disorders of diminished motivation - · pdf filedisorders of diminished motivation 379 as well...

Focus on Clinical Practice and Research ioltXTppiiiss© 2005 Uppincott Williams & Wilklns, Inc.

Disorders of DiminishedMotivation

Robert S. Marin, MD; Patricia A. Wilkosz, MD, PhD

Disorders of diminished motivation occur frequently in individuals with traumatic brain injury.Motivation is an ever-present, essential determinant of behavior and adaptation. The major syn-dromes of diminished motivation are apathy, abulia, and akinetic mutism. Depending on theiretiology, disorders of diminished motivation may be a primary clinical disturbance, a symptomof another disorder, or a coexisting second disorder. This article presents a biopsychosocial ap-proach to the assessment and management of motivational impairments in patients -w'lXh traumaticbrain injury. The recognition and differential diagnosis of disorders of diminished motivation, aswell as the mechanism and clinical pathogenesis, are discussed. Key words: abulia, akineticmutism, anterior cingulum, apathy, cholinesterase inhibitor, disorders of diminished motiva-tion, dopamine agonist, methylphenidate, traumatic brain injury, ventralpallidum

MOTFVATION is essential to adaptivefunctioning and quality of life. This is

as true for individuals with traumatic braininjury (TBI) as it is for those with stroke, de-mentia, or any other neuropsychiatric illness.Clinicians understand intuitively the impor-tance of motivation. Without motivation, in-dividuals with TBI will fail to keep appoint-ments, stay on their medications, devotethemselves to friends and family, or return totheir jobs. Motivational loss handicaps phys-ical rehabilitation and coping skills,' and itis a major source of burden for families ofindividuals with TBI.

Motivation is an ever-present, essential de-terminant of behavior and adaptation. Like at-tention, emotion, and other state variables,motivation is not a single function of thebrain. Psychologically and biologically, moti-vation is a complex of capacities; the neu-ral systems subserving it are themselvesdelimited and distributed, integrated andinterdependent.

Prom the Western Psychiatric Institute and Clinic,Department of Psychiatry, University of PittsburghSchool of Medicine, Pa.Corresponding author: Patricia A. Wilkosz, MD, PhD,Western Psychiatric Institute and Clinic, 3811 O'HaraSt, Pittsburgh, PA 15213 (e-mail: [email protected]).

This article presents an approach to the as-sessment and management of motivational im-pairments in patients with TBI. It introducesdefinitions of motivation and of the 3 majordisorders of diminished motivation (DDM):akinetic mutism, abulia, and apathy Diagno-sis of DDM is further clarified in terms ofbehavior, thought content, and affectivesymptoms. Assessment and managementof DDM are then described on the basis ofa biopsychosocial approach to the causesof motivational loss.' Investigators fromthe fields of psychiatry,'' neuropsychology,^rehabilitative medicine,^ and occupationaltherapy^ agree that DDM are a major sourceof disability for patients with TBI. Diminishedmotivation in patients with TBI contributesto loss of social autonomy,'' financial andvocational loss, and family burden.^ Giventhe frequency of diminished motivation inpatients with TBI—estimates vary from 5% to^•7%4,8,9—properly diagnosing and treatingDDM has enormous potential to alleviate theresultant personal and social burden.

DISORDERS OF DIMINISHEDMOTIVATION: RECOGNITION

Motivation refers to the characteristics anddeterminants of goal-directed behavior. The-ories of motivation are intended to account

377

378 JOURNAL OF HEAD TRAUMA REHABIUTATION/JULY-AUGUST 2005

for the "direction, vigor, and persistence of anindividual's actions,"'" that is, for how behav-ior "gets started, is energized, is sustained, isdirected, is stopped, and what kind of subjec-tive reaction is present in the organism whenall this is going on.""

Disorders of diminished motivation includeakinetic mutism, abulia, and apathy. Recentliterature'^"'^ places DDM on a continuumof motivational loss, with apathy at the mi-nor pole of severity and akinetic mutismat the major pole of severity. The 3 resultfrom dysfunction of the neural machinery thatmediates motivation.

Akinetic mutism is essentially character-ized by a total absence of spontaneous behav-ior and speech occurring in the presence ofpreserved visual tracking.'^ Traumatic braininjury may cause akinetic mutism, althoughfew cases have been reported in the TBIliterature.'^

Abutia, originally denoting a disorder ofwill (but in Latin),'^"'^ characterizes pa-tients with symptoms less severe than butqualitatively identical to akinetic mutism:poverty of behavior and speech output, lackof initiative, loss of emotional responses, psy-chomotor slowing, and prolonged speech la-tency. Abulia evolves into akinetic mutismwhen it worsens and into apathy when itimproves.

Apathy is a state of diminished motiva-tion in the presence of normal conscious-ness, attention, cognitive capacity, and mood.Patients with apathy are generally able to initi-ate and sustain behavior, describe their plans,goals, and interests, and react emotionally tosignificant events and experiences. However,these features are less extensive, less com-mon, less intense, and shorter in duration thanthey are in individuals who are not apathetic.In other words, apathy differs from normalityquantitatively rather than qualitatively.

