Locomotor activity following lateral frontal lesions in Rhesus monkeys.

Gross, Charles G.

doi:10.1037/h0048041

Cited by 34 publications

(13 citation statements)

References 6 publications

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“…For example, lesions to the PFC in monkeys induce locomotor hyperactivity and impulsive responding, similar to what is observed in children with ADHD 37–39. The PFC can guide behavioral output through its massive projections to the motor and premotor cortices, to basal ganglia structures such as the caudate and subthalamic nucleus, and to the cerebellum by way of the pons (Figure 2).…”

Section: Overview Of the Prefrontal Cortexmentioning

confidence: 68%

ADHD and the Prefrontal Cortex

Arnsten

2009

The Journal of Pediatrics

121

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Attention deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention, impulsivity, and locomotor hyperactivity. Recent advances in neurobiology, imaging, and genetics have led to a greater understanding of the etiology and treatment of ADHD. Studies have found that ADHD is associated with weaker function and structure of prefrontal cortex (PFC) circuits, especially in the right hemisphere. The prefrontal association cortex plays a crucial role in regulating attention, behavior, and emotion, with the right hemisphere specialized for behavioral inhibition. The PFC is highly dependent on the correct neurochemical environment for proper function: noradrenergic stimulation of postsynaptic alpha-2A adrenoceptors and dopaminergic stimulation of D1 receptors is necessary for optimal prefrontal function. ADHD is associated with genetic changes that weaken catecholamine signaling and, in some patients, with slowed PFC maturation. Effective pharmacologic treatments for ADHD all enhance catecholamine signaling in the PFC and strengthen its regulation of attention and behavior. Recent animal studies show that therapeutic doses of stimulant medications preferentially increase norepinephrine and, to a lesser extent, dopamine, in the PFC. These doses reduce locomotor activity and improve PFC regulation of attention and behavior through enhanced catecholamine stimulation of alpha-2A and D1 receptors. These findings in animals are consistent with improved PFC function in normal human subjects and, more prominently, in patients with ADHD. Thus, a highly cohesive story is emerging regarding the etiology and treatment of ADHD.Attention deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention, poor impulse control, and increased motor activity. 1 In the last 20 years, advances in the fields of neuroscience and genetics have provided new insights into this common disorder. We have learned how genetic alterations can affect neural circuits and lead to the symptoms of ADHD, and how correcting these alterations can lead to rational treatments. Much of the research on ADHD has pointed to weaknesses in the prefrontal cortex (PFC), the most highly evolved of the association cortices. The PFC regulates attention and behavior through its widespread connections to sensory and motor cortices, and to subcortical structures such as the basal ganglia and cerebellum. Imaging studies have demonstrated that patients with ADHD have alterations in PFC circuits and demonstrate weaker PFC activation while trying to regulate attention and behavior. The PFC requires optimal levels of norepinephrine (NE) and dopamine Edited by Accardo and WFB Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

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Section: Overview Of the Prefrontal Cortexmentioning

confidence: 68%

ADHD and the Prefrontal Cortex

Arnsten

2009

The Journal of Pediatrics

121

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“…The importance of the prefrontal cortex to inhibitory control has also been shown in monkeys with lesions to the prefrontal cortex (Petrides, 1986), and in electrophysiological (Watanabe, 1986) and imaging studies (Morita et al, 2004). There is also a classic literature demonstrating that prefrontal cortex lesions cause locomotor hyperactivity in monkeys (Kennard et al, 1941;French, 1959;Gross, 1963;Gross and Weiskrantz, 1964). Thus, some of the locomotor hyperactivity observed in ADHD may arise from prefrontal cortex dysfunction.…”

Section: Stimulants: Therapeutic Actions In Adhd Aft Arnstenmentioning

confidence: 99%

Stimulants: Therapeutic Actions in ADHD

Arnsten

2006

Neuropsychopharmacol

419

257

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Stimulants such as methylphenidate and amphetamine are currently the most common treatment for attention deficit hyperactivity disorder (ADHD). For years, it was assumed that stimulants had paradoxical calming effects in ADHD patients, whereas stimulating 'normal' individuals and producing locomotor activation in rats. It is now known that low doses of stimulants focus attention and improve executive function in both normal and ADHD subjects. Furthermore, the seminal work of Kuczenski and Segal showed that low, oral doses of methylphenidate reduce locomotor activity in rats as well. Berridge et al have now shown that these low doses produce marked increases in norepinephrine and dopamine release in the prefrontal cortex, whereas having only subtle effects on subcortical catecholamine release. ihe prefrontal cortex regulates behavior and attention using representational knowledge, and imaging and neuropsychological studies have shown that the prefrontal cortex is weaker in subjects with ADHD. This cortical area is very sensitive to levels of catecholamines: moderate levels engage postsynaptic a2A-adrenoceptors and D1 receptors and improve prefrontal regulation of behavior and attention, while high levels impair prefrontal function via a1-adrenoceptors and excessive D1 receptor stimulation. Administering low doses of methylphenidate to rats improves the working memory and attentional functions of the prefrontal cortex, while high doses impair working memory and produce a perseverative pattern of errors similar to that seen in patients. The low dose improvement is hiocked by either an a2-adrenoceptor or Dl receptor antagonist, suggesting that both norepinephrine and dopamine contribute to the beneficial actions of stimulant medications.

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“…Gross (1963) and Gross and Weiskrantz (1964) distinguished between hyperactivity and hyperreactivity: "Stimuli which increase locomotor activity of normal monkeys (such as light) increase it further after principalis lesions. Stimuli which depress locomotor activity of normal monkeys (such as novel sounds) depress it more after this lesion" (Gross & Weiskrantz, 1964, p. 86).…”

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confidence: 99%