RESUMEN

Lesion studies have historically been instrumental for establishing causal connections between brain and behavior. They stand to provide additional insight if integrated with multielectrode techniques common in systems neuroscience. Here, we present and test a platform for creating electrolytic lesions through chronically implanted, intracortical multielectrode probes without compromising the ability to acquire neuroelectrophysiology. A custom-built current source provides stable current and allows for controlled, repeatable lesions in awake-behaving animals. Performance of this novel lesioning technique was validated using histology from ex vivo and in vivo testing, current and voltage traces from the device, and measurements of spiking activity before and after lesioning. This electrolytic lesioning method avoids disruptive procedures, provides millimeter precision over the extent and submillimeter precision over the location of the injury, and permits electrophysiological recording of single-unit activity from the remaining neuronal population after lesioning. This technique can be used in many areas of cortex, in several species, and theoretically with any multielectrode probe. The low-cost, external lesioning device can also easily be adopted into an existing electrophysiology recording setup. This technique is expected to enable future causal investigations of the recorded neuronal population's role in neuronal circuit function, while simultaneously providing new insight into local reorganization after neuron loss.

Over the past three decades, the field of neuroscience has made significant leaps in understanding how the brain works. This is largely thanks to microelectrode arrays, devices which are surgically implanted into the outermost layer of the brain known as the cortex. Once inserted, these devices can precisely monitor the electrical activity of a few hundred neurons while also stimulating neurons to reversibly modulate their activity. However, current microelectrode arrays are missing a key function: they cannot irreversibly inactivate neurons over long-time scales. This ability would allow researchers to understand how networks of neurons adapt and re-organize after injury or during neurodegenerative diseases where brain cells are progressively lost. To address this limitation, Bray, Clarke, et al. developed a device capable of creating consistent amounts of neuron loss, while retaining the crucial ability to record electrical activity following a lesion. Calibration tests in sheep and pigs provided the necessary parameters for this custom circuit, which was then verified as safe in non-human primates. These experiments demonstrated that the device could effectively cause neuron loss without compromising the recording capabilities of the microelectrode array. By seamlessly integrating neuron inactivation with monitoring of neuronal activity, scientists can now investigate the direct effects of such damage and subsequent neural reorganization. This device could help neuroscientists to explore neural repair and rehabilitation after brain cell loss, which may lead to better treatments for neurodegenerative diseases. In addition, this technique could offer insights into the interactions between neural circuits that drive behavior, enhancing our understanding of the complex mechanisms underlying how the brain works.

Asunto(s)

RESUMEN

Neural activity in the premotor and motor cortices shows prominent structure in the beta frequency range (13-30 Hz). Currently, the behavioral relevance of this beta band activity (BBA) is debated. The underlying source of motor BBA and how it changes as a function of cortical depth are also not completely understood. Here, we addressed these unresolved questions by investigating BBA recorded using laminar electrodes in the dorsal premotor cortex of 2 male rhesus macaques performing a visual reaction time (RT) reach discrimination task. We observed robust BBA before and after the onset of the visual stimulus but not during the arm movement. While poststimulus BBA was positively correlated with RT throughout the beta frequency range, prestimulus correlation varied by frequency. Low beta frequencies (∼12-20 Hz) were positively correlated with RT, and high beta frequencies (∼22-30 Hz) were negatively correlated with RT. Analysis and simulations suggested that these frequency-dependent correlations could emerge due to a shift in the component frequencies of the prestimulus BBA as a function of RT, such that faster RTs are accompanied by greater power in high beta frequencies. We also observed a laminar dependence of BBA, with deeper electrodes demonstrating stronger power in low beta frequencies both prestimulus and poststimulus. The heterogeneous nature of BBA and the changing relationship between BBA and RT in different task epochs may be a sign of the differential network dynamics involved in cue expectation, decision-making, motor preparation, and movement execution.SIGNIFICANCE STATEMENT Beta band activity (BBA) has been implicated in motor tasks, in disease states, and as a potential signal for brain-machine interfaces. However, the behavioral relevance of BBA and its laminar organization in premotor cortex have not been completely elucidated. Here we addressed these unresolved issues using simultaneous recordings from multiple cortical layers of the premotor cortex of monkeys performing a decision-making task. Our key finding is that BBA is not a monolithic signal. Instead, BBA consists of at least two frequency bands. The relationship between BBA and eventual behavior, such as reaction time, also dynamically changes depending on task epoch. We also provide further evidence that BBA is laminarly organized, with greater power in deeper electrodes for low beta frequencies.

Asunto(s)