To further clarify the diagnosis of DDM, it ishelpful to relate them to the changes in overtbehavior, thought content, and emotion thatcontribute to the clinical recognition of dimin-ished motivation. Motivation is the psycho-logical domain concerned with goat-directed

behavior Thus, the recognition of diminishedmotivation requires examining goat-retatedaspects of overt behavior, thought content,and emotion. Disorders of diminished moti-vation are recognized by the simuttaneousdiminution in each of these 3 aspects ofbehavior:

Diminished overt behavior may rangefrom a subtle attenuation in social or oc-cupational functioning, for example, apathy,to profound deficits in the capacity to initi-ate any movement whatsoever, as with aki-netic mutism. Symptoms of diminished overtbehavior include diminished productivity,diminished effort, and diminished initiative.

Diminished goat-retated thought content,if mild, is indicated by decreased interests,plans, or goals for the future. If severe, there isa virtual absence of goal-related thought con-tent. The latter would characterize abulia andakinetic mutism.

Diminished emotionat responses to goat-retated events mean emotionally indifferent,shallow, or restricted responses to importantlife events. Clinically, this usually means flat-tened, labile, or shallow affect and emotionalindifference.

To summarize, diminished motivation ispresent if a patient with an intact tevetof consciousness, attention, tanguage, andsensorimotor capacity presents with a si-muttaneous decrease in goat-retated aspectsof overt behavior, thought content, andemotion. This operational definition of DDMleads to a clinical approach for differentiatingbetween DDM and other disorders.

DIFFERENTIAL DIAGNOSIS

Differential diagnosis of DDM depends onthe acuity and severity of the TBI. For se-vere cases, differential diagnosis focuses onTBI complications that produce profoundimpairment in level of consciousness, atten-tion, speech, or motor capacity, for example,vegetative states, delirium and stupor, locked-in syndrome, or quadriparesis. Patients whohave chronic and less severe impairment mustbe evaluated for depression and dementia

Disorders of Diminished Motivation 379

as well as frontal-subcortical syndromes thataffect personality and executive cognitivefunction.

Differential diagnosis requires awarenessthat if DDM are overdiagnosed, reversibleor more readily treated causes of inactivitysuch as stupor or delirium are overlooked.Underdiagnosis leads to premature attemptsat physical rehabilitation or other interven-tions w hose success depends on strong moti-vation. Antidepressant treatment may also fail,not because a reversible mood disorder is ab-sent but because it is overshadowed by a DDMthat requires treatment first.

Patients w ith diminished motivation allshow diminished activity. Inactivity, whethermotor, cognitive, or emotional, may resultfrom changes in virtually any domain of men-tal status. Therefore, differential diagnosisof DDM is simplified by considering thesedifferent aspects of mental status.

There are 2 groups of disorders to distin-guish in differential diagnosis:

1. Those in which diminished activity isactually due to another impairment: Instupor and coma, diminished activityand the appearance of apathy are dueto the diminished level of consciousness.Similarly, a person in a state of detir-ium may show diminished activity butit is primarily a disorder of attention (im-paired ability to establish, shift, or main-tain attention). Aprosodia is a disorderof emotional processing in which theability to understand or express emo-tion is impaired. '^ Aprosodia may be mis-taken for apathy because both may beassociated with truncated emotional re-sponses. Diminished motivation is nota feature of aprosodia, however.' Cata-tonia and psychomotor retardation re-semble DDM because of reduced motorand speech activity. Executive cognitiveimpairments and waxy flexibility may beseen in catatonia. Slowing of thoughtand activity, the essential features of psy-chomotor retardation, occur in manydisorders, including DDM. Therefore,psychomotor retardation should not be

viewed as a pathognomonic feature ofdepression or any other diagnosis.'^'^''Akinesia, though it may be associatedwith apathy, is a disorder of movement,not motivation.

2. Those in which diminished activity isassociated with diminished motivationbut both are due to some other disor-der: Depression is a disorder of mood.By definition, it is a dysphoric state.Negative thoughts about the self, thepresent, and the future (Beck's triad ofdepression) are characteristic. Conse-quently, one suffers from depression.By contrast, one does not suffer fromapathy or other DDM as DDM are notdysphoric states. Although motivationalsymptoms are common in depression,it is dysphoria and negative thoughtcontent that distinguish depression.Demoratization, like depression, isa dysphoric state. Demoralization isdistinguished by a sense of futility,resignation, or powerlessness to realizesome goal that is still desired. Dementiais by definition a disorder of cognition,and cognitive impairments are essentialto diagnosis. Apathy is a common anddisabling aspect of dementia, althoughit is not the defining feature of thesyndrome.

