A new study published in Neuropharmacology Light on how amphetamine, a stimulant often poorly used and prescribed to deal with the conditions related to attention, affects brain activity linked to the control of executives. The researchers found that a single dose of amphetamine disrupted the capacity of the mouse to judge time with precision by modifying how the neurons of the prefrontal cortex represent time. The results suggest that amphetamine alters cognitive functions by increasing the variability of neural signals that code time, a central component of decision -making and attention.
Amphetamine is a powerful stimulant that increases chemical levels such as dopamine and noradrenaline in the brain. Although it can temporarily improve development or vigilance, it also has well documented side effects, especially when taken in high doses or without medical supervision. An area of concern is its effect on executive functions: higher order processes which include planning, attention and self -control. The prefrontal cortex, a brain region involved in these functions, has proven to be particularly sensitive to changes in dopamine levels, which are significantly affected by the use of amphetamines.
The new study, led by Matthew Weber and Nandakumar Narayanan at Iowa University, sought to better understand how amphetamine affects brain activity during tasks requiring control of managers.
“Amphetamine is a commonly abused medication that causes the dopamine of neurons and prevents the recovering of dopamine. We know that amphetamine can have a huge impact on cognitive function, but we don’t know why or how. Neurodegeneration at Iowa University.
To study this, the researchers turned to the timing interval – a behavioral task in which animals must estimate the time intervals of several seconds to win a reward. Interval timing is widely used in animal and human research because it depends on the prefrontal cortex and requires working attention and memory. Above all, this task provides a means of measuring not only how precise a subject is in the time of judgment, but also to what extent their judgments are coherent from one trial to another.
The research team addressed this question in two parts. First of all, they conducted a meta-analysis of 15 rodent studies previously published on amphetamine and interval synchronization. They found that amphetamine had a significant effect on the accuracy of synchronization, which makes animal estimates more variable. Although it also had an effect on the precision of synchronization – if the moment was generally early or late – the impact on variability was stronger. These results have established a reliable link between the use of amphetamine and disturbed time judgment.
Then, the team conducted their own experience using mice formed on a well -established version of the interval synchronization task. The mice learned to switch between two response ports according to the amount of time spent, with rewards given for correct timing. After several weeks of training, the researchers set up electrodes in the prefrontal mouse cortex to monitor the activity of individual neurons during the task. On the first day, the mice received an injection of saline solution before the task, serving as a reference. On the second day, they received an injection of amphetamine before updating the same task.
In a behavioral way, mice showed increased variability of their calendar after receiving amphetamine. Although their average timing moved a little earlier, the most noticeable effect was the inconsistency when they made their decisions. This change has echoed the results of the anterior meta-analysis and suggested that amphetamine has made more difficult for mice to maintain stable time estimates between tests.
At the neuronal level, the researchers focused on the activity models known as the “ramp” – changes in grade of the fire rates of neurons that occur during the timed interval. It is believed that this type of activity reflects the way the brain keeps time. Under normal conditions, many prefrontal neurons have a constant increase or a decrease in activity during the interval. However, after the administration of amphetamine, this ramp activity has become significantly more variable. The average shooting rate has not changed, but the consistency of the ramp model from one test to another. This suggests that the internal brain clock no longer worked reliably.
“We have guessed that amphetamine altered the brain function, but we were surprised that amphetamine has disturbed the way these neurons work together,” Narayanan told Psypost. “We can measure how neurons work together and have found that amphetamine weakened these interactions.
The researchers also found that coordination between neurons was weakened after exposure to amphetamine. Neurons that normally showed synchronized activity during the task have become less functionally connected. By using joint activity measures between pairs of neurons, researchers have shown that the cooperative firing schemes observed under normal conditions were reduced when the medication was introduced. These weakened interactions can reflect a break in neural networks that support complex synchronization and decision -making processes.
Another key discovery involved the low -frequency brain rhythms in the 2 to 5 Hz range, often linked to cognitive control and attention. These oscillations were significantly reduced in the prefrontal cortex after administration of amphetamines. Previous research has suggested that such brain rhythms play an important role in the organization of neural activity during tasks that require durable concentration or timing. Their disturbance can also explain the loss of precision observed in behavioral data.
Overall, the results provide solid evidence that amphetamine affects how the brain deals with time by disturbing consistency and coordination of neural activity in the prefrontal cortex. The effects were observed after a single dose of the drug, indicating that even acute exposure can interfere with the fundamental aspects of the executive function.
“We focused on simple cognitive behavior – timing intervals of a few seconds, which helps to guide our daily interactions with the world,” said Narayanan. “Our study, which was in rodents and focused on the prefrontal cortex, offers a unique overview of how amphetamine affects this cognitive behavior. We think this is relevant to understand abuse drugs, treatments and also diseases such as Parkinson’s disease and schizophrenia that involve dopamine. “
As with any study, there are limits to consider. First, although the dose used is consistent with previous studies, it reflects the upper end of the beach used in rodent research and may not correspond precisely to typical human use. Second, the drug was administered systemically, affecting the whole brain. Although researchers have focused on the prefrontal cortex, amphetamine also has an impact on other regions such as striatum, which is involved in the precision of synchronization. Future research will be necessary to isolate specific contributions from different brain areas and neurotransmitter systems with observed behavior changes.
Another limitation is that the study only examined the effects of a single dose. We still do not know how much the repeated or chronic use of amphetamine could influence temporal treatment and neural coordination over time. Researchers suggest that future studies could combine this type of neuronal recording with techniques that allow more precise manipulation of cerebral circuits, such as optogenetics, to better understand the causal relationship between neural variability and synchronization behavior.
“Our study was in rodents, so we must be cautious when translation of our human results,” noted Narayanan. “However, the reason why we are studying synchronization behavior is that all mammals, from rodents to humans, have similar brain processes that help guide our actions over time.”
“Amphetamine is a complex drug that affects many different regions of the brain. We study how other brain areas are involved and develop much more specific methods to study how amphetamine affects cognitive function. ”
“Our goal is to learn how dopamine affects the neural circuits of cognition,” added Narayanan. “Thanks to hard work and rigorous science, this knowledge will lead to new biomarkers, and perhaps even to new treatments for diseases that harm cognition.”
“The only way we develop new knowledge like this is a prudent and rigorous science – we want to thank the American public and the National Institutes of Health to finance this work. We hope to continue working on this problem to find a better understanding and better treatments for amphetamine dependence, ADHD, Parkinson’s disease and schizophrenia. ”
The study, “amphetamine increases the variability of synchronization by the degrading prefrontal temporal coding”, was written by Matthew A. Weber, Kartik Sivakumar, Braedon Q. Kirkpatrick, Hannah R. Stutt, Ervina E. Tabakovic, Alexandra S. Bova, Young-Cho Kim and Nandakumar S. Narayanan.