Effect of methylphenidate on visual responses in the superior colliculus in the anaesthetised rat: Role of cortical activation

Hetherington, L; Dommett, Eleanor J.; Turner, Amy; Riley, Timothy B.; Haensel, Jennifer X.; Overton, Paul G.

doi:10.1177/0269881117730661

“…In line with previous studies, we recorded complex LFP responses in the superficial layers of the SC in response to whole-field light flashes (Clements et al, 2014;Dyer and Annau, 1977;Gowan et al, 2008). The response parameters in the vehicle-treated control group were consistent with previous work in drug-naïve dark-adapted rats for both latencies (Dyer and Annau, 1977;Hetherington et al, 2017) and peak-to-peak amplitude (Clements et al, 2014).…”

Section: Discussionsupporting

confidence: 86%

“…This is also in line with previous work showing that a reduction in dopamine causes an increase in visual responses (Rolland et al, 2013), such that amphetamine, by increasing dopamine levels would suppress activity. Indeed, we have previously hypothesized that one mechanism of action of amphetamine in conditions such as ADHD, where it reduces distractibility, may be to suppress collicular activity (Brace et al, 2015a;Clements et al, 2014;Hetherington et al, 2017;Overton, 2008). If this were to be the case, the upregulation of synaptophysin could be a neuroadaptation to moderate the impact of amphetamine on collicular output.…”

Section: Discussionmentioning

confidence: 99%

Chronic amphetamine enhances visual input to and suppresses visual output from the superior colliculus in withdrawal

Turner

¹

,

Kraev

²

,

Stewart

³

et al. 2018

Neuropharmacology

1

0

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Heightened distractibility is a core symptom of Attention Deficit Hyperactivity Disorder (ADHD). Effective treatment is normally with chronic orally administered psychostimulants including amphetamine. Treatment prevents worsening of symptoms but the site of therapeutic processes, and their nature, is unknown. Mounting evidence suggests that the superior colliculus (SC) is a key substrate in distractibility and a therapeutic target, so we assessed whether therapeutically-relevant changes are induced in this structure by chronic oral amphetamine. We hypothesized that amphetamine would alter visual responses and morphological measures. Six-week old healthy male rats were treated with oral amphetamine (2, 5 or 10 mg/kg) or a vehicle for one month after which local field potential and multiunit recordings were made from the superficial layers of the SC in response to whole-field light flashes in withdrawal. Rapid Golgi staining was also used to assess dendritic spines, and synaptophysin staining was used to assess synaptic integrity. Chronic amphetamine increased local field potential responses at higher doses, and increased synaptophysin expression, suggesting enhanced visual input involving presynaptic remodelling. No comparable increases in multiunit activity were found suggesting amphetamine suppresses collicular output activity, counterbalancing the increased input. We also report, for the first time, five different dendritic spine types in the superficial layers and show these to be unaffected by amphetamine, indicating that suppression does not involve gross postsynaptic structural alterations. In conclusion, we suggest that amphetamine produces changes at the collicular level that potentially stabilise the structure and may prevent the worsening of symptoms in disorders like ADHD.

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“…Using simple rather than high-level cognitive stimuli has the advantage that they can be used in parallel human and animal studies. Studies on mouse [103,104] and rat [105] models of ADHD will provide further insight into the neural circuits implicated in ADHD and how medications can alter these circuits [106,107].…”