MECHANISM AND CLINICALPATHOGENESIS

The motivational deficits in patients w ithTBI result from complex mechanical andphysiological processes affecting the neuralsystems that mediate motivation. These sys-tems may be affected by gross pathology, suchas contusion and hemorrhage, or by moresubtle changes, such as diffuse axonal injury,hypoxia, and microvascular changes. Neuro-logical dysfunction causing diminished mo-tivation may be approached in anatomical,physiological, and chemical terms. Anatomi-cally, the anterior cingulum (AC), nucleus ac-cumbens (NA), ventral pallidum (VP), medialdorsal nucleus of the thalamus (MD), and the


Prefrontal CortexAnterior Cingulum

Hippocampus

Amygdala

Mediodorsal NucleusofThalamus

Motor Cortex

VentralT Tegmental""vAreas

Basal Ganglia

ReticulospinalTract

PedunculopontineNucleus

Figure 1. Motivational circuitry. The core circuit (shaded) consists of the anterior cingulum, the nucleusaccumbens, the ventral pallidum, and the ventral tegmental area. Nucleus accumbens and the ventralpallidum are divided into (1) more medial portions that are associated with limbic input from the amygdalaand the hippocampus and (2) more lateral portions associated with output circuits. Output is via the motorcortex, the basal ganglia, the reticulospinal tract, and the pedunculopontine nucleus. The amygdala andthe hippocampus, as well as the prefrontal cortex, modulate information in the core circuit on the basisof the current environment and the drive state of the organism. The ventral pallidum output reaches theprefrontal cortex via the mediodorsal nucleus of the thalamus. The current motivational state is representedby the pattern of activity distributed within the core circuit. The flow of information within and throughthe core circuit permits the translation of motivation into action. Adapted with permission from Kalivaset al.2'

ventral tegmental area (VTA) are the mostimportant structures for establishing andmaintaining the current motivational state.The anterior cingulum, NA, VP, and MDcomprise a cortico-striatal-pallidal thalamiccircuit '"^^ thought to mediate motivation(Fig 1). Disruption of this core circuit pro-duces akinetic mutism, abulia, or apathy de-pending on the severity of the dysfunction.''^^Clinical effects of core circuit dysfunction cor-respond to animal research showing that the"initiation and maintenance of behavioral re-sponses" depends on the circuit composed ofNA, VP, and VTA. ' Clinical arguments for in-cluding AC in the core circuit^ are supportedby experimental evidence '*' ' that AC has anessential role to play in motivational aspectsof decision making.

A separate aspect of motivation is mod-ifying the current motivational state onthe basis of the reward value of the cur-rent environment. The reward significanceof the environment is signaled by neuronsin several forebrain regions, including VTA,striatum, ventral striatum, NA, dorsolateraland orbital prefrontal cortex, anterior cingu-late cortex, and amygdala. ^ Modifying thecurrent motivational state depends on theamygdala, the hippocampus, the prefrontalcortex,^' and the greater limbic lobe. ^ Thismay explain why disease states affecting thesestructures present as apathy: if unable to reg-ister changes in the reward significance ofthe environment, the organism will be "ap-athetic" to these stimuli. This formulationmay account for the apathy associated with


hippocampal dysfunction (amnestic disorder,Alzheimer's disease), the apathy and placid-ity seen with amygdala injury (Kluver-Bucysyndrome^^), and the "background of apa-thy and abulia" ^ associated with orbitofrontaldysfunction. Similarly, inability to develop amotivational map of the external environmentis postulated to account for the indifferenceassociated with right hemisphere injury. "

Pathogenesis of TBI symptoms may alsobe understood in terms of the neurochem-istry of the motivational circuitry, for ex-ample, dopaminergic or glutamatergic path-ways. Dopaminergic activity is of particularimportance for motivational deficits becauseof the central role that it plays in reward,novelty seeking, and response to unexpectedevents.'''^^ There is some evidence'^'^' thatdopaminergic activity is affected in TBI.''' Sev-eral other biochemical changes have been de-scribed in TBI, including changes in levels ofglutamate, acetylcholine, neuropeptides, andoxygen-free radicals. Their direct and indirectparticipation in the motivational circuitry pro-vides a rationale for the use of pharmacologi-cal therapies in DDM, including glutamatergicand cholinergic agents.'°

ASSESSMENT

The assessment of patients with diminishedmotivation depends on the etiology of dimin-ished motivation and the interaction of bio-logical, psychosocial, and socioenvironmen-tal factors that control motivated behavior.Table 1 Usts conditions associated with apa-thy, abulia, and akinetic mutism.'''^ The con-ditions that cause akinetic mutism may alsocause abulia and apathy because all 3 mayresult from dysfunction of the AC-NA-VP-MDcircuit mediating motivation. In other w^ords,when less severe, the diseases that causeakinetic mutism cause abulia and apathy. Inaddition, there are many neurological andpsychiatric disorders and psychosocial condi-tions that produce apathy but do not causeabulia and akinetic mutism because the corecircuit structures are spared. The information

given in Table 1 implies that assessment ofpatients with diminished motivation requiresa comprehensive and systematic neuropsychi-atric evaluation, including evaluation of thepatient's social and physical environment.

The psychosocial history will indicate thepatient's baseline level of motivation' andcoping skills' that characterize adult person-ality. It is also important to keep in mindthe enormous variability in individuals' ac-complishments, interests, and goals and theway these are influenced by personal experi-ence, education, social class, culture, and agecohort.

