The medialprefrontal cortex is involved in social cognition as well as inperception of movements and mental states of other per-sons (see Castelli et al. 2000). Shift of pattern of activityfrom orbitofrontal to medial prefrontal cortex may lead todysfunction of the latter. Medial prefrontal cortical dys-function may in turn result in deterioration of the ability toperceive movements and mental states from other persons.Clinically, this may be reflected in stupor, or the inability tomake either verbal or nonverbal contact with other personsat all.

In summary, deficit in orbitofrontal cortical activationduring negative emotional processing in catatonia leads toa shift of patterns of activity towards anterior cingulate andmedial prefrontal cortex. Clinically, dysfunction in anteriorcingulate and medial prefrontal cortex may be reflected inmutism and stupor.

4.2.3. Deficit in inhibitory control and planning of behav-iour: Perseverative-compulsive behaviour. In contrast toPD, catatonia can be characterized by bizarre behaviouralanomalies including negativism, stereotypies, persevera-tions, echolalia/praxia, and so on (see above), which may beclassified as perseverative and compulsive behaviour. Thesebizarre perseverative and compulsive behavioural anom-alies may be closely related with dysfunction in the or-bitofrontal cortex.

The orbitofrontal cortex, and especially the lateral partincluding the ventrolateral prefrontal cortex (VLPFC), may

be associated with control and monitoring of complex be-haviour (Deecke 1996), whereas planning of its detailsseems to be subserved rather by the dorsolateral prefrontalcortical function (DLPFC) (Jahanshahi & Frith 1998).Control and monitoring of complex behaviour may be ex-erted by inhibition (Dias et al. 1996; 1997) realized by sup-pression as an inhibitory control. Similar to VLPFC, theDLPFC shows reciprocal connections with posterior pari-etal cortex (PPC) (Cavada & Goldman-Rakic 1989; Sele-mon & Goldman-Rakic 1988). Therefore, control and mon-itoring of behaviour may be closely associated withregistration of the spatial position of the respective move-ment. It is the neural network between VLPFC, DLPFC,and PPC which may consequently subserve the control andmonitoring of complex behaviour.

Due to deficits in medial and lateral orbitofrontal corti-cal activation in catatonia, the VLPFC may be unable to ex-ert inhibitory control and monitoring of complex behaviour.Behaviour can no longer be controlled by inhibition, re-sulting in lack of suppression of once started behavior withconsecutive perseverations. It is this inability to suppressonce started behaviour that may account for perseverativesymptoms like stereotypies, echolalia/praxia, persevera-tions, and so on. Furthermore, alterations in lateral or-bitofrontal cortex are closely associated with compulsivebehaviour, for example, in obsessive-compulsive disorder.This may further support our assumption of a relation be-tween perseverative-compulsive behavioural anomaliesand dysfunction in VLPFC in catatonia.

Dysfunction in VLPFC may lead to functional alterationin DLPFC as well, because both

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Catatonia Top Down Modulation

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