Section: Possible Lower-level Neural Correlates Of Behavioral Variabimentioning

confidence: 99%

A low-level perceptual correlate of behavioral and clinical deficits in ADHD

Mihali

¹

,

Young

²

,

Adler

³

et al. 2017

Preprint

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In many studies of attention-deficit hyperactivity disorder (ADHD), stimulus encoding and processing (perceptual function) and response selection (executive function) have been intertwined. To dissociate these functions, we introduced a task that parametrically varied low-level stimulus features (orientation and color) for fine-grained analysis of perceptual function, and that also required participants to switch their attention between feature dimensions on a trial-by-trial basis, thus taxing executive processes. Our response paradigm captured task-irrelevant motor output (TIMO), reflecting failures to use the correct stimulus-response rule. ADHD patients had substantially worse perceptual function than Controls, especially for orientation. ADHD participants had also higher TIMO; this measure was strongly affected by the switch manipulation. Across participants, the perceptual variability parameter was correlated with TIMO, suggesting that perceptual deficits could underlie executive function deficits. Based on perceptual variability alone, we were able to classify participants into ADHD and Controls with a mean accuracy of about 77%. Participants' self-reported General Executive Composite score correlated not only with TIMO but also with the perceptual variability parameter. Our results highlight the role of perceptual deficits in ADHD and the usefulness of computational modeling of behavior in dissociating perceptual from executive processes.In Attention Deficit Hyperactivity Disorder (ADHD), self-reported behavioral deficits have been attributed to differences in executive function, attention, and perceptual function. These brain functions can be objectively quantified with behavioral paradigms, but the individual components are often not well separated. ADHD patients tend to have worse executive function than Controls according to several metrics [1][2][3][4], predominantly in response execution and inhibition [5][6][7], but also in switching between stimulus-response rules [8][9][10][11]. It has been pointed out that non-executive processes, such as alertness, accumulation of evidence or drift rate, motivation, or reward processing, might interact with executive ones [12][13][14][15][16]. In the realm of visual attention, differences in accuracy or reaction time have been found in some visual search tasks but not in others [17,18], and no consistent deficits have been found in visuo-spatial orienting [19][20][21][22]. Despite evidence of impaired perceptual function in ADHD from psychiatric assessments [23,24], behavioral studies that examined the quality of perceptual encoding in ADHD in the absence of executive or attentional involvement found small and inconsistent differences (see [25] for a review). There have been attempts to dissociate executive from perceptual function in ADHD within a single task, but the results have been mixed [26][27][28][29]. One complicating factor could be that commonly used stimuli such as faces, letters, or numbers are high-dimensional and have content at many levels. Anot...

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“…Using simple rather than high-level cognitive stimuli has the advantage that they can be used in parallel human and animal studies. Studies on animal models of ADHD, such as mouse (Leo & Gainetdinov, 2013 ; Majdak et al, 2016 ) and rat (Clements, Devonshire, Reynolds, & Overton, 2014 ), will provide further insight into the neural circuits implicated in ADHD and how medications can alter these circuits (Hetherington et al, 2017 ; Mueller, Hong, Shepard, & Moore, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

A Low-Level Perceptual Correlate of Behavioral and Clinical Deficits in ADHD

Mihali¹,

Young²,

Adler³

et al. 2018

Computational Psychiatry

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In many studies of attention-deficit hyperactivity disorder (ADHD), stimulus encoding and processing (perceptual function) and response selection (executive function) have been intertwined. To dissociate deficits in these functions, we introduced a task that parametrically varied low-level stimulus features (orientation and color) for fine-grained analysis of perceptual function. It also required participants to switch their attention between feature dimensions on a trial-by-trial basis, thus taxing executive processes. Furthermore, we used a response paradigm that captured task-irrelevant motor output (TIMO), reflecting failures to use the correct stimulus-response rule. ADHD participants had substantially higher perceptual variability than controls, especially for orientation, as well as higher TIMO. In both ADHD and controls, TIMO was strongly affected by the switch manipulation. Across participants, the perceptual variability parameter was correlated with TIMO, suggesting that perceptual deficits are associated with executive function deficits. Based on perceptual variability alone, we were able to classify participants into ADHD and controls with a mean accuracy of about 77%. Participants’ self-reported General Executive Composite score correlated not only with TIMO but also with the perceptual variability parameter. Our results highlight the role of perceptual deficits in ADHD and the usefulness of computational modeling of behavior in dissociating perceptual from executive processes.

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Effect of methylphenidate on visual responses in the superior colliculus in the anaesthetised rat: Role of cortical activation

Cited by 4 publications

References 71 publications

Chronic amphetamine enhances visual input to and suppresses visual output from the superior colliculus in withdrawal

Chronic amphetamine enhances visual input to and suppresses visual output from the superior colliculus in withdrawal

A low-level perceptual correlate of behavioral and clinical deficits in ADHD

A Low-Level Perceptual Correlate of Behavioral and Clinical Deficits in ADHD

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