Personal loss, psychological trauma, andphase-of-life events may alter motivation.Occasionally, apathy is the primary symptomof an adjustment disorder, for example, theempty nest syndrome or a retirement reac-tion. Apathy can also be a defense mechanismwhen it is the primary means for dealing withanxiety. The social withdrawal or emotionaldistance seen in Cluster A personality disor-ders may mistakenly be interpreted as neuro-genic motivational loss. Conversely, one canerr by attributing subtle motivation loss toCluster A personality disorder when, in fact,one has encountered the first symptoms ofneurogenic apathy.'

Interactions of medical, psychological, andneurological variables are particularly rele-vant in elderly patients because they of-ten have multiple clinical problems. Manydrugs may alter motivation. Dopaminergicagents, agonists or antagonists, are most famil-iar as mediators of motivational change. Butequally important are serotinergic, choliner-gic, and adrenergic agents because of theirinteraction with dopamine systems. Pharma-cokinetic variables have an independent in-fluence on motivation. For example, thereare case reports suggesting that selectiveserotonin reuptake inhibitors (SSRls) maydispose to apathy."' Furthermore, SSRIs, par-ticularly fluoxetine and paroxetine, are po-tent 2D6 inhibitors. If an irritable patient withTBI is treated with haloperidol and then, be-cause apathy is misdiagnosed as depression,treated with one of these SSRIs, motivation


Table 1. Conditions associated with apathy, abulia, and akinetic mutism

Neurological disorders*Frontal lobe

Frontotemporal dementiaAnterior cerebral artery infarctionTlimorHydrocephalusTrauma

Right hemisphereRight middle cerebral artery infarctionCerebral wrhite matterIschemic white matter diseaseMultiple sclerosisBinswanger's encephalopathyHIV

Basal gangUaParkinson's diseaseHuntington's diseaseProgressive supranuclear palsyCarbon monoxide poisoning

DiencephalonDegeneration or infarction of thalamusWernicke-Korsakoff disease

AmygdalaKluver-Bucy syndrome

Multifocal diseaseAlzheimer's disease (apathy may be

mediated by damage to theprefrontal cortex, the parietalcortex, and the amygdala)

Medical disordersApathetic hyperthyroidismHypothyroidismPseudohypoparathyroidismLyme diseaseChronic fatigue syndromeTestosterone deficiencyDebilitating medical conditions, for example.

malignancy, congestive heart failure, renal or heartfailure

Drug inducedNeuroleptics, especially "typical" neurolepticsSelective serotonin reuptake inhibitorsMarijuana dependenceAmphetamine or cocaine ^thdrawalSocioenvironmental (Jack of reward, loss of

incentive, iack of perceived control)Role changeInstitutionalism

*Akinetic mutism results from bilateral dysfunction ofthe cortico-striatal-pallidal-thalamic circuit, whichconsists of anterior cingulum, nucleus accumbens.ventral pallidum, and mediodorsal nucleus ofthalamus. When improving or less severe, such casespresent as abulia or apathy. Etiology may be vascular.trauma, tumor, degeneration, or toxin (eg, carbonmonoxide poisoning).

may worsen for 2 reasons. The SSRI may in-duce apathy directly and haloperidol-inducedmotor apathy may worsen because the SSRIincreases levels of haloperidol.

Neurological disorders affecting motivationand its neural machinery should direct theclinician's attention to several aspects of theneurological examination. Since frontal anddiencephalic diseases figure prominently indifferential diagnosis of DDM, it is importantto know whether olfactory function, visualacuity, and visual fields are intact. Frontal re-lease signs and paratonic rigidity (gegenhal-ten) are relevant for the same reason.

Extrapyramidal motor signs clarify theevaluation of motor subtypes of DDM. Forexample, chorea, micrographia, loss of asso-

ciated movements, or conjugate eye move-ment abnormalities suggest that dimitiishedmotivation may be due to Huntington'sdisease, Parkinson's disease, or progressivesupranuclear palsy.

Neuropsychological assessment clarifiesthe cognitive context of motivational loss.Executive cognitive assessment may suggestthat lack of activity in one patient reflectsimpairment in sequencing while in another itreflects loss of verbal fluency and initiation.Each will benefit from a different type of"psychological prosthesis."

Clinicians, especially those unfamiliar withDDM, may find it helpful to rate the sever-ity of motivational loss with formal ratingscales. The rating process can familiarize one


with the clinical signs of motivation and itsloss as well as aid differential diagnosis. Forexample, if a clinician is unsure whether apsychomotor-retarded patient is apathetic ordepressed, it may be helpful for the clini-cian to discover that the apathy rating is highwhereas the depression score is unexpectedlylow. This would suggest that the psychomotorretardation is better characterized as bradyki-nesia and akinesia. If so, the next clinical stepmay be to perform a neurological examina-tion and obtain a magnetic resonance image ofthe head rather than to have the patient starttaking an antidepressant.

Several rating methods are available forquantifying loss of motivation. Construct va-lidity is strongest for the Apathy EvaluationScale (AES),' an 18-item scale that can beadministered as a self-rated scale, a care-giver pencil-and-paper test, or a clitiician-rated semistructured inventory (Table 2).'^'^Several articles document the feasibility of rat-ing apathy with the Apathy Scale,''"'^' whichis derived from a preliminary version of theAES. The Children's Motivation Scale," ^ alsoderived from the AES, uses developmentallyappropriate behavioral anchors to permit rat-ing of apathy in children and adolescents. The

Table 2. Apathy Evaluation Scale (clinician version)

Name:.

