Disorders of Motivation

Prof. Sanjay Manohar

Nuffield Department of Clinical Neurosciences Department of Psychology University of Oxford Disorders of motivation Too much, too little,

Impulsivity Apathy

Akinetic mutism Fatigue Alien limb Split brain Dyskinesias Utilisation behaviour Functional disorders Impulse control disorders Abnormal urge or impulse, interfering with normal life

Pathological Gambling Compulsive Shopping Sexual Compulsion Dopamine Dysregulation Disorder

Punding Kleptomania, pyromania, trichotillomania, Impulse control disorders Common and disabling

14% of PD patients on D2 agonists May be subtle, not always picked up

Proposed Mechanisms • Increased reward sensitivity • Reduced sensitivity to risk / uncertainty • Novelty-seeking • Steeper temporal discounting / cost of time • Disinhibition • Less ‘reflection’ or desire for information Impulse control disorders How often do they select the more probable colour? Abnormal gambling task behaviour How much do they then bet? Amount increases or decreases during the response period

Cools et al. Neuropsychologia 2003; Clark et al. Brain 2008 Are ICDs a consequence of disinhibition?

Stop signal

Stroop Haylings ON minus OFF RT for DBS Patients with PD have to STN vs ventral impaired suppression of intermediate thalamus prepotent responses in Stop Choice RT and SSRT much signal, Stroop and Haylings prolonged A/B Van den Wildenberg et al. JoCN 2006 Impulsivity is related to time Time is more costly?

Steeper temporal discounting rate in PD with ICDs

Voon et al Psychopharmacology 2012 Reflection impulsivity PD ICD and substance abusers desire less information before choice

Blue or green beads drawn from an urn Guess the majority colour

Djamshidian et al. Mov Dis 2012 Clinical Apathy Amotivation

Diagnostic criteria Diminished motivation in comparison to previous level of function, which is not consistent with age or culture.

PLUS one of: diminished • goal-directed behaviour • goal-directed cognitive activity • emotion Clinically significant impairment (personal, social, occupational) Not explained by physical / motor disabilities or direct physiological effects of a drug

Robert et al. (2009) European Apathy and Depression Distinct but overlapping syndromes

Emotional symptoms Apathetic symptoms Overlap of depression

Pagonabarraga et al Lancet Neurol 2015 Clinical Apathy Mechanisms only studied recently

Neuroeconomic approaches Postulated mechanisms • Higher effort cost • Lower reward sensitivity •Inability to generate options • Failure of internally-guided movement

Pagonabarraga et al Lancet Neurol 2015 Rodents: Effort costs increased by

Ventral striatal dopamine depletion Medial frontal lesions

Pre-lesion Post-lesion Salamone 1994/2012 Walton 2002/2006 Motivation and mesolimbic dopamine

insula Wanting (Instrumental) Liking (Hedonic)

cingulate

OFC

accumbens VTA

Kringelbach & Berridge 2012 Role of dopamine release

Tonic Phasic Dorsal Willingness to exert effort Reward prediction error Chunking action Motor invigoration Cue value learning Habit formation Stress response Aversive / penalty Working memory Perceptual salience Zweifel et al. PNAS 2009 mesolimbic DA serves as a bridge that “ enables animals to traverse the psychological distance that separates them from goal objects or events ” Salamone & Correa 2012

a general property of a specific function? neural processing? • Goal-directed OR • Energisation • Localised • Chemical Dopamine vs. Noradrenaline in Reward- effort task

Decision time: DA = Reward – Effort NA = Reward

Action time: NA = Effort

Varazzanni…Bouret et al. 2015 Many diseases cause apathy A final common pathway?

• Depression AD • PD •TBI Stroke% • Vascular Dementia 0204060 •FTD, HD, CBD, PSP Apathy Both Depression Neuro- Kirsch-Darrow et al. 2006 degenerative Benoigt et al. J Alz D 2012 Acquired brain injury

Psychiatric

16 Kos et al. 2016 (Neurosci Biobeh Rev) AD

Healthy MCI Mild AD Mod-Sev AD 2% 39% 51% 72%

Holthoff Biol Psych 2005 Apostolova et al.,2007 Devos et al (2013) JNNP

101 cases screened 31 cases eligible

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But not in AD

Sepehry et al. 2017 Management of Apathy Holistic, multi-faceted approach

•Quantify • Psychosocial and biological contributors • Sleep, mood, drugs, pain. Patient Information. • Neuropsychology • Concurrent depression

