FUNCTIONAL MRI IMPULSIVENESS IMPULSIVENESS IMPULSIVENESS. Tests of cognitive control. Rubia. Katya Rubia. Mapping abnormal brain function.

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1 IMPULSIVENESS Mapping abnormal brain function in the effects of MPH and specificity of abnormality Rubia Dep. Child Psychiatry Institute of Psychiatry : Hyperactivity, Inattention, Impulsiveness (DSM IV) Barrat Impulsivity Scale (BIS): 3 Factors: > Motor activation, < Attention, < Planning IMPULSIVENESS : Hyperactivity, Inattention, Impulsiveness (DSM IV) COGNITION IMPULSIVENESS BEHAVIOUR Barrat Impulsivity Scale (BIS): 3 Factors: > Motor activation, < Attention, < Planning Motor inhibition Cognitive control Attention control Motivational control Timing Poor behavioural inhibition Poor attention, distractibility, novelty seeking Abnormal rewardrelated behaviour Delay aversion, premature acting temporal myopia Tests of cognitive control Motor response inhibition Selective motor response inhibition Withdrawal of a planned motor response Cognitive inhibition Inhibition of interference Inhibition of irrelevant SR associations Motivational control Timing GNG Motor STROOP SWITCH Rewarded CPT Time discrimination MAUDSLEY ATTENTION & RESPONSE SUPPRESSION Task Battery Motor inhibition: Go/nogo, Stop Inhibition of interference: Motor Stroop Cognitive flexibility: Switch Motivational control: Rewarded CPT Time estimation: Time discrimination K X H U I O L

2 MAPPG COGNITIVE (DYS)FUNCTIONS Strategy MARS ONLE FUNCTIONAL MRI NEUROPSYCHOLOGY FMRI OFFLE Specificity of cognitive dysfunctions by comparing mental disorders Cognitive impairment in offline MARS N = 35 /GNG STROOP N = 54 DEP AN N = 35 N = 25 N = 35 SWITCH CPT TE IMPULSIVENESS PSYCHIATRY Borderline Personality Disorder (BPD) Tourette s syndrome (TS) Mania/bipolar Psychopathy Substance abuse Eating disorder (Bulimia) Neural substrates of cognitive control Typical development Children (27) Adults (30) age: 918 Atypical development + MP Depression REW Abnormal development: NeuroNeurodevelopmental psychopathology age: DEP N = 23; C = 28; m, age 918 (13) + MP N = 10, m, age 918 (13) N = 10; C = 28; m; age 918 (13) N = 10; C = 10; m; age 1216 (13) DEP N = 15; C = 10; f +m; 1318 (16) Current findings on brain abnormalities

3 Why is medicationnaivety naivety important? Animal studies: longterm effect of MPH on DA function (DAT ) in FL and BG (Moll et al., 2001, Sproson et al., 2001) Human studies: longterm effect on DA function & metabolism in FL and BG/THAL after chronic stimulant abuse Dep. ( Volkow et al., 2001, Sekine et al., 2003) of Child Psychiatry Effect of Methylphenidate on brain in Health: DAT (50%) DA in striatum (Volkow et al., 2001, 2002, 2003, 2004) in DAT density or binding in () (Cheon et al., 2002, Dougherty et al., 2000, Vles et al., 2003, Krause et al., 2000, Dresel et al., 2000), n.s. (van Dyck et al., 2002, Jucaite et al., 2005) D2 downregulation (Vles et al., 2003). n.s. (Jucaite et al., 2005) FL, BG perfusion SMCx (PET/SPECT: Kim et al., 2001; ROI, Lou et al., 1984, 1989) FL, BG activation (fmri: Vaidya et al., 1998) Vaidya et al., 1998 (GNG) Proc. Nat. Acad. Sci. USA N = 10 80% TASK Press left 20% Press right Inhibit Resulting in: Inhibit Rubia et al., 2003, NI. 50% successful stop trials 50% unsuccessful stop trials IFC C > n.s. IFC Rubia et al., AJP, 2005

4 Effect of MP on Failed MPH Caud/GP/Put/Thal ACC MPH > Plac Put/Caud/Thal Rubia et al., AJP, 2005 Failed Failed Effect of MP on MPH C > MPH > Plac n.s. motor STROOP TASK STROOP Congruent (88%) Press to where arrows point DLPFC, IFC PC, PL Incongruent (12%) Press to where arrows point IFL, PC, PL, TL = C

5 STROOP STROOP Effect of MP on C > n.s. FUNCTIONAL n.s. MRI OFL TL M MP > Plac Cb ACC PCC SWITCH TASK Switch Meiran Switch task: Cognitive flexibility; Switching between spatial dimensions. IFC/S ACC/S Smith et al., 2004, HBM. Smith et al., AJP, 2005 SWITCH TIME DISCRIMIMATION Block design C > press left or right E: Which circle lasts longer on screen? B: Which circle came first? Differences: 20x 1300, 1400, 1500ms. Smith et al., NI, 2003.

6 Rubia et al., 1999 TD REWARDED CPT Effect of MP on respond to X and O (20%). REWARD Effect of MP on OFC > C Caud/Put/Thal > C MPH OFC MPH > Plac Cb Linear agecorrelation in taskspecific frontostriatal brain regions during cognitive control functions Conclusions Patients with neurodevelopmental psychiatric disorders show disorderspecific underactivation: : in agecorrelated PF areas (maturational delay) : in predom. OFC Depression: in predom. DLPFC and caudate/thalamus : in only 2 tasks in TL. MP in increases PFC + ACC + BG + Cb => areas of rich DA innervation and of impairment in Child Psychiatry Anna Smith Rozmin Halari Eric Taylor Majeed Mohammad Isobel Heyman Stephen Scott Mima Simik Brain Image Analysis Unit Mick Brammer