Rater: _

Date:.

Rate each item on an interview at the subject. The interview should begin with a description ofthe subject's interests, activities, and daily routine. Base your ratings on both verbal and nonverbalinformation. Rating should be based on the past 4 weeks. For each item, ratings should be judged:Not at All Slightly Somewhat A LotCharacteristic Characteristic Characteristic Characteristic(1) (2) (3) (4)

1. She/he is interested in things.2. She/he gets things done during the day.3. Getting things started on his/her own is important to him/her.4. She/he is interested in having new experiences.5. She/he is interested in learning new things.6. She/he puts little effort into anything.7. She/he approaches life with intensity.8. Seeing a job through to the end is important to her/him.9. She/he spends time doing things that interest her/him.

10. Someone has to tell her/him what to do each day.11. She/he is less concerned about her/his problems than she/he

should be.12. She/he has friends.13. Getting together with friends is important to him/her.14. When something good happens, she/he gets excited.15. She/he has an accurate understanding of her/his problems.16. Getting things done during the day is important to her/him.17. She/he has initiative.18. She/he has motivation.

The Apathy Evaluation Scale was developed by Robert S. Marin, MD. Development and validation studies are describedin Marin et al.'^ Scoring instructions and administrations guidelines are available from Robert S. Martin, MD, WesternPsychiatric Institute and Clinic, 3811 O'Hara St, Pittsburgh, PA 15213.

384 JOURNAL OF HEAD TRAUMA REHABILITATION/JULY-AUGUST 2005

Neuropsychiatric Inventory'*' is a multidimen-sional instrument administered to caregivers.It is widely used to assess noncognitive symp-toms of dementia and devotes 1 of 10 itemdomains to apathy.

TREATMENT

The growing interest in DDM is leading tonovel approaches to understand the copingimpairments' or neuropsychological losses^of patients with TBI. These and other newapproaches are likely to lead to new thera-pies for DDM. Psychological and socioenvi-ronmental approaches to DDM apply primar-ily to apathy and abulia. Their relevance toakinetic mutism arises once patients begin torespond to pharmacological therapies.

Some of the psychological treatments arealso appropriate for patients with depression,often because patients with depression aresuffering in part from diminished motivation.The applicability of such psychological ap-proaches to depression and to DDM leadssome to wonder if it is necessary to considerthem for DDM. Actually, these interventionshave a specific role for DDM. Once a cliniciandiagnoses a patient as apathetic and not de-pressed, the question becomes what kind ofpsychological therapies are indicated. If thesetreatments are viewed as treatments for de-pression, the clinician may fail to offer themto the patient with apathy. Clearly, this wouldbe inappropriate.

Treatment of akinetic mutism and abulia isprimarily pharmacological. Patients w ith ap-athy may require pharmacological interven-tions, but the preservation of cognitive andcommunicative capacity calls increasingly forpsychological and social interventions. Suchinterventions are based on careful character-ization of the patient's motivational and neu-ropsychological status. The general principleis to define the patient's losses and resid-ual capacities and then design a "psycho-logical prosthesis" that compensates for thedeficits and makes the best possible use ofresidual abilities. Regardless of severity, treat-

ment must consider the physical and psy-chosocial environment. Modifying the overallenvironment and attending to family and pro-fessional caregivers is an elementary but cru-cial dimension of treatment for DDM.

Preliminary evaluation requires optimizingthe patient's general medical condition. Thismay mean controlling seizures or headaches,arranging physical or cognitive rehabilitationfor cognitive and sensorimotor loss, or en-suring optimal hearing, vision, and speech.These elementary steps also increase motiva-tion because improved physical status may en-hance functional capacity, drive, and energyand thereby increase the patient's expectationthat initiative and effort will be successful.

The aim of environmental interventions isto increase the reward potential of the envi-ronment. Adaptive devices, such as motorizedwheel chairs or voice-activated computers,compensate directly for the sensorimotorand neurological impairments that deny thepatient full benefit of the environment. In im-poverished environments, either at home orinstitutions, it is important to introduce newsources of pleasure, interest, and stimulation.Increasing opportunities for socialization isalso helpful. For many, returning to the fa-miliar personal and physical circumstances oftheir homes may be the fastest way to a health-ier physical or social environment.

General psychological status contributesto motivation in the same way that gen-eral medical condition does. Goal-directedbehavior depends not only on motivationbut also on other state variables: arousal, at-tention, mood, and cognition. Psychologicaltreatments may include a variety of behav-ioral techniques '"''*'* or specialized cogni-tive rehabilitative approaches, for example,enhancing attention or performance speed.''^Psycho-education, vocational counseling, andpsychotherapy should not be overlooked. Psy-chotherapy may focus on injury-related loss,interpersonal problems, or family stressors.

Behavioral interventions should be intro-duced methodically, making clear the tasksand skills required of the patient. Goals shouldbe defined collaboratively to strengthen


engagement and enhance the patient's senseof control and expectation of success. Oncegoals are defined, staff should be careful tofollow through with the treatment plan.