• Dopamine agonists •Cholinesterase inhibitors Reduced reward sensitivity in post-stroke apathy In a monetary incentive delay task

Apathetic patients with lesions to basal ganglia show reduced effects of monetary incentive

Reward probability Rochat et al. Neurology 2013 Apathy in healthy people Measured by questionnaires and effort-sensitivity tasks

Higher effort costs in apathy Reduced willingness to squeeze a gripper for money

Lower anterior cingulum bundle integrity in apathy (Fractional anisotropy correlates negatively with apathy score)

21 Bonnelle et al (2015) Cerebral Cortex Akinetic mutism “Autoactivation deficit”

Bilateral medial frontal damage SMA, preSMA, cingulate

callosum / cingulate white matter

Nemeth et al 1988 Assorted terms for Amotivation Not always considered distinct

Akrasia

Apathy Akinetic mutism

Autoactivation deficit

Anergia Athymhormia Dimensions of apathy

“behavioural apathy” autoactivation deficit

“cognitive apathy”

“emotional apathy”

Marin 1991 Robert…Starkstein 2009 Fatigue A feeling of low energy levels

Heightened sense of effort High effort cost Very common after stroke, inflammation, infection, and in all chronic diseases

“Ego depletion” account State vs trait fatigue – fatiguability Kuppuswamy, Brain 2017 What is Chronic Fatigue Syndrome (previously Myalgic Encephalomyelitis)? • Does it exist? • Is it organic (i.e. have a biological rather than psychological cause)? • Attention to somatic feedback; Bias in interpreting information •“Illness behaviour” Alien Limb Syndrome Limb “has a mind of its own”

Anarchic hand vs asomatognosia Penfield: complex movements elicited from frontal cortex • Stimulation of PMC – “my hand just moved” • Stimulation of SMA – “I felt the urge to move” TMS – similar effects Alien limb is modulated by context

Moro, Pernigo, Scandola, Aglioti Neuropsychologia 2015 Split brain Right hemisphere can’t combine meanings of sequential words

Gazzaniga Split brain Visual word match: right hemisphere. Picture match: left hemisphere

Levy and Trevarthen, Brain 1977 Split brain Confabulation – what motivated behaviour? Dyskinesia Abnormal involuntary movements

Chorea – complex, dance-like • Huntington’s Chorea, Sydenham’s Chorea • Degeneration of striatal GABAergic neurons Hemiballismus • Unilateral flinging twisting movements • Lesions to subthalamic nucleus (inhibitory area in basal ganglia) Dystonia • Stiffness and abnormal posture Akathisia A sense of inner restlessness

Very unpleasant, disabling A few weeks after dopamine D2 agonist withdrawal in PD Drug side effect of D2 blockade in Schizophrenia Patients have to rock, march on the spot, fidget, pace about Restless legs syndrome – akathisia localised to legs? Altered agency Movements may arise through many non-volitional routes

Obsessions vs compulsions OCD – anxiety; neurosis Compulsion: experience as “desire causes action” Stereotypies

Hypnotic suggestibility cf. Cognitive dissonance / “Choice blindness” e.g. Wilson & Nisbett 1978

Made acts, delusions, depersonalisation, derealisation (Schizophrenia) Tourette syndrome Urges and habits

Tics • Stereotyped voluntary movements • Preceded by an urge • Result in satisfaction / quench the urge Coprolalia Utilisation behaviour A profound form of disinhibition?

Bilateral medial frontal lesions Unaware and unable to apply context-governed control Affordance-driven behaviour Use objects in an ‘overlearned’ manner, rather than following task instructions Utilisation behaviour More than just competition from affordances

Cup on left or right “Reach with nearest hand” Interference when handle conflicted. “Reach with hand nearest handle”, target central Distractors captured action irrespective of compatibility

Humphreys and Riddoch EBR 2000 Functional Neurological Disorders Borderline between neurology and psychiatry

Hysterical / Psychogenic / Conversion disorder • Neurological symptoms with normal neural function • Fluctuate, distractible, • Not “faked” • Triggered by emotional stress, anxiety • Often history of (repressed) major mental trauma eg. in childhood

• Can be paralysis, abnormal movement or seizures, speech disturbance, or sensations •Hard to treat Opposite: Munchausen syndrome •Patient fully aware • Secondary gain

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