Daños al medio ambiente a causa de la minería ilegal

Healthy aging brings about many changes in cognition (Cabeza et al., 2004) reflected in altered structure, function and biochemistry (Marschner et al., 2005; Alichniewicz et al., 2013) that generally cause slowing of cognitive performance (Der and Deary, 2006; Verhaeghen and Salthouse, 1997). Specific mechanisms of cognitive aging and their impacts upon impulsivity and decision-making are uncertain (Brown and Ridderinkhof, 2009; Deary et al., 2009; Mohr et al., 2010) but age-related decrements in performance on a variety of attention-related tasks, including sustained attention, selective attention, and inhibition tasks have been shown (Heuninckx et al., 2005; Mani et al., 2005; Wu and Hallett, 2005; Voelcker-Rehage and Alberts, 2007). These changes have led to the development of a “frontal aging hypothesis” (Isella et al., 2008), driven by dopaminergic (and serotonergic) changes in the aging brain accompanied by structural change in the striatum and prefrontal cortex (PFC, (Marschner et al., 2005)). Some experiments demonstrate that risk-taking behaviour in healthy volunteers changes with age (Deakin et al., 2004) and that the ability to make profitable choices declines in some older people (Denburg et al., 2005, 2007). Increased risk aversion can appear to specifically contribute to poorer decision-making (Boyle et al., 2012), but may otherwise reflect a more global cognitive decline (Albert and Duffy, 2012). Both increased risk seeking and risk aversion are found in older adults, depending upon the task design employed (Mather et al., 2012).

1.6.1

Age alters dopaminergic function in frontostriatal circuitry,

leading to changes in reward-motivated behaviours

Theories of declining cognition implicate reduced dopaminergic activity in frontostriatal networks with age (Bäckman et al., 2006, 2010; Erixon-Lindroth et al., 2005; Kaasinen and Rinne, 2002; Kaasinen et al., 2000; Klostermann et al., 2012; Li et al., 2010). One proposed mechanism for the “rise and fall” in optimal decision making ability with age is that the development of dopaminergic frontal inhibitory control (particularly by the PFC) which occurs during

adolescence is selectively impaired by the aging process (Braver et al., 2001). Younger subjects tend to outperform older ones in tasks requiring a high degree of frontal cortical activity. However, there is evidence that older subjects recruit other brain regions to replace these age- related frontal deficiencies (Park et al., 2001). Interpretation is not straightforward: younger subjects may use different strengths (e.g. learning and memory) to older subjects (who may more accurately represent valence) in order to achieve similar task outcomes (Wood et al., 2005). Apparent decision-making differences may be attributed changes in processing speed and memory rather than changes in risk/reward sensitivity (Henninger et al., 2010) and some authors report age-related changes in bias-susceptibility rather than decision-making ability per se (Kovalchik et al., 2005).

In a study of probabilistic reward-based stimulus association tasks, the older group showed poorer overall acquisition and impaired reversal learning (Weiler et al., 2008). Older subjects also required greater reward magnitudes to exhibit steep learning curves. There is increasing evidence that specific frontal D2 and D3 dopaminergic degeneration leads to these changes in reward sensitivity (Volkow et al., 1996, 2000; Kaasinen et al., 2000). Functional imaging during a slot machine task demonstrated a correlation between midbrain dopamine synthesis and reward-related pre-frontal activity (Dreher et al., 2008). There was an age-related change in the direction of the relationship, from a positive to a negative correlation. Furthermore, dopamine (L-dopa) has been shown to restore reward prediction errors to youthful levels in healthy older volunteers (Chowdhury et al., 2013). Recent experiments suggest that there are age-related differences in fronto-striatal representations of prediction errors as opposed to reward outcome (Samanez-Larkin et al., 2014).

There is also evidence for specific subcortical differences in aging and reward. Using a Go/Nogo task, correlations between MRI volumetric measures in the caudate and putamen/globus pallidus (PGp) and age have been demonstrated (Langenecker et al., 2007). Multiple task performance measures correlated with activation in the left PGp, thereby implicating this structure in mediating age related task performance differences. Similarly, in another response inhibition task (Coxon et al., 2012), functional anisotropy demonstrated that cortico-subthalamic (preSMA-STN) connection strength predicted stopping performance, thereby linking an age- related decline in in inhibitory control with structural decline in STN projections.

1.6.2

Are older people more or less impulsive or just apathetic?

Poorer IGT and antisaccade task performance suggests that frontostriatal networks work less effectively in older people (Olincy et al., 1997; Butler et al., 1999; Fein et al., 2007) and implicates aging of this system (Raemaekers et al., 2006) in the impaired inhibition of action (Sweeney et al., 2001). Conversely, improving antisaccade task performance is attributed to frontal lobe development during adolescence (Munoz et al., 1998). As a result, older adults are more susceptible to oculomotor capture and exhibit deficient selective suppression of the responses captured by the task irrelevant distracters in a saccadic task (Ridderinkhof and Wijnen, 2011). These changes in frontal executive function would lead us to expect impulsivity to increase with age. However, a study in older people found that “stimulation seeking” decreased with age

(Giambra et al., 1992). Age-related reductions in delay discounting have also been related to lower ventral striatal activations to immediate reward using fMRI (Eppinger et al., 2012).

Reaction time studies demonstrate that older subjects have a preference for accuracy over speed (Rabbitt, 1979; Welford, 1988; Smith and Brewer, 1995). Behavioural task success requires anticipation of actions that need to be executed - a capacity that specifically appears to be negatively affected by aging (Falkenstein et al., 2006; Roggeveen et al., 2007; Sterr and Dean, 2008). This may be, in part, due to changes in motivation. Apathy is common in aging and manifests as lack of interest and initiative, and emotional blunting (Ishii et al., 2009; Brodaty et al., 2010; Esposito et al., 2014). Nevertheless, there is an association with cognitive impairment (Starkstein et al., 2006; Onyike et al., 2007) which suggests that apathy should not always be considered a ‘normal’ part of aging. Moreover, a recent study suggests that, rather than apathy, age may cause a specific deficit in the acquisition of goal-directed action (Wit et al., 2014).

1.6.3

Age affects saccadic performance

Though robust compared to other motor measures (Pratt et al., 2006), SRT increases above 50 years of age (Irving et al., 2006; Pitt and Rawles, 2009) with an associated increase in variability in latency (Abel and Douglas, 2007), reduced velocity and accuracy (Schik et al., 2000; Sharpe and Zackon, 2009). Older participants are more susceptible to saccade disruption than young adults (Gottlob et al., 2007) and exhibit more hypometric and multi-step saccades (Litvinova et al., 2011), rendering their responses less reliable. Voluntary (as opposed to reflexive) saccades seem particularly vulnerable to the effects of age (Peltsch et al., 2011). A “global slowing” phenomenon (Golob et al., 2009) is manifest in differences in “gap” effect saccade latency benefit (Pratt et al., 1997): Though the absolute benefit is reduced in older people, it is of a similar proportion of the saccade latency when compared with younger individuals suggesting that though overall processing is slowed, the fundamental mechanisms of saccade production/inhibition are intact.

In Chapter 2, I introduce a novel, rewarded oculomotor task in which subjects must make speeded oculomotor decisions under risk for reward. I compare the performance of young healthy volunteers with an older group. This older group later serves as an age-matched control group for patients with Parkinson’s Disease.

1.7 Parkinson’s Disease is associated with apathy and