Finally, there is the integration of neuropsy-chological assessment with the treatment ofmotivational loss. Accurate assessment pro-vides the template for developing an individ-ualized plan for psychological treatment. Thetreatment can be thought of as a "psycholog-ical prosthesis" because it is precisely moldedto the pattern of abilities lost and retained as aresult of injury. Thus, for deficits in initiationand perseveration, the psychological prosthe-sis requires the caregiver to prompt the pa-tient when to begin or end a particular task. Ifpatients are able to itiitiate behavior but fail toact because they are unable to sequence, plan,and monitor behavior, their motivational pros-thesis requires the caregiver to tell the patient,"go into the kitchen... now open the refriger-ator door .. . now take out the sour cream onthe top shelf... bring the sour cream into theditiing room ... thank you very much." Herethe motivational prosthesis is a specific sub-stitute for the impairments in planning andsequencing.

Similar psychological prostheses aidDDM patients with other neurobehavioralimpairments. Of particular importance is theassociation of dimitiished motivation with en-vironmental dependency or stimulus-boundbehavior. A bland or unfamiliar environmentwill aggravate this condition because thereis nothing to trigger the "old" behaviors.Families complain, "All he does is sit aroundhere and do nothing." Professional caregiversmay have the same complaint. A variety ofneuropsychological impairments contributeto environmental dependency. For example,the patient may be unable to generate anidea or a goal for behavior. The psychologicalprosthesis in this instance uses the pathologyitself to treat the problem. Instead of tryingto create new habits, the caregiver returnsthe person to an environment that habituallyelicits the desired behavior. In most cases,this means returning the patient home orat least creating an environment that looks

like home, for example, by bringing in familyphotographs or favorite books.

There are 5 steps to pharmacological treat-ment: (1) Optimize medical status. (2) Diag-nose and treat other conditions more specif-ically associated with diminished motivation(eg, apathetic hyperthyroidism, Parkinson'sdisease). (3) Eliminate or reduce doses ofpsychotropics and other agents that aggravatemotivational loss (eg, SSRIs, dopamine an-tagonists). (4) Treat depression efficaciouslywhen both DDM and depression are present.When depression is associated with apathy,consider using more activating antidepres-sants (eg, sertraline, bupropion, venlafaxine).(5) Increase motivation through use of stimu-lants, dopamine agonists, or other agents suchas cholinesterase inhibitors (Table 3). Theseagents have been used for treating a variety ofbehavioral and cognitive impairments in pa-tients with TBI.' "*'' Cholinesterase inhibitors(donepezil, galantamine, rivastigmine) mayalso benefit apathy in TBI. '^•'^'^

With stimulants and dopamine agonists,treatment is initiated with minimal dosesand slowly titrated upward once improve-ment begins. Some patients respond to smalldoses, but when impairment is significantand risk factors few, higher doses should beconsidered.

There is significant and sometimes dra-matic benefit of bromocriptine in abulia andakinetic mutism. " Presumably, other andless toxic dopamine agonists have compara-ble potential. Pramipexole may have someadvantage for DDM because it has selectiv-ity for D3 dopamine receptors that are pref-erentially distributed in the limbic forebrain.All of the dopaminergic drugs dispose tobehavioral toxicity, including psychosis, mo-tor activation and restlessness, sleep distur-bance, and delirium. Caution should be takenwith the stimulants to monitor pulse andblood pressure, although serious problemsare unusual. Amantadine alters both dopamin-ergic and glutamatergic receptors, which mayactually be a clinical advantage'' since DDMare not due otily to lack of dopaminergic activ-ity. In older patients, amantadine dosage must


Table 3. Drugs used in the treatment of apathy, abulia, and akinetic mutism

Agent

StimulantsDextroamphetamineMethylphenidate

Activating antidepressantsBupropionParnateProtriptylineVenlafaxine

Dopamine agonists (selective and mixed)AmantadineBromocriptineSelegilineL-DOPA/carbidopaPergolidePramipexole

Other psychotropicsModafinil (Provigil)Donepezil (Aricept)Galantamine (Reminyl)Rivastigmine (Exelon)

Usual total daily dosage, mg'

20 (5-60)20 (10-60)

200 (100-400)45 (30-90)40 (20-60)

150(100-450)

200 (100-300)10 (5-90)10 (5-4O)t

25/100 TID -25/250 QID2(1-5)

5 TID (0.375-4.5)

200 (100-400)5 (5-10)

8 BID (4-8)3 BID (1.5-6)

'Values in parentheses represent range.t Requires diet low in tyramine, especially at doses above 10 mg; lower doses may produce serotonin syndrome ifadministered with agents that slow selegiline metabolism.

be adjusted to account for decreased creati- glutamatergic agents may prove useful asnine clearance. well.''^

