La pupila como marcador atencional en TDAH

Transcription

1 La pupila como marcador atencional en TDAH Tomás Ossandón, PhD Laboratory of Cognitive Neuroscience Department of Psychiatry - Medical School Universidad Católica de Chile

2 Corbetta et al, 2008 Attention-demanding goal directed behavior is mediated not only by distributed patterns of cerebral

3 Mantini et al, 2007 Spontaneous activity in the resting awake or anesthetized brain, is organized in multiple highly specific functional anatomical networks, called resting state networks

4 Dorsal attention network: Ventral attention network: Default mode network: top-down or executive control (DLPFC, IPS, FEF) reorientation or network reset (MFG, TPJ, VLPFC) deactivated during goal-directed behaviors and activated at rest (MPFC, PCC)

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10 Brain function largely determined by extrinsic/evoked activity Brain function largely determined by intrinsic/spontaneous activity Callard & Margulies, 2011 Sherrington (1906) T.G. Brown (1911) - the brain is primarily reflexive, driven by the momentary demands of the environment - brain s operations are mainly intrinsic involving the acquisition and maintenance of information for interpreting, responding to, and even predicting environmenta demands the nervous system is composed by an intrinsic activity, with a rhythmicity that is disturbed by the reflex system Brown, 1911

11 Brain function largely determined by extrinsic/evoked activity Brain function largely determined by intrinsic/spontaneous activity Callard & Margulies, 2011 Sherrington (1906) T.G. Brown (1911) - the brain is primarily reflexive, driven by the momentary demands of the environment - brain s operations are mainly intrinsic, involving the acquisition and maintenance of information for interpreting, responding to, and even predicting environmental demands the nervous system is composed by an intrinsic activity, with a rhythmicity that is disturbed by the reflex system Brown, 1911

12 spatial resolution temporal resolution min

13 Ossandon et al, 2011 Buckner & Carroll, 2007

14 GBD and behavior, single-trial

15 GBA (FDR corrected), 3200 recording sites across 25 patients

16 Francisco Aboitiz Laboratory of Cognitive Neuroscience Department of Psychiatry - Medical School Universidad Católica de Chile

17 Attention deficit/hyperactivity disorder (ADHD) - Is a highly prevalent neurodevelopmental condition, - inattention and impulsivity/hyperactivity. - Symptoms persist into adulthood in a majority of patients - Increased risk of depression, substance abuse, and antisocial behavior

18 NA-DA reuptake inhibitor (NDRI) NA reuptake inhibitor

19 gender and ontogenetic distribution Centers for Disease Control and Prevention, 2013, USA the prevalence in male is 4 times than females (in USA)

20 Centers for Disease Control and Prevention, 2013, USA Germany: 4.8 % of the children and adolescents altogether (B: 7.7 %, G: 1.8 %). The prevalence of ADHD in Chile is 10 %*, and the most prevalent subtype is the hyperactive/impulsive, with no gender differences hought to be a result of selective pressures on migratory behaviors. Very adaptive then, but not in our (almost

21 A real problem in over diagnosis in some countries (Chile?)

22 Centers for Disease Control and Prevention, 2013, USA Reported prevalence rates may also be affected by population characteristics; methodological, environmental

23 ADHD -Compromised executive function: visuo-spatial working memory -Attention is compromised by distraction

24 Ossandón et al, in prep - EEG recordings were obtained from 50 children (25 ADHD, combined subtype DSM- IV criteria, mean age years) using a 40-channel Neuroscan EEG system. - All ADHD children were being treated with methylphenidate, but suspended medication 24 h prior to the study. - A subgroup of 20 ADHD patients with medication performed the task in a second session (madhd) - Eye movements were recorded with an eye-tracker (Eye-link 1000, SR Research) at 1000 Hz SR.

25 pupil response Szabadi, 2012 The locus coeruleus is located in the posterior area of the rostral pons. LC is the principal site for brain synthesis of norepinephrine (noradrenaline)

26 performance Aston-Jones G, et al, 2000 LC activity LC neurons exhibit both tonic and phasic activity modes, Tonic activity is: -low in an unaroused (non-alert) state that facilitates sleep and disengagement from the environment (Aston-Jones and Bloom, 1981; Rajkowski et al., 1994) - moderate when the organism is engaged in a focused task of high utility and filters out irrelevant stimuli (Usher et al., 1999) -and high when the organism is exploring the environment, and there is uncertainty concerning the proper relationship between stimuli and responses (Aston-Jones et al., 1997) (i.e., unexpected uncertainty)

27 adapted from Ahern & Beatty, 1979 Psychophysiology, 51, 2014

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30 Ossandón et al, in prep Ossandón et al, in prep

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34 r = , p < 0.001, n = 67 r = 0.659, p < 0.001, n = 67 r = , p < 0,001, n = 67

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37 Aboitiz, Ossandon et al, goal-directed behavior is not only related with the executive control of dorsal brain regions -dysregulation between phasic and tonic cathecolamionergic responses could explain better this disorder

38 Purper-Ouakil et al, 2011 therapeutic effects of DA stimulation is thought to involve a weakening of inappropriate network connections (i.e.

39 Summary - Pupil diameter (PD) was strongly modulated by the task: Only in controls and madhd there is a strong temporal relation between the peak of the PD and the appearance of the probe. - It is possible to modulate the tonic PD response with the treatment in most of the patients - This is the first direct evidence, to the best of our knowledge, of a treatment modulation in ADHD of the LC-NE systems during a high-level attentional task, that could serve as a substrate both for further basic research and putative clinical and diagnostic applications further basic research and putative clinical and diagnostic applications

40 acknowledgements JP Lachaux (Lyon), K Jerbi (Montreal), JR Vidal (Grenoble) Sarang Dalal (Konztanz), Carlos Hamamé (Marseille), Philippe Kahane, Marcela Perrone (Grenoble) Fco. Aboitz, Pablo Billeke, Fco. Zamorano, Gabriel Wainstein, Fco. Valenzuela, Ximena Carrasco, Patricia Opazo, Juan Pablo Ramirez, Daniel Rojas (Chile) Anillo ACT1414, Fondecyt , HBP

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45 Ossandon et al, 2012

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47 Ossandón et al, 2011, 2012

48 Sherrington (1906) T.G. Brown (1911) - the brain is primarily reflexive, driven by the momentary demands of the environment - brain s operations are mainly intrinsic, involving the acquisition and maintenance of information for interpreting, responding to, and even predicting environmental demands the nervous system is composed by an intrinsic activity, with a rhythmicity that is disturbed by the reflex system Brown, 1911

49 Sherrington (1906) T.G. Brown (1911) - the brain is primarily reflexive, driven by the momentary demands of the environment - brain s operations are mainly intrinsic, involving the acquisition and maintenance of information for interpreting, responding to, and even predicting environmental demands Brain implicitly inactive in absence of environmental stimulus Rest implicitly assumed to be more restful than non-rest Brain always active irrespective of environmental stimulus Rest refigured into active psychological states

50 Sherrington (1906) T.G. Brown (1911) - the brain is primarily reflexive, driven by the momentary demands of the environment - brain s operations are mainly intrinsic, involving the acquisition and maintenance of information for interpreting, responding to, and even predicting environmental demands Brain implicitly inactive in absence of environmental stimulus Rest implicitly assumed to be more restful than non-rest Brain always active irrespective of environmental stimulus Rest refigured into active psychological states

51 Nodes of the normal DTI network in anatomical space; the size of each node is proportional to its degree Crossley NA et al, 2014 hly connected hub nodes that are functionally relevants, because their topological centrality s