Disorders of diminished motivation asso-ciated with extrapyramidal motor symptoms CONCLUSIONare treated with the same agents, includingamantadine. The goal of treatment is to ma- Motivation is fundamental for adaptive be-nipulate dopaminergic function for the sake havior. The major DDM are apathy, abulia, andof motivation, not just to improve motor abil- akinetic mutism. Depending on their etiology,ity. Overlooking this may compromise out- DDM may be the primary clinical disturbance,come in the end because the benefit of a symptom of some other disorder, or a coex-improved mobility will be undercut by lack of isting second disorder requiring independentmotivation. diagnosis and management. Differential diag-

Newer psychotropic medications may be nosis usually focuses on delirium, dementia,helpful for treating DDM. Modafmil, intro- depression, demoralization, akinesia, catato-duced recently for the treatment of nar- nia, and aprosodia. In recent years, the neuro-colepsy, has stimulating or arousing effects logical model for DDM has been based on thethat may prove usefiil in some patients. cortico-subcortical circtiit involving AC-NA-Modafinil may cause headache and gastroin- VP-MD and tlie modification of current mo-testinal symptoms, but it is relatively free of tivational state by the prefrontal cortex, themajor toxicity. The growing knowledge of amygdala, the hippocampus, and the greaterglutamate systems raises the possibility that limbic lobe. Ctirrent knowledge permits


us to approach assessment and treatment ofDDM on the basis of our understanding ofthese systems. Treatment of DDM includes thefull range of biomedical, psychological, and

socioenvironmental approaches available inneuropsychiatry. By treating DDM, we offerindividuals with TBI a way to improve theirfunctional abilities and quality of life.

REFERENCES

1. Finset A, Andersson S. Coping strategies in pa-tients with acquired brain injury: relationships be-tween coping, apathy, depression and lesion loca-tion. Brain Inj. 2000; 14:887-905.

2. Marsh NV, Kersel DA, Havill JH, Sleigh JW. Caregiverburden at 1 year following severe traumatic brain in-jury. Brain Inj. 1998;12:1045-1059.

3. Marin RS. Apathy and related disorders of dimin-ished motivation. In: Dickstein LJ, Riba MB, Old-ham JM, eds. Review of Psychiatry. Washington, DC:American Psychiatric Press Inc; 1996:205-242.

4. Kant R, Duffy JD, Pivovarnik A. Prevalence of apathyfollowing head injury. Brain Inj. 1998;12:87-92.

5. al Adawi S, Powell JH, Greenwood RJ. Motiva-tional deficits after brain injury: a neuropsycholog-ical approach using new assessment techniques.Neuropsychology. 1998;12:115-124.

6. Mazaux JM, Masson F, Levin HS, Alaoui P, Maurette P,Barat M. Long-term neuropsychological outcome andloss of social autonomy after traumatic brain injury.Arch Phys Med Rehabil. 1997;78:13l6-132O.

7. Giles GM, Clark-Wilson J. The use of behavioral tech-niques in functional skills training after severe braininjury. Arch Phys Med Rehabil. 1988;42:658-665.

8. Andersson S, Gundersen PM, Finset A. Emotional ac-tivation during therapeutic interaction in traumaticbrain injury: effect of apathy, self-awareness, and im-plications for rehabilitation. Brain Inj. 1999; 13:393-404.

9. Dunlop TW, Udvarhelyi GB, Stedem AF, et al.Comparison of patients with and without emo-tional/behavioral deterioration during the first yearafter traumatic brain injury. J Neuropsychiatry CiinNeurosd. 1991;3:15O-156.

10. Atkinson JW, Birch D. An Introduction to Motiva-tion. Princeton, NJ: Van Nostrand; 1978.

11. Jones MR. Introduction. In: Lincoln JM, ed.Nebraska Symposium on Motivation. Lincoln,Neb: University of Nebraska Press; 1955:v-x.

12. American Congress of Rehabilitation Medicine. Rec-ommendations for use of uniform nomenclaturepertinent to patients with severe alterations inconsciousness. Arch Phys Med Rehabil. 1995;76:205-209.

13. Fisher CM. Honored guest presentation: abulia minorvs. agitated behavior. Ciin Neurosurg. 1983;31:9-31.

14. Marin RS. Differential diagnosis of apathy and relateddisorders of diminished motivation. Psychiatr Ann.1997;27:30-33.

15. Mega MS, Cohenour RC. Akinetic mutism: discon-nection of frontal-subcortical circuits. Neuropsy-chiatry Neuropsychol Behav Neurol. 1997; 10:254-259.

16. Campbell JJ III, Duffy JD. Treatment strategies in amo-tivated patients. Psychiatr Ann. 1997;27:44-49.

17. Berrios GE, Gili M. Abulia and impulsiveness revis-ited: a conceptual history. Acta Psychiatr Scand.1995;92:l6l-l67.

18. Ross ED. Affective prosody and the aprosodias. In:Mesulam M-M, ed. Principles of Behavioral and Cog-nitive Neurology. 2nd ed. New York: Oxford Univer-sity Press; 2000:316-331.

19. Benson DE Psychomotor retardation. Neuropsychia-try Neuropsychol Behav Neurol. 1990;3:36-47.

20. Widlocher DJ. Psychomotor retardation: clinical, the-oretical, and psychometric aspects. Psychiatr CiinNorth Am. 1983;6:27-4O.

21. Kalivas PW, Barnes CD. Limbic Motor Circuits andNeuropsychiatry. Boca Raton, Fla: CRC Press; 1993.

22. Marin RS. Apathy: concept, syndrome, neural mecha-nisms, and treatment. Semin Ciin Neuropsychiatry.1996;l:304-3l4.

23. Pierce RC, Kalivas PW. A circuitry model of the ex-pression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res Brain Res Rev.1997;25:192-2l6.

24. Bush G. Cognitive and emotional influences in an-terior cingulate cortex. Trends Cogn Sd. 2OOO;4:215-222.

25. Bush G, Vogt BA, Holmes J, et al. Dorsal anteriorcingulate cortex: a role in reward-based decisionmaking. ProcNatlAcadSd USA. 2002;99:523-528.

26. Schultz W. Multiple reward signals in the brain. NatRev Neurosd. 2000;l:199-207.

27. Heimer L. A new anatomical framework for neu-ropsychiatric disorders and drug abuse. Am JPsychiatry. 2003; 160:1726-1739.

28. Lilly R, Cummings JL, Benson DF, Frankel M. Thehuman Kluver-Bucy syndrome. Neurology. 1983;33:1141-1145.

29. Hecaen H, Albert M. Disorders of mental function-ing related to frontal lobe pathology. In: Benson DF,Blumer D, eds. Psychiatric Aspects of NeurologicalDisease. New York: Grune & Stratton; 1975:137-149.

30. Mesulam M-M. The functional anatomy of hemi-spheric specialization for directed attention. TrendsNeurosd. 1983;6:384-387.

388 JOURNAL OF HEAD TRAUMA REHABIUTATION/^FULY-AUGUST 2005

31. Schultz W. Predictive reward signal of dopamine neu-rons. J Neurophysiol. 1998;80:l-27.

32. Gualtieri CT. Pharmacotherapy and the neurobehav-ioral sequelae of traumatic brain injury. Brain Inj.1988;2:101-129.

33. Levin H, Kraus ME The frontal lobes and trau-matic brain injury. / Neuropsychiatry CiinNeurosd. 1994;6:443-454.

34. Powell JH, al Adawi S, Morgan J, Greenwood RJ.Motivational deficits after brain injury: effects ofbromocriptine in 11 patients. J NeuropsychiatryCiin Neurosd. 1996;60:4l6-421.

35. Stuss DT, van Reckum R, Murphy KJ. Differentia-tion and states and causes of apathy. In: Borod JC,ed. The Neuropsychology of Emotion. New York:Oxford University Press; 2000:340-366.

36. Hoehn-Saric R, Lipsey JR, McLeod DR. Apathy andindifference in patients on fluvoxamine and flu-oxetine. / Ciin Psychopharmacol. 1990;32:672-674.

37. Marin RS. Apathy: a neuropsychiatric syndrome.f Neuropsychiatry Ciin Neurosd. 1991;3:243-254.

38. Marin RS, Biedrzycki RC, Firinciogullari S. Relia-bility and validity of the Apathy Evaluation Scale.Psychiatry Res. 1991;38:l43-l62.

39. Marin RS. Apathy Evaluation Scale. In: Handbook ofPsychiatric Measurements. Washington, DC: Ameri-can Psychiatric Association Press; 2000:409-411.

40. Starkstein SE, Mayberg HS, Preziosi TJ, et al. Re-liability, validity, and clinical correlates of apa-thy in Parkinson's disease. / Neuropsychiatry CiinNeurosd. 1992;4:134-139.

41. Starkstein S, Federoff JP, Price TR, et al. Apathyfollowing cerebrovascular lesions. Stroke. 1993;24:1625-1630.

42. Gerring JP, Freund L, Gerson AC, et al. Psychomet-ric characteristics of the Children's Motivation Scale.Psychiatry Res. 1996;63:205-217.

43. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsy-chiatric Inventory: comprehensive assessment ofpsychopathology in dementia. Neurology. 1994;44:2308-2314.

44. Giles GM, Clark-Wilson J. Brain Injury Rehabili-tation: A Neurofunctional Approach. New York:Chapman & Hall; 1993.

45. Palmese CA, Raskin SA. The rehabilitation of atten-tion in individuals with mild traumatic brain injury,using the APT-II programme. Brain Inj. 2000; 14:535-548.

46. Masanic CA, Bayley MT, VanReekum R, Simard M.Open-label study of donepezil in traumatic brain in-jury. Arch Phys Med Rehabil. 2001 ;7:896-901.

47. Morey CE, Berry CJ, Cusick C. The effect of Ariceptin persons mth persistent memory disorder follow-ing traumatic brain injury: a pilot study. Brain Inj.2003;9:809-815.

48. Kraus MF, Maki PM. Effect of amantadine hydrochlo-ride on symptoms of frontal lobe dysfunction in braininjury: case studies and review. / NeuropsychiatryCiin Neurosd. 1997;9:222-230.

49. Goff DC, CoyleJT. The emerging role of gluatamate inthe pathophysiology and treatment of schizophrenia.Am J Psychiatry. 2001;158:1367-1377.

disorders of diminished motivation - · pdf filedisorders of diminished motivation 379 as well...

Documents